Unit I: Cellular Accumulations Flashcards
Cell accumulation mechanisms (x5)
- cell injury/aging–MOST COMMON
- Defect in packaging/transporting mechanism (fatty change)
- genetic defects in protein folding, packaging, transport, secretion (alpha-1 antitrypsin)
- genetic enzyme deficiency (lysosomal storage diseases)
- abnormal exogenous material accumulation (ex: carbon/silica)
Types of cell accumulations (x7)
- proteins
- cytoskeletal elements
- lipids
- cholesterols
- glycogen
- pigments
- calcium salts
-
lipofuscin-define
- what does it cause?
- where is it?
- is it bad?
-
lipofuscin- primary lipid waste product–undigested remnants of lipid peroxidation–occurs with cellular aging
- causes discoloration when deposition occurs during atrophy= brown atrophy
- collects near nucleus, especially in heart and liver
- NON toxic
-
Autophagy
- process
- purpose
-
Autophagy- digestion of intracellular material
- ribosome free area of ER makes autophagic vacuole that fuses with lysosome or golgi==> autophagolysosome
- removes damaged organelles
-
Heterophagy-
- definition
- process
- cell types
-
Heterophagy- digestion of extracellular material
- Endocytosis, phagocytosis, or pinocytosis
- phagolysosome fusion
- Usually in phagocytic cells
-
Steatosis- define,
- what tissues does this occur in?
- possible Etiology?
- most common causes?
- Gross changes
- microscopic changes
-
Steatosis= Fatty change- abnormal accumulation of triglycerides in cytoplasmic vacuoles
- Tissues: usually liver, but can also occur in heart, muscle kidney
-
Etiology: toxins (EtOH), protein malnutrition, diabtetes, obesity, anorexia, CCl4 poisoning, Reye’s syndrome
- USUALLY: alcohol abuse and diabetes
- Gross changes: yellow, enlarged (liver)
- Microscopic changes: intracytoplasmic vacuoles, non staining
Non-alcoholic fatty liver pathophysiology?
- overproduction of fatty acids from glucose and glycogen
- Big part of early stage Type II Diabetes
Alcoholic fatty liver progression
- fatty deposits start as microvesicles
- cytoplasm is replaced by one large macrovesicle of lipid==> liver expansion= enlarged greasy and yellow
Clear vacuoles mean….?
Clear vacuoles can contain:
- water
- lipid - Oil Red O and Sudan black can detect lipid in frozen sections
- glycogen- PAS or periodic shiff stains
Atherosclerosis
Phagocytic cells become overloaded with lipids (triglycerides, cholesterol and choleesteryl esters).
Hyaline change- define, describe (histo), 5 examples
- Non-specific depositions of protein intracellulary OR extracellularly.
- It is pink (eosinophilic) and glassy/granular/fibrillar (depending on protein type)
-
Examples:
- Hyaline membrane (lung)
- Mallory bodies (liver)
- alpha-1 antitrypsi deficiency
- Russel bodies
- nephrotic syndrome
Hyaline Membranes
- what are they
- location
- pathophysiology?
Hyaline Membranes
- extracellular collection of fibrin and other plasma proteins
- line alveolar space
- damaged alveolar capillaries allows them to leak out
Mallory bodies
Mallory bodies= intermediate keratin filament deposition (hyaline) in alcoholic liver disease
Glycogen accumulation
- associated with:
- Microscopic appearance
- Where does it accumulate?
- abnormal glucose/glycogen metabolism= diabetes, glycogen storage disorders
- non staining cytoplasmic vacuoles–can be stained with PAS/Periodic Shiff
- renal tubulear epithelium, cardiac mycotes (pompe disease), beta cells of islets of langerhans
Russel Bodies
- Plasma cell RER accumulates newly synthesized immunoglobulins
- round, eosinophic
- Normal protein filtration in kidney?
- Nephrotic syndrome (with regards to protein accumulation)
- Normal: albumin filtered in glomerulus and pinocytosed in PCT
-
Nephrotic Syndrome: protein leakage across glomerulus==> higher rate of reabsorption in PCT==>protein accumulation in vesicles
- pink hyaline cytoplasmic droplets
Anthracosis
- carbon (most common exogenous pigment) aggregates in and blackens draining lymph nodes and pulmonary parenchyma
- carbon is phagocytsed by alveolar macrophages and transported through lymph to tracheobronchial nodes
- Not carcinogenic
Hemosiderin-define
- characteristics
- etiology
- examples
Hemosiderin- breakdown product of hemoglobin by macrophages
- Characteristics: granular gold-brown pigment from excess iron deposition
- etiology: excess bleeding, phagocytosis of red cells, hereditary increased deposition of iron (ie hemochromatosis)
- Examples: bruising (localized hemosiderosis); hemochromatosis,
Hemosiderosis
aggregation of hemosiderin (Fe granules from Hb breakdown by macrophages)
Bilirubin accumlation
- what is it
- normal method of excretion
- deposits where?
- called ____ when accumulates in tissues, ___ in eyes
Bilirubin
- non-iron part of hb
- normally excreted in bile
- extracellular or intracellular
- jaundice, icterus
What causes excess bilirubin deposition ?
- excess RBC hemolysis
- liver disease
- causes yellow discoloration of sclera (icterus) or skin (jaundice)
Calcification
- Where does it occur
- what are the two types?
- extracellular or intracellularly
- dystrophic or metastatic
Hemachromatosis
- what is it
- what does it cause?
- Excess iron causes damage (over decades) due to ROS (fenton rx).
- causes diabetes (pancreatitis, bronzing of skin, myocardial scarring and arrhythmias, and liver cirrhosis (which can progress to cancer)
Dystrophic calcification
- what is it?
- Where is it deposited?
- Features?
- Serum calcium levels?
- calcium complexes with lipid from cellular debris. the calcium is attracted to membrane phospholipids
- LOCALIZED in necrotic tissue
- amorphic basophilic deposits
- normal serum calcium
Two steps of dystrophic calcification
- initiation
- propogation
Metatstatic calcification
- serum calcium levels
- distribution
- examples
- HYPERCALCEMIA
- systemic distribution, especially in vessles, kidney and lung
- hyperparathyroidism, VitD toxicosis, tumors (associated with increased bon metabolism, renal failure (secondary to hyperparathyroidism, multiple myeloma
Aortic stenosis in old people is commonly caused by?
Dystrophic calcification
Dystrophic calcification- where do initiation and propogation occur extracellularly and intracellularly
- Initiation
- Extracellular: membrane bound vesicles derived from degenerating cells
- Intracellular: mitochondria of dead or dying cells
- Propagation: in both extra and intracellular dystrophic calcification, propagation occurs at place of initiation and depnds on concentrations of calcium, phosphate, mineral inhibitors and degree of collagenization.
matrix vesicles
physiologic place of dystrophic calcification in bones and cartilage?
Senescence
pre-programmed limits to proliferation. ie telomeres
Neoplasms reporoduce indefinitely due to….
expression of telomerase that lengthens telomeres with cell division
Mechanisms involved in cellular aging
- DNA damage
- telomeres (Werner’s syndrome have shorter telomeres)
- defective protein homeostasis (chaperones less active, less translation, more turnover)
- exposure to elements that cause cellular aging
- activation of tumor suppressor genes
- nutrient sensing
tumor suppressor genes
- usually inhibit progression from G1–> S
- defect can increase changes of cancer
Telomerase activity in different cell types?
germ cells>stem cells> somatic cells
nutrients and cell aging?
Caloric restriction ==> decreased IGF-1 and insulin==> enhanced repair
