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Flashcards in Module 2-Path Deck (40):

What is an amyloid?

Extracellular protein deposits found most commonly in the kidney


What is the pathogenesis of amyloidosis?

Protein misfolding for AL amyloidosis


In amyloidosis the organ is initially enlarged but then what happens?



What does localized amyloidosis mean?

Affects one organ


What are the individual organs that localized amyloidosis affects?

1. Kidneys: affected kidney turns brown with iodine stain --> proteinurina, enlargement and failure
2. Senile Cardiac Amyloidosis and Familial Amyloidotic Neuropathies --> Transthretin
3. Liver: deposits in Space of Disse (hepatomegaly)
4. Alzheimers --> Beta2 Amyloid, Beta Amyloid or ABeta (you also see TAU proteins but these are intracellular)
5. Spleen --> white pulp (sago spleen, see tapioca like granules); sinusoids/red pulp (lardaceous spleen) --> splenomegaly (s


What are some examples of systemic amyloidosis?

Systemic: affects multiple organs
-Multiple Myeloma -> w/Bence Jones Proteins --> AL amyloid
-Chronic Inflammatory Conditions -> Crohns, Ulcerative Colitis, TB, Osteomyelitis, RA) --> AA amyloid
--Dialysis patients form B-2 microglobulin


what is the difference between AL and AA amyloid?

AL amyloid (amyloid light chains): composed of immunoglobin light chains
AA amyloid (amyloid associated): composed of non immunoglobin protein derived from SAA (Serum-amyloid associated protein)
these are usually always chronic inflammatory diseases


Is AL or AA associated with primary amyloidosis?

Immunocyte dyscrasias is primary amyloidosis
deposition of AL in extracellular spaces throughout the body


Is AL or AA associated with secondary amyloidosis?

Reactive systemic amyloidosis aka secondary amylodiosis
deposition of AA protein in extracellular space
associated with chronic inflammation
secondary condition to autoimmune and neoplasmas


How does amyloidosis of the kidney present?

Generalized edema due to loss of proteins --> Nephrotic syndrome (in the kidney most common)


How does amyloidosis of the heart present?

Usually deposits into the myocardium so you get arrhythmias


What are the various stains for amyloidosis?

EM: non branching fibrils (beta pleated sheets) and non branching component made up of alpha 1 glycoprotein
H and E stain: amorphous, glassy pink (hyline), extracellular protein
Congo Red: salmon pink/red if this is subject to polarized light looks like apple green birefringement


Dystrophic calcification involves what kind of tissues?

Dead or dying tissues due to injury


Where is dystrophic calcification commonly seen?

Atherosclerotic plaques, enzymatic fat necrosis, damaged cardiac valves, mercury poisoning, congenital CMV, aging (degenerative with wear and tear) and Rheumatic Fever


What is the presentation of dystrophic calcification ?

Aortic stenosis, repeated syncope, SOB, CHF and murmur


What are the calcium levels for dystrophic calcification?

Ca2+ levels are normal
(exception is fat necrosis of pancreas = hypocalcemia)


What is the H and E stain for dystrophic calcification?

Ca2+ stains deep blue (Basophilic)


Where is another common site for dystrophic calcification?

Breast, indicative of breast cancer


In the picture for aortic stenosis, the area of necrosis is due to what?

Initial intracellular Ca comes from mitochondria of dying or dead cells = initiating factor for extracellular accumulation of Ca phosphate
Collagen enhances crystallization rate


How does the calcium appear in aortic stenosis?

Salts seen as white granules/clumps/gritty deposits


In metastatic calcification, Ca2+ levels are what?

Elevated in normal tissues


What are the four main causes for metastatic calcification?

1. Primary hyperparathyroidism: Increased PTH --> bone reabsorption, hydroxylation of Vit D & reabsorption of calcium in renal tubule with the excretion of phosphates
2. Sarcoidoisis: non-caseating granuloma; activates vitamin D precursors which increases renal and intestinal absorption of Ca2+ as well as bone reabsorption
3. Chronic Renal Failure
4. Vitamin D intoxication


What is the main etiology or cause of acute gout?



What are some pre-disposing factors for gout?

Red Wine
Red Meat
Lesch Nyhan (HGPRT deficiency)


Does hyperuricemia (High uric acid levels) always lead to gout?

Does not always lead to gout, but to get gout, you have to have high uric acid levels


Primary gout includes 90% and Secondary causes of gout includes 10%. Name some primary and secondary causes?

Primary --> unknown enzyme defect; HGPRT deficiency
Secondary --> Increased Na turnover, chronic renal disease and inborn errors of metabolism


What is the pathogenesis for acute gout?

Macrophages engulf uric acid crystals --> complement activation --> bring in neutrophils via secretion of IL-8 (then signs of inflammation)


For acute gout is there edema usually?

Edematous soft tissue with acute inflammatory infiltrate


What is the best investigation for gout?

Joint Aspiration/atherocentesis


What is the most common location for gout?

1st metatarsal joint of the big toe


What pathway is defective in Gout?

Disorder of purine metabolism
(Increased uric acid levels due to overproduction or reduced excretion or both)


What are the crystals seen in gout?

Monosodium Urate Crystals
Negatively Birefringment (yellow)
Needle shaped crystals


In regards to pseudogout (chondrocalcinosis), what are some characteristics?

Calcium Pyrophosphate Crystals
Loves the knee
Positive Birefringement (blue crystals)
Rhomboid crystals


Is Chronic Gout (or tophous gout) painful?

Nope just lost of function
No bradykinin, no pain
No pain normally but every chronic inflammation can have an episode of acute on chronic inflammation which causes pain


Is there swelling with chronic gout?

No histamine --> no swelling or redness


Takes about how long for chronic gout to develop?

about 20 years


In chronic gout you will see foreign body granuloma (With foreign body giant cells), explain the process

Just like for any chronic inflammation
Fibroblasts deposit collagen --> joint becomes fibrosed --> decreased ROM


Chronic gout involves granulation tissue so what hypersensitivity is it?

type IV


A classic symptom of chronic gout is Tophaceous deposits in soft tissues, which common soft tissues?

ear, nose cartilage and skin of fingertips


What are some complications of chronic gout?

Joint destruction and other complication is renal failure (tubules get damaged by uric acid crystals) and kidney stones