Exam 2 - Amyloid

Question 1

What is amyloid?

1. Not a ____ substance but a ____ of _____, _____ protein deposits in tissue
2. Located ______ or __________
3. Amyloid becuase “_____-like” staining with _____/dilute ______ ________
4. Mainly protein with some _____ components associated - glycosaminoglycans and amyloid P-component (a glycoprotein)

Answer 1

What is amyloid?

1. Not a single substance but a class of **insoluble, abnormal **protein deposits in tissue
2. Located intracellularly or extracellularly
3. Amyloid becuase “starch-like” staining with Iodine/dilute sulfuric acid
4. Mainly protein with some CHO components associated - glycosaminoglycans and amyloid P-component (a glycoprotein)

Question 2

Amyloidosis =

Answer 2

Disease condition where amyloid is deposited locally or systemically

Question 3

Systemic -

Involves more than ____ organ

Answer 3

ONE!

Question 4

Localized -

Restricted to a single ____ or ______

Answer 4

Organ or tissue

Question 5

For the following forms of amyloid, what is the precursor protein? Also name a possible site of deposition.

1. Systemic AA
2. Localized AL
3. Islet amyloid
4. Alzheimer’s plaques
5. Pulmonary vasc.

Answer 5

For the following forms of amyloid, what is the precursor protein? Also name a possible site of deposition.

1. Systemic AA -
   SAA
   kidney, liver, spleen
2. Localized AL -
   Immunoglublin light chains
   locally in plasmacytomas
3. Islet amyloid -
   Islet amyloid polypeptide
   Pancreatic islets
4. Alzheimer’s plaques -
   APP (Alz. amyloid precursor protein)
   multifocally in brain
5. Pulmonary vasc. -
   Apolipoprotein A1
   pulmonary blood vessels

Question 6

How is amyloid identified grossly?

Answer 6

How is amyloid identified grossly?

By iodine-sulfuric acid method, stains amyloid dark blue-black

Question 7

What 3 forms are used to identify amyloid?

Answer 7

What 3 forms are used to identify amyloid?

1. Grossly
2. Light microscopy
3. Electron microscopy

Question 8

How is amyloid identified by light microscopy (2 different stains)?

Answer 8

How is amyloid identified by light microscopy?

1. H&E stains – amorphous, eosinophilic, hyaline material
2. Congo red stain – orange-red staining and green birefringence with cross-polarized light

Question 9

What does amyloid look like on electron microscopy?

Answer 9

What does amyloid look like on electron microscopy?

Non-brainching fibrils which are 7-10 nm in diameter

Question 10

**Fibril = **

Secondary structure conformation?

**How many different protein precursors have been identified? **

Answer 10

Fibril =

polymerized repetitive homologous peptide subunits

Secondary structure conformation?

B-pleated sheet

**How many different protein precursors have been identified? **

20
all with regions that have a propensity to form B-pleated sheet secondary structure

Question 11

Each type of amyloid fibril is formed by _____ type of protein subunit.

Answer 11

Each type of amyloid fibril is formed by **ONE **type of protein subunit.

(e.g. IAPP in islet amyloid, immunoglobulin light chains in AL amyloid)

Question 12

Significance of Amyloid

1) Functional tissue is replaced by _____ leading to loss of normal function of that organ/tissue (E.g. Renal failure, hepatic failure, diabetes). ______ and resistance to _______ of amyloid leads to its accumulation in tissues.
2) Accumulation of amyloid tends to physically compress normal tissue resulting in ________
3) Amyloid deposits may disrupt normal tissue structures and impair normal function (E.g. Deposits in the glomerular capillaries interfere with normal filtration function of the glomerulus)
4) Amyloid oligomers and fibrils may be _______ and induce cell stress and _________

*This mechanism is suspected to occur in pancreatic islets of cats (and humans) developing diabetes mellitus and may lead to the death of insulin-producing β-cells. Also occurs in human Alzheimer’s disease where β-amyloid deposits cause neuronal death.

