0514 - Ischemia - BX

Question 1

Name the 7 sources of hypoxia and give an example

Answer 1

    -physical – trauma, temperature, radiation, shock -chemical – drugs, toxins -infectious – all infectious agents -immunologic - autoimmune -genetic - metabolic abnormalities -nutrition – too much or too little

Question 2

What does severity of outcome of hypoxia/ischemia depend on?

Answer 2

-site of injury -liver vs CNS, how organs tolerate injury-severity of injury – magnitude of insulting agent? -how much or how little O2 was available? O2 sickness-timecourse -fast? Slow? Long? Short? -formation of embolus vs. acute occlusion-environment -under what condition was the injury sustained? Other problems?-mechanism of agent -intravenous K+ injection vs KOH oral intake

Question 3

What are the cardinal signs of cell injury?

Answer 3

-ATP depletion (both ischemia and hypoxia) -from decreased mitochondrial activity -increased ROS production -integrity of membrane compromised -intracellular calcium increase -could lead to cell death -mitochondrial change (membrane and activity)

Question 4

What are some causes of hypoxia? (name 3)

Answer 4

-low oxygen partial pressure 1.altitude - environment - can cause cerebral edema 2.body – anemia (decreased PO2 in blood) 3.constriction of vessels -embolus, plaques - causes tissue atrophy, pain, colour change 4. poor delivery (pulmonary or cardiovascular) -poor gas transfer, heart failure

Question 5

What is the general course of ischemic or hypoxic injury?

Answer 5

-decreased oxygen availability due to either ischemia or hypoxia-decreased ATP production by mitochondria (less oxygen) -mitochondrial swelling -decreased Na/K ATPase function due to less ATP -cell swelling due to lack of ion balance maintenance by ATPase-Calcium influx into cells, activation of many pathways -phospholipases that degrade plasma and organelle membranes-anerobic metabolism by glycolysis -process lowers pH in the cell (lactic acid) -pH can affect a host of things in the cell-decreased protein synthesis (ribosomes detached from ER)-loss of cytoskeleton-membrane bleb formation-deposition of lipids

Question 6

What is reperfusion injury? Describe how the damage is mediated?

Answer 6

-rapid reintroduction of oxygen into tissue may cause secondary damage -increased production of ROS (free radicals) -from mitochondria and leukocytes -release of transition metals from mitochondria -cytokine production worsens inflammation

Question 7

When is ischemic/hypoxic injury irreversible?

Answer 7

Cell damage is considered irreversible once:-more calcium influx, pH changes, loss of membrane integrity-under electron microscope: mitochondrial swelling, nuclear chromatin clumping

Question 8

What is are the differences between apoptosis and necrosis?

Answer 8

Necrosis: unregulated process of cell death-3 observable nuclear changes:-Karyolysis: thechromatinof the nucleus fades due to the loss of the DNA by degradation.-Pyknosis: the nucleus shrinks and the chromatin condenses.-Karyorrhexis: the shrunken nucleus fragments to complete dispersal.-produces inflammationApoptosis:programmed cell death-important process for development, remodeling, immune response, response to injury-does not produce inflammation-clear chromatin condensation and nuclear fragmentation