Renal Disease

Basic Anatomy Renal Microanatomy

Glomerular Microanatomy The Business End of the Kidney

1 A Little Higher Please The Details

Renal Functions Amniotic Fluid

„ The Kidney does lots of stuff „ Amniotic fluid is mostly urine produced by „ RBC production the developing fetus. „ Erythropoietin the developing fetus. „ Calcium metabolism „ No urine, no kidneys or „ By means of phosphate „ Major malconnections of lower urinary elimination. Major malconnections of lower urinary tract. „ Acid-Base balance. „ Na+ and K+ balance „ If the expectant mother is ‘small for „ Processes Budweiser dates’, the fetus may have problems with into urine renal development.

Big Ticket Items

„ Immunological injury „ Glomerulus „ Interstitial tissue „ Vascular injury or compromise „ Diabetes „ Hypertension „ Infections „ Upper urinary tract „ Lower urinary tract

2 Nephritic Syndrome Clinical Syndromes „ Acute injury, multiple possible causes „ Major, acute injury to „ Nephritic syndrome the glomerular „ Nephrotic syndrome basement membrane. „ Basic clinical pattern „ Chronic renal failure „ RBCs in the urine „ Localized pain „ RBC casts in urine „ Decreased urine output „ Increased protein „ Increased B/P

Urinary Casts Clinical Syndromes „ Material cleared or shed by a sick glomerulus. „ Congeals within the „ Convoluted tubules or „ Nephritic syndrome „ Collecting ducts Collecting ducts „ Nephrotic syndrome „ Creates a ‘cast’ of the interior of the duct it „ Chronic renal failure formed in. „ Localized pain „ Is Cleared in urine. „ Observed microscopically

Nephrotic Syndrome Chronic Renal Failure

„ Many causes „ Progressive loss „ Chronic injury of the glomerulus. of renal function. „ Anemia „ Many causes Anemia „ Bleeding „ Basic clinical pattern „ Increased „ Proteinuria (>3.5 gm) Increased infections „ High serum lipids „ Accumulation of „ Lipiduria Accumulation of nitrogen wastes „ Low serum albumen „ Pericarditis „ Edema „ Uremic frost

3 Glomerulonephritis General Features

„ Mesangial cell proliferation „ Leukocyte infiltration „ BM thickening „ Regular (linear) „ Irregular (lumpy)

Immunologic Injury Acute Glomerulonephritis

„ Follows Streptoccocal infection „ Antigen-antibody complexes lodge beneath the foot processes. „ Elicit a flaming inflammatory reaction „ Complement deposited „ Huge holes in BM „ Nephritic syndrome

Acute Glomerulonephritis Acute Glomerulonephritis „ Large number of immune complexes all at once „ Collect under foot processes because of charge „ Fix C’ „ Focal destruction of BM „ Leakage of RBCs

4 Membranous Glomerulonephritis Acute Glomerulonephritis „ Slow accumulation of Ag-Ab complexes „ Small holes, but numerous „ Anti-human IgG labeled with „ Tremendous protein loss fluorescence. „ Identifies the immune complexes „ Granular pattern „ Irregular clumps „ Fix C’ „ Membrane damage

Membranous Glomerulonephritis Goodpasture’s Syndrome

„ Antibodies specifically „ Anti-human IgG against BM labeled with against BM fluorescence. „ Different from immune complex disease. „ Identifies the „ Starts as a pulmonary immune complexes infection (virus). „ Linear pattern „ Make antibodies against pulmonary BM „ Smooth contours pulmonary BM „ Cross reacts with „ Smaller holes Cross reacts with glomerular BM „ Protein loss „ No RBC loss

Membranoproliferative Glomerulonephritis Minimal Change Glomerulonephritis

„ Foot process disease „ Hybrid appearance „ Children 2-6 yrs „ Split BM „ „ Train track „ Follows viral infection „ C’ deposition „ „ Alternate pathway T-cell mediated? „ Several types based „ Tremendous loss of on what starts it protein (nephrotic) „ Steroids helpful