Answer 12

**Significance of Amyloid **

1) Functional tissue is replaced by amyloid leading to loss of normal function of that organ/tissue (E.g. Renal failure, hepatic failure, diabetes). Insolubility and resistance to proteolysis of amyloid leads to its accumulation in tissues.
2) Accumulation of amyloid tends to physically compress normal tissue resulting in atrophy
3) Amyloid deposits may disrupt normal tissue structures and impair normal function (E.g. Deposits in the glomerular capillaries interfere with normal filtration function of the glomerulus)
4) Amyloid oligomers and fibrils may be cytotoxic and induce cell stress and apoptosis

*This mechanism is suspected to occur in pancreatic islets of cats (and humans) developing diabetes mellitus and may lead to the death of insulin-producing β-cells. Also occurs in human Alzheimer’s disease where β-amyloid deposits cause neuronal death.

Question 13

Increased production of which precursor protein in seen in obese cats prior to development of diabetes?

Answer 13

Increased production of which precursor protein in seen in obese cats prior to development of diabetes?

IAPP

(islet amyloid polypeptide?)

Question 14

**Chronic inflammation causes increased production of _____ in many cases of ______ **

Answer 14

Chronic inflammation causes increased production of SAA in many cases of Systemic AA

(SAA = Serum Amyloid A)

Question 15

Neoplastic plasma cells in plasmacytomas produce large amounts of which precursor protein?

Answer 15

Neoplastic plasma cells in plasmacytomas produce large amounts of which precursor protein?

Immunoglobulin light chains

Question 16

Pathogenesis of Amyloidosis

Incompletely understood but probably multiple mechanisms involved.

1) Increased production of precursor protein
*IAPP production is increased in obese cats prior to development of diabetes.
*Chronic inflammation causes increased production of SAA in many cases of systemic AA.
*Immunoglobulin light chains are produced in large amounts by neoplastic plasma cells in plasmacytomas.

2) Mutation to precursor protein resulting in a more amyloidogenic protein. This usually involves a mutation that increases the propensity of the molecule to arrange itself in the β-sheet configuration. (E.g. Serine to glycine mutation at position 20 in human IAPP molecule which increases the propensity of the IAPP molecule to arrange in the β-sheet secondary structure and form amyloid fibrils)
3) Abnormal processing of the precursor protein which leads to the formation of an amyloidogenic protein fragment (E.g. Abnormal processing of the Alzheimer’s amyloid protein precursor to β-protein which then forms the amyloid fibrils in the brain.

Answer 16

FINISH

Question 17

Which type of amyloidosis is considered to be the most serious systemic form in mammals and birs and what may it lead to?

Answer 17

Which type of amyloidosis is considered to be the most serious systemic form in mammals and birs and what may it lead to?

Secondary (Reactive) Amyloidosis (AA)

Hepatic and Renal failure

Question 18

What does reactive (secondary) amyloidosis (AA) occur in response to?

Answer 18

What does reactive (secondary) amyloidosis (AA) occur in response to?

Chronic or recurrent disease processes - most often chronic inflammatory processes

Question 19

Reactive (Secondary) Amyloidosis (AA) Pathogenesis

involves release of _______ from ______ at sites of chronic inflammation ==>

stimulates ________ to produce and release increased amounts of ______ ==>

SAA (104 amino acids) at certain sites is aberrantly processed by ______ (and possibly other cells) to the 76 amino acid amyloidogenic protein fragment ==>

amyloid deposited and accumulates in tissue

Answer 19

Reactive (Secondary) Amyloidosis (AA) Pathogenesis

involves release of interleukin-1 from macrophages at sites of chronic inflammation ==>

stimulates hepatocytes to produce and release increased amounts of SAA ==>

SAA (104 amino acids) at certain sites is aberrantly processed by macrophages (and possibly other cells) to the 76 amino acid amyloidogenic protein fragment ==>

amyloid deposited and accumulates in tissue

Question 20

What organs can be affected by AA (secondary or reactive) amyloidosis?

Answer 20

What organs can be affected by AA (secondary or reactive) amyloidosis?

Liver, kidneys, spleen, blood vessels, GI

Question 21

**Systemic AA (secondary/reactive) amyloidosis is most serious sysemic form in canines. **

Clinical signs most often related to _____ _______ with marked _____ and renal failure

**With severe ______ involvement, _____ failure may develop. **

Answer 21

Systemic AA (secondary/reactive) amyloidosis is most serious sysemic form in canines.

