1 Kidney and its Collecting System Lecture By: Dr. Amitabha Basu. MD 2 KIDNEY WHAT WE WILL STUDY IN THIS LECTURE Few ANOMALIES NON-NEOPLASTIC NEOPLASTIC 3 ANOMALIES of kidney 1. Horseshoe" kidney 2. Agenesis 3. Ectopic kidney 4 Here is a "horseshoe" kidney. This is a congenital anomaly that most often occurs in association with other anomalies or syndromes. Complications: 1. Stone formation, 2. Infection, 5 Agenesis 1. Bilateral- Presentation: 1. Oligohydramnios 2. Potter facies: Flat nose, low set ear and recessed chin. 3. Pulmonary hypoplasia 2. Unilateral: 1. Compensatory hyperplasia ( particularly of glomeruli) of other kidney. 6 Note Any kidney disease if present in a baby in the uterus : that fetus will have pulmonary hypoplasia. Severity of the disease depends on the severity of the kidney lesion. 7 Ectopic kidney Most common: pelvis Small but normal function Present as a mass in pelvis. 8 Sequence by which we will proceed 1. TERMS and definitions (Important) 2. Cystic diseases 3. Interstitial diseases 4. Hypertensive disease 5. Kidney stone 6. Urate nephropathy. 7. Childhood Hemolytic Disease 9 Terminology You must Know 1. Azotemia and Uremia 2. Acute Renal Failure 3. Chronic Renal failure 10 AZOTEMIA Its a Biochemical Change due to a diseased Kidney 1. ELEVATION OF BLOOD UREA NITROGEN (BUN) 2. Elevated creatinine 3. Decreased GFR( GLOMERULAR FILTRATION RATE) 11 Uremia A patient with Azotemia with profound clinical signs and symptoms. (failure of renal excretory function along with, metabolic and endocrine abnormality) Clinical: Asterixis ( flapping tremor) 12 Fluid and Electrolytes Hyperkalemia Metabolic acidosis Calcium Phosphate and Bone Hypocalcemia, Secondary hyperparathyroidism HematologicAnemia, Bleeding diathesis CardiopulmonaryUremic pericarditis GastrointestinalNausea and vomiting, gastritis, colitis NeuromuscularPeripheral neuropathy, Encephalopathy DermatologicSallow color, Pruritus 13 Terms OliguriaUrine output < 500/400 ml/24 hours Cause: nephritic syndromes, Acute renal failure. AnuriaUrine output NIL Cause : Stone, ARF (some times), tumors. PolyuriaUrine output > 3000ml/24 hours ( at least 2.5 ml) Cause: Diabetes insipidus, DM 14 Acute Renal Failure 1. Acute Loss of Renal Function 2. Oliguria less urine (< 400ml/day) 3. Or, Anuria No urine 4. Recent onset azotemia 15 Cause of acute renal failure (ARF) A.Adult A.Acute Tubule necrosis B.Crescentic Glomerulonephritis C.Papillary necrosis B.Children: A.Childhood Hemolytic-Uremic Syndrome 16 Chronic Renal failure o Prolonged signs and symptoms of Uremia. Increasing BUN, creatinine. o END RESULT OF ALL CHRONIC RENAL DISEASES. o Leads to uremia. 17 End-stage renal disease (ESRD) Definition. End-stage of various kidney disease. When GFR < 5% of normal Survival only by dialysis or transplant 18 Cystic Diseases of Kidney 1. Adult polycystic Kidney Diseases 2. Childhood polycystic Kidney Diseases 4. Hemodialysis associate cyst 19 Autosomal-dominant (adult) polycystic kidney disease (ADPKD) Genetic : Mutation of PKD1 ( ch 16) and PKD 2 gene and loss of Polycystin 1 and Polycystin 2 (stromal material) respectively. Result: abnormal stroma and cell-to-cell adhesion tubular dilatation (cyst formation) and vascular dilatation. 20 MORPHOLOGY: GROSS 1.Bilateral or Unilateral : May weight up to 4 kg. 2.Composed solely of cysts of varying sizes.( 3-4cm in Diameter) no intervening parenchyma. 3.Cyst may contain serous / hemorrhagic fluid 21 ADULT POLYCYSTIC KIDNEY(APKD) CLINICAL FEATURES 1. PRODUCE SYMPTOMS usually ON AND AFTER 4th DECADE. 