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Scribe: Maggie Law
Tuesday, November 18, 2008
Proof: Kallie Law
Dr. Anderson
Cell Adaption and Injury
Page 1 of 6
I. Cellular adaption and stress response [S1, S2]
a. Pathology is all encompassing.
b. Whenever something goes wrong [in the body.]
c. Does not expect us to understand every component of every case; they are shown as examples.
d. [S3] Basic approach to pathology, cell injury and adaptation: normal state (homeostasis.)
e. Stressor comes (changes us from normal homeostasis) and things are not normal.
f. When that happens, body adapts to change. Cells and organs do this as well.
g. Our bodies adapt but either we get tired of adapting or run out of reserved capacity. May get to a point where
we are unable to adapt – point where problems/cell injury occurs.
h. [S4]How tissues adapt to stresses – what is the capacity of the cells in our tissues to respond to stress.
i. 3 cells types in our body:
i. Labile cells – continuously dividing. (skin, lining of GI tract, skin in mouth). Old cells are constantly being
replaced, stay in the cell cycle. They are dividing all the time.
ii. Quiescent or stable cell. (diagram is right out of our book) Found in liver, kidney, most organs. Mostly
sitting, doing nothing.
1. They do not usually divide.
2. They retain the ability to divide. Go from G0 phase where they are sitting, going back into G1 to
reenter the cell cycle.
3. Go out drinking – liver cells will go from G0-G1, start dividing, and replace the liver cells you
urinated. The dead cells.
iii. Permanent cell – gone totally out of the cell cycle. Cannot reenter.
1. Neurons
2. Cardiac myocytes. If you have a heart attack, you cannot grow a new heart. Research is being
done to change this, but right now new heart cannot be regrown.
3. Neuron scenario – they are not regrown. Cannot reenter cell cycle.
j. How does this effect adaptation? – if you mess with permanent cell, you lack options.
II. Response to stress [S5]
a. Cells respond to stress by 4 mechanisms. (Pathologists like lists.)
b. Atrophy, hypertrophy, hyperplasia, metaplasia.
c. [S6] cartoon of normal cells sitting on a basement membrane. Normal, homeostatic cell.
d. What happens if stress occurs and hormone stimulation is decreased? Or decrease food to tissue?
i. End up with atrophy – each of the individual cells get smaller.
e. Group of permanent cells (if you stress them) they cannot divide so they get bigger – hypertrophy.
i. Process of individual cells getting bigger – the whole organ they are a part of gets bigger as well.
f. Labile cells or quiescent cells – can be stimulated to divide. Stress them – go through hyperplasia.
i. Individual cells divide to get more cells; an increased number of cells
g. Metaplasia – switch from one cell type to another.
III. Hyperplasia [S7]
a. Increase in the number of cells in an organ or tissue.
b. Examples include:
i. Physiologic hyperplasia – hormonal induced:
1. Woman who had a baby and starts lactation. How is milk made? – glands inside of the breast divide
and make bigger glands and more glands in order to produce the milk.
2. Uterus – grows from fist sized to baby sized. Does this by smooth muscles (get bigger by
hypertrophy) but they are also stable cells, so they also divide. Gives increased numbers of cells as
well as bigger cells. Another example of physiologic hyperplasia.
ii. Pathological hyperplasia – body tries to adapt, but it is not helpful to the body.
1. Prostatic hyperplasia – older men have to urinate frequently. Prostates get hyperplasia, and as it
gets hyperplasia, the urethra gets squeezed and they have trouble urinating. Not a normal process;
caused by excess hormone stimulation.
iii. Viral induced
1. Wart (classic example) – where skin cells are infected with a virus and the virus makes/programs the
cells to keep dividing. Keeps dividing, undergoes massive hyperplasia – that’s what keeps the wart
there.
c. [S8] example of an autopsy specimen.
i. Does not expect us to know the exact anatomy – this is a cross section of the prostate.
ii. See the nodules – they are proliferative nodules. Hyperplasia. The cells that line the glands of the prostate
weren’t dividing, but started to divide after hormone stimulation.
iii. [S9] After dividing (histological section) see that this is gland.
FUN2: 10:00-11:00
Scribe: Maggie Law
Tuesday, November 18, 2008
Proof: Kallie Law
Dr. Anderson
Cell Adaption and Injury
Page 2 of 6
1. Glands are usually lined by a single layer of cells but because of the hormone stimulation and
proliferation, the cells have become piled up on each other.
