Lecture 8: Amyloid, calcification, pigments Flashcards
What is pathogenesis?
Pathogenesis is the manner of development of a disease.
Explains the formation of a lesion.
Think: Here’s the lesion, how did we get there?
As we look at lesions, it’s not a bad idea to think not just about “What does it look like, and what do I call it?” but also think “How did it get there? What were some of the forces that contributed to it?”
What is a differential diagnosis?
A differential diagnosis is a list of potential causes for a lesion or syndrome. Also called a rule out list.
You prioritize it by what is the most likely diagnosis.
Has to be specific for signalment, clinical signs, lesion.
What is a morphologic diagnosis?
A morphologic diagnosis is a succinct description of a lesion that includes:
- Location
- Distribution
- Duration
- Process (Is it necrosis? Inflammation? Tumor?)
- Severity
What is amyloid?
Amyloid is a “starch-like” hyaline substance, an abnormal protein that is usually produced in bone marrow and can be deposited in any tissue or organ.
What tests could you use to test for amyloid?
Grossly: You could do an iodine test; pouring iodine over the gross specimen. Iodine reveals starch that’s in the glomeruli; dark spots are glomeruli obliterated by amyloid
Histologically: You could do a Congo Red stain. When CRS finds amyloid it binds to it, turns an orange color. Under polarized light, it refracts a green color. Called congophillic when its positive.
When amyloid accumulates in the glomerular tufts, what happens?
Guinea pig example.
Protein should never be in the glomerular filtrate. Can’t recover it, once it’s there.
That fluid that would ordinarily stay within the vascular system moves out of it via diffusion. Abdomen of guinea pig is filled with fluid (tough to see because it’s clear).
When you have a marked decrease of oncotic pressure, due to loss of protein in the blood, then that fluid that would ordinarily stay within the vascular system moves out of it, by diffusion. So, ascites.
What are some examples of abnormal extracellular accumulations?
Abnormal extracellular accumulations:
- Gout
- Cholesterol
Gout.
What is it composed of?
What species are most commonly affected? .
Gout is an abnormal extracellular accumulation.
You may see it as a deposit of uric acid crystals, or tophi. Typically periarticular deposits, degenerative joint disease.
See it most commonly in birds and reptiles.
How could cholesterol be considered an abnormal extracellular accumulation?
Cholesterol is an integral part of cell membranes, and so if those cells break down for some reason, (say you’ve got a big hematoma) all the cholesterol has to go somewhere, and ends up forming layers within proteinaous goo, essentially.
Acicular clefts form, aka cholesterol clefts. The crystals themselves are like windowpanes. Rectangular formation, Very pretty, can see on cytology. When you line them all up and cut them in half and look at them in histology, what you’re more likely to see are linear clear spaces.
What is this an example of?
This is a positive amyloid test. The little black dots are glomeruli that have been obliterated by amyloid.
What is this an example of?
This a glomerulus that’s Congophilic, positive for Congo Red stain.
When CRS finds amyloid, it binds to it, becomes this orange color.
Under polarized light , it refracts a green color
What are you looking at here?
These are acicular clefts, aggregates of cholesterol. Not uncommon to see in places where there’s been a lot of cell breakdown.
What’s this? Both in the center, and on the periphery.
This is a bearded dragon kidney with visceral gout.
Basophillic deposit in the center, macrophages (yes, hard to see) at the periphery.
Side note: This is a bird’s main immunological response to inflammatory events, to make macrophages around it, and then pretend to ignore it. Doesn’t really work.
What’s going down here?
This is a bearded dragon joint with articular gout.
The clear spaces are areas of articular gout. It looks clear, can also be a pale grey color.
And this is…?
This is a green iguana with periarticular gout.
Grossly, it has a yellow color, finely gritty to granular texture.
Expands the joint space.
What are two kinds of pathologic calcification?
Two kinds of pathologic calcification:
- Dystrophic calcification
- Metastatic calcification
What’s dystrophic calcification?
Dystrophic calcification is the deposition of calcium in tissues that are injured or necrotic.
