1 - Cellular Accumulations Flashcards

1
Q

Does lipid accumulate inside or outside cells in cases of lipidosis?

A

Inside. It is an intracellular accumulation.

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2
Q

Lipidosis can occur in various organs but is most common and serious in one. Which one?

A

Liver. You should become familiar with the terms hepatic lipidosis and “fatty liver”.

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3
Q

Describe the appearance of a liver affected by hepatic lipidosis.

A

The liver is swollen, with rounded edges rather than sharp edges. It is paler than normal and possibly yellow or cream-coloured. It has a greasy texture and may be friable (easily crumbled or torn when bent). Sections may float (because of their fat content) in formalin or water instead of sinking like healthy liver sections do.

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4
Q

You perform a necropsy on a cat and find a swollen, yellow liver with a greasy texture. Sections of liver float in your formalin bottle, rather than sinking. What is the most likely diagnosis?

A

Hepatic lipidosis (“fatty liver”)

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5
Q

You drop a section of pale liver from a sick (now dead) cow into a formalin bottle and find it floats. What is the most likely diagnosis?

A

Hepatic lipidosis (“fatty liver”)

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6
Q

Imagine a factory that receives raw material deliveries (e.g., metal and glass). Inside the factory it converts these into intermediate forms (e.g., a battery frame and a touchscreen) over several steps. Finally, it ships a finished product out (e.g., a cameraphone).

Now think of a hepatocyte (liver cell) in the same way. What represents the “raw material” being delivered to a hepatocyte?

A

Free fatty acids

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7
Q

Imagine a factory that receives raw material deliveries (e.g., metal and glass). Inside the factory it converts these into intermediate forms (e.g., a battery frame and a touchscreen) over several steps. Finally, it ships a finished product out (e.g., a cameraphone).

Now think of a hepatocyte (liver cell) in the same way. What substances represent the “intermediate forms” being produced in a hepatocyte?

A

Triglycerides and apoproteins

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8
Q

Imagine a factory that receives raw material deliveries (e.g., metal and glass). Inside the factory it converts these into intermediate forms (e.g., a battery frame and a touchscreen) over several steps. Finally, it ships a finished product out (e.g., a cameraphone).

Now think of a hepatocyte (liver cell) in the same way. What substance represents the “finished product” being exported from the hepatocyte?

A

Lipoproteins

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9
Q

Imagine a factory that receives raw material deliveries (e.g., metal and glass). Inside the factory it converts these into intermediate forms (e.g., a battery frame and a touchscreen) over several steps. Finally, it ships a finished product out (e.g., a cameraphone).

(a) What are three ways that this factory could fill up abnormally with all these items? Don’t overthink this; it’s common sense.

(b) After you answer this tortured analogy question, replace the “factory” with a hepatocyte, and all the materials with substances. Then re-do the question.

A
  1. Too many raw materials are delivered; more than the factory is equipped to process. They end up accumulating just inside the loading bay.
  2. The factory receives the correct amount of raw materials but doesn’t process them fast enough so that raw materials, partially built battery frames and touchscreens, and not-quite-finished cameraphones end up filling the factory. Who knows why? Maybe the workers are sick or absent.
  3. The factory makes the correct amount of cameraphones but can’t get them out the door and onto the trucks, so they accumulate while trucks wait impatiently outside. Who knows why? Maybe the loading door is locked and someone’s lost the key.
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10
Q

“Lipids” as a general term can accumulate in hepatocytes because of (1) increased mobilization of free fatty acids from body tissues overwhelming the ability of hepatocytes to metabolize them, (2) abnormal hepatic metabolism of these fatty acids into lipoproteins, meaning that intermediate substances build up, or (3) impaired release of the end products - lipoproteins - by the hepatocyte.

(a) Why might situation (1) arise?

(b) Do you think this is all you’ll ever hear about this?

(c) Do you think this will be covered in more detail in several later courses, including Systemic Pathology, and that this is only your first pass at this important topic?

A

(a) Generally a sudden or increasing demand for fuel by an animal that’s on a negative plane of energy. For example, a lactating cow who’s gone off feed, or an obese cat trapped by accident in a garage for a few days.
(b) Nope, of course not.
(c) Yep, absolutely.

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11
Q

“Lipids” as a general term can accumulate in hepatocytes because of (1) increased mobilization of free fatty acids from body tissues overwhelming the ability of hepatocytes to metabolize them, (2) abnormal hepatic metabolism of these fatty acids into lipoproteins, meaning that intermediate substances build up, or (3) impaired release of the end products - lipoproteins - by the hepatocyte.

