Renal Pathology Part II - Glomerular Diseases

Question 1

Glomerular structure
* ______ cells, _____ membrane, _____, _____ cell, ____ matrix, ____ cell and _____ capsule

Answer 1

Endothelial, basement, podocytes, mesangial, mesangial, parietal, Bowman’s

Endothelial cells line capillaaries
Mesengial cells produce mesangial matrix
Filtration barrier function: Filter blood and start forming primary urine or ? filtrate.

Question 2

Label this image accordingly

Answer 2

Thick arrows = capillaries

Question 3

Water and particles with radius < __ nm (ions like ____ and ____, ____ and other ____ molecules) pass through the glomerulus. Some of these molecules are ______ in the ____ tubules

Answer 3

3.5, potassium, sodium, glucose, small, reabsorbed, proximal

If the glomerular filtration barrier stops functioning, glomerulus will no longer filtertrate, and important molecules and proteins will leak into urinary space –> tubules -> excreted –> important molecules are albumin and ATH III

Question 4

Molecules such as ____ and ______ __ stay in the
blood

Answer 4

albumin, antithrombin III

Question 5

List the Indications of glomerular injury

Answer 5

• Proteinuria = the presence of abnormal
  quantities of protein in the urine
• tubular injury can also lead to proteinuria (small molecules only;
  aminoaciduria and also glucosuria)
  protein losing nephropathy
  *Albuminuria → Hypoalbuminemia –> edema
  *Loss of ATIII → Multiple thrombi

Question 6

Answer 6

Ascites

Question 7

Answer 7

Hydropericardium and hydrothroax
No fibrin; transculent; cat was losing protein somewhere

Question 8

Answer 8

Pulmonary thrombus
Multiple thrombi formation
very common to see thrombus formation in the ?

Question 9

What are the hallmarks of glomerular disease?

Answer 9

1. Proteinuria
2. Hypercoaguable state – Due to loss of Antithrombin III
3. Nephrotic syndrome – Proteinuria + Hypoalbuminemia +
   Generalized edema + Hypercoagulable state + Hyperlipidemia

Mechanism of hyperlipidemia: liver produces albumin, B/c albumin has low amount in the blood, the liver will start to produce more albumin to compensate. During this process liver produces cholesterol?

Question 10

Define Glomerulitis.

Answer 10

inflammation restricted to glomerulus (acute septicemia [remember glomeruli are the first structure to receive blood])

Question 11

Define glomerulonephritis
Glomerulonephritis = usually of _______ origin. Glomerular
disease + ________ ________ and _______ changes
◦ _____ vs _____ (> ___% vs < ____% of glomeruli)
◦ ____ vs _____ ( _____ glomerulus vs ___)
◦ _________ vs ______ (proliferation of (3) cells along with ______ cells
vs thickening of the (2))

Answer 11

immune, secondary tubulointerstitial, vascular, Diffuse, Focal, 50, 50, Global, Segmental, entire, part, Proliferative, Membranous, endothelial/podocytes/mesangial, inflammatory, basement membrane/mesangial matrix

Question 12

Define glomerular amyloidosis

Question 14

Answer 14

Glomerulitis
* Suppurative glomerulitis
* Actinobacillus equuli in foals
* Bacteria (arrow) enter the kidney via the vasculature (bacteremia) and lodge in the capillaries of glomeruli, where they replicate and induce necrosis and inflammation

Question 15

What are the causes of glomerulonephritis?

Answer 15

Causes of glomerulonephritis
* Immune-mediated: Ag-Ab complex deposition and
complement activation
* Often associated with persistent infections or diseases that
have a prolonged antigenemia
- Dogs: Pyometra, pyoderma, chronic parasitism
(Dirofilaria), autoimmune diseases (SLE), and neoplasia
- Cats: FeLV, FIV, FIP

Question 16

Immune-mediated glomerulonephritis
1. Preformed circulating ___-___ complexes - Associated with ________
infections/disease –> prolonged ________ –> formation of soluble
immune ______
2. _____ is trapped in glomerular capillary wall and circulating ______
form _____ with them

Answer 16

Ag-Ab, persistent, antigenemia, complexes, Antigen, antibodies, complexes

Question 17

Location of immune complexes

Answer 17

Sites when the immunocomplexes are formed: Mesangial matrix, basement membranes of capillaries, between? prioces of podocytes, subepithelial (under epithelail cell layer)

Question 18

Describe the mechanism of injury to the glomerular structures and the outcome.

Answer 18

Complement activation: C38, C58 attract neutrophils which release enzymes and form ROS that will damage glomerular filtration barrier structures.

Question 19

Describe the mechanism of injury to the glomerular structures and the outcome.

Answer 19

Question 20

What are the histological patterns of glomerulonephritis?

Answer 20

1. Membranous GN: Thickened glomerular basement
   membrane/mesangial matrix
   ◦ Most common form in cats
2. Proliferative GN: Characterized by hypercellularity
   ◦ Proliferation of mesangial cells + podocytes + influx of WBCs
3. Membranoproliferative GN: Combination of thickened GBM/matrix
   and proliferation of mesangial cells and podocytes
   ◦ Most common form in dogs

Question 21

List the types of glomerulonephritis

Question 22

Answer 22

Normal

Question 23

Answer 23

Proliferative

Question 24

Answer 24

Membranoproliferative

Question 25

Answer 25

Membranous

Question 26

Answer 26

Glomerulosclerosis
???? (the end stage of chronic GN; nonfunctional)

Question 27

Answer 27

Gross apect of GN

Question 28

Prevalence of glomerulonephritis
Dogs: ?
Cats: ?
Horse: ?
Pig: ?