5 Minimal Change Glomerulonephritis

Diabetic Nephropathy Diabetes is a Vascular Disease

„ Diabetes is a small vessel disease. „ Arterioles „ Atherosclerosis „ All parts of the „ Accelerated kidney are involved. „ Arterioles -> „ Glomerulus most „ Retinal blindness significantly „ Gangrene „ „ Kimmelstiel-Wilson „ Renal failure „ Non-enzymatic „ Neuropathy glycosylation of proteins

Non-Enzymatic Glycosylation IgA Nephropathy

„ Glucose sticks to, and alters, all sorts of proteins. „ No way of getting rid of the „ Mesangial deposits of modified protein. IgA antibodies. „ BMs especially „ Mid 20’s „ Small vessels narrow „ Multiple episodes of „ Glomerular BM hematuria. „ Thickens „ „ Becomes inefficient More common than „ Loss of protein once thought „ Renal failure „ Transplant

6 Tubular and Interstitial Disease

„ Acute tubular necrosis „ Pure tubular cell condition „ Ischemia or toxic „ Interstitial (Pyelonephritis) „ Toxic „ Infectious „ Autoimmune (medications)

Acute Tubular Necrosis (ATN) Pyelonephritis

„ Ischemic or toxic „ Inflammation of the death of epithelial interstitial tissue. cells. „ Infectious „ Toxic „ Dead epithelial cells „ Immunologic fall off the tubular „ Acute pyelonephritis. BM. „ Bacteria ascend from the urinary bladder. „ They clog the tubules. „ Gram neg rods „ Blood, pus and casts in the „ No urine output. urine. „ These folks are sick. „ Loss of concentrating gradient.

Bacterial Pyelonephritis Ureteral Implant Angle

„ Actually two ways „ Lack of sphincter „ Blood borne action. „ Ascend from bladder „ Reflux „ Direct infection of renal tissue. „ Bugs go upstream „ Predisposing factors „ Congenital „ Ureteral reflux „ Problems for „ Lower urinary tract children obstruction „ Diabetes „ Surgically „ Vascular disease correctable

7 Chronic Pyelonephritis Renal Papillary Necrosis

„ Vascular insufficiency. „ Death of the papillae „ Arteriolar problem „ Slough and obstruct „ Chronic Chronic ureter inflammation „ „ Round cells Inflammatory and/or „ Tissue destruction vascular causes „ Fibrosis „ Diabetes „ Diabetes „ Analgesic nephropathy „ Hypertension „ Chronic pyelonephritis „ Repeat infections „ ‘Thyroidization’

Hypertension Hypertension and the Kidney

„ Arteriolar changes „ Onion skinning „ Loss of luminal size „ Reduced blood flow „ Release of renin „ Higher blood pressure „ Chronic pyelonephritis „ In time renal failure

Additional Vascular Problems

„ Diabetes (small vessel disease) „ Clotting related „ Emboli „ Sickle cell disease

8 Cystic Disease Tumors of the kidney

„ Polycystic renal disease „ Growth of tubular „ Benign vs. malignant epithelium causes cyst formation. „ Primary vs. metastatic „ Cysts accumulate fluid and squeeze the rest of the kidney out of existence. „ Adult and juvenile forms

Renal Cell Carcinoma Wilm’s Tumor

„ Arises from tubular „ Childhood tumor epithelium „ Embryonic appearing „ Likes to spread by tissue way of blood vessels. „ Two cell types „ Widely metastatic „ Stromal element „ Painless hematuria „ Little tubules „ Golden yellow with areas of necrosis.

Lower Urinary Tract

„ Infections „ Stones „ Cancer

9 Bladder Infections Kidney Stones

„ Most are formed of „ Very common oxalate crystals. „ Host bugs „ Contributing factors „ E. coli „ Dehydration „ High protein diet „ Other gram negatives „ Genetics „ Urethral trauma „ Very painful „ Catheterization „ Ureteral dilation „ Paraplegics especially

Kidney Stones Papillary Transition Cell Carcinoma

„ Large calculus „ Transition cell „ Hydronephrotic kidney origin „ Tobacco „ Industrial chemicals „ Hematuria

Papillary Transition Cell Carcinoma

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