(a) Why might situations (2) and (3) arise?

(b) Do you think this is all you’ll ever hear about this?

(c) Do you think this will be covered in more detail in several later courses, including Systemic Pathology, and that this is only your first pass at this important topic?

A

(a) Something is wrong with the hepatocyte. Pick your liver disease. Lipid accumulation is a non-specific change in many, many liver diseases, and just indictes hepatocellular dysfunction.
(b) Nope, of course not.
(c) Yep, absolutely.

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12
Q

In which two tissues / organs is most glycogen stored in the normal animal?

A

Liver
Skeletal muscle

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13
Q

(a) Name three relatively common conditions in which excessive glycogen accumulates in the liver. (All are more commonly seen in dogs, for you future SA vets. And please note: “glycogen storage diseases” are very rare, and are NOT among the correct answers.)

(b) Have you ever studied these three conditions in detail?

(c) Do you think you will?

A

(a) In any order:
~ Diabetes mellitus
~ Hyperadrenocorticism (Cushing’s disease)
~ Dogs receiving excessive amounts of therapeutic corticosteroids. Yes, that’s right, it’s YOU the vet who is responsible. (It’s called an iatrogenic disease when the doctor causes it).

(b) Nope, not yet. I’m still only halfway through first year.

(c) Of course I will. These are three important diseases and I need to learn a lot more about them.

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14
Q

Describe the gross appearance of a liver affected by so-called “steroid-hepatopathy” (also called “steroid-induced hepatopathy” or “glucocorticoid hepatopathy”).

A

The liver is swollen, pale brown and mottled. The pallor is caused by accumulation of glycogen (clear) within hepatocytes. It is usually less severe than the pallor caused by lipid accumulation, but you can never be sure until you check a histologic section.

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15
Q

Does glycogen accumulate inside or outside hepatocytes (liver cells) in cases of so-called “steroid-hepatopathy” (also called “steroid-induced hepatopathy” or “glucocorticoid hepatopathy”)?

A

Inside. It is an intracellular accumulation.

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16
Q

What substance accumulates inside hepatocytes (liver cells) in cases of so-called “steroid-hepatopathy” (also called “steroid-induced hepatopathy” or “glucocorticoid hepatopathy”)?

A

Glycogen. Glycogen! Glycogen!!!

~ Not glucose (which must be converted to glycogen for storage in hepatocytes, and “unconverted” back to glucose for release into the blood and use as fuel by other body cells).
~ Not glucocorticoids (which are drugs/hormones that cause the accumulation of glycogen, but do not themselves accumulate).
~ Not “steroids”! Please don’t ever write steroids.

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17
Q

The liver of a deceased dog that has been treated with a long course of corticosteroid drugs is found at necropsy to be swollen, pale brown and mottled.

(a) What has caused the liver’s appearance and,
(b) What are three synonymous terms for this liver change?

A

(a) Glycogen accumulation
(b) “Steroid-hepatopathy” (also called “steroid-induced hepatopathy” or “glucocorticoid hepatopathy”)

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18
Q

The liver of a deceased dog that had suffered from diabetes mellitus is found at necropsy to be swollen, pale brown and mottled.

(a) What has caused the liver’s appearance and,
(b) What are three synonymous terms for this liver change?

A

(a) Glycogen accumulation
(b) “Steroid-hepatopathy” (also called “steroid-induced hepatopathy” or “glucocorticoid hepatopathy”)

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19
Q

The liver of a deceased dog that had suffered from hyperadrenocorticism (Cushing’s disease) is found at necropsy to be swollen, pale brown and mottled.

(a) What has caused the liver’s appearance and,
(b) What are three synonymous terms for this liver change?

A

(a) Glycogen accumulation
(b) “Steroid-hepatopathy” (also called “steroid-induced hepatopathy” or “glucocorticoid hepatopathy”)

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20
Q

What does the term hepatopathy mean?

A

Hepato: Liver
Pathy: Non-specific term for disease
Hepatopathy: Non-specific term for disease of the liver

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21
Q

The terms hepatopathy, hepatitis, hepatosis, hepatectomy, hepatology and herpatology are all so similar that they’re pretty much interchangeable. True or false?

A

I’m not even going to dignify this with an answer.

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22
Q

Does amyloid accumulate inside or outside cells in cases of amyloidosis?

A

Outside. It is an extracellular accumulation.

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23
Q

What is amyloidosis? (Take a deep breath: this requires a complicated and quite long answer.)

