Ch1: Cellular Responses to Stress and Toxic Insults Flashcards
What is pathology?
Study of structural, biochemical, and functional changes in cells, tissues, and organs that underlie disease
What does pathology bridge?
Basic science and clinical medicine
Two categories of pathology?
General
Systemic
4 aspects of a disease
- Cause
- Pathogenesis (how it developed)
- Molecular and morphologic changes
- Clinical manifestations
If physiological stimuli are altered what happens?
Cell adapts
If cell has increased demand and increased stimulation, what can happen? (2)
Hyperplasia
Hypertrophy
If there is decreased nutrients and decreased stimulation, what happens?
Atrophy
Chronic irritation results in what?
Metaplasia
3 ways a cell can be injured?
- Reduce O2 supply
- Chemical injury
- Microbial infection
Type of injury if stimulus is acute and transient?
Reversible
Type of injury is stimulus is progressive and severe?
Irreversible –> Cell death
Cumulative sublethal injury over long time results in what?
Cellular aging
What is an adaptation?
Reversible functional AND structural response to physiologic and pathologic stresses
Cellular injury occurs if what happens?
- Limit of adaptations reached
- Injurious agents
- Nutrition deprivation
- Bad mutations
Is cell injury reversible?
Yes up to a certain point
Two types of cell death?
Necrosis
Apoptosis
When is cell death normal? 3
- Embryogenesis
- Development of organs
- Maintenance of homeostasis
Draw the chart for what is necessary for a normal cell to go through injury.
-
Besides death, how else can the cell respond to injurious stimuli? 3
- Intracellular accumulations
- Pathologic calcification
- Aging
When are intracellular accumulations common?
Metabolic derangements in cells and sublethal/chronic injury
What is hypertrophy?
Increase in size of cells
What does hypertrophy result in?
Increase in size of organ
Increased size in hypertrophy is due to what?
Synthesis of more structural components of cells
How is hypertrophy caused? 3)
- Increased functional demand/workload
- Stimulation of hormones and growth factors
- Vasoactive agents
The most common stimulus for hypertrophy of muscle is what?
Increased workload
When you lift weights, do you undergo hypertrophy or hyperplasia?
Hypertrophy
Hypertrophy is the heart is due to what?
Chronic hemodynamic overload from hypertension or faulty valves.
An example of hormones causing hypertrophy is where?
Gravid Uterus by estrogen hormones
Examples of hypertrophic growth factors? (3)
TFG-beta
IGF-1
Fibroblast growth factor
Example of vasoactive hypertrophic agents? 3
alpha-adrenergic agonists
endothelin-1
angiotensin II
Which two causes of hypertrophy are more important for pathologic states?
Agonists and growth factors
What is an example of a fetal/neonatal contractile protein taking over the adult form and causing hypertrophy?
Atrial-natriuretic factor
Where is ANF expressed?
When it’s high abnormally what does it cause?
Atrium and ventricle of embryonic heart
Cardiac hypertrophy
What is an example of subcellular organelles undergoing hypertrophy?
Smooth ER in hepatocytes hypertrophy due to alcohol and drugs such as barbituates
Hyperplasia is an increase in what?
Number of cells thus increasing the mass of organ or tissue
Two categories of physiologic hyperplasia?
Hormonal
Compensatory
Hormonal hyperplasia is seen where?
Female breast at puberty and pregnancy
Compensatory hyperplasia is seen when? (3)
- Increase tissue mass after damage
- Wound healing
- repair of liver
Pathologic hyperplasia is due to what?
Excess of hormones or GF’s
Two examples of pathologic hyperplasia?
- Warts (HPV)
2. Endometrial hyperplasia (BPH)
Hyperplasia results from what? (2)
- Growth factor driven proliferation of mature cells
2. Increased output of new cells from tissue stem cells
What is atrophy?
Reduced size of an organ or tissue resulting from a decrease in cell size and number
Two causes of physiologic atrophy?
