Ch 2 - 5/4 Dobson Flashcards by Alex Hamidi

What kind of cellular adaptation is a result of increased demand and stimulation?

Hyperplasia or hypertrophy

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What kind of cellular adaptation is a result of chronic irritation (physical or chemical)?

Metaplasia

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What cellular adaptation is most common in the uterus during pregnancy?

Endometrium from estrogen?

Hypertrophy

Hyperplasia

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What cellular adaptation is most common in muscle disuse?

Barrett esophagus?

Atrophy

Goblet cell Metaplasia

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Metabolic alterations to a cell that are due to chronic injury result in what?

Intracellular accumulations, calcification

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Cumulative sub lethal injury over long life span induce what cellular response?

Cellular aging

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What type of necrosis is associated with tuberculous infection?

What type specifically?

Caseous

Myobacterium tuberculosis

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Caseous necrosis is described as what?

How does it look on microscopic examination?

Yellow-white and “cheese-like”

Appears as a structure less collection of fragmented or lysed cells and amorphous granular debris enclosed within a distinctive inflammatory border (Granuloma)

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If there is ischemia to a cell, what happens in the mitochondria?

DEC ox-phosph and DEC ATP production

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What are the 3 consequences of DEC ATP production in the mitochondria?

DEC Na pump
INC anaerobic glycolysis
Detachment of ribosomes (dec protein synthesis)

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What are the major sequellae of increased anaerobic synthesis in the cell?

What happens structurally in the cell?

DEC glycogen
INC lactic acid and Dec pH

Clumping of nuclear chromatin

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What are the consequences of DEC activity in the Na+ pump?

What structural changes seen in the cell?

INC influx of Ca, H2O, and Na
INC effluent of K+

ER swelling, cellular swelling, loss of Microvilli and Blebbing

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What are the major causes of ATP depletion?

Reduced supply of oxygen and nutrients, mitochondrial damage, and actions of toxins (Cyanide)

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What are the consequences of membrane damage?

Loss of cellular components

Enzymatic digestion of cellular components

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What are the microscopic features of coagulative necrosis in the heart?

Wavy fibers

Widened spaces bw dead fibers containing edema fluid and scattered neutrophils

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What pathological conditions lead to apoptosis?

DNA damage
Accumulation of misfolded proteins
Cell death in infection
Pathological atrophy in parenchymal organs after duct obstruction

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Li-Fraumeni syndrome is a result of DNA damage to what gene?

TP53

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What kind of cellular adaptation is a result of decreased nutrients and and decreased stimulation?

Atrophy

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What are the 3 basic steps in the molecular pathogenesis of cardiac hypertrophy?

Actions of mechanical sensors
Signals that activate a signal transduction pathways
Signaling pathways activating TFs

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What are the the GFs of mechanical sensors in hypertrophy?

Vasoactive agents?

TGF-B, IGF-1, FGF

A-adrenergic agonists, Endothelin-1, Angiontensin II

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What are the TFs which increases the synthesis of muscle proteins responsible for muscle hypertrophy?

GATA4
NFAT
MEF2

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Cardiac hypertrophy is associated with INC/DEC gene expression of ANF?

What does this do?

Increased

Decreases blood volume and pressure

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What is an example of hormonal hyperplasia?

Compensatory hyperplasia?

Pathologic hyperplasia?

Enlargement of breast tissue during puberty

Liver regeneration

Endometrial, BPH

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What are the 6 different causes of atrophy?

Dec workload
Loss of innervation
Diminished blood supply
Inadequate nutrition / malnutrition 
Loss of endocrine stimulation
Pressure (tissue compression)

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How does the degradation of cellular protein mainly occur?

Ubiquitin-proteasome pathway

Some of the cell debris within autophagic vacuoles may resist digestion and persist in the cytoplasm as what? Example of one?