A

Amyloidosis is the pathologic accumulation of amyloid. [But this is not enough of an answer to demonstrate understanding, so let’s try again …]

Amyloidosis is the pathologic accumulation of amyloid. Amyloid derives from a normally soluble and functional protein or peptide being rendered INsoluble and NON-functional, so that it accumulates between cells and affects them simply by occupying space and compressing them. The accumulation of amyloid is called amyloidosis. There are numerous types of protein or peptide that can give rise to amyloid and several different reasons for proteins and peptides to misfold. The common thread is that, in the case of amyloidosis, the misfolded and aggregated proteins have a characteristic highly organized fibrillar structure.

Thus amyloidosis is a biochemically diverse group of disorders that have a common pathogenesis (protein misfolding) and a similar fibrillar morphologic appearance.

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24
Q

Hepatic amyloidosis / amyloid accumulation is which of the following?

(a) A protein-misfolding disorder
(b) An intracellular proteinaceous accumulation
(c) The accumulation of starch between hepatocytes (liver cells)

A

(a) A protein-misfolding disorder

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25
Q

Which of the following conditions is a result of soluble and functional proteins being rendered insoluble and non-functional by misfolding, leading to their accumulation?

(a) Amyloidosis
(b) Dystrophic mineralization
(c) Gout
(d) Icterus
(e) Lipidosis
(f) Steroid hepatopathy

A

(a) Amyloidosis

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26
Q

What is the typical appearance of amyloid, if enough has accumulated to be visible grossly?

A

If visible macroscopically, amyloid appears as yellow, waxy, coalescing nodular or amorphous deposits.

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27
Q

What is amyloid? (Take a deep breath: this requires a complicated and quite long answer.)

A

Amyloid is a biochemically diverse group of proteins or peptides that have a common pathogenesis (protein misfolding), a common morphologic appearance (regularly arranged fibrils), and a tendency to cause problems (by aggregating and accumulating).

Amyloid derives from a normally soluble and functional protein or peptide being rendered INsoluble and NON-functional, so that it accumulates between cells and affects them simply by occupying space and compressing them. There are numerous types of protein or peptide that can give rise to amyloid, and several different reasons for proteins and peptides to misfold. The common thread is that, in the case of amyloid, the misfolded and aggregated proteins have a characteristic highly organized fibrillar structure.

The accumulation of amyloid is called amyloidosis.

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28
Q

Amyloid can be classified by the biochemical identity of its precursor peptide or protein. Two major classifications are AA and AL. What do AA and AL stand for?

A

AA: Amyloid A
AL: Amyloid Light

All clear now? I’m guessing not. This is competely unhelpful. Please see later questions on AA and AL for clarification.

You do need to know what these letters stand for but also, much more importantly, how these two forms of amyloidosis develop and how they are different.

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29
Q

Amyloid can be classified by the biochemical identity of its precursor peptide or protein. Two major classifications are AA and AL. In domestic animals AA (secondary) amyloidosis is much more common than AL (primary) amyloidosis.

What is the source of the amyloid in AL (primary) amyloidosis?

A

Plasma cells.

AL amyloid consists of immunoglobulin light chains derived from plasma cells. When plasma cells dyscrasias or plasma cell neoplasms (e.g., multiple myeloma) are the source, this is called PRIMARY amyloidosis.

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30
Q

Amyloid can be classified by the biochemical identity of its precursor peptide or protein. Two major classifications are AA and AL. In domestic animals AA (secondary) amyloidosis is much more common than AL (primary) amyloidosis.

What is the source of the amyloid in AA (secondary) amyloidosis?

A

Initially the liver.

The liver upregulates production of serum amyloid A protein (SAA) in response to chronic inflammation at any site in the body. SAA is an termed an “acute phase protein”.

For poorly understood reasons, in certain individuals SAA is cleaved into fragments that are deposited as amyloid fibrils in various tissues, particularly the kidney, liver, and spleen.

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31
Q

Amyloid can be classified by the biochemical identity of its precursor peptide or protein. Two major classifications are AA and AL. In domestic animals AA (secondary) amyloidosis is much more common than AL (primary) amyloidosis.

In domestic animals, which three organs are the most common sites of AA (secondary) amyloid deposition?

A

Kidney, liver and spleen

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32
Q

Amyloid can be classified by the biochemical identity of its precursor peptide or protein. Two major classifications are AA and AL. In domestic animals AA (secondary) amyloidosis is much more common than AL (primary) amyloidosis.

In domestic animals what, in very general terms, is the most common reason for AA (secondary) amyloidosis to develop?

A

Chronic inflammation.