Grossly, looks like white lesions that are gritty or chalky.
We’ve seen this previously as fat necrosis.
Will also see calcium deposits in cells that are undergoing coagulative necrosis; it’s an early indication of coagulative necrosis. Helpful because you still have the outline of the cell membrane, can still see definition of cell borders. If there’s mineralization in the middle of it, that really helps.
If the cells are lysed, like in caseasous necrosis, you’ll still see mineralization but there’s no cell present anymore, for the calcium to be in the middle of.
What’s metastatic calcification?
Metastatic calcification is the deposition of calcium in normal tissues secondary to hypercalcemia.
Here, the tissue in which calcium is being deposited is perfectly normal. Occurs only when there’s hypercalcemia going on in the animal
What’s a type of dystrophic calcification that’s a lesion that we see in young dogs or in dogs over a pressure point, like the elbows or hips, or sometimes it’s suture sites?
This is calcinosis circumscripta.
Occurs in injured or necrotic areas. May be coagulative necrosis, may be caseous necrosis
Would appear as a mass and if you take it off, should be self-resolving. And you should take it off, vs leaving it on. The surface could get ulcerated, as it’s protruding.
What are we looking at here?
Another example of calcinosis circumscripta, which is a type of dystrophic calcification.
What is the pathogenesis of dystrophic calcification?
Dead/dying cells -> Denaturation/breakdown of proteins -> Calcium is more than happy to bind to it -> Results in the histologic and gross appearance of mineral deposition
Where would you see presentation of dystrophic calcification in cells undergoing coagulation necrosis? What about caseous necrosis?
Coagulation necrosis - Would see dystrophic calcification intracellularly, because the cells are still intact.
Caseous necrosis - Would see dystrophic calcification extracellularly, because there are no intracellular spaces left. Debris is no longer in a cell, the cells ARE the debris.
Tell me again about Metastatic calcification.
Metastatic calcification is the deposition of mineral (calcium salts) in tissue not previously injured but due to altered Calcium/Phosphorus regulation.
Metastatic calcification is the precipitation of Ca in organelles (mitochondria)
“Innocent bystander” tissues.
What’s the serum concentration levels of Calcium and Phosphorus that puts an animal at high risk for Metastatic calcicification?
[Ca] x [P] > 70
What are some causes of hypercalcemia?
Causes of hypercalcemia:
- High Ca diet
- Vitamin D excess
- Parathyroid tumor
- Paraneoplastic -> PTH
- Renal failure
What are some common locations where you’d see metastatic calcification?
Common locations for metastatic calcification:
- Basement membranes of kidneys, lungs
- Blood vessels
- Gaatric mucosa
- Intercostal pleura of the lungs
Qué es esto?
This is a Von Kossa stain that looks for calcium
Stains the Ca black. Don’t normally expect to find calcium in the alveolar septa. This is quite a bit.
What are the sequential colors of a bruise and what specifically accounts for each color?
Red - Hemorrhage of RBCs
Purple - Deoxygenated RBCs
Green - Biliverdin
Yellow - Bilirubin
Brown - Hemosiderin
What is bilirubin?
Bilirubin is a pigment produced in macrophages from the heme portion of hemoglobin.
It’s a pigment produced during the breakdown of RBC’c in the macrophages.
How can you get excessive bilirubin in the blood?
Excessive bilirubin could be due to:
- Large amounts of hemoglobin release (due to a disease process, blood parasite, etc)
- Hepatic dysfunction
- Blocked bile duct
There are ways that you can determine which of the three consequences is most likely, by looking at the blood work
What are we seeing here (how would you classify the fat)?
What is the name of the pigment that causes this color change?
Icterus/jaundice
Bilirubin is the pigment that causes this change.
Describe the pathogenesis for the occurrence of icterus in a cat with a pancreatic carcinoma, where the nodule of the carcinoma blocked the exit of the gall bladder/bile duct.
Blocked bile duct -> Cholestasis -> Regurgitation of conjugated bilirubin into serum -> post-hepatic icterus
Clinical evidence?