Residual bodies Lipofuscin granule (brown color)

What is the order of change in a cell during irreversible cell injury? (Fig. 2-7)

Biomechanical alterations leading to cell death Ultrastructural Light microscopic Gross morphologic BULGe

How does the cell size change in necrosis? Apoptosis?

Swell Shrinks

Describe the plasma membrane in necrosis? Apoptosis?

Disrupted Intact with altered structure

What happens to the cellular contents in necrosis? Apoptosis?

Enzymatic digestion, may leak out of cell Intact, released into apoptotic bodies

What is it called on microscopic examination, small clear vacuoles may be seen within the cytoplasm, representing distended and pinched-off segments of the ER? The may show what kind of staining?

Hydropic change or vacuolar degeneration Increased eosinophilic staining

What are the Ultrastructural changes of reversible cell injury?

Blebbing, blunting, loss of Microvilli Mitochondrial swelling and amorphous densities Dilation of the ER with detachment of polysomes Nuclear alterations -> disaggregate on of granular and fibrillar elements

What do necrotic cells show in a H&E stain? Due to what?

Increased eosinophilia Loss of cytoplasmic RNA and denatured cytoplasmic proteins

Dead cells may be replaced by whirled phospholipid masses called what? Derived from where?

Myelin figures Damaged cell membranes

In living patients, if necrotic cells and cellular debris are not promptly destroyed and reabsorbed, what happens to them?

Dystrophic calcification

What kind of necrosis is characteristic of malignant hypertension and vasculitis?

Fibroid necrosis

What are the major causes of depletion of ATP?

Reduced supply of oxygen and nutrients, mitochondrial damage, toxins

What are 3 consequences of mitochondrial damage?

Formation of the mitochondrial permeability pore Formation of ROS Increased permeability of the outer mitochondrial membrane

Increased intracellular calcium activates what enzymes? | What do they do?

Phospholipase and proteases do membrane damage Endonucleases do nuclear damage ATPases hasten ATP depletion

How does intracellular calcium affect mitochondrial membrane permeability?

Increases it, thus decreasing ATP production

What ROS is the most reactive and principally responsible for damaging lipids, proteins, and DNA?

OH radical

How is hydrogen peroxide converted to oxygen?

``` Catalase (in Peroxisomes) and Glutathione peroxidase (cytosol, mitochondria) ```

What agents act as antioxidants??

Vitamins A, C, E and glutathione

What are the pathological effects of ROS?

Lipid peroxidation in membranes Protein modification (misfolding and breakdown) DNA damage -> mutations

How is membrane permeability damaged and what is responsible?

Phospholipid loss due to decreased phospholipid synthesis (ROS) Increase in phospholipid breakdown via INC in intracellular Ca2+ Cytoskeleton damage via activation of proteases

If there is duct obstruction that may occur in the pancreas, parotid, or kidney what may this lead to?

Pathologic apoptosis

What is the most characteristic feature of apoptosis? Describe it

Chromatin condensation Chromatin aggregates peripherally and becomes dense, may fragment

What are the anti-apoptotic proteins? What domains do they contain? What do they prevent?

BCL2, BCL-XL, MCL BH1-4 Cytochrome c leakage

What are the pro-apoptotic proteins? What domains do tha even have?

BAX and BAK BH1-4

What are the major sensors of apoptosis? Domains?

BAD, BIM, BID, Puma, Noxa BH3 ONLY

What happens once cytochrome c is released into the cytosol?

Binds APAF-1 forming apoptosome Binds caspase 9 which activates caspase 3

What is responsible for inhibiting anti-apoptotic proteins?

Smac and Diablo

What are the death receptors of the extrinsic pathway?

TNFR1 and Fas (CD95)

What is the adaptor protein that begins the pathway of apoptosis once Fas binds FasL?

FADD

Once the adaptor protein of the extrinsic pathway is activated what happens leading up to apoptosis?

Caspase 8 and 10 are activated, which will activate executioner caspases 3 and 6

What protein is capable of inhibiting the death receptor pathway of apoptosis? How? What contains this protein?

FLIP Binds pro-caspase-8 Viruses and normal cells

What are the most prominent signals for cells indicating apoptosis?

Phosphatidlyserine Thrombospondin C1q

What is triggered when abnormal proteins accumulate in the ER?

Unfolded protein response

What does the unfolded protein response trigger?

INC production of chaperones INC proteasomal degradation of abnormal proteins Slows protein translation (and DEC protein synthesis)

Tay-Sachs disease is due to what defective protein?

Hexoaminidase Beta subunit

Familial hypercholesterolemia disease is due to what defective protein?

LDL receptor

Creutzfeldt-Jacob disease is due to what defective protein?

Prions (abnormal folding of PrPsc)

Alzheimer's disease is due to what defective protein?

AlphaBeta peptide

What is the distinguishing feature of necroptosis? Triggered by mostly what? What else?

NO activation of Caspases TNFR1 and by viruses

Ligation of TNFR1 recruits what in necroptosis?

RIP1 and RIP3

Necroptosis occurs where? Associated with what diseases?

Formation of mammalian bone growth plate Cell death in steatohepatitis, acute pancreatitis, reperfusion injury, neurodegenerative diseases

Caspase-1 is involved of what? It activates what?

Pyroptosis IL-1

What cell processes involves inward invagination of lysosomal membranes for delivery?

Microautpohagy

What marker is used to identify cells in which Autophagy is occurring?

LC3

Deletion of what gene leads to increased susceptibility to tuberculosis?

Atg5

Autophagy plays a role in what main diseases?

