Chapter 2 part 4 Flashcards
3 types of autophagy
1) chaperone-mediated = direct translocation across the lysosomal membrane by chaperone proteins
2) microautophagy = inward invagination of lysosomal membrane for delivery
3) macroautophagy = major form of autophagy involving sequestration and transportation of portions of cytosol in a double-membrane bound authophagic vacuole
Steps of autophagy
1) initiation- triggered by formation of invitation complex and nucleation complex
2) elongation- via LC3
3) maturation of autophagosome
4) fusion with lysosome
5) degradation
4 main pathways of abnormal intracellular accumulations
1) abnormal metabolism (fatty liver)
2) defect in protein folding/transport ;eating to accumulation of abnormal proteins
3) lack of enzyme leading to accumulation of endogenous material (lysosomal storage disease)
4) ingestion of indigestable materials leading to accumulation of exogenous materials
Steatosis
accumulations of triglycerides within parenchymal cells ; often seen in liver, heart, muscle, kidney
Causes: toxin, protein malnutrition, diabetes, obesity, anoxia
Atherosclerosis
smooth muscle cells and macrophages within the intimal layers of aorta and large arteries are filled with lipid vacuoles made up of cholesterol (foam cells)
Xanthomas
intracellular accumulation of cholesterol within macrophages; clusters of foamy cells found in sub epithelial connective tissue of skin and in tendons
Cholesterolosis
focal accumulations of cholesterol-laden macrophages in the lamina propria of the gallbladder
Niemann-Pick disease, type C
lysosomal storage disease caused by mutation affecting an enzyme involved in cholesterol trafficking, resulting in cholesterol accumulation in multiple organs
How do intracellular accumulations of proteins appear?
rounded, eosinophilic droplets, vacuoles, or aggregates in the cytoplasm
What condition are reabsorption droplets in proximal renal tubules seen in?
renal diseases associated with protein loss in the urine
When proteins accumulate and the ER becomes largely distended, what does the ER produce?
Russel Bodies = large, homogenous eosinophilic inclusions
What condition is associated with defective intracellular transport and secretion of critical proteins?
a1-antitrypsin deficiency; build up of partially folded intermediated that aggregate in the liver ER and deficiency of circulating enzymes leading to emphysema
What are some of the. cytoskeletal proteins that can build up?
- microtubules
- thin actin filaments
- thick myosin filaments
- intermediate filaments: keratin, neurofilaments, dessin filaments, vimentin filaments, glial filaments
What condition is associated with aggregation of abnormal proteins
amyloidosis
Hyaline change
homogenous, glassy, pink appearance
Examples of exogenous pigments
- carbon (coal dust): causes anthracosis in the lungs
- tattooing
Examples of endogenous pigments
- lipofuscin
- hemosiderin
- melanin
Lipofuscin
insoluble pigment composed of polymers of lipids and phospholipids in complex with protein; sign of free radical injury and lipid peroxidation; prominent in liver and heart of aging patients
Melanin
endogenous black pigment formed when tyrosinase catalyzes oxidation of tyrosine to dihydroxyphenylalanine in melanocytes (alkaptonuria)
Hemosiderin
hemoglobin derived, golden yellow to brown, granular or crystalline pigment that is one of the major storage forms of iron; when body breaks down heme into iron and biliverdin, the body traps the released iron in hemosiderin
Hemosiderosis
when there is a systemic overload of iron, hemosiderin deposits in organs and tissues
Causes: increased dietary iron absorption, hemolytic anemias, repeated blood transfusions
Pathologic calcification
abnormal tissue deposition of calcium salts with small amounts of iron, magnesium, and other mineral salts
Dystrophic calcification
when the deposition occurs locally in dying tissues
Metastatic calcification
results from hypercalcemia secondary to some disturbance in calcium metabolism
Causes: increased secretion of PTH (hyperparathyroidism), resorption of bone tissue, abnormal sensitivity to vitamin D, renal failure causing the retention of phosphate leading to secondary hyperparathyroidism
