1 - Cellular Accumulations Flashcards
(90 cards)
Does lipid accumulate inside or outside cells in cases of lipidosis?
Inside. It is an intracellular accumulation.
Lipidosis can occur in various organs but is most common and serious in one. Which one?
Liver. You should become familiar with the terms hepatic lipidosis and “fatty liver”.
Describe the appearance of a liver affected by hepatic lipidosis.
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.
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?
Hepatic lipidosis (“fatty liver”)
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?
Hepatic lipidosis (“fatty liver”)
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?
Free fatty acids
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?
Triglycerides and apoproteins
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?
Lipoproteins
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.
- Too many raw materials are delivered; more than the factory is equipped to process. They end up accumulating just inside the loading bay.
- 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.
- 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.
“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) 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.
“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) 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.
In which two tissues / organs is most glycogen stored in the normal animal?
Liver
Skeletal muscle
(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) 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.
Describe the gross appearance of a liver affected by so-called “steroid-hepatopathy” (also called “steroid-induced hepatopathy” or “glucocorticoid hepatopathy”).
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.
Does glycogen accumulate inside or outside hepatocytes (liver cells) in cases of so-called “steroid-hepatopathy” (also called “steroid-induced hepatopathy” or “glucocorticoid hepatopathy”)?
Inside. It is an intracellular accumulation.
What substance accumulates inside hepatocytes (liver cells) in cases of so-called “steroid-hepatopathy” (also called “steroid-induced hepatopathy” or “glucocorticoid hepatopathy”)?
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.
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) Glycogen accumulation
(b) “Steroid-hepatopathy” (also called “steroid-induced hepatopathy” or “glucocorticoid hepatopathy”)
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) Glycogen accumulation
(b) “Steroid-hepatopathy” (also called “steroid-induced hepatopathy” or “glucocorticoid hepatopathy”)
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) Glycogen accumulation
(b) “Steroid-hepatopathy” (also called “steroid-induced hepatopathy” or “glucocorticoid hepatopathy”)
What does the term hepatopathy mean?
Hepato: Liver
Pathy: Non-specific term for disease
Hepatopathy: Non-specific term for disease of the liver
The terms hepatopathy, hepatitis, hepatosis, hepatectomy, hepatology and herpatology are all so similar that they’re pretty much interchangeable. True or false?
I’m not even going to dignify this with an answer.
Does amyloid accumulate inside or outside cells in cases of amyloidosis?
Outside. It is an extracellular accumulation.
What is amyloidosis? (Take a deep breath: this requires a complicated and quite long answer.)
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.
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 protein-misfolding disorder