Hypoxic injury - ✔✔1. Decrease in oxygen in the air (high altitudes, asphyxiation, drowning)
2. Loss of hemoglobin function (hemorrhage or sickle cell anemia)
3. Decrease in production of red blood cells (anemia or leukemia)
4. Diseases of cardiopulmonary systems (ischemia, blood supply loss, arteriosclerosis)
Hypoxic injury clinical manifestations - ✔✔1. Increased CK (muscle and heart)
2. Increased LDH (muscle, liver, lung, heart, RBC, brain)
3. Increased ALT and AST (liver)
4. Increased troponin (heart)
Reperfusion injury - ✔✔Oxygen supply is restored to ischemic tissues. Triggers oxygen
intermediates which causes cell membrane damage and mitochondrial calcium overload.
Xanthine dehydrogenase --> xanthine oxidate. This makes large amounts of free radicals,
superoxide, and hydrogen peroxide. Causes cell membrane damage and *mitochondrial
calcium overload*
Reperfusion injury clinical manifestations - ✔✔White blood cell count is impaired. Seen in
tissue transplantation, ischemic syndromes of the heart, liver, intestines, kidneys, and
cerebrum.
Free Radical - ✔✔Molecules that have an unpaired electron on its outer shell. This makes the
molecule unstable.
Cause cellular injury, aging, and disease to occur.
,Reactive Oxygen Species (ROS) - ✔✔Produced as a normal byproduct of ATP production in
mitochondria. ROS can overwhelm the mitochondria and exhaust intracellular antioxidants.
Also produced by absorption of high energy sources like radiation or UV light.
Ethanol - ✔✔Acute affects in the liver include inflammation, fatty infiltration, hepatomegaly,
acute liver necrosis, suppressed fatty acid oxidation. Chronic ethanol use is mainly seen in the
stomach and liver, and is caused by free radicals.
*Elevated anion gap and osmolar gap >10 is diagnostic*
Infarct - ✔✔Form of necrosis that is a SUDDEN insufficiency of arterial blood flow. (ie: heart
attack, cold leg, MI)
Apoptosis - ✔✔Programmed cell death (normal). Needed to prevent cellular proliferation
that would result in a large body.
Clinical implications: neurodegenerative disease, ischemic injury, death of virus infected cells
Autophagy - ✔✔Autodigestion of the cell. When cells lack nutrition, autophagy is triggered.
During times of metabolic stress, autophagy provides ATP and other macromolecules for energy
and cell survival. When stress progresses, it leads to cell death
Aging - ✔✔Body released more cytokines and proinflammatory substances which results in
chronic inflammation
What lab values are elevated as we age? - ✔✔Interleukin 1, tumor necrosis factor-alpha, and
C-reactive protein
Role of hepatocytes - ✔✔Acetyl CoA is processed by hepatocytes and transforms to 3 ketone
bodies:
1. Acetoacetate
, 2. Acetone
3. B-hydroxybutyrate
Role of mitochondria - ✔✔Ketogenesis: occurs mostly in the hepatocytes
What triggers ketogenesis? - ✔✔Unavailability of glucose. Keto diet = no sugar. Starvation
and Type 2 DM can lead to this.
Role of Acetyl-CoA - ✔✔Returns to citric acid cycle and combines with oxaloacetate to form
citrate. Also transforms into ketone bodies by hepatocytes
Oxaloacetate - ✔✔Used in gluconeogenesis (process of getting sugars from carbs). During
starvation or uncontrolled diabetes, oxaloacetate levels are insufficient because it has been
completely used by gluconeogenesis. Depletion of oxaloacetate increases amount of Acetyl
CoA.
Normal cells - ✔✔Will not grow unless attached to a firm surface. Normal cells have a limited
life span and divide 10-50 times. Uniform in size and shape.
Cancer cells - ✔✔Cells continue to crowd and eventually pile over. Immortal and divide for
years. Divide rapidly and are parasites. Must grow in a hypoxic or acidic environment.
Which cancer produces alpha fetoprotein? - ✔✔Liver and germ cell tumors secrete this into
the blood. Found in liver, testicles, or ovaries.
Which cancer produces carcinoembryonic antigen? - ✔✔GI, pancreas, lung, breast, large
intestine, colon, rectal
Which cancer produces beta human chorionic gonadotropin? - ✔✔Germ cell (reproductive)
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