2. Flank pain, heavy dragging sensation 3. Intermittent gross Hematuria. 4. Hypertension /Urinary infections (75%) 5. Saccular aneurism in Circle of Willis. 6. 1/3 rd cases Asymptomatic Liver Cyst found. 7. Colonic Diverticulum. 22 ADULT POLYCYSTIC KIDNEY(APKD) Prognosis A. Progresses slowly ( many years with azotemia ) B. Endstage Renal failure occur at about age 50. C. Uremia or Hypertensive complications ( read hypertensive complications). 23 Childhood Polycystic Kidney 24 Childhood Polycystic Kidney Autosomal Recessive Progress to renal failure Gross: Bilateral and sponge like appearance 25 Micro: Cysts are elongated and radially. Present in cortex and medulla These cysts are dilated distal tubules and collecting ducts. 26 Clinical features 1. Clinical Features are present at birth 2. Young adult die due to renal failure 3. Hepatic fibrosis lead to early cirrhosis 4. If the disease is present in a fetus: Pulmonary hypoplasia may be presents. 27 28 ACQUIRED (DIALYSIS-ASSOCIATED) CYSTIC DISEASE Due to repeated dialysis in chronic renal failure. Cysts at the corticomedullary junction and in the medulla. 29 ACQUIRED (DIALYSIS-ASSOCIATED) CYSTIC DISEASE Complications 1.May deposit Amyloid (A2 micro- globulin) in the kidney. 2.And high chance Renal cell carcinoma. 30 Can occur at any level in urinary collecting system. Symptomatic Urolithiasis is more common in Males My kidney stone: What a beauty! 31 Renal stone: urolithiasis 1. Calcium oxalate (or phosphate) 75% 2. Magnesium ammonium phosphate (struvite, or "triple phosphate") 10-15% 3. Uric acid 6%. 4. Cystene stone. 32 Calcium stone Calcium Oxalate and Phosphate 1.Idiopathic Hypercalciuria (normal serum calcium) 2.Hypercalciuria and hypercalcemia ( primary hyperparathyroidism / others) 3.Ethylene glycol toxicity with acidosis 4.No known metabolic abnormality (15-20%) Increase in the Urine Concentration (super saturation) of stones constituents( calcium) 33 Hypercalcemia Non neoplastic cause: Sarcoidosis ( due to 1,25-dihydroxyvitamin D ) Pagets disease Primary hyperparathyroidism ( due to PTH) Neoplastic cause ( due to PTH like peptides) Renal cell carcinoma Squamous cell carcinoma Breast carcinoma Metastatic tumor in bone (High alkaline phosphatase is the marker). Multiple Myeloma. 34 Calcium oxalate Crystal in Urine and kidney Envelop Positive crystal in polarized light 35 Struvite stones Cause : Infection" by Proteus Vulgaris that split urea to ammonia, favor their formation. Present in alkaline urine Urine: coffin lid crystal found in urine. Morphology: stag horn calculi. 36 A large "staghorn" calculus Create a cast of renal pelvis and calyceal system. Associated with pyelonephritis and atrophy of cortex of kidney. 37 Uric acid stones Cause: Hyperuricemia (gout) Leukemia undergoing chemotherapy ( massive cell damage) Urine: Needle like crystal in acid urine. X ray: cannot be seen 38 Clinical 1.Their passage is marked by intense abdominal or back or flank pain: known as renal or ureteral "colic. 2.Hematuria 3. Bacterial Infection (pyelonephritis) 4. Hydronephrosis, hydroureter. 39 Hydronephrosis and its cause 40 What is Hydronephrosis ? Def: Dilation of renal Pelvis and calyces, associated with atrophy of the parenchyma. 41 Pathogenesis 1. Initially the renal Pelvis and calyces are dilated 2. Result in the atrophy of the Cortex and infection (pyelonephritis). 42 MORPHOLOGY Bilateral Hydronephrosis: 1. Obstruction in the urethra (urethral valve-child), 2. Pregnancy, 3. Benign Hyperplasia of Prostate. 