Chp. 1 Cellular Injury Flashcards
When does cellular injury occur? What tissue is particularly susceptible to ischemic injury? What tissue is not? What is the difference btwn slow developing ischemia vs acute ischemia?`
Cellular injury occurs when the stress is too strong and the cell can’t adapt.
Neurons highly susceptible to ischemia, (only last for 3-5 mins which is why stroke pts need care rt away) vs skeletal muscle which can withstand it for much longer.
Slow developing ischemia (i.e. arterial atherosclerosis) leads to ATROPHY where acute ischemia (embolus) leads to INJURY
What are common causes of cell injury?
Inflammation, nutritional excess or deficiency, hypoxia, trauma, genetic mutations, etc
What is hypoxia and how does it cause cellular injury?
Hypoxia is low O2 delivery to tissues. O2 is the final e- acceptor in OxPhos which creates ATP. W/o O2, little to no ATP made which means the cell lost its power.
What are the causes of hypoxia?
Ischemia, hypoxemia, decreased O2 carrying capacity of blood
Describe Ischemia and what are the three ways it can happen.
Ischemia is decreased blood flow through an organ.
- Atherosclerosis which causes decreased ARTERIAL BLOOD FLOW
- Decreased venous drainage. ex. Budd Chiari Syndrome
- Shock where there is a systemic HYPOTENSION so organs aren’t getting perfused.
What is Budd Chiari syndrome, and what type of injury does it create?
Budd Chiari is the occlusion of hepatic veins that arises with the triad of symptoms: ABD PAIN, ASCITES, HEPATOMEGALY. #1 cause is polycythemia vera, also Lupus. It’s basically due to a hyper coagulable state.
What are the 5 types of shock?
Cardiogenic, Neurogenic, Septic, Hypovolemic, Anaphylactic
What is hypoxemia and what are the 4 ways it can happen?
Hypoxemia is a low PARTIAL PRESSURE of O2 in the blood. It arises with:
High Altitude: lower Barometric P leads to Lower PAO2 (in alveoli)
Hypoventilation: Increased PACO2 leads to decreased PAO2
Diffusion Defect: PAO2 not enough to push O2 across the alveoli into the blood due to a thickened barrier i.e. interstitial pulmonary fibrosis
V/Q Mismatch: Blood bypasses O2’ing lung (right to left shunt) OR the O2’d air can’t reach the blood vessels (ventilation prob, i.e. atelactasis)
What is atelactasis?
Atelactasis is the collapse or closure of the lung which leads to decreased gas exchange. It’s a ventilation problem that is an ex of a V/Q mismatch that will lead to hypoxemia.
What is responsible for decreased O2 carrying capacity of the blood? What are three examples where this is seen?
Decreased O2 carrying capacity is due to Hb loss or dysfunction.
- Anemia: decrease in RBC mass. The PaO2 and SaO2 are normal.
A decrease in RBC mass leads to a decrease in O2 carrying capacity–>hypoxia not hypoxemia which is lower PaO2 in blood). There is no prob with FiO2, PAO2, PaO2, or SaO2
(SaO2 is what %age of Hb is bound to O2…so whether you have 2 or 2million RBCs, if they are all bound to O2, then its 100% SaO2.
- CO Poisoning: CO binds Hb better than O2 so normal PaO2, BUT LOW SaO2 bc CO stole most of the Hb. Presents with cherry red skin, early sign is headache!!! can lead to coma and death.
- MetHbemia: Fe2+ oxidized to Fe3+. Hb with Fe3+ can’t bind O2 like Fe2+ can. PaO2 normal, SaO2 decreased
Seen with oxidant stress, i.e. sulfa and nitrate drugs or in newborns. Presents: CHOCOLATE SKIN WITH CYANOSIS. Treat with IV Methylene Blue which reduces Fe3+ to Fe2+
Fe2 Binds O2!!!
What key cellular functions are lost due to hypoxia?
Hypoxia–>decreased ATP.
Na/K ATPase so Na floods the cell and water follows. This is Cellular swelling.
Ca ATPase which leads to influx of Ca into the cell.
Aerobic glycolysis is impaired so Anaerobic pthwy takes over. Get a buildup of Lactic Acid–>Low pH–>denature proteins and precipitates DNA
What is the initial phase of cellular injury? What cellular component is lost as a result?
It is cellular swelling and it is REVERSIBLE. The cytosol swells due to all of the water entering the cell. Cellular swelling causes the microvilli to be lost and you get membrane blabbing. The RER swells as well, and since the ribosomes are NOT covalently bound, they pop off quite easily. Now protein synthesis is decreased
What is the hallmark of irreversible cellular injury? What can this damage lead to?
MEMBRANE DAMAGE!!!
For Plasma Membrane:
The damage results in cytosolic enzymes leaking into serum (cardiac troponin or transaminases)
Even more Ca entering the cell (Ca first started to enter due to inactive Ca pump no longer being able to pump Ca out)
For Mitochondrial Membrane:
Loss of ETC which is on the INNER MEMBRANE
Cyto C leaks into cytosol. This activates caspases which activates APOPTOSIS
For Lysosome Membrane:
Hydrolytic Enzymes spill out into cytosol. These proenzymes are activated by the Ca that has invaded the cell.
All this irreversible injury leads to cell death.
