1. Kidney Introduction Pathogenesis of glomerular diseases

2. Objectives By the end of this session the student should be able to:
List the major clinical presentation of disorders of the kidney.
Describe the anatomical components of the kidney and list the major diseases of each.
List and describe the types of immune mechanisms in glomerular diseases.

3. Introduction Kidney function Components of Blood
RBC
WBC
Plasma (water, electrolytes, protein)
Anatomical/Histological components:
Glomeruli
Tubules
Interstitium
vessels

4. Diseases of the kidney Glomeruli Tubulointerstitium Vessels
Glomerulonephritis
Primary
Secondary
Chronic
Tubulointerstitium
Acute tubular necrosis
Pyelonephritis
Acute
chronic
Vessels
Nephrosclerosis
Benign
Malignant
Urinary obstruction
Stones
Hydronephrosis
Cystic diseases of the kidney
Tumors

5. Renal dysfunction Urea, creatinine Azotemia (high urea, creatinine)
Pre renal
Renal
Post renal
Uremia (azotemia+ clinical features)
Features of uremia

6. Major clinical presentations
Acute nephritic syndrome
Gross hematuria, mild-moderate proteinuria, hypertension, azotemia, edema
Nephrotic syndrome
Heavy proteinuria (>3.5g/day), hypoalbuminemia, edema, hyperlipidemia, lipiduria
Asyptomatic hematuria or proteinuria

7. Major clinical presentations
Rapidly progressive glomerulonephritis
Acute renal failure
Chronic renal failure
UTI urinary tract infection
Renal colic (stones)
Obstruction
Mass lesion

8. Kidney Biopsy

9. Kidney Biopsy Send fresh Routine processing Immunoflourescence (IF)
Electron microscopy (EM)
Light microscopy (formaline fixed)

10. Case Presentation

11. A 47-year-old black male truck driver presents to the emergency room with intractable nausea and vomiting, dyspnea on exertion, and dizziness. The nausea began about two weeks prior to admission; vomiting has occurred within the last few days. The chest pain has been present for only 2-3 days and is described as retrosternal, burning, and worse on inspiration. There is no history of medication or toxin exposure. His past medical history is positive for hypertension diagnosed 14 years ago with no follow-up. He has smoked 1 ppd for 27 years.

12. On physical examination, he is a thin, black man in moderate distress
On physical examination, he is a thin, black man in moderate distress. His blood pressure is 160/120, temperature 36.7°C, pulse 100 (nl /min). His skin is pale with numerous areas of bruising. Lung exam reveals bilateral rales to the mid lung fields, and cardiac exam reveals muffled heart sounds, a friction rub, and a I/VI systolic ejection murmur. Chest x-ray shows moderate cardiomegaly with increased pulmonary vascular markings and hazy obliteration of the lower lung bases. Abdominal ultrasound examination shows a right kidney size of 7 cm (nl approx. 10 cm) and a left kidney size of 6.8 cm without evidence of pelvicalyceal dilation.

13. Urinalysis: protein - 1+ blood - 1+ glucose - neg casts - neg
bacteria - neg

14. WBC: 6,700/mm3
Platelets: 250,000/mm3
Hematocrit: 26%
Creatinine: 200 mmol/L (high, normal <120)
BUN: 215 mg/dL (high, normal <25)
Calcium: 6.2 mg/dL (low, normal 8-10mg/dl)
Uric Acid: 16.5 mg/dL (high, normal 5-7)
Cardiac markers of MI: negative

15. An echocardiogram reveals a moderate amount of fluid around the heart
An echocardiogram reveals a moderate amount of fluid around the heart. A pericardiocentesis is performed, and 250 cc of serosanguineous fluid is removed. An urgent request for hemodialysis is made, and the patient is dialyzed with some relief in his breathing and chest pain. However, the next morning, the patient complains of abdominal pain and passes several melanotic stools, followed by gross blood. Hypotension and arrhythmias follow, and death supervenes. An autopsy is performed.

