Cellular adaptation, injury, death (part 1) Flashcards
What are 6 causes of cellular injury?
- Hypoxia/most common
- Reperfusion injury/free radical
- Chemical injury
- Physical (intentional or accidental)
- Infection
6.Immunologic, inflammatory
Injured cells can reverse damage (potentially), die or adapt (cell is changed/injured due to chronic stress). List 5 ways cells can adapt
- Atrophy
- Hypertrophy
- Hyperplasia
- Metaplasia
- Dysplasia
What will cause a cell to undergo atrophy? Give example
Atrophy: cell decreases in size and function. Due to decreased O2, malnutrition or lack of use. Ex: paralysis of a limb will lead muscle atrophy
Difference between hypertrophy vs hyperplasia?
Hypertrophy: cells increase in SIZE, function. Can be physiologic (uterus enlarges in pregnancy) or a result of increased demand (enlarged heart due to high BP, OR body builders intentionally building muscle mass)
Hyperplasia: Increased in cell NUMBER within an organ or tissue. Many causes, including injury (liver regeneration after partial lobectomy), hormone (breast feeding), recovery from skin loss (dermal layer regeneration) or increased elevation (more red blood cells)
Difference between metaplasia vs dysplasia?
Metaplasia: replacement of one type of cell by another. Occurs in response to irritation. Represents survival mechanism to withstand changed conditions. Ex: smokers lung cells change from columnar to squamous, making less mucous. Also healing bone fracture initially has a callous before cartilage
Dysplasia: cells change size, shape, organization. Usually precursor to cancer but can also be bone. Hip dysplasia occurs when hip socket or femur’s trochanter head are poorly shaped
Explain ischemia injury (not on study guide but leads to reperfusion injury))
- ischemia leads to decreased O2, glucose, nutrients to cell/tissue . This leads to increased cell membrane permeability/”leaky”
- Cell tries to maintain membrane, using glycogen in anaerobic metabolism since it doesn’t have enough O2 for aerobic.
- Glycogen breaks down to ATP and lactic acid. Eventually makes tissue pH decrease/more acidic
- Leads to feedback loop, more acid limits ATP production
What is the most common cause of cellular injury? Why does this occur?
Hypoxia/decreased oxygen. Can be a result of
1 decreased O2 available (ex: drowning)
2 loss of hemoglobin, so unable to transport O2 to cells (blood loss).
3) decreased production of RBC (which carry hemoglobin, think of anemia)
4) cardio-respiratory condition (emphysema, pneumonia)
5) poisoning of oxidative enzymes in cell (cytochromes/protein in cells that carry heme)
6) ischemia (reduced or restricted blood flow, like a stroke).
7) Ischemia-reperfusion injury (tissue damage that occurs when blood suddenly returns to ischemic area)
Define reperfusion injury
Damage that occurs when blood supply returns after ischemia. Triggers activation of inflammatory response and release of cytokines causing further cell/tissue damage
Pathophysiology of reperfusion injury?
1.Oxygenated blood enters tissue after ischemia
2. Increased O2 leads to pathways using the enzyme Xanthine oxidase that will increase production of ROS (reactive oxygen species AKA free radicals)
3. Xanthine oxidase sticks to membrane lipids and nucleic acid, causing damage
4. Damaged membranes leads to inflammation response (influx of leukocytes, macrophages)
5. Overwhelming inflammatory response results in local cell death
What is a “free radical”, also known as reactive oxygen species (ROS)?
They are unstable molecules. Have an odd # of electrons instead of even. Will steal electrons from other molecules, causing damage to other cells, can go as far as DNA level. Can be inactivated (“paired”) with antioxidants, limiting damage
CELL INJURY. Give example of direct, indirect injuries
Direct: think heavy metals like lead (from contaminated water, old paint), mecury (old thermometers). Also, alcohol
Indirect: paint fumes, drug metabolites (too much Tylenol for liver to handle)
CELL INJURY. Give examples of physical intentional and unintentional injuries
Intentional: planned radiation therapy, sunbathing, tattoo
Unintentional: trauma including abrasions, fracture, contusions, punctures. Asphyxia including hanging, strangulation
CELL INJURY. Give example of infectious injuries
Bacterial: survival dependent on ability to grow/multiple and avoid detection (Pneumococcus has a saccharaide covering)
Virus: dependent on host, can be DNA driven (like herpes) or RNA driven (HIV)
CELL INJURY. Give example of immunologic/
inflammatory injury
Inflammatory: allergic response, an exaggerated immune response to a harmless stimuli (pollen, foods)
Immunologic: Disturbance in B and T cells, causing immune system to mistakenly attack/destroy healthy cells
What is necrosis/nectrotic tissue?
necrosis: final end point of cell changes after death, including autodigestion. Exposes nearby cells to damaging substances, could lead to extending necrotic area. Multiple causes: virus, bacteria, cancer. Common in diabetic wounds
Name the 3 steps in cell death
- pyknosis: clumping of nucleus (chromatin condense)
- karyorrhexis: nucleus fragments
- karyolysis (nucleus shutdown, cell membrane rupture)
Define apoptosis
Programmed cell death.Orderly
Difference between apoptosis vs necrosis?
Apoptosis is planned cell death. Does not involve inflammation
Necrosis is usually accidental/not planned, releases inflammatory contents
Explain process of hypoxic cellular injury
Hypoxic injury could come from decreased O2, decreased hemoglobin for O2 transport and/or decreased blood flow delivery (ischemia, like a blood clot)
1. As O2 falls, cell shifts from aerobic to anearobic metabolism. Leads to less ATP as well as lactic acid build-up. Cell membrane becomes leaky/more permeable
2. With decreased ATP, cell cannot repair membrane. Sodium/potassium pump begins to fail. K+ leaks out, NA+ leaks in. (HINT: where sodium goes, water will follow) Now water moving into cell along with NA+, causes swelling
3. Eventually calcium enters cell in an effort to restore electron balance (as cell falls, is becoming more (-) charged inside, attracting calcium). calcium = CA++
4. With membrane disruption, inflammatory response activated. ROS is generated from inflammation
5. Damage enters as far as mitochondria, results in cell death