Clinical signs most often related to renal glomerulus with marked proteinuria and renal failure

With severe liver involvement, hepatic failure may develop.

Question 22

Gross/Microscopic Features of AA Amyloidosis

1) Spleen
- -multifocal deposits in ____ pulp “_____ spleen”

– ______ deposits in the red pulp “_______ spleen”
with generalized splenomegaly

Answer 22

Gross/Microscopic Features of AA Amyloidosis

1) Spleen
- -multifocal deposits in white pulp “sago spleen”
- - diffuse deposits in the red pulp “lardaceous spleen” with generalized splenomegaly

Question 23

Gross/Microscopic Features of AA Amyloidosis

2) Liver

–hepato-____, pale-_____, heavy, friable

–deposits occur first in spaces of _____ and expand causing atrophy of hepatic cords and compression of hepatic ________

Answer 23

Gross/Microscopic Features of AA Amyloidosis

2) Liver

–hepato-megaly, pale-yellow, heavy, friable

–deposits occur first in spaces of Dissé and expand causing atrophy of hepatic cords and compression of hepatic sinusoids

Question 24

Gross/Microscopic Features of AA Amyloidosis

3) Kidneys

–may be slightly ______

• -mottled pale _____-tan and _____
• • ________ may be more prominent (grainy appearance of cortex)
• -deposits in the glomeruli occur in the _____ ______ and in the ______
• -glomerular lesions lead to ______ and eventually to ________ failure

Answer 24

Gross/Microscopic Features of AA Amyloidosis

3) Kidneys

–may be slightly enlarged

• -mottled pale yellow-tan and red
• -glomeruli may be more prominent (grainy appearance of cortex)
• -deposits in the glomeruli occur in the basement membranes and in the mesangium
• -glomerular lesions lead to proteinuria and eventually to renal failure

Question 25

Familial form of AA amyloidosis in _____ ____ dogs develops secondary to “____ _____ Fever”

AA amyloidosis with ____ _____ ______ deposits and chronic _____ failure

AA amyloid sequence is the same as other breeds – not the genetic cause

Recently mustation in ______ gene has been linked to this condition.

Answer 25

Familial form of AA amyloidosis in Shar Pei dogs develops secondary to “Shar Pei Fever”

AA amyloidosis with renal medullary interstitial deposits and chronic renal failure

AA amyloid sequence is the same as other breeds – not the genetic cause

Recently mustation in HAS2 gene has been linked to this condition.

Question 26

**What is the most common systemic form of canine amyloidosis? **

Found in a large proportion of aged dogs
(____% of dogs >10 years old)

Derived from _______ _____

Usually no clinical manifestations but rarely may be associated with ______ hemorrhages

Answer 26

What is the most common systemic form of canine amyloidosis?

Pulmonary Vascular Amyloid

Found in a large proportion of aged dogs
(22% of dogs >10 years old)

Derived from Apolipoprotein A1

Usually no clinical manifestations but rarely may be associated with pumonary hemorrhages

Question 27

**Canine Amyloidosis **

_ Beta-protein derived cerebral amyloid_

–Amyloid plaques occur in ___ of Beagles 11-13 years old and in ____ of Beagles 15-18 years old

• -Neuropathology includes senile plaques (amyloid) and ______ _______ amyloidosis
• -Associated with ______ ______ – similar pathologically and clinically to Alzheimer’s disease

Answer 27

Canine Amyloidosis

Beta-protein derived cerebral amyloid

–Amyloid plaques occur in 36% of Beagles 11-13 years old and in 73% of Beagles 15-18 years old

–Neuropathology includes senile plaques (amyloid) and **cerebral vascular **amyloidosis

–Associated with cognitive dysfunction – similar pathologically and clinically to Alzheimer’s disease

Question 28

What is the most serious systemic form of canine amyloidosis?

Answer 28

What is the most serious systemic form of canine amyloidosis?

Systemic secondary/reactive amyloidosis

Question 29

What 3 types of canine amyloidosis have we discussed?

Answer 29

What 3 types of canine amyloidosis have we discussed?

1. Systemic secondary/reactive amyloidosis (AA)
2. Pulmonary vascular amyloidosis (AApoA1)
3. Beta-protein derived cerebral amyloid

Question 30

What two types of feline amyloidosis were discussed?

