Multisystemic diseases Flashcards
What is Amyloidosis?
Proteinaceous material deposited in organs– due to a variety of clinical disorders
How is amyloidosis defined/diagnosed? How does it appear on H&E? On a Congo red stain? Under polarized light? By electron microscopy
-Defined by appearance on light microscopy
H&E:appears as a pink material between cells
Congo red stain: appears red
Under polarized light: apple-green birefringence
electron microscopy: fibrils in a beta-pleated sheets
What are the different clinical causes of amyloidosis?
- multiple myeloma
- reactive systemic amyloidosis due to chronic inflammatory disease
- Hemodialysis-associated amyloidosis
- hereditary amyloidosis
- localized amyloidosis (plasma cells found around nodules)
- amyloid of aging
What does amyloid look like on a macroscopic level?
When it accumulates in larger amounts, the organ is frequently enlarged and has a waxy, firm consistency
What does amyloid look like and do to cells microscopically?
Deposition begins between cells, then surrounds and literally squeezes the cells to death
What is the prognosis of amyloidosis?
- Depends on organs involved
- can be clinically silent or cause serious dysfunction and death
What is hemochromatosis?
- Excessive accumulation of iron, most in the liver and pancreas
- Humans do not have a major excretory pathway for iron
- -genetic defect causing excessive iron absorption
- -administration of iron (transfusions)
What does hemochromatosis look like for different organs?
Liver? Pancreas?
Liver cirrhosis rusty appearance Pancreas diabetes mellitus Heart, pituitary, adrenal, thyroid, parathyroid, joints Skin slate-gray pigmentation
Clinical term: “bronzed diabetes”
What chromosome causes the genetic defect for hemochromatosis? What gender gets it more?
ch. 6
males
Treatment for hemochromatosis
phlebotomy
iron chelation
What is Wilson Disease?
-Copper Accumulation in organs, especially liver, brain, eye (also kidneys, bones, joints, parathyroids)
What are the manifestations of Wilson Disease in the Liver, Brain and Eye?
Liver: cirrhosis
Copper stains
Gold standard: quantify copper content in liver
Brain: toxic injury to basal ganglia
mild behavioral changes to psychosis or Parkinson’s-like disease
Eye: Kayser-Fleischer rings: green-brown deposits of copper
What genetic defect causes Wilson Disease?
ch. 13!!!!
How do we diagnose and treat Wilson Disease?
Lab tests:
decreased serum ceruloplasmin
increased copper in liver
increased urinary excretion of copper
Treatment
copper chelation therapy (D-penicillamine)
liver transplantation
What will a lysosomal storage disease cause
accumulation of partially degraded metabolites in lysosomes
What is Tay Sachs disease? What deficiency does it have?
- Deficiency in Hexosaminidase A
- Accumulation of gangliosides in brain
- Brain principally affected because most involved in ganglioside metabolism
Electrons Microscopy:
-Neurons with lysosomes with whorled configurations
Infants:
- mental retardation, blindness, severe neurologic dysfunctions
- death within 2-3 years
What is Niemann-Pick disease?
Deficiency in sphingomyelinase (break down a lysosome enzyme)
–Accumulation of sphingomyelin (a lysosome enzyme) and cholesterol
Organs affected
-spleen, liver, bone marrow, lymph nodes, lungs, central nervous system
Microscopy:
Cells with foamy appearance
Massive enlargement of organs and severe neurologic deterioration
death within 5 years
What is Gaucher disease?
Deficiency in glucocerebrosidase
Accumulation of glucocerebrosides (ceramide)
Clinical features:
Massive enlargement of spleen, filling entire abdomen, may get neurological disturbances
Microscopy: Cells with "wrinkled tissue paper" Therapy enzyme replacement potential gene therapy infusion of stem cells transfected with normal glucocerebrosidase gene in vitro
What is Hurler syndrome?
- deficiency of alpha-L-iduronidase
- Accumulation of mucopolysaccharides
Clinical features:
Coarse facial features, corneal clouding, joint stiffness, skeletal deformities (gargoylism), mental retardation
Death due to cardiac complications from deposition
Life expectancy 6-10 years
What is Hunter syndrome?
X-linked
Deficiency of L-iduronate sulfatase
Accumulation of mucopolysaccharides
Milder clinical course than Hurler syndrome
What is Pompe disease?
Deficiency in glucosidase
Accumulation of glycogen in virtually every organ, cardiomegaly is most prominent
—Cardiorespiratory failure within 2 years
Milder adult form with only skeletal muscle involvement
What is rheumatoid arthritis generally?
- Systemic, chronic inflammatory disease that affects principally the joints and sometimes many other organs.
- Leads to destruction of articular cartilage
- Symmetric arthritis in small joints
- Chronic inflammation with lymphocytes, macrophages, plasma cells
-More common in women (3-5x)
Where do Rheumatoid subcutaneous nodules occur and what causes them for Rh. Arthritis?
Occur along extensor surface of forearm
Central necrosis surrounded by macrophages
What is the etiology of rheumatoid arthritis?
- Genetic predisposition
- Activation of helper T cells (microbe?)–> Cytokines
Cytokines–>
Activation of B cells–>antibodies to self
–Rheumatoid factors (60-80% of patients)
—-autoantibodies directed to Fc portion of IgG
