Extracellular Accumulation, Pathological Pigments, Circulatory Disturbances Flashcards
What are substances that primarily accumulate as a result of aberrations?
Cellular homeostasis
In terms of pathologic calcifications, what is dystrophic?
- Deposition occurs in dead or dying tissues
- No derangement of serum levels of calcium
In terms of pathologic calcifications, what is metastatic?
- Deposition of calcium salts in normal tissues
- Secondary to derangement in calcium metabolism
- Hypercalcemia
True or False: Pathological calcifications occur in a wide variety of disease states.
True
Abnormal deposition of calcium salts in soft tissue, is a result of what?
iron, magnesium, phosphorus and carbonates
If calcification is extensive, how will it appear?
it appears grossly as chalky white deposits
with a brittle or gritty texture.
The loss of the ability to regulate cellular Ca2+ balance is a critical turning point that converts reversible to….
The mechanism of dystrophic calcification is most prominent where?
mitochondria
What will be seen with increasing deposition of calcium salts?
- The entire cell and even extracellular tissue can be calcified
- Intense and widespread basophilia histologically
What is the 1st evidence of dystrophic calcification histologically?
basophilic stippling of the dead cell
What are the 4 types of dystrophic calcification?
- Nutritional myopathy (White muscle disease)
- Calcinosis cutis
- Calcinosis circumscripta
- Liver/lung injury
What is the pathogenesis of nutritional myopathy?
Selenium/Vit E deficiency
What are free radicals?
chemical specimens that have an unpaired electron in the most external orbit of the atom
The pathogenesis of nutritional myopathy is responsible for the protection of cell membrane against what?
Free radical
What are some examples of free radicals?
UV rays, exercise, Peroxisomes, Inflammation, Arachidonate pathways, Ischemia/reperfusion injury, Cigarette smoke, Environmental pollutants
What type of stain demonstrates the amount of dystrophic mineralization
of damaged myofibers in the sample?
a Von Kossa
What are the two types of dystrophic calcification on the skin?
- Calcinosis cutis
- Calcinosis circumscript
What is Calcinosis cutis?
a poorly understood form of epithelial and
collagenous calcification
What is an example of calcinosis cutis?
Canine hyperglucocorticoids
What is calcinosis circumscript?
Localized deposit of calcium salts
Calcinosis circumscript is affected by what parts of the body?
- Dermis or subcutis
- Other soft tissues
- The tongue, footpad, tongue, spine, salivary gland, and aorta
What calcification of the skin is a common over bony prominences of distal aspects of the limbs in young dogs of large breeds or horses?
Calcinosis circumscripta
What type of calcification targets the intima and tunica media of vessels?
Metastatic calification
Metastatic calcification will result in
- Chronic kidney disease
- Toxicosis with vitamin D or its analogues is also characterized by
calcium-phosphate imbalance - Inappropriately elevated concentrations of parathyroid hormone
(PTH) or secretion of PTH-related peptide
For Metastatic Calcification in chronic kidney disease, what is the primary defect?
is an imbalance in calcium and
phosphate concentrations in the blood
As a result of the imbalance in calcium and phosphate concentration in the blood what will you see?
Phosphate retention (Binding bioavailable
calcium as CaHPO4)
- Prominent in the lungs, pleura, stomach and
endocardium
- Damage to arteries and arterioles results in
ischemic injury
What are some examples of the imbalance between calcium and phosphate concentration? * reword
- Uremic gastropathy
- Uremic pneumonitis
Toxicosis with vitamin D or its analogues is characterized by what type of imbalance?
calcium-phosphate imbalance
Where is Cestrum diurnuma located?
Does it affect herbivores or carnivores?
It contains what type of glycosides?
It affects what organs in the body?
- West Indies, Gulf Coast of the United States
- Herbivores
- 1,25-dihydroxycholecalciferol (1,25-(OH)2D3)
- Lungs, kidney, and heart
– especially the atrial endocardium and ascending aorta.
Elevated blood concentrations of what tell you that there is severe metastasis calcification..
Elevated serum calcium concentration
Rodenticides containing cholecalciferol affect what two animals?
Dogs and Cats
Elevated PTH or secretion of PTH-related
peptide can be broken down into two different types, what are they?
Primary hyperparathyroidism
Non-parathyroid neoplasms
Between Primary hyperparathyroidism and
Non-parathyroid neoplasms, which one is more common and which is uncommon
Primary hyperparathyroidism (uncommon)
Non-parathyroid neoplasms (common)
What is usually the result of neoplasia of the parathyroid glands?
Primary hyperparathyroidism
What is the Humoral hypercalcemia of malignancy?
Non-parathyroid neoplasms
Neoplastic cells secrete
PTH-related peptide or because the
neoplasm invades and lyses bone
What are two tumors that can secrete PTH-related peptide?
