Lecture 2: Urinary 2

Question 1

Name two conditions that commonly cause hemoglobinuric nephrosis in dogs.

Answer 1

(1) IMHA (immune-mediated hemolytic anemia). (2) Leptospirosis.

Question 2

In which species of domestic animal is glomerulonephritis the most common cause of renal failure?

Answer 2

Dogs.

Question 3

Name one dog breed that has a familial/hereditary/genetic predisposition to renal amyloidosis.

Answer 3

Shar Pei.

Question 4

You are performing a necropsy on a dog and notice that both kidneys are very darkly stained and that the renal pelvic fat is yellow. This dog has a history of passing red-brown urine. What is the most likely cause of this?

Answer 4

Hemoglobinuric nephrosis due to intravascular hemolysis (several causes, including IMHA in dogs, copper toxicity in sheep, leptospirosis in cattle & dogs & red maple toxicosis in horses). Myoglobinuric nephrosis is less likely because it tends not to stain fat yellow.

Question 5

Explain the pathogenesis of the hypercholesterolemia that may be seen in the nephrotic syndrome.

Answer 5

Loss of plasma proteins into urine –> liver responds by generalized increased protein production, and cholesterol production is also upregulated.

Question 6

Proteinuria, although suggestive of glomerular disease, is not exclusively caused by glomerular disease. What else can cause proteinuria?

Answer 6

Inflammation of the lower urinary tract.

Question 7

Which type of cell in the renal corpuscle is responsible for phagocytosis of deposited immune complexes?

Answer 7

Mesangial cell.

Question 8

How are the basement membranes of the glomerular capillary tufts different from basement membranes elsewhere in the body?

Answer 8

The glomerular basement membrane is thick (300-350 nm). Its negative charge and collagen network impede the passage of large protein molecules, most importantly albumin and hemoglobin.

Question 9

Describe the typical gross appearance of a kidney affected by amyloidosis.

Answer 9

Grossly, kidneys affected by amyloid deposition are diffusely tan, waxy (firm), friable and of normal size or slightly enlarged.

Question 10

What clinicopathologic finding is the hallmark of glomerular disease?

Answer 10

Proteinuria.

Question 11

Why is it deleterious to the glomerulus having immune complexes deposited in the glomerular basement membrane? Explain the pathogenesis.

Answer 11

Deposition in glomeruli –> Complement fixation –> Chemotaxis of neutrophils –> Release of harmful mediators of inflammation –> Continued damage by release of inflammatory mediators from monocytes in chronic stages. All this leads to thickening of the glomerular basement membrane. Paradoxically, this thickening makes the GBM “leaky”, probably due to changes in charge and pore size.

Question 12

How often is the specific cause of glomerulonephritis in domestic animals identified?

Answer 12

Rarely.

Question 13

You are performing a necropsy on a foal and notice that both kidneys contain dozens to hundreds of randomly scattered pinpoint white foci. What is the most likely bacterial cause of this?

Answer 13

Actinobacillus equuli.

Question 14

Name a condition that commonly causes hemoglobinuric nephrosis in horses.

Answer 14

Red maple toxicity.

Question 15

What are the two major categories of immune complex deposition in the glomerular basement membrane and which is by far the more common in domestic animals?

Answer 15

(1) Deposition of circulating antibody-antigen complexes that have formed in response to a variety of chronic diseases. (2) Autoantibodies directed at the glomerular basement membrane. Cause number 1 is by far the most common in domestic animals.

Question 16

Name a condition that commonly causes hemoglobinuric nephrosis in cattle.

Answer 16

Leptospirosis.

Question 17

Which parts of the lily (leaves or flowers) are nephrotoxic to cats?

Answer 17

Both leaves and flowers are toxic.

Question 18

How are the endothelial cells lining the glomerular capillary tufts different from endothelial cells elsewhere in the body?

Answer 18

Glomerular capillary endothelial cells have pores (fenestrations) in their cytoplasm that make them “leaky” (i.e., freely permeable to most blood constituents except red blood cells, white blood cells and platelets).

Question 19

Give two reasons why renal tubules are preferentially damaged by circulating toxins.