43 Unilateral Hydronephrosis Obstruction from: 1.Within Lumen of ureter: Stone, necrotic Papilla. 2.From the wall of the Lumen: transitional cell carcinoma 3.Outside the ureter: Enlarged lymph node, Tumor 44 Unilateral Hydronephrosis: note blunted calyces 45 Clinical Features Unilateral- unfortunately remain Silent, so it may cause major renal damage. Recurrent urinary tract infection. 46 DISEASE AFFECTING TUBULES AND INTERSTITIUM 1.Pyelonephritis 1.Acute 2.Chronic 2.Acute tubular Necrosis 47 Pyelonephritis TYPES ACUTE AND CHRONIC 48 ACUTE PYELONEPHRITIS ETIOLOGY & PATHOGENESIS Gram Negative Rods ( from urine) E. coli, Proteus, Klebsiella, Enterobacter and Pseudomonas. Others = 1. Staphylococcus Aureus (from blood). 49 Route of spread of infection 1. Ascending Infections: reach the kidney either by ascending up the urinary tract common in female. 2. Hematgenous spread with sepsis or infective Endocarditis, abscess (Staphylococcus Aureus). 50 Ascending Infection :: Pathogenesis 1.Colonization of bacteria take place in the distal urethra (introitus of female). 2.Then they are carried up to wards the bladder with urine, 3.Infected urine enter ureter by vesicoureteral Reflux. 4.And reach kidney 51 Less angle of ureter Normal angle of ureter 52 Predisposing Factors for Pyelonephritis 1. Obstruction, short urethra. 2. Patient Age = adult female > male 3. Diabetes mellitus: hyperglycemia 4. BPH, Uterine prolapse. 5. Hospital procedure: Urethral catheterization, cystoscopy, urethral trauma. 53 Morphology of pyelonephritis 1. Abscess (Neutrophils in the interstitium): patchy 2. Papillary necrosis : is common in Diabetes (involve apical 2/3 rd of renal papilla) 54 Papillary necrosis is common in Diabetes ( involve apical 2/3 rd of papilla) 55 Clinical courses: Acute Pyelonephritis < 1 year : presence of urethral valve Upto 40 years: F>M After 40 years : M=F Sudden temperature,chill,malise, pain in costovertebral angle, Dysuria, increased frequency,ungency 56 Urinary Findings Acute Pyelonephritis 1. Leucocytes (mainly neutrophil) 2. Bacteriuria ( urine culture +ve) 3. WBC cell cast. 57 Chronic Pyelonephritis 58 Etiology Repeated lower urinary tract infections for years. Obstruction Chronic reflux 59 Pathogenesis Two Forms 1. Chronic obstructives Pyelonephritis Obstruction predispose to infection. 2. Chronic Reflux associated Pyelonephritis. Common form of chronic Pyelonephritic Scarring. 60 Key word: Broad Scars, irregular shape of both kidney. Chronic reflux associated Pyelonephritis 61 Microscopy 1. Colloid Cast in tubules (Thyroidization) 2. The large collection of chronic inflammatory cells 3. Intersitial fibrosis 62 63 Clinical Finding: chronic Pyelonephritis Produce polyuria and Nocturia (usually in a bilateral involvement). Important cause of Chronic renal Failure. 64 Other interstitial disease Drug-induced interstitial nephritis Analgesic Nephropathy Urate Nephropathy 65 Drug-induced interstitial nephritis Etiology: Synthetic penicillin, rifampicin, thiazides, phenylbutazone. Clinical: Onset 15 days (avg.) after exposure of the drug Fever, rash, eosinophilia and renal abnormality. Withdrawal of the drug is followed by recovery. 66 Kidney change Micro: eosinophilc infiltrate Urine: eosinophil +++ Mild protenuria 67 Analgesic Nephropathy Etiology: only after consuming large amount of medicine: Like: Phenacetin, acetaminophen, aspirin, Caffeine, Codeine. Morphology: papillary necrosis and intestinal nephritis 68 Analgesic Nephropathy 1. Clinical Features 1. CRF, Hypertension, anemia, massive protenuria. 