This document outlines a lecture on renal pathology for medical students. It begins with the intended learning outcomes, which are to understand kidney embryology, structures, disease classification, and glomerular disease terminology and pathogenesis. It then covers the normal kidney anatomy and histology, as well as its functions. Kidney diseases are classified based on the structures involved or clinical presentations. Glomerular diseases cause damage to the glomeruli that disrupt blood filtration and cause protein or blood in the urine. Immune complexes or antibodies deposited in the glomerular basement membrane can activate the complement system and recruit cells that damage the filtration barrier. A quiz ends the lecture material.

1. Renal Pathology
for medical students
Professor Wadie M Y Elmadhoun
E-mail: wadie2222@yahoo.com
Kidney – Pathology – Lecture one – Prof. Wadie 1

2. Kidney Diseases
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3. Presentation outlines
1. Intended Learning outcomes (ILOs).
2. Normal structure of the kidney: histology,
gross anatomy and embryology.
3. Functions (physiology) of the kidney.
4. Classification of renal diseases.
5. Glomerular diseases- Part 1.
6. Quiz.
7. Further sources for learning.
Kidney – Pathology – Lecture one – Prof. Wadie
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4. Intended Learning outcomes (ILOs)
• By the end of this session, students are expected to:
1. Identify the embryology of the kidney.
2. Describe the normal structures of the kidney: grossly,
histologically and under electron microscope.
3. Classify diseases of the kidney in a scientific way.
4. Explain the most commonly used Terminology of glomerular
diseases.
5. Explain the pathogenesis of glomerular diseases.
6. Relate the symptoms and signs of renal disease to kidney
structure and function
7. Justify the derangements that occur in the body when there
is renal pathology.
8. Appreciate the importance of the normal kidney in
homeostasis.
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5. The kidneys
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6. Embryology of the kidney
• From the mesoderm.
• Two parts:
1. Mesonephros: that
gives rise to glomeruli.
2. Mesonephric duct:
that form the renal
tubules and collecting
ducts.
Kidney – Pathology – Lecture one – Prof. Wadie 6

7. Introduction
• Bean shaped, reddish brown.
• Located retroperitoneallybetween T12 – L3 vertebral
level.
• Size approx. 10 x 6.5 x 3 cm.
• Weighs around 135-150 grams.
• Highly vascular organ: Receives25 % of cardiac
output.
• Kidney produces urine - ultrafiltrateof blood, which
is then modifiedby selectiveresorption and specific
secretionby cells of kidney.
Kidney – Pathology – Lecture one – Prof. Wadie 7

8. Blood supply to various parts
• 90-95 % of blood passing through kidney is in
cortex, and
• 5-10 % is in medulla.
• What does that mean?
• In case of ischemia: the medullary structures
(Tubules) to be affected more than the cortical
structures (glomeruli).
Kidney – Pathology – Lecture one – Prof. Wadie 8

9. Gross anatomy of the kidney
• Cortex, medulla and
renal pelvis.
• Blood vessels.
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Can you label the structures1 to 15
in this kidney?
Try 7 of them at least!

11. Structures of the kidney
1. Renal Vein
2. Renal Artery
3. Renal Calyx
4. Medullary Pyramid
5. Renal Cortex
6. Segmental Artery
7. InterlobAR Artery
8. Arcuate Artery interlobular
9. Arcuate Vein
10. Interlobar Vein
11. Segmental Vein
12. Renal Column
13. Renal Papillae
14. Renal Pelvis
15. Ureter
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16. S.E.M. T.E.M.
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18. Normal functions of the kidneys
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Blood in via afferent arteriol, leaves out via
efferent arteriole and filtrate out through
tubules.

20. Functions of the kidney
1.Regulates and maintains
composition and volume of
extracellular fluid.
2.Maintains acid base balance by
excreting H+ ions or HCO3- ions.
Kidney – Pathology – Lecture one – Prof. Wadie 20

21. Functions of the kidney
3. Endocrine organ :
a) Synthesis of acid protease RENIN – enzyme
involved in control of blood pressure and blood
volume: Renin- Angiotensinogen - Angiotensin.
b) Erythropoietin synthesis –
- regulates RBCs formation in response to
decreased O2 concentration.
Kidney – Pathology – Lecture one – Prof. Wadie 21

