Cellular Pathology Flashcards
What are the causes of cell damage?
Hypoxia Ischaemia Chemical exposures Physical damage Microbiological infections Immune reactions Genetic + inborn genetic errors Nutritional deficiencies Ageing
Why do cells have to adapt to stress exposure?
Maintain steady physiological + functional state
How do cells adapt?
Increase cell activity
Decrease activity
Alter morphology
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
What are the two types of cell injury?
Reperfusion
Chemical
What happens if free radicals not neutralised?
Can damage cells
How many mechanisms do free radicals damage cells by?
3
What is the 1st free radical damage mechanism?
Lipid peroxidation of membranes
Double bonds in poly unsaturated membrane lipids vulnerable to O2 FR
What is the 2nd free radical damage mechanism?
DNA fragmentation
FR react with thymine in nuclear + mitochondrial DNA = single strand breaks
What is the 3rd free radical damage mechanism?
Protein cross-linking
FR promote protein cross-linking = increased degradation + loss of activity
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
What is hypertrophy?
Increase in size of organs + cells due to protein accretion
What is hypertrophy in response to?
Increased work load/hormone stimulation
In hypertrophy what happens to permanently differentiated cells?
They cannot resume the cell cycle to increase number = get bigger
What is hyperplasia?
Increase cell number + organ size
What is hyperplasia in response to?
Hormone stimulation/damage
In hyperplasia what happens to cells?
Stem cells resume cell cycle to increase number
What is dysplasia?
Change in cellular organisation, size + organ architecture
What is dysplasia in response to?
Irritation + damage
What is metaplasia?
Substitution of one cell type for another within an organ
Indigenous cells are replaced by cells better suited to abnormal environment
What is metaplasia in response to?
Different conc or assortment of growth factors
What is atrophy (hypoplasia)?
Decrease in cell size + number
What is atrophy in response to?
Decreased work loads, hormonal/neuronal stimulation, blood supply, nutrition or aging in adults or during development
What are the type of cellular damage?
Sub-lethal cellular injury
Lethal cellular injury
Necrosis
Programmed cell death
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?
NO
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
