nephrology lec for 4th year

1. Parenchymal kidney diseases
Umm Al-Qurra university- Faculty of medicine- 4th year
Department of pathology
Dr.Raid Jastania
Dr. Abeer Shaker

2. Learning Outcomes
At the end of this lecture the student should be able to
• Discuss the most common systemic disease that affect the kidney illustrating
pathology of lupus nephritis
• Discuss the most common causes of glomerular diseases
• Understand the difference between nephrotic and nephritic syndrome
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3. Introduction
 Glomerular diseases constitute some of the major problems in nephrology.
 Glomerulonephritis is an inflammation of the glomerulus, while glomerulopathy
is a term for disorder affecting this structure.
 Glomeruli may be injured by variety of factors and in course of several systemic
diseases.
 Most of the glomerular diseases are immunologically mediated
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4. Glomerular diseases
Glomerulopathies in Systemic diseases
 SLE
 Diabetes mellitus
 Goodpasture
 Bacterial endocarditis
 Amyloidosis
 Vascular disorders
• Hypertension
• PAN
• Wegener’s granulomatosis
• Henoch-Schönlein purpura.
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Primary Glomerular diseases
- Minor Glomerular abnormalities:
Minimal Change disease
- Focal and/or segmental lesions:
- Focal glomerulosclerosis
- Focal proliferative glomerulonephritis
- Diffuse glomerulonephritis
- Chronic GN (most common cause of
CRF)

5. Clinical classification of renal diseases
1. Nephritic syndrome
2. Nephrotic syndrome
3. Asymptomatic hematuria or proteinuria,
4. Rapidly progressive glomerulonephritis
5. Acute renal failure : oliguria or anuria, with recent onset of zotemia.
6. Chronic renal failure
7. Urinary tract infection
8. Nephrolithiasis (renal stones)
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6. Immune mechanisms underlie most forms of primary glomerulopathies and many of
secondary glomerular disorders.
ANTIBODY MEDIATED
IN SITU IMMUNE COMPLEX DEPOSITION
CIRCULATING IMMUNE COMPLEX MEDIATED
CYTOTOXIC ANTIBODIES CELL MEDIATED IMMUNE INJURY
ACTIVATION OF ALTERNATIVE COMPLEMENT PATHWAY
Pathogenesis of glomerular injury

7. Immune mechanism in immune glomerulonephritis
1. Antigen or Antibody or immune complex deposition.
2. Immune reaction
3. Activation of complement system
4. Destruction of glomerular structure
5. Inflammation
6. Affect renal function
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8. Clinical-Pathological correlations
 Almost any variety of histopathologic findings can be found in any of the
clinical syndromes and vice versa
 There are broad correspondences between prognosis and histologic
findings.
 Each morphologic type of glomerular disease has a clinical correlation as
well as etiology and pathogenesis.
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9. What is Nephrotic syndrome?
marked Proteinurea
≥3.5 g/day
(protein: creatinine ratio >3-3.5)
Hypoalbuminaeia
<3g/L
Hyperlipidemia &
hyperlipiduria
Generalized
Oedema
Clinical complex that includes the following:

10. The most important causes that characteristically lead to the
nephrotic syndrome are
Primary (idiopathic):
•Membranous nephropathy
•Minimal change disease
•Focal segmental glomerulosclerosis
•Membranoproliferative GN
•IgA nephropathy (rare cause)
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11. Secondary to:
Diabetes mellitus
Amyloidosis
Systemic lupus erythrematosus
Ingestion of drugs (gold, penicillamine , "street heroin")
Infections (malaria, syphilis, hepatitis B, HIV)
Malignancy (carcinoma & melanoma)
Miscellaneous (bee-sting allergy, hereditary nephritis)
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12. Case1#
A 5 years old child presented to pediatric clinic by his parents suffering from
swelling which was noticed around the eyes, legs and abdomen with
recurrence of the symptoms. The swelling was noticeable in the morning.
The color of urine had turned straw colored. It is not associated with
burning or pain during urination.
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13. Case 2#
6 years old male child presented to
pediateric clinic with burning urination
and hematuria. His mother noticed that
the child has 2 attacks of follicular
tonsillitis in previous 3 months before the
presenting symptoms go through
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As a future
doctor can
you give us
the main
difference
between
case1# & 2