22. Classification of kidney diseases
• Kidney diseases can be classified based upon:
1. Major structures of the kidney:
glomeruli, tubules, interstitium and blood
vessels.
2. Clinical syndromes/manifestations:
nephrotic, nephritic, acute kidney injury (AKI),
Chronic kidney disease (CKD), ………
Kidney – Pathology – Lecture one – Prof. Wadie 22

23. Renal Pathology
• GLOMERULAR
• TUBULAR/INTERSTITIAL
• BLOOD VESSELS
• OBSTRUCTION
• CONGENITAL
• “CYSTS”
• TUMORS
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24. GLOMERULAR DISEASES
aka, glomerulonephropathies
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25. • Renal glomeruli excrete urinary substances and excess
water as an ultrafiltrate into the urine by selectively
filtering the blood.
• Any damage to the glomeruli disrupts the filtration process
and results in edema and the appearance of blood
components (proteins and red blood cells) in the urine.
• Glomerular damage is commonly caused by immune-
mediated processes, which often lead to
glomerulonephritis.
• Non-inflammatory causes, such as metabolic disease (e.g.,
diabetes, amyloidosis), can also result in significant damage
to the glomeruli.
Kidney – Pathology – Lecture one – Prof. Wadie 25

26. • The pathophysiologyof glomerular diseases is
complex; most patientspresent with either
nephritic syndrome (low-levelproteinuria,
microhematuria,oliguria, and hypertension)or
nephrotic syndrome (high-levelproteinuria and
generalizededema).
• All glomerular diseases can progress to acute or
chronic renal failure.
• Thus, quick diagnosis and immediateinitiationof
immunosuppressivetherapy are required to
preventirreversiblekidney damage.
Kidney – Pathology – Lecture one – Prof. Wadie 26

27. Terminology of glomerular diseases
• Diffuse: all glomeruli are affected
• Focal: only a number of glomeruli are affected
• Global: the entire glomerulus is affected
• Segmental:only part of the glomerulus is affected
• Proliferative: an increasednumber of cells in the
glomerulus
• Sclerosing: scarring of the glomerulus
• Necrotizing:cell death within the glomerulis
• Crescentic: accumulationof cells such as
macrophages, fibroblasts,and epithelialcells in
Bowman's space
Kidney – Pathology – Lecture one – Prof. Wadie 27

28. Clinical manifestations of renal
diseases
1. Nephrotic Syndrome
2. Nephritic Syndrome
3. Rapidly Progressive Glomerulonephritis
4. Asymptomatic hematuria or
proteinuria
5. Acute/Chronic Renal Failure
6. Obstruction of urinary outflow
7. Tumors
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29. Renal response to injury
• Cellular proliferation
–Mesangial
–Endothelial
• Leukocyte infiltration
• CRESCENTS (RAPIDLY progressive)
• Basement membrane thickening
• Hyalinization
• Sclerosis
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30. Etiology
• The etiological factors of glomerular diseases
are variable, including:
1. immune-mediated,
2. hereditary,
3. drug-induced,
4. metabolic
5. infectious, and
6. idiopathic causes.
Kidney – Pathology – Lecture one – Prof. Wadie 30

31. Electron microscopic photo of a glomerulus
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32. • The glomerular filtration barrier consists of 3 parts Initial
segment: Fenestrated glomerular capillary endothelium
prevents large proteins from passing through.
• Second segment: The glomerular basement membrane
(GBM) contains a negative charge produced by heparan
sulfate.
• Final segment: Visceral epithelial cells produce/maintain
the GBM and contain intercellular junctions created by
podocytes that prevent further protein loss.
• Damage to the glomeruli → disruption of the glomerular
filtration barrier → can lead to nephritic or nephrotic
syndrome
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33. Electron microscopic photo of a glomerulus
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34. Pathogenesis: immune
responses
1. Antibodies against inherent GBM
2. Antibodies against “planted” antigens
3. Trapping of Ag-Ab complexes
4. Antibodies against glomerular cells, e.g.,
mesangial cells, podocytes, etc.
5. Cell mediated immunity, i.e., sensitized T-cells
as in TB
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35. Mediators of immunological
damage
• Neutrophils, monocytes
• Macrophages, T-cells, NK cells
• Platelets
• Mesangial cells
• Soluble: cytokines, chemokines, coagulation
factors.
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36. Overview
– Immune-mediated injury to the glomerulus typically
arises from the deposition of antibodies within the
glomerulus.
– Whatever the mechanism, the presence of antibodies
within the glomerulus results in a final common pathway
of immune-mediated injury.
– Deposition of immunoglobulins activates complement,
resultingin deposition of complement proteins.
– In some cases, deposited complement proteins perform
the bulk of the damage, leading to impairment of the
glomerularbarrier.
– However,in other cases, activatedcomplement proteins
lead to recruitmentof macrophages which then initiate
damage of glomerularstructures and in doing so impair
the selectivity of glomerular filtration.
Kidney – Pathology – Lecture one – Prof. Wadie 36