Canine lymphoma and apocrine carcinoma of the anal sac glands
Parathyroid adenoma is more common at what percentage?
87%
Primary Hyperparathyroidism is most common in what type of dog breed?
True/False is it a gene mutation in this breed of dog
Keeshond
True
Neoplasms associated PTHrP
• Lymphoma (common)
• Anal sac apocrine gland adenocarcinoma (common)
• Carcinoma (sporadic): lung, pancreas, skin, nasal cavity, thyroid,
mammary gland, adrenal medulla
• Thymoma (rare)
Hematologic malignancies (bone marrow osteolysis – local osteolytic
hypercalcemia)
Lymphoma
• Multiple myeloma
• Myeloproliferative disease (rare)
• Leukemia (rare)
Hypercalcemia in cases of multiple myeloma can result from:
- Osteoclastic bone resorption: Released by osteoclasts secondary to cytokine secretion by
myeloma cells - Hypercalcemia of malignancy: secrete parathyroid hormone-related peptide
- Hyperglobulinemia: Calcium binding by the paraprotein
Protein have this type of characteristic, in terms of Extracellular protein accumulations?
- Acidic
- Have affinity for the eosin dye of the H&E stain
- Appearance on pink H&E
Examples of extracellular protein accumulations are?
Amyloid
Hyalin-appearance (collagen)
Fibrinoid
What is amyloid?
• Misfolded, non-soluble protein
or protein fragments
• Deposits are nonbranching
fibrils 7.5-10 nm in diameter
• Form B-sheet polypeptide
chains that wound together
What is amyloidosis?
group of
disorders that are
characterized by the
deposition of abnormally
folded proteins in tissues.
What are the mechanisms of amyloidosis?
1) Propagation of misfolded proteins that serve as a template for selfreplication (e.g., prion diseases)
(2) Accumulation of misfolded precursor proteins due to failure to
degrade them
(3) Genetic mutationsthat promote misfolding of precursor proteins
(4) Protein overproduction because of an abnormality or proliferation
in the synthesizing cell (e.g., plasma cell dyscrasia or neoplasia),
(5) Loss of chaperoning molecules or other essential components of
the protein assembly process.
What is Systemic amyloidosis?
What is the localization of this?
Amyloidosis involving several tissues and
organs throughout the body
- AL-amyloidosis
- AA-amyloidosis or Familial amyloidosis
What is Localized amyloidosis?
What is the localization of this?
Amyloid substance may be confined at a given
area in the body
Aβ protein in Alzheimer’s disease
- AIAPP in pancreatic islet
The precursor peptides or intermediate oligomers, not amyloid fibrils
The Amyloid protein, AA has what clinical description
Reactive (secondary)
amyloidosis
The Amyloid protein, AL/AH has what clinical description
Idiopathic (primary)
amyloidosis associated with
myeloma/macroglobulinaemia
The amyloid protein, AScr has what clinical description
Creutzfeldt-Jakob disease,
Scrapie, BSC, CWD
The amyloid protein, AIns/AIAPP has what clinical description
In islets of Langerhans,
diabetes type II, insulinoma
(Cats)
The amyloid protein, AApoAII has what clinical description
Amyloidosisin senescence,
accelerated mice
The amyloid protein, Aβ protein has what clinical description
Alzheimer’s disease (Dogs)
What is the characteristics of AL-amyloidosis
- Unstable monoclonal immunoglobulin light chains
- Produced by a plasma cell dyscrasia
What is the characteristics of AA-amyloidosis/Familial?
Increased level of Serum Amyloid A (SAA) (acute phase protein)
- Synthesized by hepatocytes
- Extrahepatic SAA expression and production is reported in several
species of animals and humans
As a result of AA-amyloidosis/Familial, Shar-Pei dogs and Abyssinian cats are likelky to have?
Renal medullary interstitium
Immunocyte-associated amyloidosis more often involves
Heart, GI & respiratory tracts, peripheral nerves, skin, and tongue
True or False? Deposits may also occur in organs listed for reactive systemic
amyloidosis
True
Systemic amyloidosis typically affects?
More specifically what does it affect
kidneys, liver, spleen, lymph nodes, adrenals, thyroid, and other tissues
- Renal glomerulus, Space of Disse, Splenic white pulp
How do you diagnosis amyloidosis?
Light microscopic level: homogeneousto indistinctly, fibrillar, and pale
eosinophilic
• Confirmed by Congo red staining and green birefringence under polarized
light
What does Congo Red Dye do?
Binds to the fibrils and producesred-green dichroism
- Orange-red hue (i.e., congophilia)
- Refract polarized light into two rays that vibrate in perpendicular waves
How do you diagnosis amyloid Macroscopically
amyloid appears as yellow, waxy, coalescing nodular or amorphous deposits
How is Iodine used when diagnosing amyloidosis?
Used on occasion as a gross technique to stain amyloid