Answer 30

What two types of feline amyloidosis were discussed?

1. Systemic secondary/reactive Amyloidosis
2. Localized amyloidosis - Ilset Amyloidoisis (Aiapp)

Question 31

Feline Amyloidosis

1) Systemic secondary/reactive amyloidosis

–Uncommon except for ______ cats which develop a familial form with _____ and ______ amyloid deposits

–Mutation in _____ increases the amyloidogenicity of the molecule

Answer 31

Feline Amyloidosis

1) Systemic secondary/reactive amyloidosis

–Uncommon except for Abyssinian cats which develop a familial form with renal and hepatic amyloid deposits

–Mutation in SAA increases the amyloidogenicity of the molecule

Question 32

**Feline Amyloidosis **

2) Localized amyloidosis—islet amyloidosis (AIAPP)

–Nearly all ______ cats have partial replacement of their islets with amyloid derived from _____ ______ _____ (IAPP)

–IAPP is produced by pancreatic ______ and is co-secreted with ________

–Long-standing ______ resistance (due to obesity most often) leads to increased production of IAPP. Factors allowing polymerization of IAPP into oligomers and then amyloid fibrils are not well-understood but may involve aberrations in chaperone protein function.

–Once formed, small IAPP oligomers are ______, may disrupt cell membranes or may induce ______ apoptosis by unknown mechanisms.

Answer 32

**Feline Amyloidosis **

2) Localized amyloidosis—islet amyloidosis (AIAPP)

–Nearly all diabetic cats have partial replacement of their islets with amyloid derived from islet amyloid polypeptide (IAPP)

–IAPP is produced by pancreatic β-cells and is co-secreted with insulin

–Long-standing insulin resistance (due to obesity most often) leads to increased production of IAPP. Factors allowing polymerization of IAPP into oligomers and then amyloid fibrils are not well-understood but may involve aberrations in chaperone protein function.

–Once formed, small IAPP oligomers are cytotoxic, may disrupt cell membranes or may induce β-cell apoptosis by unknown mechanisms.

Question 33

**What two forms of Equine Amyloidosis were discussed? **

Answer 33

What two forms of Equine Amyloidosis were discussed?

1. Systemic AA (in horses used for antiserum production)
2. Localized forms of AL amyloidosis (in the skin)

Question 34

Equine Amyloidosis

1) Systemic AA form occurs _____, and often in horses used for ______ production.

_____ and the ____ _____ are most often affected.

Answer 34

Equine Amyloidosis

1) Systemic AA form occurs occasionally often in horses used for antiserum production.

Liver and the gastrointestinal tract are most often affected.

Question 35

**Equine Amyloidosis **

2) Localized forms of AL amyloidosis occur in the**_____ **( ______-like deposits) and in the ______ _______ which may obstruct airflow.

Answer 35

Equine Amyloidosis

2) Localized forms of AL amyloidosis occur in the skin (plaque-like deposits) and in the nasal mucosa which may obstruct airflow.

Question 36

What is the most common form of amyloidosis encountered in birds?

Answer 36

What is the most common form of amyloidosis encountered in birds?

Systemic AA amyloidosis

Question 37

**What type of birds have a particularly high incidence of systemic AA amyloidosis? **

Answer 37

**What type of birds have a particularly high incidence of systemic AA amyloidosis? **

Waterfowl

Question 38

What is systemic AA amyloidosis in birds associated with?

Answer 38

What is systemic AA amyloidosis in birds associated with?

Chronic inflammatory diseases

Cannibalism (chickens in high stress conditions)

Possible genetic influence (some chicken breeds are more susceptible)

Question 39

**What species are affected by BSE (Bovine Spongiform Encephalitis)? **

3

Answer 39

**What species are affected by BSE (Bovine Spongiform Encephalitis)? **

Cattle, Humans, Sheep

Question 40

What species are affected by Scrapie?

2

Answer 40

What species are affected by Scrapie?

Sheep & Goats

Question 41

What species are affected by Chronic Wasting Disease?

2

Answer 41

What species are affected by Chronic Wasting Disease?

Elk, deer

Question 42

What species are affected by Transmissable Mink Encephalopathy?

Answer 42

What species are affected by Transmissable Mink Encephalopathy?

Mink

Question 43

What species are affected by Feline TSE?