Try to remember this example: a caged or hospitalized duck with a chronic bacterial foot infection from standing on a hard surface may develop hepatic amyloidosis, leading to its death from liver failure.

This is completely non-intuitive and it’s easy for amyloidosis to fall off a vet’s diagnostic radar because the predsposing disease (e.g., a foot infection) is so much more apparent. Always keep amyloidosis at the back of your mind!

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33
Q

Amyloid can be classified by the biochemical identity of its precursor peptide or protein. Two major classifications are AA and AL. In domestic animals AA (secondary) amyloidosis is much more common than AL (primary) amyloidosis.

In domestic animals chronic inflammation is the most common reason for AA amyloidosis to develop. However, there are also familial / hereditary forms that arise spontaneously in certain breeds without needing chronic inflammation as a trigger. What are two commonly affected breeds (one dog, one cat)?

A

Shar Pei dogs and Abyssinian cats

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34
Q

Shar Pei dogs and Abyssinian cats. What should this seemingly random pairing of breeds and species make you think of?

A

AA amyloidosis.

In domestic animals chronic inflammation is the most common reason for AA amyloidosis to develop. However, there are also familial / hereditary forms that arise spontaneously in Shar Pei dogs and Abyssinian cats without needing chronic inflammation as a trigger.

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35
Q

Describe the appearance of a liver affected by diffuse hepatic amyloidosis.

A

The liver is enlarged, pale, waxy and friable. This sounds a lot like hepatic lipidosis doesn’t it? The key difference is that amyloidosis is “waxy” and lipidosis is “greasy.” These can be subtle differences and are not always apparent. Both conditions are good to include in your differential diagnosis.

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36
Q

Describe the appearance of a kidney affected by diffuse renal amyloidosis.

A

The kidney is enlarged, pale, waxy and friable.

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37
Q

Amyloidosis can be systemic (extracellular deposits in multiple organs or tissues, independent of the site of synthesis of the precursor protein) or localized (restricted to tissues in which the precursor protein or peptide is synthesized).

Which form - systemic or localized - is more likely to be life-threatening?

A

Systemic amyloidosis is more likely to be life threatening, depending on the organs or tissues involved and on the volume of amyloid deposits.

38
Q

Amyloidosis can be systemic (extracellular deposits in multiple organs or tissues, independent of the site of synthesis of the precursor protein) or localized (restricted to tissues in which the precursor protein or peptide is synthesized).

Which form - systemic or localized - is less likely to be life-threatening?

A

Localized amyloidosis is less likely to be life-threatening.

Systemic amyloidosis, on the other hand, is more likely to be life threatening, depending on the organs or tissues involved and on the volume of amyloid deposits.

This isn’t always true. For example, the localized amyloidosis (β-amyloid or Aβ) that occurs in the brain of humans with Alzheimer’s disease is very definitely life-threatening.

39
Q

What is the term for the deposition of sodium urate crystals or urates in tissue?

A

Gout

40
Q

What is deposited in tissues in the disease gout?

A

Sodium urate crystals or urates

41
Q

Gout is the term for the deposition of sodium urate crystals or urates in tissue.

Gout doesn’t occur in domestic mammals. So why bother learning about it as a vet? Can you name three types of animal in which gout does occur, justifying you learning about the disease?

A

Birds
Reptiles
Primates (including you!)

42
Q

Gout is the term for the deposition of sodium urate crystals or urates in tissue. Gout doesn’t occur in domestic mammals but does occur in birds, reptiles and primates, all of which may be your patients.

Gout comes in two forms: articular and visceral. Which form is most common in primates?

A

Articular. Really sore fingers and toes usually!

In the most common human form, urate crystals are deposited in the articular and periarticular tissues and elicit an acute inflammatory response characterized by the presence aggregates of urate crystals called tophi. Tophi may be visible grossly and are pathognomonic for gout. Later in the course of the disease, the inflammation becomes chronic, and a foreign body reaction to the tophi develops.

43
Q

Gout is the term for the deposition of sodium urate crystals or urates in tissue. Gout doesn’t occur in domestic mammals but does occur in birds, reptiles and primates, all of which may be your patients.

Gout comes in two forms: articular and visceral. Which form is most common in birds?

A

Visceral. The serosal surfaces of internal organs, particularly the pericardium and kidneys, are covered with a thin layer of off-white granules. This gross appearance is diagnostic.

Uric acid and urates are the end products of purine metabolism, and in birds and reptiles these products are eliminated as semisolid urates.

Visceral gout is usually diagnosed at necropsy and is seen sporadically as the result of vitamin A deficiency, high-protein diets, and renal injury.

