Cellular Adapt & accumulations II Flashcards
What are subcellular reponses to injury?
Distinctive alterations involving subcellular organelles and cytosolic proteins
What are lysosomes filled with?
Hydrolytic enzymes
What are primary lysosomes?
Small membrane-bound vesicles budding from the Golgi
Primary lysosomes form secondary ones how?
By fusing with pinocytotic or phagocytic vesicles derived from invaginated plasma membrane (phagolysosomes)
What is heterophagy?
Materials from extracellular environment taken up through endocytosis
What is autophagy?
Lysosomal digestion of cells own components
What are residual bodies formed from in cells?
indigestible material resulting from intracellular free radical lipid peroxidation
Hereditary lysosomal storage diseases result in what?
Abnormal accumulation of intermediate metabolites
What happens to the sER during increased chemical intake? What is the consequence of this?
Hypertrophy to increase p450 enzymes
This may lead to the production of more ROS
EtOH abuse leads to what mitochondrial changes in the liver?
Enlarged and abnormal shapes
What are mitochondrial myopathies?
Mitochondrial alterations (like MEERF, MELAS, Leber’s Hereditary optic neuropathy)
What comprises the cytoskeleton (3)?
Thin filaments
Microtubules
Intermediate filaments
Abnormalities in the cytoskeleton reflects what?
Defects in cell function or intracelluarl accumulation of fibrillar material
What are the thin filaments?
Actin, myosin, movement, phagocytosis
What are microfilaments used for?
Motility, phagocytosis mitotic spindles
What are intermediate filaments used for?
Intracellular scaffold maintain cellular architecture
What are cytoskeletal elements’ role in signal transduction?
Linked to cellular receptors to transduce signals
Intracellular accumulation are the result of what?
Metabolic derangements
What are the three categories of intracellular accumulations?
- Normal endogenous substance produced at normal or increased rate, but metabolism cannot remove it
- Normal or abnormal endogenous substance accumulates
- Abnormal exogenous substances is deposited
What are four mechanisms of intracellular accumulations?
- Abnormal metabolism
- Alterations in proteins folding and transport
- Deficiency of critical enzymes
- Inability to degrade phagocytosed particles
What happens in intracellular accumulations?
Normal substances are produced at normal or increased rates, but metabolism cannot keep up
What is steatosis? What is this usually caused by?
Abnormal accumulations of triglycerides within cells
DM or EtOH use
What are the causes of steatosis?
Toxins
Protein mutations
Malnutrition
EtOH
The significance of steatosis depends on what?
Cause and severity
FAs accumulate as what?
Triglycerides
FAs are usually metabolized to what? (3)
Phospholipids
Cholesterol esters
Ketones
What are xanthomas?
Macrophages accumulate cholesterol underneath the skin
What is cholesterolosis?
Gallstones
What is atherosclerosis?
Abnormal accumulation of cholesterol/esters in the tunica intima of arteries
What are foam cells? What happen if these rupture?
Macrophages that accumulate lipids.
If rupture = cholesterol clefts form
What are atheroma?
Aggregates of cholesterol macrophages
What is the MOA of atherosclerosis?
Accumulation of foam cells on vessel walls
Strawberry gallbladder is d/t what?
Cholesterolosis of gallbladder
What are the histological features of cholesterolosis?
Foam cells in gallbladder
What causes proteins to accumulate within a cell?
Misfolding
What is hyaline?
Pink material in the cytoplasm
What are the causes or protein accumulations?
Reabsorption
Increased synthesis
Defect in folding
What does protein accumulation appear like histologically (e.g. in the renal tubules)?
Vacuoles accumulation of pink hyaline
What are Russell bodies? Is this pathogenic
Immunoglobulins packing into b (plasma) cells–abnormal
What are Mallory bodies?
alcoholic hyalin (structural protein) accumulations in the liver
Hyaline is eosinophilic or basophilic?
Eosinophilic
How can protein misfolding lead to accumulations?
Partially folded intermediates vulnerable to aggregate
What are chaperones used for?
