disease of the glomerulus Flashcards
list 2 glomerular disease of domestic animals
- glomerulonephritis
- glomerular amyiloidosis
hallmark for glomerular disease
proteinuria
most common causes of proteinuria
lower urinary tract
upper urinary tract sometimes
determinant of proteinuria
- molecular weight
- size
- charge of protein
- filtration barrier
- fixed negative charge
- tubular resoption/catabolism
filtration barrier in kidney for proteins
- endothelium
- basement membrane 9negative charge)
- epithelial cells
*
Classical definition of nephrotic syndrome
- Proteinuria
- Hypoalbuminemia
- Hypercholesterolemia
- Edema and/or ascites
function of the mesanchymal cells
- produce mesangial matrix
Are phagocytic and may clear filtration residues
Contain microfilament
Respond to vasoactive substances (e.g.angiotensin II) and alter surface area of glomerulus available for
filtration
- May play role in mediating glomerular injury
discuss the characteristics of the glomerulus
- Is both a size and charge selective barrier
- (-) charges in endothelium, GBM and podocytes
- Type IV collagen in GBM contributes to size
selectivity
what is the number 1 cause of glomerulonephritis
immune mediated injuries
causes of immune complex GN in Dogs
- Pyometra
- Heartworm disease
- Systemic lupus erythematosus
- Canine adenovirus-1
- Chronic infections
- Endocarditis, ehrlichiosis, borreliosis, leishmaniasis, etc.
- Neoplasia (e.g. lymphoma)
- Most cases are idiopathic !!!
Causes of Immune Complex GN in Cats
- Feline leukemia virus (FeLV)
- Feline infectious peritonitis (FIP)
- Chronic progressive polyarthritis (Mycoplasma gatae)
- Neoplasia (e.g. lymphoma)
- Most cases are idiopathic !!!
discuss the signalment for Membranoproliferative GN in familial Familial Glomerular Diseases
Soft-coated Wheaten terriers (often associated with PLE)
Bernese Mountain dogs (often associated with borreliosis)
CIII deficiency in Brittany Spaniels
discuss the signalment for Basement membrane disorders in Familial Glomerular Diseases
Autosomal recessive in English Cocker spaniels
X-linked dominant in Samoyeds
Suspected in Doberman pinschers and Bull terriers
Diverse group of diseases
characterized by
extracellular deposition
of protein subunits that
form -pleated sheets
amyloidosis
discuss the classification of amyloidosis based on Distribution of deposits
Systemic (most common in veterinary medicine**)
Localized (pancreatic islet cells of cats - islet amyloid polypeptide)
discuss classification of amyloidosis based on Nature of responsible protein
Reactive (AA)
Immunoglobulin-associated (AL)
Transthyretin (ATTR)
2-microglobulin (A2M)
Islet amyloid polypeptide (AIAPP)
Many others
2 main classification groups for amyloidosis
- Distribution of deposits
- Nature of responsible protein
discuss Reactive Systemic Amyloidosis
- associated with chronic infectious and non infectious inflamatory diseases
- associated with neoplasia
- most common causes in dogs and cats:idiopathic or familial
most causes of reactive systemic amyloidosis in dogs and cats
idiopathic or
familial
dogs most affected by reactive systemic amyloidosis
Shar pei
Beagle
English foxhound
cats mostly affected by reactive systemic amyloidosis
Abyssinian
Siamese
Oriental shorthair
Tissue Tropisms of Amyloid Proteins
Tissue distribution of amyloid deposits in dogs and
cats can be widespread but clinical signs are due to
kidney involvement and renal failure
Exception: Severe liver involvement in Shar pei dog,
Siamese cat, and Oriental shorthair cat can lead to
