Session 1 - Cell Injury Flashcards by Raegan Chambers

What are the seven big reasons given in lecture for cell injury?

Hypoxia + Toxins + Infectious agents + Immunological Reactions + Genetic derangements + Nutritional Imbalances

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What is the acronym for building a differential list?

(D) AMNIIT-V

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What does the acronym for differential list stand for?

Anomalous 
Metabolic/Nutritional 
Neoplastic 
Infection/Inflammatory 
Traumatic 
Toxic 
Vascular

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What occurs to the cell commonly when sublethal cell injury is occurring?

Cellular swelling + Accumulation of Cytoplasmic material

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Why is there cellular swelling in sublethal injury to a cell?

Plasma membrane pumps are unable to work due to lack of ATP, from lack of oxygen
Leads to the accumulation of water within the cell

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Why is there accumulation of cytoplasmic material in sublethal injury?

W/ increase of water within the cytoplasm organelles start to swell as well
Ribosomes are lost (they pop of the ER)
Lipid and other metabolic products build up because they are no longer able to be processed

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What is hydropic dengeneration?

Accumulation of water in the cell

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What is vacuolar change?

Small clear vacuoles become present in the cytoplasm, from distended pinched off segments of the ER

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What is lipid degeneration?

aka steaosis

Abnormal retention of lipids within the cell, due to problem with synthesis/elimination of triglycerides

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Describe what happens in fatty change?

FA’s fail to be converted to lipoprotein and transported out of the cells, accumulate in the cytoplasm of hepatocytes (or other cells)

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What makes lipid accumulation become hepatic lipidosis?

When the accumulation is significant enough to be seen grossly

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What are two main reasons given in lecture for there to be fatty change?

Ketosis + Pregnancy toxemia

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Why is there fatty change with Pregnancy Toxemia?

Excess fat stores + Drive for increased mobilization in late pregnancy/early lactation

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What can inappetence and anorexia lead to in regards to fatty accumulation?

Fat cow + Feline fatty liver syndromes

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What other diseases are briefly mentioned in the lecture in regards to lipid accumulation in hepatocytes?

High fat diets 
Obesity 
Hepatotoxins 
Hypoxia 
Diabetes mellitus 
Hypothyroidism

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What is the gross color/texture of lipids within the cell?

Pale yellow/friable

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What is the gross color/texture of glycogen?

Pale tan-white/firm

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What disorders are associated with glycogen accumulation in hepatic cells?

Excess glucocorticoids
Diabetes mellitus
Young animals
Glycogen storage disease

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What are two possible reasons given in lecture for excess glucocorticoids?

Iatroogenic + Cushing’s

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What is the histological appearances seen with lipid accumulation in hepatic cells?

Nuclei often pushed periphery

Vacuoles have distinct borders

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What is the histological appearance of glycogen accumulation within hepatocytes?

Nuclei often stay central

Vacuole margins often irregular or indistinct

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Why do you see glycogen accumulation within hepatocytes with diabetes mellitus?

Hyperglycemia pushes glucose into the cell

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What the basic reason lysosomal storage disease?

Lysosomal contents that cannot be released due to lack of enzymes

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What are three basic causes of oxygen deprivation that are given in lecture?

Profound anemia + Vascular obstruction + Cardiac failure

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What occurs in hypoxia leading to ATP production being decreased?

aerobic cell metabolism stops decreased oxidative phosphorylation in mitochondria decreased ATP production

Once ATP production decreases in the cell is the cell done for yet?

What happens once cell starts to lose the ability to use ETC?

Will switch over to anaerobic cell metabolism Intracellular acidosis Protein synthesis machinery falls apart +Ribosomes lost Cell membrane defects + Lysosome rupture Released RNAases + DNAases Digest contents of cells

What are the two types of cell deaths?

Apoptosis + Necrosis

What are the general characteristics of apoptosis?

Cell suicide Cell death via internally programmed series of events Clean

What are the general characteristics of necrosis?

Cell murder Cell death via exogenous irreversible cell injury Messy

What are the two major morphologic features seen in the chromosome during cell death?

Pyknosis + Karyorrhexis

What is pyknosis?

