Lecture 20

Question 1

What are the mechanisms of intracellular accumulations?

Answer 1

1. Inadequete removal of a normal substance secondary to defects in metabolism of packaging and transport (e.g. hepatic lipodosis)
2. Accumulation of an abnormal endogenous substance as a result of genetic or aquired defects
3. Failure to degrade a metabolite due to inherited enzyme deficiencies (e.g. LSD’s)
4. Deposition and accumulation of an abnormal exogenous substance (cell has neither enzymatic machinary to degrade the substance nor ability to transport it to other sites (e.g. carbon, silica)

Question 2

What are some examples of exogenous pigment disorders?

Answer 2

1. Inhalation of inert carbon particles (smoke/soot) causing anthracosis - often and incidental finding
2. Tattoo ink is an example

Question 3

Breifly explain how this defect occurs:

Answer 3

Tyrosine is converted to melanin via the enzyme tyrosinase. This process also require copper in the tissue, hence excess copper causes accumulations of melanin (as above)

Question 4

Briefly describe how a congenital melanin deficiency occurs (for example in an albino animal)?

Answer 4

Tyrosinase mutation (even though the precursor tyrosine is present it cannot be converted melanin)

Question 5

Provide an example of an acquired melanin deficiency:

Answer 5

1. Local injury (e.g. branding)
2. Dietary copper deficiency

Question 6

What causes the lipid peroxidation into lipofuscin?

Answer 6

Aging - “wear and tear” pigment

Question 7

What types of cell does lipofuscin accumulate in?

Answer 7

accumulates in non-dividing cell (neurons, cardiac muscle) and in hepatocytes

Question 8

Is the accumulation of ceroid in tissues physiological or pathological?

Answer 8

ceroid is generally pathological

Question 9

Briefly describe the slide below and describe the process that is occuring:

Answer 9

Coarse, granular, golden-brown pigment. Haemoglobin in RBC breaks down into haemosiderin (an accumulation in tissues)

Question 10

Provide an example of a localised cause of haemosiderin accumulation and a generalised cause of haemosiderin accumulation:

Answer 10

Localised: haemorrhage/brusing, chronic congestion e.g. lungs - heart failure cells

Generalised: haemochromatosis, red blood cell transfusions, iron supplements, haemolysis

Question 11

What is the jaundice and what is the cause of it?

Answer 11

Yellow tissue discolouration. Caused by hyperbilirubinaemia

Question 12

What are the three causes of hyperbilirubinaemia? (provide and example of each)

Answer 12

1. Unconjugated - haemolytic (pre-hepatic) - haemolysis, RBC parasites, massive skeletal muscle damage/necrosis
2. Mixed - toxic (hepatic) - hepatic necrosis
3. Conjugated - obstructive (post-hepatic): Intrahepatic- hepatitis, drug toxicity, alcoholism, liver neolasia, extrahepatic - gall stones and pancreatitis

Question 13

What are the four different types of photosensitivity?

Answer 13

Type 1 (primary) - photodynamic agent ingested, injected or absorbed

Type 2 (aberrant metabolism) - inherited defects in enzymes involving haeme synthesis (resulting in porphyrin accumulation)

Type 3 (secondary/ hepatogenous) - liver disease resulting in build up of phylloerythrin (a porphyrin) normally derived fro breakdown of chlorophyll by GIT microflora - normally abosrbed into the circulation and effectively excreted by liver into bile

Type 4 - idiopathic

Question 14

What are the four different types of amyloidosis?

Answer 14

Immune/primary amyloid: plasma cell tumours > Ig light chains produced by monoclonal cells > AL amyloid (systemic)

Endocrine/inherited amyloid: Oritental cat breeds - pancreatic islet localised > islet polypeptide (localised)

Prions: prion protein (localised to CNS)

Reactive/secondary amyloid: chronic inflammation (TB, osteomyletitis, glomerulonephritis) > Macs activated > Macs release IL1 and Il2 > serum amyloid A protein made in the liver > AA amyloid

Question 15

How does amyloidosis cause pathology?

Answer 15

Extracellular eosinophillic deposit > compress tissue > cell atrophy/death > loss of function

Question 16

Name the process that is occuring in the tissue below:

Answer 16

AA Amyloidosis

Question 17

Relate the causes of lysosomal storage conditions to the pathology that is commonly observed:

Answer 17

1. Genetic and congestion (autosomal reccessive) e.g. a-mannisidosis OR aquired swainsonine toxicity
2. Defective enzyme function (e.g. a-D-mannosidase)
3. Metabolite accumulates (e.g. oligomannoside polysaccharides)
4. Lysosomal storage disease
5. Distended lysosomes causes adundant foamy cytoplasm (lysosomes)

Question 18

Name the condition that is shown below:

Answer 18

Lysosomal storage disease - abundant foamy cytoplasm

Question 19

What is the cause of glycogen accumulation within tissues?

Answer 19

Abnormalities in either glucose or glycogen metabolism are generally caused by metabolic diseases e.g. diabetes mellitus, hyperadrenocorticism, glucorticoid adminisitration, alcoholism, liver diseases, genetic glycogen storage diseases

Question 20

What is the condition below?

Answer 20

Glycogen accumulation within tissues

Question 21

What is the cause of lipid accumulation within tissues?

Answer 21

Common causes include toxins, protein malnutrition, diabeties mellitus, obesity, alcohol abuse, late term pregnancy and liver disease

Question 22

What is the name of the condition within the liver below?

Answer 22

Lipidosis

Question 23

Briefly describe the pathogensis of gout:

Answer 23

1. Impaired purine metabolism (alcoholics), high protein diets (dalmations)
2. Uric acid/urates
3. Deposits in joints or viscera
4. Chronic inflammation
5. Gout

Question 24

How does renal failure result from crystal depostion (provide the pathogenesis)?

Answer 24

1. Oxalate rich plants, ethylene glycol
2. Oxalate crystals
3. Deposit within the nephron
4. Renal failure