Renal Pathology I

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Renal Pathology I

• Review gross/microscopic anatomy of the kidney
• Clinical Manifestations of Renal Diseases
• Pathology of Selected Renal Diseases

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Gross Anatomy

• 150 grams each (5-6 oz.)
• cortex (1.2-1.5 cm), columns of Bertin
• medulla (pyramids papillae)
• ureters, pelvis, calyces

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Histology

• Glomeruli cortical and juxtamedullary
• Tubules proximal distal
• Interstitium space between the tubules and the
  glomeruli
• Vasculature
• all 4 compartments are affected by most disease
  processes

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Glomerular Histology

• network of capillaries
• fenestrated endothelial cells (70-100 nm)
• GBM avg. thickness 3500 angstroms
• type IV collagen, proteoglycans (heparin)
• visceral parietal epithelium
• podocytes (visceral) form the foot processes
• 20-30 nm filtration slit
• mesangium supporting structure

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Tubules

• Many subdivisions
• Proximal distal tubules
• Collecting ducts
• Major function reabsorb specific portions of
  the filtrate Na, water, glucose, amino acids,
  K, phosphates, and proteins

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Vasculature

• receives 25 cardiac output
• renal cortex receives 90 of this flow
• main-segmental-interlobar-arcuate branches,
  afferent/efferent arterioles
• peritubular capillaries vasa recta
• diseases that affect the vessels of the
  glomeruli will also affect the tubules (!)

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Clinical Manifestations of Renal Diseases

• Azotemia biochemical problem elevated BUN
  creatinine
• decreased GFR
• prerenal, renal or postrenal causes
• Uremia azotemia with clinical symptoms
• gastroenteritis, dermatitis, metabolic acidosis,
  pericarditis, peripheral neuropathy, hyperkalemia

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Major Clinical Renal Syndromes

• Acute Nephritic syndrome glomerular syndrome
  with acute onset of hematuria, mild to moderate
  proteinuria and hypertension
• Nephrotic syndrome heavy proteinuria,
  hypoalbuminemia, edema, hyperlipidemia and
  lipiduria

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Major Renal Syndromes

• Acute renal failure sudden onset of azotemia
  with oliguria (or anuria)
• rapid glomerular injury, acute tubular necrosis,
  interstitial injury
• Asymptomatic hematuria or proteinuria
• detected by lab studies
• mild glomerular abnormalities

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Major Clinical Renal Syndromes

• Renal tubular defects polyuria, nocturia, and
  electrolyte problems (metabolic acidosis)
• Chronic renal failure prolonged uremia
• Urinary tract infections bacteria and pyuria
• Nephrolithiasis (stones) renal colic, hematuria,
  recurrent stone formation

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Diagnosis of Renal Disease

• Renal Biopsy
• Light microscopy
• HE, PAS, Jones and Trichrome stains
• Immunofluorescence microscopy
• immune complexes, fibrin, light chains
• Electron microscopy
• basement membranes and location of ICs

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Congenital Anomalies of the Kidney

• affects 10 of the population
• cause of chronic renal failure in 20 of kids
• Polycystic kidney disease is responsible for 10
  of CRF in adults
• Other anomalies - Agenesis, hypoplasia, ectopic,
  horseshoe kidneys

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Autosomal Dominant (Adult) Polycystic Kidney
Disease

• fairly common, 1 in 1000 persons affected
• autosomal dominant, 95-100 penetrance
• gene is (APKD1) on chromosome 16 (90)
  polycystin (cell membrane protein)
• 1st symptoms usually not until 30-40s
• Renal insufficiency by then
• Hemorrhage pain in many
• chronic renal failure

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Autosomal Dominant Polycystic Kidney Disease

• enlarged bilaterally (can be marked!)
• numerous cysts, filled with clear to red-brown
  fluid
• cysts arise from various segments, thus the
  epithelial lining varies too
• 40 have cysts elsewhere (liver)
• 10 of pts will require dialysis or
  transplantation

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Autosomal Recessive (Childhood) Polycystic Kidney
Disease

• rare, with many subcategories
• mutation on chromosome 6p
• renal failure develops shortly after birth
• cysts are bilateral in the cortex medulla
• liver cysts, progressive liver fibrosis later
  (cirrhosis)

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Glomerular Diseases

• Primary Glomerular Diseases
• kidney is the primary organ involved
• e.g. IgA Nephropathy
• Secondary Glomerular Diseases
• kidney is one of multiple organs involved by a
  systemic disease process
• SLE, Diabetes mellitus, Amyloidosis

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Glomerular Diseases

• some of the most common causes of chronic renal
  failure
• Glomeruli may be injured by many processes
  immunologic, vascular
• Mechanisms
• Immune complexes deposited in glom BM
• Auto-antibodies directed to the BM
• Injury to the glomerular epithelial cells
  (podocytes)

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Diabetes Mellitus

• Systemic disease that causes Nephrotic Syndrome
• major cause of renal morbidity/mortality
• Proteinuria develops 12-20 yrs after the clinical
  onset
• Progressive loss of GFR
• ESRD in almost 30 of IDDM pts
• also affects the arterioles tubules too

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Diabetes Mellitus

• thickened capillary basement membranes
• diffuse glomerular sclerosis
• thickened GBM
• increased mesangial matrix
• nodular glomerular sclerosis
• Kimmelsteil-Wilson disease
• pathognomonic lesion for DM

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Diabetes Mellitus

• Two processes play role in the lesions
• Defect leading to glycosylation
• Thickened basement membranes
• Hemodynamic effects lead to sclerosis
• May also have HTN
• Tight glucose control, ACE-inhibitors

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Minimal Change Disease

• lipoid nephrosis, common in ages 2-6 yrs
• nephrotic syndrome (selective - albumin)
• EM shows fusion of foot processes
• gt 90 respond to steroids (kids)
• by light IF normal, no ICs

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Membranous Glomerulonephritis

• Primary GN causing Nephrotic syndrome
• IF granular deposits of Ig C
• 85 of MGN are idiopathic
• secondary MGN may be seen in pt with
• tumors, SLE, gold/mercury exposure, drugs,
  infections, DM, thyroiditis
• 10 die or develop renal failure in 10 yrs
• course is variable

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Focal Segmental Glomerulosclerosis (FSG)

• 10-15 of nephrotic syndrome
• Some glomeruli are normal
• Idiopathic and secondary FSG
• HIV infection, heroin abuse
• poor response to steroids
• 20 have a rapid course
• 50 develop ESRD in 10 yrs

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