44
Q

Gout is the term for the deposition of sodium urate crystals or urates in tissue. Gout doesn’t occur in domestic mammals but does occur in birds, reptiles and primates, all of which may be your patients.

Gout comes in two forms: articular and visceral. Which form is most common in reptiles?

A

Visceral. The serosal surfaces of internal organs, particularly the pericardium and kidneys, are covered with a thin layer of off-white granules. This gross appearance is diagnostic.

Uric acid and urates are the end products of purine metabolism, and in birds and reptiles these products are eliminated as semisolid urates.

Visceral gout is usually diagnosed at necropsy and is seen sporadically as the result of vitamin A deficiency, high-protein diets, and renal injury.

45
Q

You perform a necropsy on a bird and find that the serosal surfaces of internal organs, particularly the pericardium, are covered with a thin layer of off-white granules. What is your presumptive diagnosis?

A

Visceral gout.

Uric acid and urates are the end products of purine metabolism, and in birds and reptiles these products are eliminated as semisolid urates.

Visceral gout is usually diagnosed at necropsy and is seen sporadically as the result of vitamin A deficiency, high-protein diets, and renal injury.

46
Q

You perform a necropsy on a bird and find that the serosal surfaces of internal organs, particularly the kidneys, are covered with a thin layer of off-white granules. What is your presumptive diagnosis?

A

Visceral gout.

Uric acid and urates are the end products of purine metabolism, and in birds and reptiles these products are eliminated as semisolid urates.

Visceral gout is usually diagnosed at necropsy and is seen sporadically as the result of vitamin A deficiency, high-protein diets, and renal injury.

47
Q

You perform a necropsy on a lizard and find that the serosal surfaces of internal organs, particularly the pericardium, are covered with a thin layer of off-white granules. What is your presumptive diagnosis?

A

Visceral gout.

Uric acid and urates are the end products of purine metabolism, and in birds and reptiles these products are eliminated as semisolid urates.

Visceral gout is usually diagnosed at necropsy and is seen sporadically as the result of vitamin A deficiency, high-protein diets, and renal injury.

48
Q

You perform a necropsy on a lizard and find that the serosal surfaces of internal organs, particularly the kidneys, are covered with a thin layer of off-white granules. What is your presumptive diagnosis?

A

Visceral gout.

Uric acid and urates are the end products of purine metabolism, and in birds and reptiles these products are eliminated as semisolid urates.

Visceral gout is usually diagnosed at necropsy and is seen sporadically as the result of vitamin A deficiency, high-protein diets, and renal injury.

49
Q

What is the term for the deposition of calcium salts, typically as phosphates or carbonates, in soft tissues (i.e., tissues that would not be calcified in a healthy state)?

A

Pathologic calcification

50
Q

What is meant by the term pathologic calcification?

A

The deposition of calcium salts, typically as phosphates or carbonates, in soft tissues (i.e., tissues that would not be calcified in a healthy state).

51
Q

Pathologic calcification is divided into two subtypes of calcification, each with a different pathogenesis.

Name these two subtypes, and the cause of each.

A

Metastatic calcification: soft tissue calcification as the result of elevated serum calcium

Dystrophic calcification: the calcification of dead tissue as part of the process of necrosis.

52
Q

What is the term for the pathologic calcification of soft tissue as the result of elevated serum calcium?

A

Metastatic calcification

53
Q

What is meant by the term metastatic calcification?

A

The pathologic calcification of soft tissue as the result of elevated serum calcium

54
Q

What is the term for the pathologic calcification of dead tissue as part of the process of necrosis?

A

Dystrophic calcification

55
Q

What is meant by the term dystrophic calcification?

A

The pathologic calcification of dead tissue as part of the process of necrosis

56
Q

If pathologic calcification in a tissue is extensive, what is the gross appearance of the tissue?

A

The tissue will have chalky white deposits with a brittle or gritty texture.

57
Q

White muscle disease in ruminants, caused by vitamin E / selenium deficiency, is named for the chalky white deposits in cardiac and skeletal muscle. What do these chalky white deposits represent?

A

Areas of dystrophic calcification that have occurred in areas of muscle necrosis.

58
Q

Dystrophic calcification can occur in any area of necrosis, regardless of type of necrosis (e.g., coagulative, liquefactive, or caseous) or anatomic location (e.g., muscle, liver, fat etc.).

Having said this, dystrophic calcification is an especially common finding in five diseases / conditions. What are these?

