5. Cell Injury: Cellular Accumulations

excessive production, or normal amount, of substance that is accumulating faster than can get rid of

accumulations

Why can’t the body get rid of the accumulations?

due to problems metabolizing, packaging, and excreting (genetic or acquired disabilities)

What are common accumulations? What is an example?

indigestible exogenous substance; carbon

accumulations of a substance within the cell

intracellular accumulations

What are examples of intracellular accumulations?

L
G
P
V
C
L

• lipid

• glycogen

• protein absorption

• viral inclusions

• crystalline protein inclusions

• lead poisoning produced intranuclear inclusions

accumulations that occur outside the cell in the interstitium

extracellular accumulations

What are examples of extracellular accumulations?

A
G
C
F
F

• amyloidosis

• gout

• cholesterol

• fibrosis
  fatty infiltration

True or false: Some of the accumulation substances are harmless while others, when present in enough quantities, can lead to cell injury and death.

true

What are causes of accumulations?

M
G
I

• metabolic abnormalities which result in excessive production of a substance

• genetic abnormalities which lead to excessive storage or inability to break down or release a substance (lysosomal storage disease)

• indigestible substance where the cell lacks machinery to break down material or transport out of a cell (carbon)

accumulation of lipid within parenchymal cells, which can develop in many organs and tissues

steatosis

Where can you see steatosis most notably? Why?

the liver it is extremely important in lipid metabolism

What are causes of hepatic lipidosis?

I
A
I

• increased mobilization of free fatty acids

• abnormal hepatocellular metabolism of lipids

• impaired release of lipoproteins

Grossly, lipid accumulation in the liver will be visualized as a ________ liver with ________ edges, which is often ________/________-________ with an accentuated ________ pattern. It is also ________ to the touch. This type of liver will also frequently ________ in formalin rather than ________ like a normal liver would.

swollen; rounded; yellow/yellow-brown; centrolobar; greasy; float; sink

True or false: Histologically, lipid accumulation in the liver shows hepatocytes that have one or more colorless punctate cytoplasmic vacuoles which can displace the nucleus and result in degeneration and necrosis if severe enough. The lipid vacuoles are colorless and punctate because the lipids have leached from the cell in the process of processing.

true

What histochemical stains confirm lipid?

Sudan black or Oil-Red-O

What does this liver show?

lipid accumulation

What is this showing of a histologic slide of the liver?

lipid accumulation

What disease is this monitor lizard suffering from?

hepatic lipidosis

Where is glycogen stored in homeostasis?

liver and skeletal muscle cells

What happens to glycogen stores in sick and starving animals?

they are depleted

When do you often see glycogen accumulations?

in the same sites, such as with storage disease, or alternatively with certain endocrine diseases, such as canine hyperadrenocorticism or diabetes mellitus

Grossly, how will the liver appear with glycogen accumulations?

enlarged with rounded edges, pale/light brown, and mottled in appearance

How will the liver appear on histopathology with glycogen accumulations?

hepatocytes are enlarged and swollen with intracytoplasmic fine, lacy vacuolations

Since cell swelling (hydropic degeneration) can appear the same in hepatocytes, what can pathologysts do to differentiate between cell swelling and glycogen accumulation?

can apply special stains

What stain is used to determine glycogen accumulations?

PAS

To differentiate between cell swelling and glycogen accumulations, 2 slides are stained with ________ and one is ________ treated. In the ________ slide, we expect to see positive ________, which confirms ________ accumulation. If the pink is not present in the ________ treated slide, then that confirms ________.

PAS; diastase; PAS; cytoplasm; carbohydrate; diastase; glycogen

What is this an example of?

glycogen accumulations

Lead poisoning produced intranuclear inclusions, which are a mixture of lead and proteins, are ________ and ________. They stain with ________ ________ stains.

pale; eosinophilic; acid fast

What is this an image of?

lead poisoning produced intranuclear inclusions

rhomboidal inclusions seen in the renal and hepatocyte epithelial cells in dogs that are often seen in increased frequency in aged dogs and their significance is unknown

crystalline protein inclusions

What is this image showing?

crystalline protein inclusions

How do protein often stain in H & E stained tissue sections?

pink to orange

What is this an example of?

protein absorption

Viral inclusion can be ________ or ________ depending on the viral agent.

intranuclear; cytoplasmic

True or false: Some viruses (herpes, adenoviruses, parvoviruses) produce exclusively intranuclear inclusions. Other viruses produce cytoplasmic inclusions (pox viruses, rabies). A few viruses, such as canine distemper, produce both intranuclear and intracytoplasmic inclusions. Inclusions can range from round and eosinophilic to basophilic or amphophilic depending on the viral agent.

true

What is this image showing?

viral inclusions

biochemically diverse group of disorders with a common pathogenesis and is a protein misfolding disorder converting them into insoluble non-functional aggregates (rich in beta pleated sheet)

amyloidosis

In what dog breed is amyloidosis common in?

shar pei

Where does amyloid frequently deposit?