``` Cancer Alzheimer's Huntington's IBD and Crohn's Infections diseases ```

Intracellular accumulation of cholesterol within macrophages is also characteristic of acquired and hereditary hyperlipidemic states is called what? Found where?

Xanthomas (clusters of foamy cells) Us epithelial CT of the skin and tendons

The focal accumulations of cholesterol-laden macrophages in LP of the gallbladder is referred to what?

Cholesterolosis

What is the name of a lysosomal storage disease caused by mutations affecting enzyme involved in cholesterol trafficking, resulting in cholesterol accumulation in organs?

Niemann-Pick type C disease

Large, homogenous eosinophilic inclusions produced from a distended ER are called what?

Russell bodies

This subclass of intermediate filaments resists forces applied to it in epithelial cells? Muscle cells? CT cells?

Keratin filaments Desmin Vimentin

What is the most common exogenous pigment? Accumulations of this tissue in the lung is called what?

Carbon (coal dust) Anthracosis

What is an insoluble pigment produced from wear-and-tear?

Lipofuscin

What is the only endogenous brown-black pigment?

Melanin

What is of a yellow-brown color and is a tell-tale sign of free radical injury and lipid peroxidation?

Lipofuscin

What is of a golden yellow-to-brown, granular or crystalline pigment? Major storage form of what?

Hemosiderin Iron

When there is local or systemic excess of iron, what will form hemosiderin granules?

Ferritin

What are the major causes of hemosiderosis?

INC absorption of dietary iron (hemochromatosis) Hemolytic anemia Repeated blood transfusions

What is the abnormal deposition of calcium salts, together with iron and magnesium called?

Pathologic calcification

What kind of calcification occurs locally in dying tissues with normal serum levels of calcium? Frequently occurs where?

Dystrophic Aging or damaged heart valves

Deposition of calcium salts in normal tissues is what? Results from what?

Metastatic calcification Hypercalcemia secondary to disturbance in calcium metabolism

What may be formed in the focus of calcification?

Heterotopic bone

Papillary cancers (thyroid) are apt to develop what? Describe them

Psammoma bodies Grains of sand, lamellated configurations

Where does metastatic calcification most often occur?

Gastric mucosa, kidneys, lungs, systemic arteries, PV

patients with Werner syndrome show what? Defective gene is what?

Premature aging DNA helicase

What does the CDKN2A locus encode for? Controls what phase progression of the cell cycle?

p16 G1 to S