14. Clinical picture of nephritic syndrome
Abrupt onset of acute nephritic syndrome 1- 4 weeks after upper respiratory tract or skin
infection leading to:
Gross hematuria (urine appears smoky brown)
Oliguiria and azotemia
Hypertension
Proteinuria and peri-orbital edema
High titre of anti-streptolysin O (ASO) in serum
Low serum complement level (hypocomplementenemia)
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15. Causes of Nephritic syndrome
1. Infection inducing acute diffuse proliferative GN (primary glomerular diseases)
2. Post-streptococcal GN
3. Non-streptococcal GN (certain pneumococcal and staphylococcal infections, some
viral infection as HCV, and HBV)
4. Secondary to systemic diseases as SLE
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16. Diagnostic features of glomerular diseases
Light microscopy
Cellularity
Extracellular matrix
Special stains
(PAS, amyloid)
Immunofluorescence microscopy
(Linear, granular, mesangial, irregular deposits)
Electron microscopy
(deposits of immune complexes, BM changes, amyloid)
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17. The kidney can be affected in different diseases including
autoimmune diseases diabetes infections cardiac and liver diseases
Kidney involvement usually affect mode of therapy response to
therapy and outcome
The kidney in systemic disease

18. Systemic Lupus Erythrematosus (SLE)
 A recent study on Taif University in 2015 showed that a high
percentage of familial lupus in Saudi patients may be a consequence of
high consanguinity rate in Saudi Arabia*
 Another study in Western Saudi Arabia found that lupus nephritis (LN)
in 2014 that compare with other results from other series a high
prevalence of LN in Saudi population especially Class IV was the most
frequent type of nephritis. * *
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* Albishri, J.A., Alshehri, S.S., Altowairqi, A.M. and Aljuaid, R.M. (2015) Familial Lupus and Clinical Characteristics in Saudi Arabia. International
Journal of Clinical Medicine, 6, 899-905. http://dx.doi.org/10.4236/ijcm.2015.612117
** Wafaey .G, Sami.B, Wael.H, Maimoona.M, Saeed.A.G., Jaudah.A.M: (2014) Clinicopathological characteristics of lupus nephritis in Western
region of Saudi Arabia: An experience from two tertiary medical centres. Journal of Microscopy and Ultrastructure, Volume 2, Issue 1, March 2014,
Pages 12-19 open access. https://doi.org/10.1016/j.jmau.2014.02.001

19. Lupus Nephritis
Renal involvement is variable from mild asymptomatic proteinuria and
hematuria to ever renal impairment that may require dialysis
The clinical picture can change rapidly to a very aggressive disease
There might be a discrepancy between the clinical picture and
histological findings
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20. Pathophysiology
Autoimmunity plays a major role in the pathogenesis of lupus
nephritis.
The histologic type of lupus nephritis that develops depends on
numerous factors, including the antigen specificity and other properties
of the autoantibodies and the type of inflammatory response that is
determined by other host factors.
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Immunologic
mechanism
Production of
antibodies
Against nuclear
elements

21. Pathogenesis of lupus nephritis
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22. Lupus Nephritis ISN/RPS classification
Class I: minimal mesangial lupus glomerulonephritis (LGN)
Class II: mesangial proliferative LGN
Class III: focal LGN (involving less than 50% of the total number of
glomeruli)
Class IV: diffuse LGN (involving 50% or more of the total number of
glomeruli)
Class V: membranous LGN
Class VI: advanced sclerotic LGN (>90% of glomeruli globally
sclerosed without residual activity)
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International Society of Nephrology (ISN)/Renal Pathology Society (RPS) Classification of lupus nephritis (LN)

23. Lupus nephritis

24. 21 year old lady known to have SLE and lupus nephritis for the last 4 years . Biopsy
was done at the time of diagnosis and showed class IV with active disease but no
chronic changes . Which one of the following histopathologic finding will be found in
her renal biopsy?
A.Diffuse LGN
B.Focal LGN
C.Membranous LGN
D.Mesangial proliferative LGN
E.Minimal mesangial lupus glomerulonephritis
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Can you
answer
this
question

25. References:
Robbins Basic Pathology 10th Edition; Chapter
5, 121-188 & Chapter 14, 549-581
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