Pathophysiology of Tubulointerstitial Disease (Cianciolo)

Question 1

Cats tend to get ___________

Answer 1

Tubulointerstitial disease

Question 2

Requires knowledge of creatinine or urinalysis etc

Answer 2

AKI (Clinical diagnosis)

Question 3

• Acute necrosis
• Acute inflammation
  Describes:

Answer 3

Acute Renal Lesions (pathologist)

Question 4

What are some things that cause acute tubular epithelial injury?

Answer 4

• Ischemic
• Toxic
• Obstructive (crystals/ cellular casts/ pigment casts / ureteral blockage etc)

Question 5

(T/F) Chronic kidney disease may present acutely

Answer 5

True

Question 6

(T/F) Even if animal is acutely azotemic, that doesn’t mean that the lesions will be “acute”

Answer 6

True

Question 7

(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”

Answer 7

False

Question 8

Epithelial cells don’t reabsorb glucose or amino acids appropriately

Answer 8

Fanconi’s Syndrome

Question 9

(T/F) You can have tubular problems w/o actual evidence of injury

Answer 9

True

Question 10

Glucosuria with normoglycemia and amino aciduria

Answer 10

• Fanconi’s syndrome
• Jerky treat exposure
  *Proximal tubulopathy is probably the correct term

Question 11

• Injured but viable epithelial cell detaches from the tubular basement membrane and exits in urine
• Very common in kidney

Answer 11

Anoikis

Question 12

The cell starts apoptotic cascade but can’t finish so it undergoes necrosis

Answer 12

Necroptosis

Question 13

• Controlled, does not incite inflammation
• Suicide

Answer 13

Apoptosis

Question 14

Cytokine expression of tubular epithelial cells
- __________ induces interstitial fibrosis

Answer 14

TGF-beta

Question 15

Cytokine expression of tubular epithelial cells
- _____________ attenuates fibrosis

Answer 15

BMP-7

Question 16

Cytokine expression of tubular epithelial cells
- Macrophage chemotactic protein (MCP-1) -> attracts ______________________

Answer 16

inflammatory cells

Question 17

Cytokine expression of tubular epithelial cells
- Epidermal Growth Factor helps _________ regenerate

Answer 17

tubules

Question 18

(T/F) In recovery from ATEI, recovering cells are thought to be more resistant to insult than mature cells

Answer 18

True

Question 19

• 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 ________________

Answer 19

Ischemic ATEI / ATN

Question 20

• 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

Answer 20

Aminoglycosides (antibiotic)
**is a cause of Toxic ATEI

Question 21

• 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

Answer 21

NSAIDs

Question 22

• 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

Answer 22

Ethylene Glycol (Toxic + obstructive)

Question 23

Other Causes of Oxalate Crystals
Cruciferous vegetables are:

Answer 23

• Rhubarb
• Spinach

Question 24

(T/F) Can see scattered oxalates in animals with chronic kidney disease because they have lost the ability to process endogenous or dietary oxalates

Answer 24

True

Question 25

* 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

Answer 25

Oak Nephrotoxicity

Question 26

* 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

Answer 26

Melamine / Cyanuric Acid (toxic + obstructive)

Question 27

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

Answer 27

Lilies in cats

Question 28

Other Nephrotoxins in Small Animals – Seems to be idiosyncratic – Mechanism of toxic action is unknown

Answer 28

Grapes or Raisins in dogs

Question 29

* RBC lysis -> anemia -> ischemic necrosis * And hemoglobin releases -> toxic to tubules

Answer 29

Pigmentary Nephropathy (Ischemic + toxic + obstructive)

Question 30

The source of the infectious agent determines the anatomic pattern of inflammation - Hematogenous:

Answer 30

embolic and / or glomerulonephritis

Question 31

The source of the infectious agent determines the anatomic pattern of inflammation - Urogenous:

Answer 31

Pyelonephritis - Suppurative inflammation centered on the renal pelvis - Can cause loss of concentrating ability due to renal papillary necrosis

Question 32

The source of the infectious agent determines the anatomic pattern of inflammation - Interstitial:

Answer 32

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

Question 33

(T/F) Biopsy will help determine if lesion are reversible or irreversible

Answer 33

True

Question 34

Chronic Irreversible Lesions - In between peritubular capillaries and tubules - Hallmark of chronic disease

Answer 34

Interstitial fibrosis

Question 35

Chronic Irreversible Lesions - Thickened tubular basement membranes and attenuation (reduction) of tubular epithelium - Likely due to some degree of hypoxia

Answer 35

Tubular atrophy

Question 36

- Glomerulosclerosis (especially global glomerulosclerosis) - Arteriosclerosis These are:

Answer 36

Chronic Irreversible Lesions

Question 37

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)

Answer 37

Promote fibrosis

Question 38

Molecular Mediators of Fibrosis * BMP-7 * Smads (also mediate BMP-7 pathway) * HGF * Some components of the RAAS

Answer 38

Slow or inhibit fibrosis