Answer 43

What species are affected by Feline TSE?

Domestic Cats, Cheetahs

Question 44

What species is affected by Exotic Ungulate Encephalopathy?

3

Answer 44

What species is affected by Exotic Ungulate Encephalopathy?

Nyala

Greater Kudu

Oryx

Question 45

What species are affected by CJD, vCJD, FFI, Kuru?

1

Answer 45

What species are affected by CJD, vCJD, FFI, Kuru?

Human

Question 46

Prions

essentially are _____ ______ that have the ability to gain entrance to a new host and self-replicate.

Self replication is done by recruitment of host _____ (a normal protein) by conversion into PrPsc involving a conformational change from _____ helical secondary structures into____ _____ structures with subsequent formation of amyloid fibrils.

It is thought that ____ serves as a template which facilitates conversion of PrPc to PrPsc.

Answer 46

Prions

essentially are amyloid fibrils that have the ability to gain entrance to a new host and self-replicate.

Self replication is done by recruitment of host PrPc (a normal protein) by conversion into PrPsc involving a conformational change from alpha helical secondary structures into beta sheet structures with subsequent formation of amyloid fibrils.

It is thought that PrPsc serves as a template which facilitates conversion of PrPc to PrPsc.

Question 47

Prions

Best evidence to date indicates that no ____ or ____ is present in the TSE-infective material and that disease can be produced from synthetic ______.

Competing hypothesis that a conventional infectious agent (Spiroplasma sp.) is responsible also has some supporting data but is generally out of favor at present.

Answer 47

Prions

Best evidence to date indicates that no DNA or RNA is present in the TSE-infective material and that disease can be produced from synthetic PrPsc.

Competing hypothesis that a conventional infectious agent (Spiroplasma sp.) is responsible also has some supporting data but is generally out of favor at present.

Question 48

Scrapie (sheep, goats)

• First described over ____ years ago
• Occurs in sheep and goats throughout the USA
• Present in Minnesota flocks
• 0.2% prevalence
• $20,000,000/yr losses US sheep producers
• Experimentally transmitted to _____ and ______

Answer 48

Scrapie (sheep, goats)

• First described over 250 years ago
• Occurs in sheep and goats throughout the USA
• Present in Minnesota flocks
• 0.2% prevalence
• $20,000,000/yr losses US sheep producers
• Experimentally transmitted to hamsters and mice

Question 49

Clinical signs of Scrapie (sheep/goats)

*Progressive ______ signs beginning with subtle behavioral changes leading to scraping behavior (pruritus).

*Progressign to incoordination, weight loss, biting feet & limbs, lip smacking, gait abnormalities, trembling, recumbency, and death after ___ to ____ months.

* Onset of signs may begin as early as 1.5 years of age with peak between ___ to ____ years of age.

Answer 49

Clinical signs of Scrapie (sheep/goats)

*Progressive neurological signs beginning with subtle behavioral changes leading to scraping behavior (pruritus).
*Progressign to incoordination, weight loss, biting feet & limbs, lip smacking, gait abnormalities, trembling, recumbency, and death after **1-6 ** months.

* Onset of signs may begin as early as 1.5 years of age with peak between ** 3-4** years of age.

Question 50

Pathogenesis of Scrapie (sheep/goats)

1) Infectious prions are ingested and cross mucosa expecially at _____, _______ patches, and other sites?
2) Prions accumulate in _______ in ____ ______ (or other lymphoid tissues).
3) Spread to ____ via retrograde transport in nerves or may also circulate to brain via lymph and blood.
4) Sheep with particular genotypes at codons 136 and 171 (mainly tested for in USA due to scrapie strain in USA) have increased susceptibility to scrapie: ____** ** (Q = glutamine; R = arginine) genotype _____ susceptible, QR and RR are more resistant.

5) Site(s) of prion formation and mechanisms of cell injury are not well defined but may involve:
a) induction of apoptosis
b) oxidative stress
c) autophagy
d) endosome-lysosome system malfunction
e) others?

Answer 50

Pathogenesis of Scrapie (sheep/goats)

1) Infectious prions are ingested and cross mucosa expecially at tonsils, Peyer’s patches, and other sites?
2) Prions accumulate in macrophages in lymph nodes (or other lymphoid tissues).