2. Cases occur when the whole gland is filled by proliferated cells because the hyperplasia has gone
too much.
3. This is showing the increased proliferation, stimulated by hormones. Pathologic type of hyperplasia.
IV. Hypertrophy [S10]
a. Increased size of an individual cell because it cannot go through hyperplasia because it is a stable cell.
b. Can only get bigger; cannot divide. If cells get bigger, organ gets bigger.
c. Physiologic hypertrophy examples:
i. Uterus during pregnancy because the cells can divide, but also get real big.
d. Pathologic hypertrophy – classic example:
i. Increased functional demanded leading to left ventricular hypertrophy in a patient with high blood pressure,
hypertension or a value stenosis.
1. Stenosis is a narrowing of the value so the heart has to work harder to pump.
e. [S11] Example of a human heart (aorta is cut off, looking straight down to the aortic valve.)
i. Aortic valve has 3 leaflets. Can tell they are fused and solid as a rock. The leaflets are calcified –
dystrophic calcification.
ii. Hard as a rock (note the hole left.) Every time the heart beats, it has to force blood through the tiny hole.
f. [S12] What happens – blood comes into lungs from the left ventricle and the left ventricle has to squeeze
through the tiny little hole.
i. See the calcified aortic valve and a thin jet of blood going out; forces ventricle to work hard.
g. [S13] Section of normal heart (on right). On left is a patient with calcific aortic stenosis.
i. See the tight little valve. The heart is much bigger and the left ventricular wall is very thick compared to the
normal heart.
ii. Cells cannot proliferate – they can NOT divide any – but each individual cell is bigger.
h. [S14] Histology of this – on the left is a normal heart cell. On the right is a section of a hypertrophied heart.
i. Cell is much bigger in hypertrophied heart than in non hypertrophied heart.
ii. Each individual cell gets bigger because it has to pump really hard to force the blood out of the stenotic
aortic valve.
i. [S15] autopsy specimen. Renal artery stenosis. We have cut out aorta, head comes this way, legs down here
– branches into both iliac arteries. These are the kidneys.
i. In renal artery there is an artherstenotic plaque. It is partially occluding the blood flow to kidney.
ii. Lack of blood flow to kidney causes atrophy. Not getting enough food – causes atrophy, getting smaller.
iii. What happens if that kidney atrophies and is bad – other kidney hypertrophies to compensate.
iv. In this cause we see hypertrophy – cells getting bigger and they proliferate. Organ gets bigger to
compensate for atrophy in other kidney.
V. Atrophy [S16]
a. Shrinkage of the cell by loss of structural components. Reasons for atrophy:
i. Decreased workload
ii. Loss of intervention
iii. Diminished blood supply
iv. Inadequate nutrition (similar to decreased blood supply/decreased nutrition per se)
v. Loss of endocrine stimulation
vi. Aging.
b. All cause atrophy of the cells and decrease in the size of the tissues.
c. [S17] Classic example – disuse atrophy.
i. Break ankle, muscles in the leg atrophy.
ii. Muscles in calf will go through atrophy.
d. [S18] histologic sample of a muscle that has gone through atrophy.
i. Similar to that of a quadriplegic, someone who has nerve damage. Without nervous stimulation, the
muscle will atrophy.
ii. Cross sections of muscle fibers (semi-normal sized) but they have shrunk.
iii. The tiny fibers on slide are what show the atrophy. The cells are still there, they just lose all of their cellular
components.
iv. When each cell gets smaller, tissue or organ gets smaller.
e. [S19] Senile atrophy of a brain. Left is a normal brain, right is atrophied.
i. Seen in older people – pathologic atrophy because of Alzheimer’s disease.
ii. Tangles cause damage within the brain; neurons get smaller because they are not stimulated.
f. [S20] Kidney – gone through atrophy.
FUN2: 10:00-11:00
Scribe: Maggie Law
Tuesday, November 18, 2008
Proof: Kallie Law
Dr. Anderson
Cell Adaption and Injury
Page 3 of 6
i. Had a stone in the ureter – got stuck.
ii. Kidney continues to produce urine, hits the stone and backs up. Kidney fills up with urine and because you
filter blood through the kidney – the blood pressure forcing the fluid out in through the kidney and filling up
the renal pelvis at 100 mm pressure.
iii. Kidney gets tight, causes pressure on the tissue. The cortex gets thin, and collapsed. The cortex has
completely atrophied; has varying thickness.
iv. What happens as atrophy occurs – kidney is not working anymore because the stone is blocking the ureter.