2. Complications Transitional Cell Carcinoma who survives renal failure. 69 Chronic urate nephropathy Cause : Cellular necrosis of tumor cells with chemotherapy Gout ( painful great toe; increased uric acid). Morphology: Tophi in interstitium with a foreign body reaction. ( chalky white material on trans section) 70 Acute Tubular Necrosis (ATN) Definition Types (morphology) Pathophysiology of renal failure Urine findings Clinical 71 ACUTE TUBULAR NECROSIS A. Definition: Necrosis of tubular epithelium B. Most common cause of Acute renal Failure in adult. C. Reversible renal lesion( if taken care of immediately). 72 Two patterns (ETIOLOGY): 1. Ischemic ATN due to : Shock, mismatched blood transfusion, myoglobinuria ( damage of skeletal muscle). 2. Nephrotoxic ATN due to : poisons, mercury, gentamicin, radiographic contrast agent etc. 73 Distribution of ATN (very important): recall the causes PATCHYDIFFUSE 74 Necrotic epithelial cell in ATN: note there is no inflammatory cells Features of reversible cell injury due to hypoxia. Cell swelling, clumping chromatin Biochemical feature of cell: High Na High water Increased lactic acid 75 Urinalysis Protein (hyaline) cast or tubular epithelial (cellular) cast seen in the tubules 76 ATN : Natural history of disease. Featured by Anuria /oliguria and rapid rise in blood urea nitrogen. Initiation phaseslight decline in urine output with a rise in BUN Maintenance phase Oliguria: rising BUN, hyperkalemia, metabolic acidosis, uremia Recovery phase Due to Regeneration of tubular epithelium occur increase in urine volume (> 3 L/day). Hypokalemia, infection. 77 DISEASE INVOLVING THE BLOOD VESSELS Benign Nephrosclerosis Malignant nephrosclerosis Thrombotic Microangiopathies 78 Benign Nephrosclerosis Associated with long-standing hypertension, Patients are usually old. o This infrequently cause Uremia and death o A mild proteinuria is present. o GFR mildly diminished. 79 Benign nephrosclerosis. (Morphology- Gross) Symmetrically atrophic kidney (weighing 110 to 130 g) Characteristic finely granular appearance as seen here. Granular Surface 80 Identify the microscopic picture below Hyaline arteriolosclerosis 81 Malignant Nephrosclerosis *** Its a Medical Emergency 82 Malignant nephrosclerosis: Diastolic BP>120mmHg flea-bitten appearances on gross 83 Malignant Hypertension: more terms about the blood vessels change Necrotizing Arteriolitis Hyperplasic arteriosclerosis Fibrinoid necrosis 84 Malignant nephrosclerosis :Clinical features 1. Papilledema, encephalopathy, cardiovascular abnormality, and 2. Renal failure: A.Nausea, vomiting B.Marked proteinuria C.Hematuria. D.Visual impairment 85 Thrombotic Microangiopathies 1. Childhood Hemolytic Disease 2. Thrombotic Thrombocytopenic Purpura (adult) Clinical Presentation 1. Hemolytic anemia ( jaundice, increased reticulocytes, schistocytes) 2.Thrombocytopenia 3. Acute renal failure 86 Childhood Hemolytic Disease Etiology: E. coli infection - Shiga-like toxin. Pathogenesis: Shiga toxin injury to endothelium increased endothelin and tissue factor and loss of endothelial Nitric Oxide vasoconstriction and fibrin thrombosis in glomeruli acute renal failure. 87 Fibrin thrombi in microcirculation/ glomeruli Increased fibrin degradation product, prolonged aPTT, PT, clotting time and bleeding time. 88 Clinical A bloody diarrhea is followed in a few days by renal failure. Jaundice Azotemia/uremia Prognosis: rapidly fatal, but recover in a few weeks with supportive dialysis. 89 Do not eat infected Hamburger !!! 90 THANK YOU