Aid in protein folding and transport repair misfolded proteins
What is ubiquitin?
Marker for degradation by a proteosome
What are the four cellular responses to increased misfolded proteins?
- Increase chaperones
- Decrease translation
- Increase degradation
- Apoptosis
What is ER stress? What does this lead to?
Demand for proteins is greater the capacity to produce
Leads to misfolded response
What is alpha-1-antitrypsin deficiency? What does this lead to?
Build up of proteases d/t misfolded antiprotease (alpha 1 antitrypsin)
Leads to tissues damage (cirrhosis/ COPD etc)
True or false: there is a balance of proteases and antiproteases
True
What are the histological features of alpha-1-antitrypsin def?
Red globules with PAS stain in the liver
What are the histological features of amyloidosis?
Orange-red stain on Congo red stain
What is amyloidosis?
Build up of amyloid in issue
What is a hyaline change?
A non-specific morpholiogical change; pink homogenous appearance on H&E staining
Hyaline change can be seen in intracellular or extracellular aggregations?
Both
Hyaline change in the walls of arterioles occur in what disease?
DM and HTN
Glycogen appears like what histologically? (with H&E)
Clear cytoplasmic vaculoes
In DM, glycogen can be seen in what?
Cytoplasm of renal tubular epithelium via glycosylation of proteins
What are the two types of diseases where glycogen is accumulated?
DM
GSDs
How do GSDs appear histologically (with H&E)?
empty vacuoles
Pompe’s disease = ?
Type II GSD
Pigments are endogenous or exogenous?
Both
What is the most common exogenous pigment?
Carbon
What happens to carbon inhaled?
Picked up by macrophages and transported to lymph nodes
What is anthracosis? What can this lead to in severe conditions?
Macrophage accumulation of carbon.
May lead to fibrosis if too large and pneumoconiosis
What is the MOA of tattooing?
Localized exogenous pigmentations of skin d/t dermal macrophages
What is lipofuscin?
Brown pigment resulting from lipochrome (lipids and phospholipids)
Where does lipofuscin accumulate?
Heart, liver, brain
Lipofusin is a marker of what?
Past free radiacal injury
How does lipofusin appear grossly?
Brown
What is melanin? What cells produce it?
Normal pigment in basal epithelial cells produced by melanocytes (via oxidation of Y by tyrosinase)
Melanin accumulates where?
Keratinocytes in skin or dermal macrophages
What is spitz nevus?
Benign melanin mole found in children
What is hemosiderin?
Hb derived gold-yellow/brown pigment in which Fe is stored
Excess Ferritin forms what in the body?
Hemosiderin granules that accumulate into micelles in cells
Hemosiderin pigments represents what?
Aggregates of ferritin micelles
Excesses of Fe build up leads to what?
Hemosiderosis
What are the causes of hemosiderosis? (4)
Increase Fe intake
Impaired use of iron
Hemolytic disease
Transfusions
Hemochromatosis = ?
Accumulation of Fe, in the liver d/t protein absorption in the gut that causes it to absorb more
What is the stain for Fe?
Prussian blue
Hemochromatosis leads to what?
Liver damage
What is bilirubin?
Hb, NOT Fe
What is dystrophic calcification?
Local processes where normal serum Ca leads accumulation organ dysfunction
What is metastatic calcification?
Increased serum calcium (hypercalcemia) leading to increase deposition in tissues
What are the three major ways that hypercalcemia is brought about?
- CA in bone
- High PTH levels
- Vit D disorder
What is the ultimate end product of dystrophic calcification? Metastatic?
Calcium phosphate for dystrophic, leading to tissue destruction
Thin Ca layer without dysfunction of tissue
What do protein inclusions look like histologically?
Dark, eosinophilic inclusions in cells
Hemosiderin-laden macrophages indicate what disease process?
Heart failure
Where is Fe stored in the body?
Macrophages in the bone marrow
Apoprotein + triglyceride = ?
Lipoproteins
What is the main secondary structure associated with Amyloid? What does this stain?
Beta pleated sheets that stain with congo red, and fluoresces