A

White muscle disease
Granulomas of tuberculosis or similar diseases
Parasitic granulomas
Necrotic fat
Lipomas (benign neoplasms of adipocytes)

Note: I would never ask this type of list question in an exam. I just want you not to be surprised when your knife encounters gritty areas in these lesions, and to know what these represent.

59
Q

Match the following types of pathologic calcification to their correct description.

(a) Dystrophic calcification
(b) Metastatic calcification

(1) Occurs in dead tissue as part of the process of necrosis
(2) Occurs in soft tissue as the result of elevated serum calcium

A

(a)-(1)
(b)-(2)

60
Q

Match the following types of pathologic calcification to their correct description.

(a) Metastatic calcification
(b) Dystrophic calcification

(1) Occurs in dead tissue as part of the process of necrosis
(2) Occurs in soft tissue as the result of elevated serum calcium

A

(a)-(2)
(b)-(1)

61
Q

Metastatic calcification occurs in soft tissues as the result of elevated serum calcium (hypercalcemia).

Certain specific soft tissues in certain specific organs are particuarly prone to calcification caused by hypercalcemia. What are they?

A

Metastatic calcification targets the [SOFT TISSUES]:
~ tunica intima and
~ tunica media of blood vessels …

….especially those in the [ORGANS] :
~ lungs
~ pleura
~ endocardium
~ kidneys
~ stomach

62
Q

Metastatic calcification occurs in soft tissues as the result of elevated serum calcium (hypercalcemia).

What are the four most common diseases / conditions that lead to hypercalcemia (and potentially metastatic calcification) in veterinary medicine?

Be assured that you will learn a lot more about each disease / condition in Systemic Pathology next year. This is just your first pass over this topic and simply learning the names of these conditions, even if you don’t fully understand them, is very valuable.

A

~ Chronic kidney disease
~ Toxicosis with vitamin D or its analogues
~ Inappropriately elevated concentrations of parathyroid hormone (PTH) or secretion of PTH-related peptide
~ Bone destruction from primary bone tumors or metastatic tumors in bone

63
Q

If erythrocytes (red blood cells) are lysed within vessels (intravascular hemolysis), the released hemoglobin imparts what colour to plasma or serum? This is important to notice when assessing a blood sample you’ve collected.

A

A transparent pink tinge

64
Q

If erythrocytes (red blood cells) are lysed within vessels (intravascular hemolysis), the released hemoglobin can pass through the kidneys and into the urine. What colour will the urine be?

A

Reddish discoloration of the urine

65
Q

If erythrocytes (red blood cells) are lysed within vessels (intravascular hemolysis), the released hemoglobin can pass through the kidneys and into the urine. This can impart a distinct colour to the kidneys. What colour?

A

Dark red to “gunmetal blue” whatever the heck that colour is to people unfamiliar with guns. Maybe Google this colour?

66
Q

You perform a necropsy on a sheep after ante-mortem blood sampling and euthanasia and note that (a) the blood plasma has a transparent pink tinge, (b) the urine has a reddish discolouration and (c) the kidneys are dark red to blue.

What process has likely occurred in this sheep?

A

Erythrocytes (red blood cells) have been lysed (ruptured) within blood vessels (intravascular hemolysis). The hemoglobin released has discoloured the plasma and, after filtration by the kidneys, discoloured the kidney parenchyma and urine.

There are numerous causes for intravascular hemolysis, which you will learn about later. A common one in small ruminants is chronic copper poisoning.

67
Q

Bilirubin is a breakdown product of which type of cell?

A

Erythrocyte (red blood cell)

More detail than you need to know for this course, but you’ll need it later: Effete erythrocytes are phagocytized and lysed by macrophages. The globular protein components of hemoglobin are broken down into amino acids. After removal of iron, the rest of the heme is converted by heme oxygenase to biliverdin, then by biliverdin reductase to bilirubin.

68
Q

Bilirubin is a product released from the breakdown of red blood cells.

Is it recycled or excreted after its release?

A

It’s excreted through the bile into the small intestine.

More detail than you need to know for this course, but you’ll need it later: The unconjugated bilirubin is released into the blood to be carried as an albumin-bilirubin complex to the liver for conjugation with glucuronic acid and secretion into the bile canaliculus, where it becomes a component of bile.

69
Q

Bilirubin is a product released from the breakdown of red blood cells.

If the serum or plasma bilirubin level is excessive (hyperbilirubinemia), it may result in what change in many body tissues?

A

Yellow staining of tissues called icterus or jaundice.