liver rupture and hemoabdomen
in which animals is Medullary > Glomerular distribution of amyloidosis due to reactive systemic amyloidois
- cat including abyssian
- cow
in which animals is Glomerular > Medullary Distribution of Deposits within Kidney
humans
dogs (except shapei)
horses
DISCUSS LEVELS OF PROTEINURIA IN GLOMERULAR AMYLODIOSIS
Expect proteinuria; positive biopsy results
what should u expect with medullary Amyloid Distribution in the Kidney
Expect minimal proteinuria; negative biopsy results
what do we use to o presumptively identify
medullary amyloid deposits at necropsy
Lugol’s iodine
discuss SIGNALMENT OF Amyloidosis in Shar Pei Dogs
Mean age - 4 yrs
Males & females
Black & fawn
Familial relationship
cs of amyloidosis in shapei
- Signs usually consistent with CRF
- May have history of recurrent acute self-limiting fever and tibiotarsal joint swelling (“Sharpei fever”)
- Severe liver involvement may cause icterus or hemoabdomen due to liver rupture
discuss the lesions in Amyloidosis in Shar Pei Dogs
Glomerular involvement
- proteiunuria
- hypercholesterolemia
- hypoproteinemia
discuss the cs of Medullary involvement (more common) in Amyloidosis in Shar Pei Dogs
Isosthenuria without proteinuria with medullary
involvement
Clinical findings of Amyloidosis in Abyssinian Cats
Poor haircoat
Weight loss
Lethargy
Polyuria/polydipsia
Dehydration
Small irregular kidneys
laboratory findings of Amyloidosis in Abyssinian Cats
- Nonregenerative anemia
- Azotemia
- Hyperphosphatemia
- Metabolic acidosis
- Isosthenuria
- Variable proteinuria
which kidney celss plays a role inmediating glomerular injuries
mesanchymal cells
how does prognosis for survival from amyloid differ from GN
amyloid-relentlessprogression is the rule
the best stain for amyloid
congo red
signalment for glomerular dz
middle aged- to older
no gender predilection-cats with gn are mostly male
any breed bt remember familial syndromes
6 possible presentations of glomerular dz
TQ
signs related to crf most common
signs related to underlying infectious,inflamatory,neoplastic disorders.
proteinuria may be an incidental finding
signs related to “nephrotic syndrome’
signs related to thromboembolism–loss of antethrombin
sudden blindness due to hypertention and retinal detarchment
n.b remember that hypertension is related to glomerular dz
discuss physical findings of glomerular dz
- related to CRF(most common)
- poor haircoat and body condition
- dehydration
- small irregular kidneys
- related to underlying infectious,inflamatory or neoplastic dz
- ascites or edema
- retinal detarchment,vascular tortuosity,retinal detachment
u see a dog with retinal detarchment .which kidney dz do u suspect
- fundic lesion due to hypertention secondary to glomerular dz
- retinal hemorrhages
- intra-retinal retinal transdudate
- retinal edema
discuss urinalysis of glomerular dz
proteinuria is the hallmark
hyaline and granular casts
lipid droplets
isosthenuria(most animals with glomerular dz dnt hav it)
biochemistry finding s of glomerular dz
- Laboratory abnormalities of CRF
Azotemia
Hyperphosphatemia
Metabolic acidosis
- Hypoalbuminemia (other differentials?)
Up to 75% of dogs with amyloidosis
Up to 60% of dogs with GN
- Hypercholesterolemia (other differentials?)
Up to 90% of dogs with amyloidosis
Up to 60% of dogs with GN
does increase in urin protein creatine ratio(upc) mean u hav glomerular dz
not necessarily
cannot differentiate protein coming from upper or lower urinary system
upc ratio of less than .5 is?