B
B
S

• blood vessels

• basement membrane (liver and kidney)

• spleen

Mechanisms of Amyloidosis:

1. Propagation of ________ proteins, which serve as a ________ for self replication.

2. Accumulation of ________ ________ ________ with failure to degrade them.

3. Genetic ________ which promote protein misfolding.

4. Protein ________ because of abnormality or ________ in synthesizing cells.

5. Loss of ________ molecules or other essential components of the protein assembly process.

1. misfolded; template

2. misfolded precursor peptides

3. mutations

4. overproduction; proliferation

5. chaperoning

What are the types of amyloidosis?

• AL amyloid

• AA amyloid

• hereditary amyloidosis

• B-amyloid

secreted in B cell proliferative disorders (plasma cell tumors, multiple myeloma)

AL amyloid

What amyloid does the liver secrete during inflammation?

SAA

What is the AA amyloid synthesized from?

SAA

True or false: Hereditary amyloidosis is not induced by chronic inflammation.

true

In what breeds in hereditary amyloidosis common?

• shar pei

• abyssinian cats

amyloid present in dogs with cognitive dysfunction and Alzheimer’s disease

B- amyloid

What is this image showing?

amyloidosis

Grossly, what does amyloid do to an organ?

enlarges it, gives it a pale red/tan color, and rounded edges and would feel waxy to the touch

What does this liver have?

amyloidosis

How do you diganose amyloidosis?

I
S

• iodine stain on fresh tissue

• special stain used on formalin fixed tissue

What is the special stain used with amyloidosis?

congo red

True or false: An organ that appears to have yellow waxy deposits can be stained grossly with iodine. Amyloid is not pure protein and has carbohydrate moities which the iodine binds to.

true

How will amyloid stain with congo red?

bright red

What is significant and unique to amyloid and staining with congo red?

amyloid with congo red stain is the only thing that fluoresces bright green under polarized light

What is this showing?

amyloidosis

deposition of sodium urate crystals (tophi) in tissues extracellularly

gout

What is gout common in?

birds and reptiles

What is gout due to?

D
R
E

• dehydration

• renal failure

• excess protein intake

What are the 2 types of gout?

1. visceral

2. articular

chalky white deposits on the surface of viscera

visceral gout

chalky white deposits within and overlying joints

articular gout

Grossly, how does gout appear?

chalky white deposits and feels gritty

What is this macaw suffering from?

gout

What is this chameleon suffering from?

articular gout

What is this snake suffering from?

visceral gout

What is this chicken suffering from?

visceral gout

Where do cholesterol crystals form at? What do they typically illicit?

sites of necrosis; granulomatous inflammation

What happens to cholesterol crystal in the histologic processing? What does this mean?

they dissolve; not seeing the actual crystal, just seeing where it was

How do cholesterol crystal appear on histology?

needle shaped clefts

What is this an image of?

cholesterol accummulations

excessive fibrosis with proliferation of small vessels termed neovascularization

granulation tissue

collagen deposition, predominantly type I collagen in the interstitium of organs or tissues

fibrosis

What is fibrosis generally a result of? What is this a part of?

necrosis or inflammation; healing

In general, if there is excessive fibrosis, what can this do to organ function?

can impair organ function

What is this showing?

fibrosis

What is this horse suffering from?

exuberant granulation tissue/proud flesh/fibrosis

increase in the number of adipocytes in an organ or tissue

fatty infiltration

Why can fatty infiltration occur?

O
C

• obesity

• certain mardiomyopathies

What are the types of pathologic calcification?

D
M

• dystrophic

• metastatic

What does dystrophic calcification result from? What occurs?

dying cells (necrosis); intracellular calcium is released from sequestered places within the cell or into the extracellular space

What does metastatic calcification result from? What is this?

hypercalcemia; calcium/phosphorus imbalance

What can the hypercalcemia be due to?

V
H
C
I
C

• vitamin D toxicosis

• hyperparathyroidism

• chronic kidney disease

• iatrogenic supplementation

• certain neoplasias

What does metastatic calcification target?

tunica intima and media of blood vessels, particularly in the lungs, pleural surface, kidneys, and stomach

True or false: Both types of calcification look the same.

true

What is this showing?

myocyte degeneration, necrosis, and mineralization

What does this show?

chalky white lesions within the myocardium of the heart of this calf due to dystrophic mineralization due to an underlying mineral deficiency (vitamin E/selenium deficiency) → myocyte degeneration, necrosis, and mineralization

brown black intracellular pigment produced by melanocytes

melanin

congenital lack of pigmentation

albinism

What occurs in multiple diseases conditions?

depigmentation

What are two diseases that lead to depigmentation?

• copper deficiency

• partial albinism in Chediak-Higashi syndrome

What are symptoms of copper deficiency?

fading of coat (leukotrichia), wiry hair coat, hair loss

LYST mutation affection lysosomal trafficking

Chediak-Higashi syndrome

When does hyperpigmentation occur?

chronic inflammatory states or neoplasia

non-pathologic process that can happen in any organ

congenital melanosis

In what species is congenital melanosis common?
S
C
C

• sheep (black faced)

• cattle

• chow chows

What is this an image of?

congenital melanosis

What is this an image of?

congenital melanosis

lipoprotein which accumulates in long lived post mitotic cells (neurons, cardiac myocytes) seen in greater quantities in aged animals and is an intracellular wear and tear pigment that can be age associated

lipofuscin

Where is lipofuscin common?

liver, heart, and CNS