More detail than you need to know for this course, but you’ll need it later: Icterus is classified as prehepatic, hepatic, or posthepatic.
~ Prehepatic icterus is caused by hemolysis or any process that increases the turnover of erythrocytes and delivers more unconjugated bilirubin to the liver than it can accommodate.
~ Hepatic icterus is the result of hepatocellular injury that decreases the uptake, conjugation, or secretion of bilirubin.
~ Posthepatic icterus is the result of the outflow of bile from the liver into the intestine via the biliary system being reduced by an obstruction.

70
Q

Bilirubin is a product released from the breakdown of red blood cells.

If the serum or plasma bilirubin level is excessive (hyperbilirubinemia), it may result in yellow staining of various body tissues. What are two synonymous terms for this yellow staining?

A

Icterus and jaundice.

Icterus is a bit more “medical” so it’s a better term to use than jaundice.

71
Q

Bilirubin is a product released from the breakdown of red blood cells. When present in excessive amounts it may discolour tissues bright yellow (icterus or jaundice).

In which tissues is this yellow discoloration most easily seen?

A

Grossly, the yellow discoloration of icterus is easiest to see in pale or colorless tissues, such as plasma, the sclera, tunica intima of the great vessels such as the aorta, adipose tissue, and even in a pale liver.

72
Q

Have you read the section on proteins (pp. 26L-29L) and taken away the following important messages, even if you haven’t memorized all the details?

~ Proteins are complicated.
~ The 3D form of a protein (its folding) is as important as its amino acid sequence.
~ Proteins are like enormous cruise ships that require a secondary fleet of smaller vessels (called chaperones) to escort them places, make sure they’re working, flag them for repair or dismantling if they’re broken, and prevent them from crashing into one another.
~ “Broken” (unfolded or misfolded) proteins are normally removed by an elegant tagging and dismantling process within certain cells. Therefore, they don’t accumulate. If they are unable to be dismantled, and begin to stick to one another (aggregation) and/or build up (accumulation) a whole host of diseases can develop.

A

Yep.

73
Q

Some (NOT ALL) types of viruses leave characteristic “dots” inside cells that represent their cast off machinery. The location (cytoplasmic or intranuclear), colour (pink, blue or pinkish-blue), and size of these “dots” can help a pathologist make an educated guess as to the type of virus that’s present.

What’s the correct term for these “dots”?

A

Viral inclusions, or viral inclusion bodies

74
Q

What are viral inclusions (AKA viral inclusion bodies)?

A

Some (NOT ALL) types of viruses leave characteristic “dots” inside cells that represent their cast off machinery. The location (cytoplasmic or intranuclear), colour (pink, blue or pinkish-blue), and size of these “dots” can help a pathologist make an educated guess as to the type of virus that’s present.

75
Q

Fill in the blank: choesterol crystals often form in tissue at sites of _________ or _________.

A

Hemorrhage or necrosis.

This wouldn’t be something worth learning unless there wasn’t one particular equine condition where this is relevant: cholesterol granulomas (“cholesteatomas”) of the choroid plexus. These are common in the choroid plexus of old horses and can become large enough to obstruct the flow of cerebrospinal fluid (although they are more often an incidental finding). Grossly, they appear as friable pale yellow nodules in the choroid plexus of the lateral or fourth ventricles.

76
Q

What type of crystal often forms in tissues at sites of hemorrhage or necrosis?

A

Cholesterol.

This wouldn’t be something worth learning unless there wasn’t one particular equine condition where this is relevant: cholesterol granulomas (“cholesteatomas”) of the choroid plexus. These are common in the choroid plexus of old horses and can become large enough to obstruct the flow of cerebrospinal fluid (although they are more often an incidental finding). Grossly, they appear as friable pale yellow nodules in the choroid plexus of the lateral or fourth ventricles.

77
Q

Name the lesions that appears as friable pale yellow nodules in the choroid plexus of the lateral or fourth ventricles in old horses. They can become large enough to obstruct the flow of cerebrospinal fluid, although they are more often an incidental finding.

A

Cholesterol granulomas (“cholesteatomas”).

78
Q

Heterotopic ossification results in hard spicules or nodules of bone in unusual locations. Areas of heterotopic ossification are commonly encountered as incidental findings in the lungs of spinal dura mater of old dogs.

You learned an alternate name for this change. What is is?

A

Osseous metaplasia

79
Q

Osseous metaplasia results in hard spicules or nodules of bone in unusual locations. Areas of osseous metaplasia are commonly encountered as incidental findings in the lungs of spinal dura mater of old dogs.

There is an alternate name for this change. What is it?