3) Spread to CNS via retrograde transport in nerves or may also circulate to brain via lymph and blood.
4) Sheep with particular genotypes at codons 136 and 171 (mainly tested for in USA due to scrapie strain in USA) have increased susceptibility to scrapie: QQ (Q = glutamine; R = arginine) genotype most susceptible, QR and RR are more resistant.

5) Site(s) of prion formation and mechanisms of cell injury are not well defined but may involve:
a) induction of apoptosis
b) oxidative stress
c) autophagy
d) endosome-lysosome system malfunction
e) others?

Question 51

Pathologic Changes Scrapie (sheep/goats)

________ and ______ vacuolar change (clear cytoplasmic vesicles) giving the typical ________ appearance to the CNS, _______ and proliferation of astrocytes (astrocytosis), extracellular amyloid deposits (____)

Answer 51

Pathologic Changes Scrapie (sheep/goats)

Neuronal and astrocytic vacuolar change (clear cytoplasmic vesicles) giving the typical spongiform appearance to the CNS, hypertrophy and proliferation of astrocytes (astrocytosis), extracellular amyloid deposits (APrP)

Question 52

Scrapie Diagnosis (sheep/goats)

1) Post mortem histopathology of _____ and IHC demonstration of ____ in brain, _______ lymph node, and _____.
2) ____ _____ biopsy with IHC for PrPsc
3) ELISA—not currently approved

Answer 52

Scrapie Diagnosis (sheep/goats)

1) Post mortem histopathology of brain and IHC demonstration of PrPsc in brain, retropharyngeal lymph node, and tonsil.
2) 3rd eyelid biopsy with IHC for PrPsc
3) ELISA—not currently approved

Question 53

Chronic Wasting Disease (deer, elk)

Clinical Features:
*Adults: 17 months to >15 years
*Most 3-5 years
*Sex: males, females
*No strict ________
*Clinical duration: days to > ___ _____, usually months
*Incubation period: min: ~ ____ months, max:unknown

Answer 53

Chronic Wasting Disease (deer, elk)

Clinical Features:
*Adults: 17 months to >15 years
*Most 3-5 years
*Sex: males, females
*No strict seasonality
*Clinical duration: days to >1year, usually months
*Incubation period: min: ~17 months, max:unknown

Question 54

Chronic Wasting Disease (deer, elk)

*Experimental study

Paddock #1: Healthy deer exposed to infected deer
Paddock #2: Healthy deer exposed to carcasses
Paddock #3: Healthy deer exposed to a paddock that previously confined infected deer

**The healthy animals in all three paddocks developed CWD

** Clinical Signs:**
*Loss of body condition (_____) and changes in ______.
* Ataxia, wide based stance, head tremors, ________.
*Continue to eat but eat less and gradually lose body condition.
*_________ and drooling evident in terminal animals.
*______ is inevitable once clinical disease occurs. The clinical course of CWD varies from a few days to approximately a year, with most animals surviving from a few weeks to several months.

Answer 54

Chronic Wasting Disease (deer, elk)

*Experimental study

Paddock #1: Healthy deer exposed to infected deer
Paddock #2: Healthy deer exposed to carcasses
Paddock #3: Healthy deer exposed to a paddock that previously confined infected deer

**The healthy animals in all three paddocks developed CWD

Clinical Signs
*Loss of body condition (cachexia) and changes in behavior.

* Ataxia, wide based stance, head tremors, somnolence.

*Continue to eat but eat less and gradually lose body condition.

*Salivation and drooling evident in terminal animals.

*Death is inevitable once clinical disease occurs. The clinical course of CWD varies from a few days to approximately a year, with most animals surviving from a few weeks to several months.

Question 55

Chronic Wasting Disease Pathologic Changes:

*Gross post mortem lesions include ______ and often _______ pneumonia. Generally other tissues including brain do not show gross lesions.

Answer 55

Chronic Wasting Disease Pathologic Changes:

*Gross post mortem lesions include cachexia and often aspiration pneumonia. Generally other tissues including brain do not show gross lesions.

Question 56

Chronic Wasting Disease

Histopathology:
_______ Tissues: Few or no detectable morphologic changes but PRPsc is demonstrable by immunohistochemistry before neuropathology is detectable (tonsils and retropharyngeal lymph nodes).

