Renal Pathology Part II - Glomerular Diseases Flashcards
Glomerular structure
* ______ cells, _____ membrane, _____, _____ cell, ____ matrix, ____ cell and _____ capsule
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.
Label this image accordingly
Thick arrows = capillaries
Water and particles with radius < __ nm (ions like ____ and ____, ____ and other ____ molecules) pass through the glomerulus. Some of these molecules are ______ in the ____ tubules
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
Molecules such as ____ and ______ __ stay in the
blood
albumin, antithrombin III
List the Indications of glomerular injury
- 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
Ascites
Hydropericardium and hydrothroax
No fibrin; transculent; cat was losing protein somewhere
Pulmonary thrombus
Multiple thrombi formation
very common to see thrombus formation in the ?
What are the hallmarks of glomerular disease?
- Proteinuria
- Hypercoaguable state – Due to loss of Antithrombin III
- 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?
Define Glomerulitis.
inflammation restricted to glomerulus (acute septicemia [remember glomeruli are the first structure to receive blood])
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))
immune, secondary tubulointerstitial, vascular, Diffuse, Focal, 50, 50, Global, Segmental, entire, part, Proliferative, Membranous, endothelial/podocytes/mesangial, inflammatory, basement membrane/mesangial matrix
Define glomerular amyloidosis
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
What are the causes of glomerulonephritis?
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
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
Ag-Ab, persistent, antigenemia, complexes, Antigen, antibodies, complexes
Location of immune complexes
Sites when the immunocomplexes are formed: Mesangial matrix, basement membranes of capillaries, between? prioces of podocytes, subepithelial (under epithelail cell layer)
Describe the mechanism of injury to the glomerular structures and the outcome.
Complement activation: C38, C58 attract neutrophils which release enzymes and form ROS that will damage glomerular filtration barrier structures.
Describe the mechanism of injury to the glomerular structures and the outcome.
What are the histological patterns of glomerulonephritis?
- Membranous GN: Thickened glomerular basement
membrane/mesangial matrix
◦ Most common form in cats - Proliferative GN: Characterized by hypercellularity
◦ Proliferation of mesangial cells + podocytes + influx of WBCs - Membranoproliferative GN: Combination of thickened GBM/matrix
and proliferation of mesangial cells and podocytes
◦ Most common form in dogs
List the types of glomerulonephritis
Normal
Proliferative
Membranoproliferative
Membranous
Glomerulosclerosis
???? (the end stage of chronic GN; nonfunctional)
Gross apect of GN
Prevalence of glomerulonephritis
Dogs: ?
Cats: ?
Horse: ?
Pig: ?
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
Define what an amyloid is?
Amyloid –
◦ Extracellular, eosinophilic, homogeneous, insoluble fibrillar
protein, resistant to normal degradation
What are the different types of amyloidosis?
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
What are the different types of amyloidosis?
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
What part of the body does amyloidosis affect?
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
Describe the morphological characteristics of a kidney affected by glomerular amyloidosis.
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
Glomerular amyloidosis
In cases of Glomerular amyloidosis
- Amyloid deposited in both the _________ and ________ of glomerular capillaries
- _______ and ________ can also be affected
- Confirmed ________
◦ _______ ____ stain
◦_______ _____ birefringence with ________ light
mesangium, subendothelium, Tubules, interstitium, microscopically, Congo red, Apple green, polarized
Describe what is occurring in each image pictured?
List the downstream changes of Glomerulonephritis
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
Hyaline casts (protein) are indicative
of glomerular disease
Tubules are dilated and filled with eosinophilic amorphous material (protein)
List the sequelae of chronic glomerular diseases
- Chronic renal failure
- Nephrotic syndrome
- Hypercoagulable state
Renal infarction
- Renal Infarction - _________ areas of _______ necrosis
- Obstructive material: ______ (_________ state), ______ emboli, _______ emboli
- Predisposing conditions: ?
localized, coagulative, thrombi, hypercoagulable, septic, neoplastic, Valvular endocarditis, Feline cardiomyopathy (HCM), endotoxemia, neoplasia
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
entire, necrotic, cortex, medulla, cortex
Describe what can be seen in this image?
Renal medullary/papillary/crest necrosis
What causes Renal medullary/papillary/crest necrosis?
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
Crest necrosis = dog with amyloidosis
Papillary necrosis = Phenylbutazone treatment