A

Heterotopic ossification

80
Q

The deep yellow color of adipose tissue in herbivores on lush green pasture can be striking, especially in horses and dairy cattle of high milk-fat breeds, such as Jersey dairy cattle.

What causes this colour?

A

Carotenoid pigments, such as β-carotene, which are abundant in leafy green plants and impart a yellow coloration to plasma, adipose tissue, and other lipid-laden cells.

This is NOT a lesion and should NOT be confused with icterus (jaundice), which IS a lesion. Carotenoid pigments only stain fat; icterus turns any pale tissue yellow: sclera, skin, gums, footpads, as well as adipose tissue.

81
Q

What colour do dietary carotenoid pigments, which are abundant in leafy green plants, impart to plasma, adipose tissue, and other lipid-laden cells in grazing herbivores?

A

Bright yellow

82
Q

You perform a necropsy on a Jersey dairy cow euthanized for lameness. The adipose tissues in the abdominal cavity are bright yellow. What is the most likely cause?

A

Ingestion of dietary carotenoid pigments, such as β-carotene, from lush pasture. These are are abundant in leafy green plants and impart a yellow coloration to plasma, adipose tissue, and other lipid-laden cells.

This is NOT a lesion and should NOT be confused with icterus (jaundice), which IS a lesion. Carotenoid pigments only stain fat; icterus turns any pale tissue yellow: sclera, skin, gums, footpads, as well as adipose tissue.

83
Q

Which drug, if given to young animals during the time of mineralization of the teeth, results in permanent discoloration of the teeth? And what colour do the teeth turn?

A

The antibiotic tetracycline. Initially the staining is yellow, but after tooth eruption and exposure to light, oxidation changes the color to brown.

84
Q

If the antibiotic tetracycline is given to young animals during the time of mineralization of the teeth what occurs?

A

Permanent discoloration of the teeth. Initially the staining is yellow, but after tooth eruption and exposure to light, oxidation changes the color to brown.

85
Q

What striking but insignificant change may be seen in the aortic intima in ruminants with pigmented coats and in the lungs of red or black pigs?

A

Black patches caused by localized deposits of melanin. This condition is called melanosis, which is 100% NOT melanoma, a neoplasm of melanocytes. Melanosis is merely a color change and not a lesion because it is not a response to injury and has no ill effect on the animal.

86
Q

Fill in the blanks: Black patches caused by localized deposits of melanin are common in the aortic intima of ____(a)____ and in the lungs of ____(b)____.

A

(a) Ruminants with pigmented coats
(b) Red or black pigs

This condition is called melanosis, which is 100% NOT melanoma, a neoplasm of melanocytes. Melanosis is merely a color change and not a lesion because it is not a response to injury and has no ill effect on the animal.

87
Q

Fill in the blanks: Black patches caused by localized deposits of melanin are common in the ____(a)____ of ruminants with pigmented coats and in the ____(b)____ of red or black pigs.

A

(a) Aortic intima
(b) Lungs

This condition is called melanosis, which is 100% NOT melanoma, a neoplasm of melanocytes. Melanosis is merely a color change and not a lesion because it is not a response to injury and has no ill effect on the animal.

88
Q

Which inhaled toxin colors the blood cherry red and imparts a bright pink color to the tissues?

A

Carbon monoxide (CO).

Hemoglobin has a much higher affinity for CO than for oxygen, so even a small amount of CO reduces oxygen transport capacity. When hemoglobin binds CO, it forms carboxy- hemoglobin, which colors the blood cherry red the tissues bright pink.

Change those CO detector batteries today!

89
Q

Describe the colors of the blood and tissues of an animal that died from carbon monoxide (CO) poisoning.

A

CO colors the blood cherry red and imparts a bright pink color to the tissues.

Hemoglobin has a much higher affinity for CO than for oxygen, so even a small amount of CO reduces oxygen transport capacity. When hemoglobin binds CO, it forms carboxy- hemoglobin, which colors the blood cherry red the tissues bright pink.

Change those CO detector batteries today!

90
Q

Which ingested toxin converts hemoglobin to methemoglobin, which has low affinity for oxygen and, in addition, turns the blood a deep chocolate brown?

A

Nitrates / nitrites.

Nitrite poisoning can be associated with con- sumption of nitrate-accumulating plants by livestock, usually ruminants, or from a water source contaminated with nitrate runoff from fertilized fields. Nitrate is converted in the rumen to nitrite, which can oxidize the iron in the heme group of the hemoglobin molecule to the Fe+3 (ferric) state, converting hemoglobin to methemoglobin.