Cell and Tissue Injury (R. Low) Flashcards
What is the source of all human disease?
Some form of cell and tissue injury.
What does “injury” mean in a pathological sense?
Non-lethal, physical damage or alteration from normal of one or more components of the structure of the cell.
What does an injury do to a cell?
Perturbs normal physiology.
Contrast acute and chronic injury
acute - producing effects in cells within seconds or minutes
chronic - cell stress and damage that can persist days, months, or even years.
What type of immune response cells accompany acute injury?
PMN
What type of immune response cells accompany chronic injury?
lymphocytes and macrophages
What cell type is most commonly injured?
Epithelium
What are the four basic tissue types?
epithelium (surface/internal)
muscle (cardiac, smooth, skeletal)
nerve (CNS, PNS)
connective (bone, joint, fat, blood, bone marrow, lymph glands, etc.)
How many different cell types are in the body?
> 200
Why is epithelium so commonly injured?
Tissue that first encounters injurious agents and stimuli from the environment.
What is the major killer of adults?
Atherosclerosis - injury to the epithelial cells that line arteries.
Where do adult cancers reside?
> 90% in epithelia
Name some non-epithelial diseases
arthritis
leukemia/lymphoma
AIDS
lupus
Related effect of damage to a tissue?
Affects other adjacent tissue types (i.e., helicobacter pylori infection leads to damage of underlying connective tissue)
What is the natural result of cell/tissue injury?
morphologic change
What are morphologic changes?
characteristic change in the appearance of the affected tissue that can be seen “grossly” or microscopically
What is a post-mitotic cell, and where would you find them?
Cells that no longer divide, as in skeletal muscle, cardiac muscle, and nerve tissue.
What are the commonly seen changes in injured cells?
1) Cell membranes - membrane breakage, inactivation of ion pumps
2) Mitochondria - swelling due to accumulation of H2O in the matrix compartment
3) Endoplasmic Reticulum - distended cisternae, detached polyribosomes fom RER -> decreased protein production
4) Nucleus - some effect on synthesis of rRNA -> decreased protein production
Name some reversible cellular injuries
If the injurious stimulus is removed, cell, mitochondrial, and ER swelling and dysfunction are potentially reversible
Once membranes and ion exchange pumps are restored, intracellular ion concentrations normalize
How do cells and tissues adapt to injury?
1) Hypertrophy - increase in size of cell secondary to increase in cell function, typically from increased in number of mitochondria and ER
2) Atrophy - decrease in size and functional capacity, as in shrinkage of skeletal muscle after motor neuron loss due to poliovirus
3) Metaplasia - Replace one tissue type with another, as in stratified squamous epithlium in distal esophagus morphing into columnar type
4) Hyperplasia - increase in number of cells, as in increased number of adrenal cortical cells secondary to a tumor
What happens to cell/tissue that does not adapt to injury?
It dies either by necrosis or apoptosis
Describe classic cell necrosis
Usually seen following ischemia, also called ischemic or coagulative necrosis. Large portions of tissue with thousands of contiguous cells die all at once. ATP synthesis shuts down, lysosomal hydrolases are released, Ca++ leaks across cell membrane and releases from storage in ER and mitochondria. DNA degenerates.
What is ischemia?
hypoxic injury caused by a problem with the vascular blood flow to the tissue
Apoptosis v ischemic necrosis?
Apoptosis is programmed cell death, affects scattered individual cells. Apoptosis is highly regulated, involves signalling pathways that activate caspases (proteases).
Dead cell appearance?
Apoptotic - shrunken, nuclear DNA compact and uniformly dense
Ischemic - swollen
Coagulative, liquefactive, caseous, and fat necrosis
Coagulative - dead cell remains a ghost-like remnant of its former self. Nucleus shrinks and chromatin clumps
Liquefactive - dead cell dissolves away as lysosomal hydrolases digest cellular components (brain and spleen)
Caseous - seen on in TB, central portion of infected lymph node is necrotic with a chalky white appearance
Fat - necrotic adipose tissue, fats hydrolyzed into free fatty acids that precipitate with Ca++, looks chalky gray
Name 7 causes of cell/tissue injury
Physical agents, chemical and drug, infection, immunologic insults, genetic derangement, nutritional imbalance, hypoxia
Describe hypoxia
Insufficient oxygen in tissue, leads to ischemic injury, single most important type of injury seen in clinical medicine.
How do different cell types respond to hypoxia
Varying lengths of time tolerance:
Neurons 3-5 minutes, fat and skeletal muscle cells many hours
Irreversible changes due to hypoxia?
1) activation of lysosomal enzymes
2) DNA, protein degradation
3) Increased Ca++ influx
Reversible changes due to hypoxia?
1) Decrased ATP
2) cellular swelling from decreased Na pumping
3) Increased glycolysis -> decreased pH (lactic acid)
4) Decreased protein synthesis
Adverse effect of oxygen therapy?
Production of oxygen radicals, especially damaging to lungs
Adverse effect of reperfusion?
In hypoxia, xanthine dehydrogenase proteolytically converted to xanthine oxidase. When hypoxia corrected, xanthine oxidase produces activated oxygen species.
Acute inflammation adverse effect?
PMNs have enzyes such as myeloperoxidase that produce oxygen radicals. PMNs infiltrate hypoxic tissues
Superoxide?
O2 goes to O2- (extra unpaired e-) via oxidase
How is O2- removed?
Superoxide Dismutase (SOD) 2O2- + 2H+ -> H202 + O2-
What happens to H2O2 (hydrogen peroxide)?
Can break down to hydroxyl radical
Name a couple antioxidants
uric acid, vitamin E
Extreme ranges of human temperature to avoid injury?
30-42C
Burn morbidity and mortality depend on:
total surface area affected
depth of burn injury (dermis, epidermis)
thermal injury to lungs
effective treatment
Four complications of serious burns
1) neurogenic shock and fluid loss
2) infetion
3) hypermetabolic state
4) anemia - suppression of bone marrow production