16. What are the possible causes of this appearance of the kidneys?

17. Hypertension, D.M., Chronic glomerulonephritis

18. Describe the four compartments (glomeruli, tubules, interstitium, and vasculature)

19. Describe the abnormality

20. What is the abnormality?

21. What is the abnormality?

22. Colon mucosa: What is the abnormality?

23. Four parathyroid glands

24. Discussion Hypertension Chronic Renal Failure Uremia Urinalysis
Blood work
Kidney findings
Secondary hyper parathyroidism

25. Glomerular diseases

26. Glomerulus Structure Filtering membrane
1. Endothelial cells
2. GBM glomerular basement membrane
3. Visceral epithelium
GFR: glomerular filtration rate
Mesangium
Permeablility
Water, albumin
Size, charge

30. Glomerular disease
Primary
Seconday
Hereditary

31. Membranoproliferative GN Diffuse proliferative GN Crescentic GN
Glomerular disease
Primary
Minimal change GN
Membranous GN
Focal segmental GS
Membranoproliferative GN
Diffuse proliferative GN
Crescentic GN
Seconday
SLE, DM, Amyloidosis, Goodpasture, vasculitis
Hereditary
Albort syndrome

32. Pathogenesis of Glomerular Disease
Immune disorder
Kidney involvement
Injury by inflammation and other mediators
Glomerular dysfunction

33. Pathogenesis of Glomerular Disease
Immune disorder
Circulating immune complex
Immune complex formation
Cell-mediated
Glomerular dysfunction

34. Pathogenesis
1. Circulating Immune complex nephritis (type III hypersensitivity)
Antigen is not glomerular origin
Intrinsic- SLE
Extrinsic- Poststreptococcal GN, HepB, Malaria
Ag-Ab complex is trapped in glomeruli
Complement activation
injury

35. Pathogenesis
1. Circulating Immune complex nephritis (type III hypersensitivity)
Morphology:
IF: deposits (glomerular)
EM: electron-dense deposits (mesangial, subendothelial, subepithelial)
Proliferative: leukocytes, endothelial, mesangial, epithelial

36. Pathogenesis
1. Circulating Immune complex nephritis (type III hypersensitivity)
What happen
Short lived Ag-Ab complex---- Recovery
Repeated Ag-Ab complex chronic GN

37. Pathogenesis of Glomerular Disease
Immune disorder
Circulating immune complex
In-situ Immune complex formation
Cell-mediated
Glomerular dysfunction

38. Pathogenesis 2. In-situ Immune complex nephritis In-situ Intrinsic
Extrinsic/planted

39. Pathogenesis 2. In-situ Immune complex nephritis Anti-GBM
Goodpasture syndorme
In human: auto antibodies
Pathology:
Severe glomerular damage
Cresentic GN
Ag: alpha3 chain of collagen type IV
(Rabbits Masugi Nephritis) injury to rats by antibodies of rabbit
IF: linear deposits

40. Pathogenesis 2. In-situ Immune complex nephritis Haymann Nephritis:
Immunizing rats to proximal tubular brush border
IF: granular deposits of Ig and complement along the GBM
Ag (megalin) on visceral epithelial cells
Result in membranous GN

41. Pathogenesis 2. In-situ Immune complex nephritis Planted antigen DNA
Bacterial products (groupA strep)
IgG/complex
IF: granular pattern

42. Pathogenesis of Glomerular Disease
Immune disorder
Circulating immune complex
In-situ Immune complex formation
Cell-mediated
Glomerular dysfunction

43. Pathogenesis
Cell mediated Immune GN
Sensitized T cells
suspected

44. Pathogenesis of Glomerular Disease
Immune disorder
Circulating immune complex
In situ Immune complex formation
Cell-mediated
Glomerular dysfunction

45. Pathogenesis of Glomerular Disease
Immune disorder
Kidney involvement
Injury by inflammation and other mediators
Glomerular dysfunction

46. Mediators of Immune Injury
Cells
Plasma products

47. Mediators of Immune Injury
Cells
Neutrophils
Proteases, oxygen free radicals
Monocytes
Platelets
Epithelial cells
Plasma products

48. Mediators of Immune Injury
Cells
Plasma products
Direct cytotoxicity by Ab
Fibrin related products
Complement activiation
C5-C9 membrane attack complex

49. Epithelial cell injury
Ab to visceral epithelium
Toxins
Cytokins
Loss of foot processes, vacuolization, detachment
proteinuria

50. Pathogenesis of Glomerular Disease
Immune disorder
Kidney involvement
Injury by inflammation and other mediators
Glomerular dysfunction

51. Renal ablation glomerulopathy
Any disease resulting in decrease GFR to 30-50%
Progress to end-stage renal failure
glomerulosclerosis

52. Renal ablation glomerulopathy
Glomerulosclerosis—hypertrophy—increase in single nephron GRF—increase blood flow—capillary hypertension—endothelial/epithelial inury—protein/fibrin/lipid deposition—capillary collapse—lyaline degeneration—proliferation of mesangial cells—increase mesangial matrix—sclerosis.

53. Objectives By the end of this session the student should be able to:
List the major clinical presentation of disorders of the kidney.
Describe the anatomical components of the kidney and list the major diseases of each.
List and describe the types of immune mechanisms in glomerular diseases.