Cellular Pathology Flashcards by Holly Grey

What are the causes of cell damage?

Hypoxia
Ischaemia 
Chemical exposures
Physical damage
Microbiological infections
Immune reactions
Genetic + inborn genetic errors
Nutritional deficiencies
Ageing

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Why do cells have to adapt to stress exposure?

Maintain steady physiological + functional state

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How do cells adapt?

Increase cell activity
Decrease activity
Alter morphology

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What are the biochemical cell injuries?

Loss of energy (ATP/O2 depletion)
Mitochondrial damage
Loss of Ca2+ homeostasis
Defects in membrane permeability
Generation of reactive O2 species + free radicals

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What are the two types of cell injury?

Reperfusion

Chemical

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What happens if free radicals not neutralised?

Can damage cells

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How many mechanisms do free radicals damage cells by?

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What is the 1st free radical damage mechanism?

Lipid peroxidation of membranes

Double bonds in poly unsaturated membrane lipids vulnerable to O2 FR

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What is the 2nd free radical damage mechanism?

DNA fragmentation

FR react with thymine in nuclear + mitochondrial DNA = single strand breaks

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What is the 3rd free radical damage mechanism?

Protein cross-linking

FR promote protein cross-linking = increased degradation + loss of activity

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What is the mechanism for reperfusion injury?

Restoration of flow may expose compromised cells to high [Ca2+]
Reperfusion increase FR production
From compromised mitochondria + inflammatory cells

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What is hypertrophy?

Increase in size of organs + cells due to protein accretion

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What is hypertrophy in response to?

Increased work load/hormone stimulation

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In hypertrophy what happens to permanently differentiated cells?

They cannot resume the cell cycle to increase number = get bigger

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What is hyperplasia?

Increase cell number + organ size

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What is hyperplasia in response to?

Hormone stimulation/damage

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In hyperplasia what happens to cells?

Stem cells resume cell cycle to increase number

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What is dysplasia?

Change in cellular organisation, size + organ architecture

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What is dysplasia in response to?

Irritation + damage

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What is metaplasia?

Substitution of one cell type for another within an organ

Indigenous cells are replaced by cells better suited to abnormal environment

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What is metaplasia in response to?

Different conc or assortment of growth factors

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What is atrophy (hypoplasia)?

Decrease in cell size + number

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What is atrophy in response to?

Decreased work loads, hormonal/neuronal stimulation, blood supply, nutrition or aging in adults or during development

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What are the type of cellular damage?

Sub-lethal cellular injury
Lethal cellular injury
Necrosis
Programmed cell death

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What is sub-lethal cellular injury?

Blebbing of membrane | Alteration in protein synthesis/organelle genesis

What are examples of sub-lethal cellular injury?

Hydropic degeneration | Fatty change

What is lethal cellular injury?

Several damage to stimuli Prolonged sub-lethal damage Leads to cell death

What is necrosis?

Cell death by injury Mechanical damage Exposure to toxic chemicals

What is programmed cell death?

Cell death by suicide | Internal/external cellular signals

Describe the process of necrosis

``` Cells receive chemical or structural insult Swell up Activation of lysosomal enzymes Enzymatic digestion of cells invasion of phagocytes + inflammation Tissue damage Passive cell death ```

Describe coagulative necrosis

Dead tissue = pale + firm | Architecture + tissue outline preserved

Where does coagulative necrosis occur?

Cells with few lysosomes

What does coagulative necrosis do?

Damages enzymes = blocks proteolysis

What are the causes of coagulative necrosis?

Occlusion of arterial blood supply (kidney + heart) | Proteins released from dead cells aid diagnosis

Describe liquefactive necrosis

Dead tissue = semi-solid | Dissolution of tissue: hydrolytic enzymes

What are the causes of liquefactive necrosis?

Bacterial/fungal infections | Ischaemia in CNS

What is the liquefactive necrosis pattern?

Cerebral infarction Neurons have high lysosomal content Lack extracellular structural proteins - eg. collagen

Describe enzymatic fat necrosis

Escape of lipases | Damages fat = soft, chalky white areas

What is an example of enzymatic fat necrosis?

Acute pancreatitis Vague cellular outline Lost peripheral nuclei Cytoplasm pink amorphous mass

Describe caseous necrosis

Bacterial liquefaction Coagulative + liquefactive necrosis Caused by tuberculosis

What are the signs of caseous necrosis?

Confluent cheesy tan granulomas | Extensive tissue destruction = cavitation

Describe gangrenous necrosis

Necrosis grossly advanced + visible

What are examples of gangrenous necrosis?

Dry gangrene | Wet gangrene

What is dry gangrene?

Mostly coagulated | Site dried up before bacteria could over grow

What is wet gangrene?

Mostly liquefactive | Foul-smelling oozing foot infection

What are the two types of programmed cell death?

Autophagic cell death | Apoptosis

What is autophagic cell death?

Cytoplasm actively destroyed long before nuclear changes appear

What is apoptosis?

Chromatin marginates + cell and nucleus fragment before morphological changes are seen

What are examples of apoptosis?

Embryonic development Cell turnover in adult tissues T-cell clonal deletion

Since apoptosis is active cell death what does it require?

Energy RNA Protein synthesis

Describe the process of apoptosis

Cell shrinks + chromatin condenses Cell blebs + chromatin condenses Cell fragments into apoptotic bodies Apoptotic bodies phagocytosed by neighbouring cells

Why does apoptosis happen?

Withdrawal of positive (growth) signals Receipt of negative (death signals) Interference in cell death pathway mechanism Failure to replicate

What are the negative (death) signals?

Increased oxidants DNA damage Death activators = TNF alpha

What are the 2 pathways that initiate apoptosis?

Intrinsic/mitochondrial apoptosis = regulated by mitochondria Extrinsic apoptosis = activated by ligation of death receptors

What happens to DNA involved in apoptosis?

Internucleosomal cleavage

What happens to DNA involved in necrosis?

Random degradation

What happens in the nucleus in apoptosis?

Chromosome margination

What happens in the nucleus in necrosis?

Pyknosis

What happens to membrane integrity in apoptosis?

Persists till late

What happens to membrane integrity in necrosis?

Compromised early

What happens to mitochondria in apoptosis?

Appears normal

What happens to mitochondria in necrosis?

Appears swollen

Is there inflammation in apoptosis?

Is there inflammation in necrosis?

YES

What is the pattern of apoptosis?

Individual cells

What is the pattern of necrosis?

Multiple cells

What happens to cell volume in apoptosis?

Decreases

What happens to cell volume in necrosis?

Increases

Is there cell fragmentation in apoptosis?

YES (apoptotic bodies)

Is there cell fragmentation in necrosis?

NO (cell lysis)

Where does nephrotoxicity of antibiotic Gentamicin occur?

Proximal tubule cells in kidney | Drug accumulates in cells

What does accumulation of Gentamicin cause?

Phospholipid dialysis | = releases degrative enzymes

What does Gentamicin act on?

Mitochondria = activates apoptosis

Is Gentamicin OK in low doses?

YES

Cellular Pathology Flashcards

(74 cards)