Irreversible condensation of chromatic in nucleus of a cell

What is karyorrhexis?

Fragmentation of nucleus

What are the two types of initiation for apoptosis?

Extrinsic + Intrinsic

How is extrinsic initiation carried out with apoptosis?

Cytokines - fas ligands or TNF-alpha) | Activate cell surface death receptors

How is intrinsic initiation of apoptosis carried out within the cell?

Mitochondrial or DNA damage activate proapototic factors p21 + p53

What are four major events that occur with apoptosis overall?

Caspases activated Cytoskeleton + Nuclear proteins degraded Nuclear chromatin fragments Apoptotic bodies

What are apoptotic bodies? What do they do?

Contain intracellular organelles | Form and present ligands for phagocytic cells to bind to

What is commonly seen histologically with APOPTOSIS?

Cell shrinkage Chromatin condensation Cytoplasmic blebs + Apoptotic bodies Phagocytosis of apoptotic bodies

What are the key morphologic features of necrosis?

``` Increased eosinophilia Glassy appearance Cytoplasmic vacuolation Karyohexis moves to Karyolysis Ghost cells ```

Why do you see increased eosinophila with necrosis?

RNA degradation

Why do you see a glassy appearance in cells with necrosis?

Loos of glycogen

What causes cytoplasmic vacuolation with necrosis?

Cells start to fill with debris as membranes break down and enzymes are released

What are ghost cells?

Pale eosinophilic outlines of residual cell cytoplasm

What are the general steps of necrosis leading to acute inflammation?

Uncontrolled released of antigens Activation of immune system INFLAMMATION

What often follows necrosis/acute inflammation?

Calcification

What cells are triggered when necrotic cell changes occur?

Leukocytes

What do leukocytes do once they have reached the area of necrosis?

Release enzymes from lysosomes | Causing heterolysis --> dissolves the cell

What do nuclei look like that have become pyknotic?

Shrunken + Dark

What do nuclei look like when they have undergone karorrhexis?

Fragmentation

What do nuclei look like once they have undergone karyolysis?

Dissolved

What is the order of the chromosomal degradation in necrosis?

Pyknotic --> Karorrhexis --> Karyolysis

What are the five major types of necrosis?

``` Coagulative Liquefactive Caseous Fat Gangrenous ```

What is the basic description of coagulative necrosis?

Denaturation with dense/rigid texture to dead cells

What is the basic description of liquefactive necrosis?

Complete enzymatic digestion of cells | Normally with marked suppuration

What is suppuration?

Liquid pus

What tissue does necrosis happen as liquefactive?

Brain

What is the basic description of caseous necrosis?

Cheesy coagulation | Usually a granulomatous reaction

What is the basic description of Fat necrosis?

Saponified fat due to FA's mixing with calcium - chalky white appearance

What is gangrenous necrosis?

Necrosis due to ischemia of the distal extremities and GI tract

What type of necrosis is renal papillary necrosis?

Coagulative necrosis

What causes renal papillary necrosis?

Ischemia following NSAID use

How do NSAIDS cause renal papillary necrosis?

Local prostaglandin synthesis normally protects glomeruli and tubules from ischemia Inhibition from NSAID's predisposes the kidneys to renal hypoprefusion

What are the two components of prostaglandin synthesis that are inhibited by NSAID use?

COX-1 + COX-2

What is different about the macrophages within the brain that are active in the necrosis process?

White matter contains abundant lipids therefor the phagocytic macrophages have a vacuolated appearance to them

What disease can cause casaeous necrosis with in the lungs?

Tuberculosis

What is caseous necrosis a combination of?

Coagulative + Liquefactive

What are some histological characteristics of necrotic fat cells?

Have vague cellular outlines Lost peripheral nuclei Cytoplasm has become pink to pale basophilic

What is wet gangrene?

Combination of coagulative necrosis + liquefactive necrosis

What causes the coagulative necrosis in wet gangrene?

Loss of blood supply

What cause the liquefactive necrosis in wet gangrene?

Superimposed infection

What are the two most basic types of cell injury?

Reversible + Irreversible