- Atrophy of embryonic structures during normal development
2. Uterus decrease in size after parturition
6 causes of pathologic atrophy?
- Decreased workload (atrophy of disuse)
- Loss of innervation (denervation atrophy)
- Ischemia
- Inadequate nutrition
- Loss of endocrine stimulation
- Pressure
The specific change that occurs in atrophy? (2)
- Decreased protein synthesis in cells
2. Increased protein degradation in cells
Degradation of cellular proteins mainly through what pathway?
Ubiquitin-proteasome pathway
Nutrient deficiency and disuse activate what enzymes?
What do these do?
For what purpose?
Ubiquitin lipases
Attach ubiquitin to proteins
Once combined, these are targeted for degradation
What might the Ub-Pro pathway contribute to in cancer?
Cancer cachexia which is increased erosion of host body cell mass in response to a malignant growth
What is autophagy?
Process in which starved cell eats its own components in an attempt to find nutrients and survive
What is metaplasia?
Reversible change in which one differentiated cell type is replaced by another cell type
3 types of metaplasia
Which is most common?
- Columnar to squamous (most common)
- Squamous to columnar
- CT metaplasia
Where is columnar to squamous metaplasia seen? (2)
- Respiratory tract with Vitamin A deficiency or smoking
2. Stones in excretory ducts of salivary glands, pancreas, of bile ducts
Why does columnar to squamous metaplasia occur?
Sqamous epithelium can survive tougher conditions than fragile columnar epithelium can
What cells change in metaplasia, the actual cells or stem cells?
Stem cells
Where is squamous to columnar metaplasia seen?
Barrett esophagus which can lead to adenocarcinoma
What is the hallmark sign of barrett esophagus metaplasia?
Goblet cells
What is CT metaplasia?
Formation of cartilage, bone or adipose tissue in tissues that don’t normally have these
What is bone formation in muscle called?
Myositis ossificans
What is CT metaplasia more likely the result of?
Cell or tissue injury
Signals that cause stem cells to become metaplasic? 3
Cytokines, GF’s, and ECM environments
3 reversible causes of cell injury?
- Decreased oxidative phosphorylation
- Cellular swelling
- Alterations in intracellular organelles
What are usually the two components of necrosis?
- Damage to membranes allows lysosomal enzymes to enter cytoplasm and digest cell with cellular constituents leaking out.
- Severe mitochondrial damage with depletion of ATP
What cell type is involved in Necrosis?
Neutrophils
What is apoptosis?
DNA or protein damaged beyond repair
What is involved in apoptosis? (3)
- Nuclear dissolution
- Fragmentation of cells with complete loss of membrane integrity
- Rapid removal of cellular debris
Causes of cell injury and death? (7)
- oxygen deprivation
- physical agents
- chemical agents
- Infectious agents
- Immune reaction
- Genetic derangements
- Nutritional imbalances
What is hypoxia?
Deficiency of oxygen?
Hypoxia results in what?
Cell injury by reducing aerobic oxidative respiration
Hypoxia is seen in what instances? (5)
- ischemia
- Cardiorespiratory failure
- anemia
- CO poisoning
- Severe blood loss
Physical agents capable of cell injury and death? (5)
- Mechanical trauma
- Extreme temperatures
- pressure changes
- Radiation
- Electric shock
Examples of chemical agents whose appearance will cause problems? 3
- Arsenic
- Cyanide
- Mercuric salts
- pollutants
- insecticides
- herbicides
- CO
- Asbestos
Example of chemical agents whose high concentrations will cause problems? (3)
- Glucose
- Salt
- Therapeutic drugs
Infectious agents that cause cell injury and death include? (5)
- prions
- viruses
- bacteria
- fungi
- parasites
2 immune reactions that will cause cell injury and death?
- Autoimmunity
2. hypersensitivity reactions
What is down syndrome’s genetic problem?
