Cellular Adapt & accumulations II Flashcards by tcarlso 3

What are subcellular reponses to injury?

Distinctive alterations involving subcellular organelles and cytosolic proteins

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What are lysosomes filled with?

Hydrolytic enzymes

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What are primary lysosomes?

Small membrane-bound vesicles budding from the Golgi

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Primary lysosomes form secondary ones how?

By fusing with pinocytotic or phagocytic vesicles derived from invaginated plasma membrane (phagolysosomes)

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What is heterophagy?

Materials from extracellular environment taken up through endocytosis

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What is autophagy?

Lysosomal digestion of cells own components

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What are residual bodies formed from in cells?

indigestible material resulting from intracellular free radical lipid peroxidation

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Hereditary lysosomal storage diseases result in what?

Abnormal accumulation of intermediate metabolites

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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

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EtOH abuse leads to what mitochondrial changes in the liver?

Enlarged and abnormal shapes

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What are mitochondrial myopathies?

Mitochondrial alterations (like MEERF, MELAS, Leber’s Hereditary optic neuropathy)

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What comprises the cytoskeleton (3)?

Thin filaments
Microtubules
Intermediate filaments

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Abnormalities in the cytoskeleton reflects what?

Defects in cell function or intracelluarl accumulation of fibrillar material

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What are the thin filaments?

Actin, myosin, movement, phagocytosis

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What are microfilaments used for?

Motility, phagocytosis mitotic spindles

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What are intermediate filaments used for?

Intracellular scaffold maintain cellular architecture

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What are cytoskeletal elements’ role in signal transduction?

Linked to cellular receptors to transduce signals

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Intracellular accumulation are the result of what?

Metabolic derangements

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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

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What are four mechanisms of intracellular accumulations?

Abnormal metabolism
Alterations in proteins folding and transport
Deficiency of critical enzymes
Inability to degrade phagocytosed particles

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What happens in intracellular accumulations?

Normal substances are produced at normal or increased rates, but metabolism cannot keep up

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What is steatosis? What is this usually caused by?

Abnormal accumulations of triglycerides within cells

DM or EtOH use

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What are the causes of steatosis?

Toxins
Protein mutations
Malnutrition
EtOH

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The significance of steatosis depends on what?

Cause and severity

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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?

1. Increase chaperones 2. Decrease translation 3. Increase degradation 4. 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?

1. CA in bone 2. High PTH levels 3. 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