Answer 28

Membranoproliferative GN
◦ Lyme: Borrelia, Heart worm: Dirofilaria, pyometra, pyoderma, lupus

Membranous GN; FeLV; FIP; FIV

Membranoproliferative GN; Streptococcus equi; Equine infectious
anemia

Membranoproliferative GN ; PCV-2

Question 29

Define what an amyloid is?

Answer 29

Amyloid –
◦ Extracellular, eosinophilic, homogeneous, insoluble fibrillar
protein, resistant to normal degradation

Question 30

What are the different types of amyloidosis?

Answer 30

Types:
◦ Primary: AL amyloidosis - plasma cell tumors → immunoglobulin light
chain protein
◦ Secondary: AA amyloidosis - reactive, associated with chronic
inflammatory diseases → an acute phase protein, serum amyloid –a (SAA)
protein – Most common in domestic animals
◦ Familial – Shar-Peis, Abyssinian or Siamese cats

Question 31

What are the different types of amyloidosis?

Answer 31

Types:
◦ Primary: AL amyloidosis - plasma cell tumors → immunoglobulin light
chain protein
◦ Secondary: AA amyloidosis - reactive, associated with chronic
inflammatory diseases → an acute phase protein, serum amyloid –a (SAA)
protein – Most common in domestic animals
◦ Familial – Shar-Peis, Abyssinian or Siamese cats

Question 32

What part of the body does amyloidosis affect?

Answer 32

Location:
◦ Glomeruli - primary site – in the mesangium and
subendothelial zones of glomerular capillaries
◦ Medulla - Abyssinian or Siamese cats, Shar-Peis dogs
- Develop progressive renal insufficiency and
proteinuria
- Progressive disease and prognosis is poor

Question 33

Describe the morphological characteristics of a kidney affected by glomerular amyloidosis.

Answer 33

Glomerular amyloidosis
Subtle; similar ot glomerulur nephritis
Treat fresh kidney with iodine and see the amyloid deposition in the glomeruli (black foci).
◦ Pale kidney
◦ Cortex has a granular appearance
(similar to GN)
◦ Iodine solution (lugol’s iodine), red-
brown staining of glomeruli

Question 34

Answer 34

Glomerular amyloidosis

Question 35

In cases of Glomerular amyloidosis
- Amyloid deposited in both the _________ and ________ of glomerular capillaries
- _______ and ________ can also be affected
- Confirmed ________
◦ _______ ____ stain
◦_______ _____ birefringence with ________ light

Answer 35

mesangium, subendothelium, Tubules, interstitium, microscopically, Congo red, Apple green, polarized

Question 36

Describe what is occurring in each image pictured?

Question 37

List the downstream changes of Glomerulonephritis

Answer 37

1) Glomerulosclerosis = compression of capillaries of the glomeruli leading to chronic hypoxia –> tubular cell apoptosis and with time tubular loss —> tubular replaced by interstitial fibrosis
2) Tubular injury
◦ Sclerotic glomeruli cause downstream tubular ischemia (connective tissue
compresses the capillaries)
◦ Proteins damage tubular epithelium
3) Interstitial fibrosis – tubular ischemia lead to tubular atrophy and
replacement by fibrous connective tissue

Question 38

Answer 38

Hyaline casts (protein) are indicative
of glomerular disease
Tubules are dilated and filled with eosinophilic amorphous material (protein)

Question 39

List the sequelae of chronic glomerular diseases

Answer 39

• Chronic renal failure
• Nephrotic syndrome
• Hypercoagulable state

Question 40

Renal infarction
- Renal Infarction - _________ areas of _______ necrosis
- Obstructive material: ______ (_________ state), ______ emboli, _______ emboli
- Predisposing conditions: ?

Answer 40

localized, coagulative, thrombi, hypercoagulable, septic, neoplastic, Valvular endocarditis, Feline cardiomyopathy (HCM), endotoxemia, neoplasia

Question 41

Renal infarction
1. Renal artery- Occlusion of the renal artery: ______ kidney will be _______
2. Arcuate artery - wedge shaped necrosis of ______ and _______
3. Interlobular artery - necrosis of ______ only

Answer 41

entire, necrotic, cortex, medulla, cortex

Question 42

Describe what can be seen in this image?

Answer 42

Question 43

Answer 43

Renal medullary/papillary/crest necrosis

Question 44

What causes Renal medullary/papillary/crest necrosis?

Answer 44

Causes – ISCHEMIA
1) Non-steroidal anti-inflammatory drugs (NSAIDs)
◦ Aspirin, phenylbutazone, flunixin meglumine, meloxicam
Pathogenesis: NSAIDs → block prostaglandin production (PGE2)
→ ischemia of renal medulla → necrosis
◦ Associated with Dehydration
◦ Analgesic nephropathy – Dehydrated horses treated with
phenylbutazone
2) Medullary amyloidosis: Compression of medullary capillaries
3) Chronic pyelonephritis: Scarring – fibrous connective tissue
compresses medullary capillaries
4) Pelvic calculi or tumor: pressure necrosis

Question 45

Answer 45

Crest necrosis = dog with amyloidosis

Question 46

Answer 46

Papillary necrosis = Phenylbutazone treatment

Question 47