Answer 19

[Any two] (1) The kidneys receive 25% of cardiac output, therefore a circulating toxin inevitably reaches the kidneys. (2) Substances are filtered by the glomerulus and concentrated in the renal tubules. (3) Renal tubular epithelial cells are metabolically active (especially proximal convoluted tubules) so these are damaged first.

Question 20

What is the most common cause of renal failure in dogs?

Answer 20

Immune-mediated glomerulonephritis.

Question 21

Draw a simple flowchart explaining the pathogenesis of renal ethylene glycol (antifreeze) toxicity.

Answer 21

Antifreeze ingested –> absorbed from gut –> metabolized in liver to various toxic metabolites –> filtered by glomeruli –> directly toxic to renal tubular epithelial cells –> calcium oxalate crystals precipitate in renal tubules –> tubular obstruction & mechanical damage to lining.

Question 22

What are the five major components of the nephrotic syndrome?

Answer 22

(1) Proteinuria. (2) Hypoalbuminemia. (3) Edema / ascites. (4) Hypercholesterolemia. (5) Hypercoagulability.

Question 23

You notice that a horse passes dark red-brown urine the day after an intense training session. What pigment is most likely responsible for this urine discoloration?

Answer 23

Myoglobin. This disease is exertional rhabdomyolysis or “Monday morning disease”.

Question 24

What is the most salient clinical sign of acute tubular necrosis?

Answer 24

Oliguria or anuria (i.e., scant or no urine production).

Question 25

Where, precisely, in the kidney is amyloid typically deposited in cats?

Answer 25

The renal medulla.

Question 26

What general condition is associated with pathologic deposition of amyloid in domestic animals?

Answer 26

Chronic inflammatory disease.

Question 27

Why is hemoglobin, which is not directly toxic to renal tubules, so commonly associated with acute tubular necrosis?

Answer 27

(1) If hemoglobin is released due to intravascular hemolysis then an animal becomes anemic and hypoxic. Renal tubules are very susceptible to hypoxic damage. (2) If hemoglobin is released due to intravascular hemolysis then it passes into the glomerular ultrafiltrate. Proximal tubules, which are already hypoxic due to anemia, then attempt to resorb this hemoglobin and are placed under an increased workload.

Question 28

What type of disease, in general terms, most commonly results in immune complex deposition in the GBM in domestic animals?

Answer 28

Chronic inflammatory diseases that produce a persistent antigenemia.

Question 29

Explain in simple terms the pathogenesis of glomerulonephritis in dogs.

Answer 29

Deposition of circulating antibody-antigen complexes in the glomerular basement membrane –> Complement fixation –> Chemotaxis of neutrophils –> Release of harmful mediators of inflammation –> Glomerular damage.

Question 30

What renal disease or lesion is the single most important cause of ACUTE renal failure?

Answer 30

Acute tubular necrosis (usually due to nephrotoxins or ischemia).

Question 31

In general terms, what three characteristics of a substance prevent it from crossing the glomerular filtration barrier?

Answer 31

(1) Large size. (2) Negative charge. (3) Being bound to carrier proteins.

Question 32

What is the syndrome that may result from chronic, severe proteinuria?

Answer 32

Nephrotic syndrome.

Question 33

Grapes and raisins are toxic to which organ in dogs?

Answer 33

Kidneys.

Question 34

Explain the pathogenesis of the hypercoagulability that may be seen in the nephrotic syndrome.

Answer 34

Loss of anticoagulant antithrombin III into urine –> hypercoagulability –> thrombus formation.

Question 35

Name a condition that commonly causes hemoglobinuric nephrosis in sheep.

Answer 35

Chronic copper toxicity.

Question 36

A captured wild moose is noted to be passing red-brown discolored urine. What pigment is most likely responsible for this discoloration and what is the pathogenesis for the condition?

Answer 36

Myoglobin. This is capture myopathy. Damage to muscle caused by capture and attempts at escape –> release of myoglobin –> filtered by glomerulus –> myoglobinuria.

Question 37

What are the three components of the glomerular filtration barrier?

