A+ 2025/2026
4. Defects in membrane permeability- Certain medications that can lead to liver or kidney damage
The disease mechanism that is the basis of much of the disease today- and most of the cases involve
hypoxia. Refers to the inability of the cell to produce adequate energy to fuel normal activities of that
particular cell type (cell membrane pumps and protein synthesis) and function. - ATP depletion
A very inefficient method of ATP production (yields 2 ATP) - glycolysis
Is a very efficient method of ATP production (yields 36 ATP) - Oxidative Phosphorylation
What is the most common method of impairing oxygen and ATP production? - hypoxia
Can lead to irreversible cell injury directly through impairment of energy production in the cell. -
Ischemia
What are the cellular events that occur with ischemia-induced- hypoxic injury? - 1. The amount of ATP
production within the mitochondria declines
2. The drop in ATP causes NA-K- ATPase pump on CM to fail. Which then leads to increase in NA+,H2O,
and Ca+ in cell and decrease in K+ in cell.
3. Increase in water in cell causes cell and it's organelles to swell.
4. When RER swell it's ribosomes fall off and protein synthesis stops.
5. ATP production through phosphorylation declines and glycolysis (anaerobic metabolism) increases.
When glycolysis increases in the cell glycogen stores are depleted.
6. Glycolysis also produces lactic acid as by-product. Glycolysis also = intracellular pH decline ( the cell
functions within narrow range of pH and even slight drop can incapacitate the cell).
7. Drop in pH causes clumping of nuclear material called pyknosis. Leads to fragmentation of the nuclear
material (karyorrhexis) and then to dissolution of nuclear membrane (karyolysis). Decline in pH= rupture
of already swollen lysosomes and release of proteolytic enzymes= autodigestion of cell contents and cell
membrane.
,8. Disruption of CM also increases Ca+ influx into the cell and organelles= activate proteases,
endonucleases, and phospholipases that proceed to destroy the cell.
Unstable compounds with an unpaired electron in its outer ring. They have a particular affinity for lipid
substances. They combine avidly with cell or organelle membrane. "Drill a hole" in the membrane of cell.
They are normal byproducts of cellular metabolism, and they are always present in the body. - Free
radicals
Chemically reactive molecules that are formed as natural oxidant species in cells during mitochondrial
respiration and energy generation. Most sources come from the mitochondria. Made during the process
of making ATP. - Reactive oxygen species (ROS)
Remove free radicals and ROS from our system. - Antioxidants
When free radicals are produced in amounts that overwhelm our antioxidants or when antioxidants are
decreased. - Oxidative Stress
What can occur within the cell when injury is induced by free radicals? - 1. membrane damage
2. protein modifications
3. mutations in DNA
4. Damage to cell signaling pathways
Genetic disturbances can be _______ if they involve the germ cell line of an individual - inherited
Genetic disturbances can also be _______ by exposure to some mutagenic/ carcinogenic environmental
factors - acquired
Enzymes secreted by microorganisms can breakdown cell membranes once introduced into the body=
_______
Allows the organisms to dissolve surrounding tissues and allows them to move deeper into the tissues,
blood, and lymphatics. - lysis by enzymes
, Certain viruses, once they have infected a cell, will cause membrane rupture as newly produced viral
particles (virions) leave the host cell= ________. Sometimes referred to as lytic viruses. Examples include
HIV and Hep B. - Lysis by virus
Involve the abnormal accumulation of substances that are normally found in the body (endogenous
agents) or not normally found in the body (exogenous agents). - Metabolic derangements
Give 2 examples of endogenous accumulations in the body. - 1. Lipids: Fatty changes occurs most often in
liver cells but can also be problem in myocardial cells. Liver handles fats and synthesizes complex fats
and lipoproteins. Slow accumulation of fat within hepatic or myocardial cells usually does not impair the
function of those cells until the problem is extreme. However, fatty change can occur in acute basis and
can lead to acute heart or liver failure.
2. Bilirubin: Pigment released when RBCs break down/destroyed. Bilirubin is released/diffuses into blood
where it is called unconjugated (indirect) bilirubin. Unconjugated bilirubin is fat-soluble and can't be
eliminated through kidney (urine). So, it's taken up by liver cells bound to a substance called glucuronic
acid and becomes bilirubin glucuronide or conjugated (direct) bilirubin. Conjugated bilirubin is water-
soluble and can be eliminated through the kidney.
Describe the 2 ways in which conjugated bilirubin leaves the liver cells. - 1. As concentration of
conjugated bilirubin in the liver cells increases, it begins to diffuse out of the cell into the blood (down its
concentration gradient).
2. In addition, some of the conjugated bilirubin becomes part of a substance called bile; bile exits the
liver cell through the hepatic duct and common bile duct and then into the duodenum.
Explain 3 problems that may result in hyperbilirubinemia. - 1. Excessive amounts of Hgb breakdown
occur, as with hemolytic anemia or after birth when babies rapidly destroy their excess RBC mass. This
results in excessive amounts of unconjugated bilirubin being delivered to the liver at a rate greater than
the liver can handle. Unconjugated bilirubin accumulates in the blood. This is referred to as hemolytic
jaundice.
2. Second problem area occurs when the amount of bilirubin released from RBC breakdown is normal,
but the liver cells are sick and are unable to uptake unconjugated bilirubin from the blood, conjugate it,
and/or excrete it into the bile. This is called hepatocellular jaundice because the problem is within the
liver cell.
3. The third problem occurs when there is an obstruction to the flow of bile in the hepatic and/or
common bile duct. Conjugated bilirubin accumulates in the liver cell and more diffuses into the blood