• Neuropathology:*
  * Earliest lesions occur in _________ _______ nucleus (located in the medulla at the level of the obex) .
  * IHC detection of ______ is diagnostic even without substantial spongiform change.
  * Characteristic spongiform encephalopathy consists of _______ change in astrocytes and neurons along with ________.
  * Astrocytosis may be prominent but lesions notably lack inflammatory cell infiltrates

Answer 56

Chronic Wasting Disease

• Histopathology:*
• • Lymphoid** Tissues: Few or no detectable morphologic changes but PRPsc is demonstrable by immunohistochemistry before neuropathology is detectable (tonsils and retropharyngeal lymph nodes).

Neuropathology:
* Earliest lesions occur in parasympathetic vagal nucleus (located in the medulla at the level of the obex) .
* IHC detection of PrPsc is diagnostic even without substantial spongiform change.
* Characteristic spongiform encephalopathy consists of vacuolar change in astrocytes and neurons along with demyelination.
* Astrocytosis may be prominent but lesions notably lack inflammatory cell infiltrates

Question 57

Diagnosis of CWD:

*Histopathology — Characteristic ________ degeneration in brain

*Immunohistochemistry for ______ in affected brain regions (obex), lymph nodes, or _____ (biopsy may potentially be used for antemortem diagnosis)

*ELISA—medial _________ lymph node only (approximately 90% sensitivity)

Answer 57

Diagnosis of CWD:

*Histopathology — Characteristic spongiform degeneration in brain

*Immunohistochemistry for PrPsc in affected brain regions (obex), lymph nodes, or tonsil (biopsy may potentially be used for antemortem diagnosis)

*ELISA—medial retropharyngeal lymph node only (approximately 90% sensitivity)

Question 58

Bovine Spongiform Encephalopathy

*Only TSE of animals which has been shown to be transmissible to ______

*Causes human ______

*Rare cases may be spontaneous (not transmitted) as with human CJD

*4 bovine cases reported in USA

*Pathogenesis and pathologic features similar to _____ and _____

*Diagnosis: IHC for ____ on obex region (vagal parasympathetic nucleus)

Answer 58

Bovine Spongiform Encephalopathy

*Only TSE of animals which has been shown to be transmissible to humans

*Causes human vCJD

*Rare cases may be spontaneous (not transmitted) as with human CJD

*4 bovine cases reported in USA

*Pathogenesis and pathologic features similar to Scrapie and CWD

*Diagnosis: IHC for PrPsc on obex region (vagal parasympathetic nucleus)

Question 59

Significance of Amyloid

1) Functional tissue is replaced by ______ leading to loss of ____ ______ of that organ/tissue (E.g. Renal failure, hepatic failure, diabetes). Insolubility and resistance to ______ of amyloid leads to its accumulation in tissues.
2) Accumulation of _____ tends to physically compress normal tissue resulting in atrophy
3) Amyloid deposits may disrupt normal tissue structures and impair normal function (E.g. Deposits in the _____ _______ interfere with normal filtration function of the glomerulus)
4) Amyloid oligomers and fibrils may be______ and induce cell stress and apoptosis

*This mechanism is suspected to occur in pancreatic islets of cats (and humans) developing diabetes mellitus and may lead to the death of insulin-producing β-cells. Also occurs in human Alzheimer’s disease where β-amyloid deposits cause neuronal death.

Answer 59

Significance of Amyloid

1) Functional tissue is replaced by amyloid leading to loss of normal function of that organ/tissue (E.g. Renal failure, hepatic failure, diabetes). Insolubility and resistance to proteolysis of amyloid leads to its accumulation in tissues.
2) Accumulation of amyloid tends to physically compress normal tissue resulting in atrophy
3) Amyloid deposits may disrupt normal tissue structures and impair normal function (E.g. Deposits in the glomerular capillaries interfere with normal filtration function of the glomerulus)
4) Amyloid oligomers and fibrils may be cytotoxic and induce cell stress and apoptosis

*This mechanism is suspected to occur in pancreatic islets of cats (and humans) developing diabetes mellitus and may lead to the death of insulin-producing β-cells. Also occurs in human Alzheimer’s disease where β-amyloid deposits cause neuronal death.