normal
upc of .5 to1.0 is
questionable
upc of greater than 1 is
upc ratio of greater than 5
nephrotic range
how is upc ration unreliable
- magnitude of upc ratio correlates with severity of glomerular dz in non azotemic patients
- unreliable in presence of pyuria or severe hematuria
- decrease in upc ratio in azotemic patients with declining GFR is not a sign of improvement
tq
if there are wbc in a Q, then dnt pick upc ratio
on average,the highest upc ratio are seen in
glomerular amyloidosis
presence of an amount of protein in urine greater than normal but below detection limit of conventional dipstick
- microalbuminuria
- it will detect proteinuria b4 it can be detected in dipstick
- if anything less than 10 then your dipstick will be -ve
*
- if anything less than 10 then your dipstick will be -ve
established risk factor for progression of renal dz in human patients
type 1 and type 2 diabetes
essential hypertension
other factors that can lead to proteinuria
corticosteroids
microalbunemia increases with age
discuss what -ve/+ve microalbunemia means
-ve great–glomerular barriwer working well
+ve -worrisome
breakdown of glomerular barrier fxn
increase in number of holes or size of holes
things to do if your test is postive for microalbuminuria
r/o systemic hypertension
r/o endocrinopathy
r/o occult neoplasia
r/o occult infections
what is the most common cause of proteinuria
lower urinary tract
what is the most sensitive test to detect proteinuria
microalbumininuria
the only test to differetiate Gn and amyloidosis
renal biopsy
Gn is best assessed by
immunohistochemistry
immunofluroscence
electron microscopy
remember that if proteinuria is in the renal medula u might miss it
how to tx glomerular dz
identify and tx any underlying predisposing inflamatory or neoplastic dz
tx crf if present
if u have a patient with proteinuria and hypertension,which drug should be your drug of choice?
ACE inhibitor
explain how ace inhibitors reduce hypertention in glomerular dz
they decrease glomerular capillary hydrostatic p and proteinuria
side effects of ace inhibitors
potentially can aggrevate azotemia
which drugs can u use to tx thromboembolism in glomerular dz
aspirin
specific tx for GN
no
immunosuppresants hav not been proven that they work
fatty acids can be used coz they are antiinflamatory
specifiic tx for amyloidosis
no specific tx has been shown to be beneficial
consideration:colchicine
discuss how colchicine works
tx amyloidosis by decreasing serum amyloid A protein (SAA) conce by imparing hepatic secretion
prevents developments of amyloidosis in humans with familial mediterianian fever (FMF)
complications in glomerular dz
hypoalbunemia
na retention
thromboembolism
hyperlipidermia
hypertension
discuss hypoproteinemia as a complication of glomerular dz
- low oncootic pressure stimulates hepatic albumin synthesis
- increased hepatic albumen synthesis insufficient for degree of hypoalbunemia
- increased renal catabolism of filtered proteins
- increasing diatery protein only worsens urinary protein loss
discuss nephroembolism
nephrotic syndrome is a hypercoagulble state
thromboembolism events may be main reason for presentation
why do u get hypercoagulability in nephrotic syndrome
loss of antithrombin 111
discuss hyperlipidermia in nephrotic syndrome
- increased hepatic syntheses and decreased peripheral catabolism of lipoproteinscaused by hypoalbunemia and urinary loss of lipid regulatory factors
- plasma cholesterol and triglyceride concentrations inversely correlated with serum albumin conc.
- can lead to non specific gi signs and pancreatitis
discuss mechanisms of hypertension
- primary intrarenalmechanism for Na retention(early)
- activation of RAS(later)
- hypertension occurs in 50-80% of dogs with glomerular dz
*
targets for hypertension
eyes
kidney
kidney
which test should u perform in dogs with glomerular dz
blood p
control of bp can slow progression of renal dz
tx for hypertension in nephrotic syndrome
enalpride
may reduce proteinuria in addition to reducing bp
monitor BUN and SCr
may slow progression of renal dz
best tx option of GN
ACE
reason why dogs with renal amyloidosis and GN die
progressive CKDto failure
prognosis of amyloidosi
poor
reasons why dogs with renal amyloidosis and gn die
progressive ckd to failure
prognosis for gn
variable
spontaneous remission(role of tx)
stable course for months to years with ongoing proteinuria
progression tocrf over mnths to yrs
