Accumulations

Endogenous or exogenous substances, usually a result of

metabolic derangements, genetic mutations, or indigestible stuff that accumulates. Sometimes harmless, sometimes detrimental to cellular function.

What are examples of intracellular accumulations

Lipid

Glycogen

Cholesterol

Proteins

Inclusions

Pigments

What are examples of extracellular accumulations

Amyloid

Urates

Pigments

Four main mechanisms leading to abnormal accumulation:

1. Inadequate removal of a normal substance (altered metabolism)

2. Accumulation of endogenous substance due to defects in folding, transport or secretion

3. Failure to degrade a metabolite

4. Abnormal exogenous substance that is indigestible

What is Abnormal metabolism

accumulation of lipid in the hepatocyte

What do we mean by fatty change

lipid accumulation within cells

Where do we normally see lipid accumulation

(Primarily seen in liver because liver is particularly important in lipid metabolism)

What are the mechanisms of lipid accumulation

Excessive entry of fatty acids

Defective oxidation of fatty acids

Decreased apoprotein synthesis

Defective secretion of lipoproteins

What does lipid accumulation look like grossly

• Enlarged, tan-brown, friable, may float

What does lipid accumulation look like microscopic

• Clear, round discrete cytoplasmic vacuoles, often displaces the nucleus

Where do we normally find glyogen

normally found in small amounts in liver and skeletal muscle - storage form of glucose

Abnormal glucose or glycogen metabolism: Diabetes mellitus

• Hyperglycemia → excessive glycogen accumulation

Abnormal glucose or glycogen metabolism: Canine steroid hepatopathy

• In either exogenous corticosteroid administration or Cushing’s syndrome

• Induction of glycogen synthase

What does glycogen accumulatio look like grossly

Enlarged, tan-brown

What does glycogen accumulation look like microscopic

• Wispy (diaphanous) cytoplasmic vacuolation (midzonal → diffuse) (may be difficult to differentiate from lipidosis or hydropic degeneration)

What is PAS

periodic acid shift, would stain the intracelluar compontnet as little pink globules where lipids are located. kind of difficult to differentate from the other swelling thing that is hydrophpoic degenration to stain that stains for glycogen

What is Intracellular Accumulations

• Defect in protein folding or transport (not well characterized in vet med)

Whare are mott cells

• Plasma cells constipated with immunoglobulin

• big pink cells that have alot of large eosinophilic globules distendant with abundant immunoglobin)

Intracellular Accumulations – Lysosomal storage lack whar

Lack of a cellular enzyme leads to an accumulation of substrate

How does one get Intracellular Accumulations – Lysosomal storage dz

• Usually inherited-

• But can be acquired ( by eating plants that inhibit lyzomes)

What is Nieman Pick disease

absent of an enzyme that break down normal cell component

Describe Hyaline substances

pink homogeneous, “glassy”

What is Hyaline substances

• Accumulation of proteins (hyaline proteins)

• Not a distinct chemical entity

Hyaline substances extracellar or intracellular

• May be intracellular or extracellular

Hyaline substances describe key features

• Renal protein casts

• Membranes along alveolar walls

• Plasma proteins in vascular walls

• Thickened basement membranes

We can see hyaline substances commonly where

in the vascular walls or in the basement membrane

Extracellular Accumulations - Amyloid what is it

“starch-like” — repeated sugars

How does Extracellular Accumulations - Amyloid occur

• Extracellular aggregates of misfolded proteins ( indigestible causes bcause of the folding of protein errors)

• Beta-pleated sheets

Is there inflammation for amyloid

• NO inflammation, damage via

pressure atrophy of adjacent

tissues

What are the consquecnes of amyloids

• Depends on where and how much

Classification of Amyloid: type of protein

• Primary Amyloidosis (AL amyloid)

• Secondary/Reactive Amyloidosis (AA amyloid)

• Acute phase protein produced through inflammation

Classification of Amyloid are by

• Type of protein

• Distribution

Are amyloids distrubted

• Systemic

• Localized

Primary Amyloidosis=

• AL amyloidosis

• Abnormal plasma cells → secrete immunoglobulins

• Light chains accumulate

• May be localized or systemic

Why does Primary Amyloidosis occur

accumulation of misfolded light chain into a beta chain sheet that cant be digested

Abnormal plasma cell is caused by

a plasma cell malignacny (plasmoyotoma) can be a begin tumor or it can maligant

Secondary/Reactive Amyloidosis= AA amyloid

• Serum amyloid A (SAA) secreted from the liver

• Produced during inflammation

• *Most common form in animals*

Secondary/Reactive Amyloidosis where is it distrubuted

• Kidney (glomeruli)

• Liver- space of Disse

• Splenic white pulp

Where is amyloid produced

in the hepatocytes

Amyloidosis look grossly how

• Depends on amount and location

• Organs may appear enlarged and “waxy”

Amyloidosis of the liver describe it

• Space of Disse

• Enlarged with rounded margins, soft and pale, waxy

• Compresses adjacent hepatocytes

• Also may result in hepatic rupture

Amyloidosis of the spleen describe it

• Deposited in the white pulp

• Spleen is enlarged, pale and soft

Amyloidosis describe it in the kidney

• Glomeruli

• No gross changes

• Results in marked proteinuria

Why do we put iodine on the kidny for a necropsy

put iodine on the kidney on the necropsy because its something that can be done when the amlyoid accumulates it leaks and protein leaves via urine

Amyloidosis Microscopically look like

• Extracellular

• Eosinophilic amorphous hyaline substance

What kind of stain we use for Amyloidosis

• Special stain: Congo red

• Apple green fluorescence

What are other forms of amyloid

• Senile amyloid

• Alzheimers

• Familial/hereditary amyloid

• Shar-pei, Abyssinian cats

• Renal medullary interstitium

• Localized amyloid

• Nasal turbinates of horses

• Pancreatic islets in cats

Amyloid Clinical significance is important why

• Depends on cause

• Depends on amount and site of deposition

Clinical signifance of amyloid in the kidney

• Glomerular deposition can cause proteinuria

Clinical signifance of amyloid in the liver

• Small amounts- may have little effect on function

• Can cause dysfunction due to compression of adjacent cells (remember, it is EXTRAcellular)

• Can cause rupture and intrabdominal hemorrhage

Extracellular Accumulation - Urates what is a gout

deposition of urates or uric acid in tissues

Where do use gouts commonly in

• Reptiles, birds

What does gout or urates look like

• White chalky material

• Serosal surfaces (visceral.gout)

• Periarticular (articular gout)