Intracellular accumulations

Question 1

List the 4 main pathways of abnormal intracellular accumulations

Answer 1

1. Defects in packaging and transport mechanisms, lead to normal substances abnormally inadequate removal
2. Genetic or acquired defects in folding, packaging, transport or secretion = Abnormal endogenous substances accumulation
3. Enzyme deficiencies = failure to degrade a metabolite
4. Missing enzymatic machinery to degrade or transport it out = deposition and accumulation of exogenous substances

Question 2

Steatosis

Answer 2

Aka = Lipidosis
Accumulation of lipids within parenchymal cells

Question 3

Steatosis Lx

Answer 3

Lx = Liver most common (as main lipid processing organ)
also seen in heart, muscle and kidney

Question 4

Steatosis cause(4)

Answer 4

Causes
1. excessive fatty acids delivered from fat stores or diet
2. Abnormal hepatocellular metabolisms = decreased oxidation or use of fatty acids, impaired
3. synthesis of apoproteins or impaired lipoprotein synthesis
4. Impaired lipoprotein release from hepatocytes

Question 5

Steatosis Gross appearance

Answer 5

swollen, yellow liver with greasy texture

Question 6

Steatosis histological appearance

Answer 6

lipid vacuoles are sharply defined and unstained
Distend the cytoplasm
Displacing the nucleus to the periphery of the cell

Question 7

Excessive intracellular deposits of glycogen - when does it occur

Answer 7

Occurs when
there are abnormalities of either glucose or glycogen metabolism
Eg - hyperadrenocorticism —> glucocorticoids increases hepatic glycogen storage. (Called- steroid -induced hepatopathy)

Eg- Glycogen storage disease ( rare genetic disorder of enzymes that reverse glycogen) = end result of mass accumulation of glycogen)

Question 8

Excessive intracellular deposits of glycogen –> Histological viewing

Answer 8

• vacuoles of glycogen are less sharply defined and more irregularly shaped than the vacuoles of lipidosis and may contain granular eosinophilic material.

Question 9

Intracellular accumulations of protein cause

Answer 9

Causes —> Intracellular accumulation of proteins to the point of morphologically visible accumulation have diverse causes

Question 10

Intracellular accumulations of protein –> histology appearance (4)

Answer 10

rounded
Eosinophilic droplets
Vacuoles
Aggregates in the cytoplasm

Question 11

Intracellular accumulations of protein –> 4 ways

Answer 11

1. Reabsorption droplets in proximal renal tubules
2. Plasma cells engaged in active synthesis of immunoglobulins
3. Intracellular transport and secretion of critical proteins malfx
4. Aggregation of abnormal proteins- either intracellular, extracellular or both.

Question 12

Intracellular accumulations of proteins - reabsorption droplets in proximal renal tubules

Answer 12

Proteinuria
Normally pinocytosis in proximal tubule
Disorder- heavy protein leakage = increased reabsorption = pink hyline droplets
Reversible= proteinuria diminishes = droplets metabolise and disappear

Question 13

Intracellular accumulations of protein –> Plasma cells engaged in active synthesis of immunoglobulins

Answer 13

accumulation of normal secreted proteins

Question 14

Intracellular accumulations of protein –> Intracellular transport and secretion of critical proteins malfx

Answer 14

eg “alpha 1-antitrypsin deficiency, mutations in protein significantly slow folding = end result of aggregate in ER of liver

Question 15

Intracellular accumulations of protein –> Aggregation of abnormal proteins

Answer 15

ither intracellular, extracellular or both. The aggregates may. Cause direct or indirect cause pathologic changes

Question 16

Extracellular accumulations

Answer 16

Hyaline substances = intra or extracellular accumulation of proteinaceous material
eg amyloid

Question 17

Amyloidosis

Answer 17

extracellular deposits of proteinaceous substance
Hyaline appearance
Cause = inherited and inflammatory disorders
Deposits of fibrillar proteins cause tissue damage and functional compromise
The aggregation is usually of misfiled proteins

Question 18

Amyloidosis - Appearance histologically

Answer 18

eosinophilic, hyaline, extracellular

Question 19

Amyloidosis - Appearance macroscopically

Answer 19

• appears yellow, waxy, coalescing nodular or amorphous deposits
• with progressive accumulation it puts pressure on adjacent cells

Question 20

Amyloidosis - why is there the build up?

Answer 20

normal—> misfolded proteins are degraded by proteaseomes or macrophages. But malfx

Question 21

Two types of proteins that form amyloid

Answer 21

Normal proteins that have an inherent tendency to misfold —> form fibrils

Mutant proteins that are prone to misfiling and subsequent aggregation (very rare in vet med)

Question 22

Explain the contents of amyloid material

Answer 22

95% consists of fibril proteins
5% being the P component and other glycoproteins

Question 23

List the three types of amyloid

Answer 23

List the three types of amyloid
AL = amyloid light chain
AA = amyloid associated
AB = B- amyloid protein

Question 24

explain Amyloid light chain

Answer 24

all immunoglobulin light chains
Produced by free Ig light chains secreted by a monoclonal population of plasma cells
Deposition associated with certain plasma celll tumours.
When neoplastic proliferations of plasma cells are the source of amyloid = amyloidosis is called primary

Question 25

Amyloid-associated

Answer 25

derived from unique non-Ig protein made by liver
Derived by proteolysis of larger precursor in the serum called SAA (serum amyloid-associated)
SAA- synthesised by liver and circulated bound to high-density lipids
SAA production increases when in inflammatory states (part of acute response)
Therefore, often called secondary amyloidosis as it associated with chronic inflammation
Lx = mainly in kidney, liver and splenic white pulp

Question 26

B- amyloid protein

Answer 26

constitutes the core of cerebral plaques of Alzheimer

Derived by proteolysis from much larger transmembrane glycoprotein, called amyloid precursor protein

Question 27

Other extracellular accumulations

Answer 27

Collagen (fibrosis)
Fatty infiltration
Cholesterol crystals

Question 28

Collagen (fibrosis)

Answer 28

is an excess in fibrous collagen in the intersitium of organs or tissues
commonly associated with inflammation and tissue injury

Question 29

Fatty infiltration

Answer 29

increased no. or volume of adipocytes in the intersitium of organ or tissue secondary to obesity or atrophy

Question 30

Cholesterol crystals

Answer 30

often form in haemorrhaged or necrotic tissues = a granulomatous inflammation