Cell Injury Flashcards
Concept of the nature of disease
May be thought of as a reaction of a cell or group of cells to an injury
Possible disruptions caused by cell injury
Disruption of chemical processes or direct damage to components of the cell
Eight categories of injury
- Hypoxia
- Chemical
- Physical
- Infectious
- Immunologic
- Genetic
- Nutritional
- Degenerative
What happens to living cells when injured?
They change structure and function.
What happens with prolonged injury?
Clinically apparent as physical signs and symptoms
Describe in words the chart of general categories of cell reactions.
A normal cell in homeostasis undergoes stress and adapts. If there is an inability to adapt or a homeostatic cell undergoes injurious stimulus, it becomes injured. If the injury is mild, it is reversible and can continue to homeostasis. If the injury is severe/progressive, the injury is irreversible and the cell will either die or undergo apoptosis.
Example of early physiologic response to exercise to maintain homeostasis
Tachycardia
Definition of cell adaptation
Process by which cells change in size, number, and appearance in response to changes in the cell environment
What types of changes can occur with cell adaptation?
Either physiologic or pathologic changes may occur
Definition of hyperplasia
Increase in the number of cells
Example of physiologic hyperplasia
Increase in the number of glandular breast tissue during pregnancy
Example of pathologic hyperplasia
Abnormally high levels of estrogen in circulation can cause abnormal proliferation of the endometrium
Definition of hypertrophy
Increase in the size of a cell because of increased cellular substance
Physiologic example of hypertrophy
Muscle fibers become bigger for an athlete who repeatedly lifts weights
Pathologic example of hypertrophy
Patient with systemic hypertension will increase cardiac muscle mass because heart must work harder to overcome vascular resistance (cardiac muscle loses ability to become mitotic)
Definition of atrophy
Decrease in the size of a cell because of loss of cellular substance
Physiologic example of atrophy
Decreased estrogen ultimately results in atrophic uterus; decrease in number and size of myometrium
Pathologic example of atrophy
Muscles will atrophy when leg is placed in a plaster cast for a broke bone
Common example of atrophy
Normal atrophy over time of brain in elderly patients
Definition of metaplasia
Substitution of one type of an adult cell for another type of adult cell
Clinical example of metaplasia
Normal trachea and bronchi are lined by ciliated columnar epithelium, but chronic irritation of the respiratory epithelium by cigarette smoking may cause replacement of columnar cells by stratified squamous cells
Two features of irreversible injury to a cell
Non-repairable mitochondrial dysfunction
Profound membrane dysfunction
What part of the cell is affected first?
Function
Four vulnerable biochemical systems
- Mitochondria
- Cellular calcium
- Integrity of membranes
- Integrity of genetic material
What happens with increased numbers of reactive oxidative species (ROS)?
Damage to lipids, proteins, and DNA
What increases the number of free ROS?
Mitochondrial damage
What two downstream effects are mediated by the increase of calcium entry into the cell?
Increase in mitochondrial permeability and activation of multiple cellular enzymes
What happens with plasma membrane damage?
Loss of cellular components
What happens with damage to the lysosomal membrane?
Enzymatic digestion of cellular components
What happens with protein misfolding or DNA damage?
Activation of pro-apoptotic proteins
Describe what happens with cessation of ATP production (three main processes)
Amount of sodium in the cell increases due to non-functioning Na/K ATPase pumps. Sodium is osmotically active and pulls water into the cell, causing swelling of the cell.
No oxidative respiration can occur, increasing the amount of lactic acid produced. This decreases the pH of the cell and causes chromatin clumping.
Ribosomes detach from the endoplasmic reticulum, decreasing protein synthesis and increasing fat deposition.
What happens with permeability of injured cells, and how can this be of clinical importance?
Membrane permeability is altered and allows for intracellular enzymes to leak from the cell into vascular compartments. These levels can be measured with lab tests to diagnose injury.
Definition of free radical
A free radical is an atom or group of atoms which have a single unpaired electron in the outer orbit. They are chemically unstable and very reactive with components of the cell
Why is free radical damage so concerning?
