Pathophysiology of Tubulointerstitial Disease (Cianciolo) Flashcards
Cats tend to get ___________
Tubulointerstitial disease
Requires knowledge of creatinine or urinalysis etc
AKI (Clinical diagnosis)
- Acute necrosis
- Acute inflammation
Describes:
Acute Renal Lesions (pathologist)
What are some things that cause acute tubular epithelial injury?
- Ischemic
- Toxic
- Obstructive (crystals/ cellular casts/ pigment casts / ureteral blockage etc)
(T/F) Chronic kidney disease may present acutely
True
(T/F) Even if animal is acutely azotemic, that doesn’t mean that the lesions will be “acute”
True
(T/F) Because significant renal dysfunction occurs with overt necrosis of the tubular epithelial cells, the term has been changed in human medicine to “Acute Tubular Necrosis”
False
Epithelial cells don’t reabsorb glucose or amino acids appropriately
Fanconi’s Syndrome
(T/F) You can have tubular problems w/o actual evidence of injury
True
Glucosuria with normoglycemia and amino aciduria
- Fanconi’s syndrome
- Jerky treat exposure
*Proximal tubulopathy is probably the correct term
- Injured but viable epithelial cell detaches from the tubular basement membrane and exits in urine
- Very common in kidney
Anoikis
The cell starts apoptotic cascade but can’t finish so it undergoes necrosis
Necroptosis
- Controlled, does not incite inflammation
- Suicide
Apoptosis
Cytokine expression of tubular epithelial cells
- __________ induces interstitial fibrosis
TGF-beta
Cytokine expression of tubular epithelial cells
- _____________ attenuates fibrosis
BMP-7
Cytokine expression of tubular epithelial cells
- Macrophage chemotactic protein (MCP-1) -> attracts ______________________
inflammatory cells
Cytokine expression of tubular epithelial cells
- Epidermal Growth Factor helps _________ regenerate
tubules
(T/F) In recovery from ATEI, recovering cells are thought to be more resistant to insult than mature cells
True
- Hypovolemic shock
- Cardiogenic shock
- Septic shock
- Disseminated Intravascular Coagulation
- Straight portion of the proximal tubule (pars recta) is most susceptible (high metabolic demand)
– Also worry about the thick ascending limb of the Loop of Henle +/- medulla
** CANNOT definitively differentiate from nephrotoxic acute tubular injury
These are causes of ________________
Ischemic ATEI / ATN
- Eliminated from the body mostly by glomerular filtration
- Foals and reptiles are particularly sensitive
- In animals with decreased GFR, we would be very careful to use this drug
Aminoglycosides (antibiotic)
**is a cause of Toxic ATEI
- Grossly, can see papillary necrosis –> obstructs the outflow of urine
- Medulla and papilla are at increased risk b/c they work hard and have limited blood flow
- Inhibits Cycloxygenase (COX) -> decreases renal prostaglandin E (PGE2) and PGI2 levels -> afferent arteriolar vasoconstriction -> decreased GFR -> renal ischemia
NSAIDs
- Common in dogs and cats (cats more susceptible)
- Rapidly absorbed from the GI tract -> metabolized in the liver by alcohol dehydrogenase to oxalate (& other compounds)
- These metabolites are nephrotoxic
- Calcium oxalate crystals precipitate in tubules
Ethylene Glycol (Toxic + obstructive)
Other Causes of Oxalate Crystals
Cruciferous vegetables are:
- Rhubarb
- Spinach
(T/F) Can see scattered oxalates in animals with chronic kidney disease because they have lost the ability to process endogenous or dietary oxalates
True
- Ruminants and camelids
- Ingestion of oak leaves, buds, stems or acorns
- Clinical disease: anorexia, depression, rumen atony, constipation, diarrhea, elevated
- Acute cases die 1-3 days; chronic cases linger for weeks
- Gross: swollen pale kidneys with cortical petechiae
- Can see colitis, perirenal edema, anasarca
Oak Nephrotoxicity
- Compounds that crystalize in tubules of small animal kidneys
– Crystals are yellow-brown - Compounds added to pet food in order to increase ammonia content
– Falsely elevates protein content on the label
Melamine / Cyanuric Acid (toxic + obstructive)
Other Nephrotoxins in Small Animals
– All parts of the plants are toxic
– Mechanism of toxic action is unknown
– See overt necrosis of entire proximal tubule cross-sections
Lilies in cats
Other Nephrotoxins in Small Animals
– Seems to be idiosyncratic
– Mechanism of toxic action is unknown
Grapes or Raisins in dogs
- RBC lysis -> anemia -> ischemic necrosis
- And hemoglobin releases -> toxic to tubules
Pigmentary Nephropathy (Ischemic + toxic + obstructive)
The source of the infectious agent determines the anatomic pattern of inflammation
- Hematogenous:
embolic and / or glomerulonephritis
The source of the infectious agent determines the anatomic pattern of inflammation
- Urogenous:
Pyelonephritis
- Suppurative inflammation centered on the renal pelvis
- Can cause loss of concentrating ability due to renal papillary necrosis
The source of the infectious agent determines the anatomic pattern of inflammation
- Interstitial:
A generic term used if the source is not apparent or if the inflammation has extended from the original location
** Please note that interstitial inflammation might not be due to infectious process
(T/F) Biopsy will help determine if lesion are reversible or irreversible
True
Chronic Irreversible Lesions
- In between peritubular capillaries and tubules
- Hallmark of chronic disease
Interstitial fibrosis
Chronic Irreversible Lesions
- Thickened tubular basement membranes and attenuation (reduction) of tubular epithelium
- Likely due to some degree of hypoxia
Tubular atrophy
- Glomerulosclerosis (especially global glomerulosclerosis)
- Arteriosclerosis
These are:
Chronic Irreversible Lesions
Molecular Mediators of Fibrosis
* Angiotensin II
* TGF-β
* Connective Tissue Growth Factor
* FGF-23 (might predict the development of azotemia in normal healthy cats)
* Smads (mediate the TGF-β pathway)
Promote fibrosis
Molecular Mediators of Fibrosis
* BMP-7
* Smads (also mediate BMP-7 pathway)
* HGF
* Some components of the RAAS
Slow or inhibit fibrosis