Trisomy 21
Consequences of down syndrome? (3)
- mental retardation
- congenital heart defects
- Increased risk of acute leukemia
What is sickle cell anemia’s genetic problem?
Single amino acid substition
What are some enzymatic deficiencies that can cause cell injury/death
- Phenylketonuria
- SCID
- Tay-sachs
What are 4 nutritional imbalances that will cause cell injury and death?
- Kwashiorkor
- Marasmus
- Vitamin deficiency
- Obestiy
What is Kwashiorkor?
Protein malnourishment
What is Marasmus?
Total calorie malnourishment
What is B12 vitamin deficiency called?
One prominent symptom?
Pernicious anemia
Peripheral neuropathy
Will folate fix B12 anemia?
No.
What is a vitamin C deficiency called?
Scurvy
Main consequence of Vitamin C deficiency?
Bad collagen
Obesity can result in what disease?
Type II diabetes mellitus
How long can it take to see gross changes between the stressor and the morphological reaction to stress?
Hours or days
So all in all, what are 9 reversible cell injuries?
- Depletion of ATP
- Swelling of cell and organelles
- Blebbing of PM
- Detachment of ribosomes from ER
- Clumping of chromosomes
- Loss of PM integrity
- Defects in protein synthesis
- Cytoskeletal defects
- DNA damage
What causes cell to pass through point of no return from reversible injury to irreversible?
Persistent or excessive injury
Two main things you can see under LM of reversible injury?
- Cellular swelling
2. Fatty change
When does cell swelling occur?
When cells are incapable of maintaining ionic and fluid homeostasis
What is fatty change in reversible cell injury?
Appearance of lipid vacuoles in cytoplasm
What are ultrastructural changes in reversible cell injury?
- Plasma membrane alterations (blebbing, blunting, loss of microvilli)
- Mitochondrial changes
- Dilation of ER
- Nuclear alterations
Compare necrosis and apoptosis in terms of cell size?
Necrosis: Enlarged (swelling)
Apoptosis: Reduced (shrinkage)
Compare necrosis and apoptosis in terms of nucleus?
Necrosis: Pynknosis –> Karyorrhexis –> Karyolysis
Apoptosis: Fragmentation into small fragments
Compare necrosis and apoptosis in terms of PM
Necrosis: Disrupted
Apoptosis: Intact; altered structure
Compare necrosis and apoptosis in terms of cellular contents?
Necrosis: Enzymatic digestion and may leak
Apoptosis: Intact: may be released in apoptotic bodies
Compare necrosis and apoptosis in terms of adjacent inflammation?
Necrosis: Frequent
Apoptosis: None
Compare necrosis and apoptosis in terms of physiologic or pathologic role?
Necrosis: Pathologic (result of injury)
Apoptosis: Physiologic usually (unwanted cells)
The morphologic appearance of necrosis is what?
Denaturation of intracellular proteins and enzymatic digestion of lethally injured cells
How long does it take for myocardial necrosis to become apparent?
4-12 hours
What color are cells in necrosis?
Eosinophilic (Red)
What are the three nuclear changes in necrosis?
- Karylysis
- Pyknosis
- Karyorrhexis
What is karyolysis
Basophilia of chromatin fades
What is pyknosis?
Nuclear shrinkage and increased basophilia
What is karyorrhexis?
Pyknotic nucleus undergoes fragmentation
What is coagulative necrosis?
Localized area in which dead cells have preserved architecture
What may cause coagulative necrosis?
Vessel obstruction causing ischemia
What type of necrosis is the wedge shaped infarct in kidneys?
Coagulative
What is liquefactive necrosis?
Where is it seen the most?
Digestion of dead cells resulting in a liquid viscous mass.
Brain
Liquefactive necrosis is the feature of what?
- infections
2. hypoxic death of cells in CNS
What is gangrenous necrosis?
When blood supply is lost resulting in coagulative necrosis across multiple tissue planes
When bacterial infection combines with gangrenous necrosis what develops?
Wet gangrene (more liquefactive)