Free radical damage causes a chain reaction; when the free radicals combine with other molecules, they create more free radicals
Common free radical in the past
Carbon tetrachloride (CCl4)
What happened with CCl4?
It was converted to CCl3 in hepatocytes, which oversteps the ability of the superoxide dysmutase to combat the ROS of CCl3, causing cell death in the liver.
What organelles/processes are affected by CCl3?
ER membranes, protein synthesis, lipid export, mitochondria, and plasma membranes
Explain reperfusion injury.
Cells start to get reperfused and “wake up,” causing more free radical production, as well as infiltration of white blood cells that also release free radicals as a “protective” mechanism.
Morphology of reversible cell injury (5)
- Cellular swelling
- Steatosis
- Myelin figures
- Endoplasmic reticulum swelling
- Membrane blebs
What are myelin figures?
Little clumps of protein and lipid that form in the cytoplasm
What is eosinophilia?
Manifestation of cellular injury; cells appear more red on slides.
What causes eosinophilia?
Less uptake of blue dye because the ER is not functioning, so more pink dye is taken up by the cytoplasm
What characterizes necrosis?
Presence of leukocytes infiltrating dead tissue from adjacent living tissue
What causes morphologic changes in cells after necrosis?
Enzymatic breakdown of cell and denaturation of proteins
Common descriptive terms used for the histological patterns of necrosis
- Coagulation necrosis
- Liquifactive necrosis
- Caseous necrosis
- Enzymatic fat necrosis
- Gangrene
Describe coagulation necrosis.
Pattern of necrosis associated with severe ischemia, usually in solid organs like the heart and kidney
Histological pattern of coagulation necrosis
Ghost-like remnants of intact cells which lack nuclei; cell outline is preserved and cytoplasm stains intense pink.
Macroscopic description of coagulation necrosis
Firm tissue in early stages
Examples of coagulation necrosis
Myocardial infarct, renal infarct
Three classic histologic signs of coagulation necrosis
- No nuclei
- No cellular components
- More red
Describe liquefactive necrosis
Pattern of necrosis often associated with bacterial infections
Microscopic observations of liquefactive necrosis
Bacteria release enzymes causing a rapid loss of cellular structure and a collection of liquid, amorphous debris. Ring of neutrophils surrounds the necrotic tissue
Macroscopic observations of liquefactive necrosis
Creamy yellow material usually housed in an ABSCESS
What type of histological pattern of necrosis is exhibited by the brain?
Liquefactive necrosis ONLY
Describe caseous necrosis
Associated with an inflammatory reaction called a “granuloma.”
Histological description of caseous necrosis
Amorphous granular debris in the center of granulomatous cell reaction
Macroscopic description of caseous necrosis
Soft, white, friable; looks like cheese curds
Describe enzymatic fat necrosis
Cell death in the pancreas and adjacent fat
How does enzymatic fat necrosis occur?
Damage to the pancreas causes release of the pancreatic enzymes that then start breaking down peripancreatic fat
What also happens when pancreatic enzymes are released into the abdomen?
Large amount of calcium released by dead cells, which causes calcium soap formation when calcium combines with fat
Describe gangrene
Clinical term that represents ischemic necrosis in the extremity, bowel, or gallbladder
Describe wet gangrene
Bacteria contaminates dying tissue and superimposes liquifactive necrosis
Describe apoptosis
Regulated pattern of cell death characterized by nuclear condensation and fragmentation coupled with fragmentation of cytoplasm into “apoptotic bodies”
Is there an inflammatory reaction with apoptosis
No
What happens to the cells that underwent apoptosis?
Recognized and removed by phagocytes
Ischemic injury to the central nervous system from right internal carotid arterial occlusion suffered by a 72 year old man will result in what pattern of necrosis?
Liquefactive
Which are the major mechanisms which result in membrane damage typical for a reperfusion injury following myocardial ischemia in a 68 year old woman?
Reactive oxygen species
An endocervical biopsy in a 23 year old woman demonstrates the presence of squamous epithelium (not columnar epithelium). What process has occurred?
Metatrophic changes