Answer 37

(1) Glomerular capillary endothelial cells. (2) Glomerular basement membrane. (3) Podocytes / visceral layer of Bowman’s capsule.

Question 38

Name one cat breed that has a familial/hereditary/genetic predisposition to renal amyloidosis.

Answer 38

Abyssinian.

Question 39

You are performing a necropsy on a dog and notice that both kidneys are pale tan, waxy and friable. What is the most likely cause of this?

Answer 39

Amyloidosis.

Question 40

Name the toxin in grapes and raisins that is nephrotoxic in dogs.

Answer 40

Tartaric acid

Question 41

Name four conditions or classes of condition that could lead to renal ischemia and, hence, acute tubular necrosis,

Answer 41

[Any four] (1) Decreased cardiac output (many causes of this, including heart failure, cardiac tamponade, arrhythmia etc.). (2) Intravascular volume depletion (many causes including dehydration, vomiting, blood loss etc.). (3) NSAID-induced interference with renal autoregulation during hypotension. (4) Altered renal and systemic vascular resistance (many causes, including hypothermia, anaphylaxis, sepsis, heatstroke). (5) Increased blood viscosity (e.g., polycythemia, multiple myeloma)

Question 42

Explain the pathogenesis of the ascites that may be seen in the nephrotic syndrome.

Answer 42

Loss of plasma proteins into urine –> decreased plasma oncotic pressure –> movement of fluid from circulation to interstitial space and body cavities.

Question 43

Lilies are toxic to which organ in cats?

Answer 43

Kidneys.

Question 44

Draw a simple flowchart explaining the pathogenesis of hemoglobinuric nephrosis.

Answer 44

There are two pathways, each beginning with intravascular hemolysis and ending in acute tubular necrosis. (1) Intravascular hemolysis –> Hypovolemia / Anemia / Hypoxia –> Tubular ischemia –> Acute tubular necrosis. (2) Intravascular hemolysis –> Hemoglobinemia –> Hemoglobin crosses into ultrafiltrate –> Increased demand on proximal tubules (resorption) –> Tubular ischemia –> Acute tubular necrosis.

Question 45

Explain how chronic heartworm infection in a dog may lead to glomerular disease.

Answer 45

Heartworm infection –> Chronic antigenemia –> formation of circulating antigen-antibody complexes (immune complexes) –> Deposition in glomerular basement membrane –> Complement fixation –> Chemotaxis of neutrophils –> Release of harmful mediators of inflammation –> Glomerular damage.

Question 46

What, in general terms, may give rise to the nephrotic syndrome?

Answer 46

Severe, chronic proteinuria due to glomerular disease.

Question 47

Explain how a chronic suppurative uterine infection (pyometra) in a dog may lead to glomerular disease.

Answer 47

Pyometra –> Chronic antigenemia –> formation of circulating antigen-antibody complexes (immune complexes) –> Deposition in glomerular basement membrane –> Complement fixation –> Chemotaxis of neutrophils –> Release of harmful mediators of inflammation –> Glomerular damage.

Question 48

Name the nephrotoxic compound that should be used to make plastic dinnerware instead of artificially bolstering the measured protein content of baby formula and pet food.

Answer 48

Melamine.

Question 49

Which type of amyloidosis (primary or secondary) most commonly leads to renal disease in domestic animals?

Answer 49

Secondary amyloidosis (reactive systemic amyloidosis) is the most common form of amyloidosis in animals. It is a complication of chronic inflammatory disease. The amyloid is derived from an acute phase protein synthesized by the liver in response to inflammation. [Primary amyloidosis is caused by immune dyscrasias and neoplasms. The amyloid is derived from excessive secretion of immunoglobulins, usually by a plasma cell neoplasm. Primary amyloidosis is rare in domestic animals.]

Question 50

What are the two major non-infectious categories of insult that can cause renal tubular necrosis?

Answer 50

(1) Toxins. (2) Ischemia.

Question 51

Where, precisely, in the kidney is amyloid typically deposited in dogs?

Answer 51

Glomeruli (except in the familial form in Shar Pei dogs).