- Pale feces (decreased stercobilin)
- Large gall bladder
- Increased conjugated bilirubin
It’s not always easy to determine if an animal is icteric, on visual inspection.
Where would you look?
Non-haired structures
- Ears
- Sclera
- Subq tissues
Why do we care about bile acids?
What would potentially happen to bile acids in an animal with diarrhea?
Bile acids are important for cholesterol homeostasis, and absorption of fats.
Bile acids have a 95% recirculation rate. Animal with diarrhea will lose bile acids, which makes it harder for that animal to absorb fats and gain weight back
Name as many endogenous pigments as you can think of.
Endogenous pigments:
- Hemoglobin (red)
- Bilirubin (yellow)
- Hematoidin (yellow)
- Hemosiderin (brown)
- Lipofuscin (brown)
- Melanin (black)
- Hematin (black)
You’re a massively skilled pathologist, doing a necrospy on a black-faced sheep that expired from suspicious causes, and you find a black lesion on the aorta and on the pleura. What’s going on?
This is an example of melanosis: grossly visible, random areas of black pigmented tissue/pleura.
This is a normal finding, commonly seen in black faced cattle and black faced sheep.
What are we seeing here?
Hematin.
We’re looking at a histological view of fluke exhaust, or fluke poop.
Qu’est-ce que c’est?
This is the liver of an ox, showing a gross example of hematin.
This is also from Fluke exhaust. Flukes poop a lot.
What is this an example of?
This is a positive amyloid test. The little black dots are glomeruli that have been obliterated by amyloid.
O que é isso?
(Portuguese)
This is a glomerulus that’s Congophilic, positive for Congo Red stain.
When CRS finds amyloid, it binds to it, becomes this orange color.
Under polarized light , it refracts a green color
Beth yw hwn?
(Welsh)
These are acicular clefts, aggregates of cholesterol. Not uncommon to see in places where there’s been a lot of cell breakdown.
What’s this? Both in the center, and on the periphery.
This is a bearded dragon kidney with visceral gout.
Basophillic deposit in the center, macrophages (yes, hard to see) at the periphery.
Side note: This is a bird’s main immunological response to inflammatory events, to make macrophages around it, and then pretend to ignore it. Doesn’t really work.
Was ist das?
(German)
This is a bearded dragon joint with articular gout.
The clear spaces are areas of articular gout. It looks clear, can also be a pale grey color.
Hva er dette?
(Norweigan)
This is a green iguana with periarticular gout.
Grossly, it has a yellow color, finely gritty to granular texture.
Expands the joint space.
What’s a type of dystrophic calcification that’s a lesion that we see in young dogs or in dogs over a pressure point, like the elbows or hips, or sometimes it’s suture sites?
This is calcinosis circumscripta.
Occurs in injured or necrotic areas. May be coagulative necrosis, may be caseous necrosis
Would appear as a mass and if you take it off, should be self-resolving. And you should take it off, vs leaving it on. The surface could get ulcerated, as it’s protruding.
What are we looking at here?
Another example of calcinosis circumscripta, which is a type of dystrophic calcification.
Qué es esto?
(Spanish)
This is a Von Kossa stain that looks for calcium
Stains the Ca black. Don’t normally expect to find calcium in the alveolar septa. This is quite a bit.
What are we seeing here (how would you classify the fat)?
What is the name of the pigment that causes this color change?
Icterus/jaundice
Bilirubin is the pigment that causes this change.
You’re a massively skilled pathologist, doing a necrospy on a black-faced sheep that expired from suspicious causes, and you find a black lesion on the aorta and on the pleura. What’s going on?
This is an example of melanosis: grossly visible, random areas of black pigmented tissue/pleura.
This is a normal finding, commonly seen in black faced cattle and black faced sheep.
What are we seeing here?
Hematin.
We’re looking at a histological view of fluke exhaust, or fluke poop.
Qu’est-ce que c’est?
(French)
This is the liver of an ox, showing a gross example of hematin.
This is also from Fluke exhaust. Flukes poop a lot.