37. 1. Preformed Immune Complex
Deposition
– Preformed, circulating immune complexes composed
of particles of antibody bound to antigen can easily
become trapped in the glomerulus either within the
glomerular basement membrane or the mesangium.
– In essence, this is a renal manifestation of Type III
Hypersensitivity.
– Immune complexes deposited within the glomerulus
generally result in a granular pattern when
immunoglobulin proteins are detected by
immunofluorescence.
Kidney – Pathology – Lecture one – Prof. Wadie 37

38. 2. In Situ Immune Complex Formation
 In this scenario, circulatingantibodiesreact with clumpsof
antigen which werepreviouslypresent withinthe (GBM).
 Therefore, the immune complex is formed 'in situ' (i.e. at its
site of deposition) rather than having been preformed in the
plasma.
 The clumps of antigenmay be from circulating antigensthat
become trapped in the GBM; importantly,these antigens
may be either from an endogenous or exogenous source.
 Alternatively,antigenicclumpsmay representproteins
normally presentin the GBM.
 In situ immune complexes will also result in a granular
patternwhen immunoglobulins are detected by
immunofluorescence. Kidney– Pathology– Lecture one – Prof.Wadie 38

39. 3. Anti-Glomerular Basement Membrane
Antibody Deposition
 In this scenario, a specific antibody develops that binds
to a normalprotein componentof the GBM, in essence
a form of Type II Hypersensitivity.
 Here, no immune complexes are present and insteadthe
antibody diffusely deposits along the entire length of the
GBM.
 Anti-GBMantibody deposition appears as a ribbon-like,
linear band tracking the GBM upon imunofluorescent
detection of immunoglobulinproteins.
 The prototypical disease involving this pathogenesis is
GoodpastureSyndrome.
Kidney – Pathology – Lecture one – Prof. Wadie 39

40. Linear antibody deposition on GBM
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41. Granular immune complex depositions
in GBM
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45. So what happens if an antibody binds to renal
cell or structure e.g. GBM
Kidney – Pathology – Lecture one – Prof. Wadie 45
ADCC= Antibody-dependent Cell-mediated cytotoxicity

46. Quiz 1
Kidney– Pathology– Lecture one – Prof.Wadie 46
Find and Name
the structures
labeled
1- 15

47. Quiz 2
• How can you classify renal diseases on
basis of:
1. Structures?
2. Clinical presentations?
Kidney – Pathology – Lecture one – Prof. Wadie 47

48. Quiz 3
• What functional abnormalities
do you expect when the
functions of the kidney are
jeopardized?
Kidney – Pathology – Lecture one – Prof. Wadie 48

49. Quiz 4
• Explain the following terms used to describe
glomerular diseases:
1. Diffuse
2. Focal
3. Segmental
4. Proliferative
5. Sclerosis
6. Uremia
7. Azotemia
Kidney – Pathology – Lecture one – Prof. Wadie 49

50. Quiz 5
•What is the main
pathogenetic mechanism
in glomerulonephritis?
Kidney – Pathology – Lecture one – Prof. Wadie 50

51. Quiz 6
What are the differences between these 2 types
of immunofluorescence pictures of immune
reactions on glomeruli?
Kidney – Pathology – Lecture one – Prof. Wadie 51

52. Further sources for learning
1. https://glomcon.org/overview-of-gn/basic-
principles-of-renal-pathology-part-1/
2. https://www.kidneypathology.com/English_v
ersion/Tutorial_index.html
3. https://en.wikipedia.org/wiki/Kidney
4. https://en.wikipedia.org/wiki/Glomerulonep
hritis
5. http://www.pathwaymedicine.org/basic-
glomerular-pathogenesis
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