Patient gets hypertrophy; called contra lateral kidney.
VI. Metaplasia [S21]
a. Reversible change in which one adult epithelial type is replaced by another adult epithelial type.
b. [S22] diagram showing metaplasia. If you irritate an epithelial layer, cells switch from normal to squamous.
i. Image of a smoker. Cells lining trachea and bronchi are columnar, ciliated, and epithelial.
ii. Starting to smoke irritates these components, get killed.
iii. Reserve cells have to start dividing to replace killed cells.
iv. Dead tissue and inflammation sends signals that change the gene program in reserve cells. If they were
planned to be a columnar, ciliated epithelium, the cells realize they will die. Instead, choose to be a
squamous epithelium.
v. Squamous epithelium is on skin (like a callus – resistant to mechanical pressure.)
vi. The cell chooses to be squamous to prevent death. The cell does not change into a squamous cell (once
they are differentiated, they cannot change.) Instead, the reserve cells along the BM that are NOT
differentiated, receive a signal to differentiate into a different, normal adult epithelium
c. [S23] Clinical example of a kidney stone. (Note that cigarette smoke is the classic example of squamous
metaplasia.
i. Cross section of a kidney and kidney stone.
ii. Stone is rough, like sandpaper. From the inside of the kidney, it rubs the surface of the renal pelvis.
d. [S24] Histologically what a normal renal pelvis should look like.
i. Single layer of cuboidal cells.
ii. Called transitional because when the renal pelvis fills with urine, cells stretch.
iii. Either cuboidal or flatten out – transitional.
iv. Rock inside of the renal pelvis. Rubbing occurs, irritation ensues.
v. [S25] sample of kidney with a rock in it. Note the inflammatory cells – inflamed/irritated.
1. On the surface, cells are thicker than normal.
2. On the other side, very thick.
3. At a higher power, see the squamous epithelial cells.
vi. [S26] Switch from transitional that is not robust (being mutilated by rock) to a callus.
vii. getting mutilated by the “sandpaper” rock; switch over to a callus in the inside of the renal pelvis by laying
down squamous epithelial cells that are keratinized, just like our skin—to form a protective layer on the
surface to protect the kidney from the rock
viii. cells on the border are very active and proliferating—keep proliferating because the cells are constantly
getting rubbed off by the rock
e. [S27] 26:28 ARS question
VII. Cell Injury—go through hypertrophy, hyperplasia, all these things and respond to stress---what happens if you can’t
respond to stress well enough and end up dying?
a. [S28] Some sort of stimulation that will alter the normal homeostasis of the cell. Two phases of cell injury
i. 1) reversible cell injury: hurt the cell but have not killed it—quit hurting the cell and it will come back to
normal
ii. 2) magical point of irreversibility—not sure what causes this transition, but no one knows for sure---if you
cross the line, you are deader than a doornail and can’t come back—this leads to necrosis or apoptosis.
iii. With apoptosis and necrosis the cell will die and never come back
b. [S29] Case Scenario: 65 year old man goes to emergency room due to crushing sensation in chest and pain
radiating in his jaw.
c. [S30] Do a physical exam, draw blood for cardiac workup. The STAT blood work shows an elevated CK-MB
and troponin I. (The only cell in the body with troponin I is a cardiac myocyte.)
1. How would an intracellular molecule get into the blood? The cell had to spit it out. It was spit out
because the cell was dead.
2. We know this guy is having a heart attack so send him for an emergency catheterization and
possible angioplasty.
FUN2: 10:00-11:00
Scribe: Maggie Law
Tuesday, November 18, 2008
Proof: Kallie Law
Dr. Anderson
Cell Adaption and Injury
Page 4 of 6
d. [S31] He goes to the cath lab and they inject dye into him —here’s the left main coronary artery. The left
circumflex coronary artery is shown and LAD and you can see there is a lesion present. The injected dye is
slowed down right there where the arrow is pointing. There is a stenosis there.
e. [S32] What’s happened here is that this patient had atherosclerosis and then got a blood clot that formed in the
atherosclerotic lesion in his coronary artery—this blocked the blood flow to the heart and he ended up with a
myocardial infarction. These cells are injured and if the artery is not opened up and so blood can get back
through there will be irreversible cell injury.
VIII. [S33] Ischemia
a. What happens when blood flow stops coming to a tissue? –You stop blood flow and this is called ischemia.
b. Definition of ischemia: decrease in blood flow below a level that sustains life in the tissues.
c. Does not mean total occlusion of the artery but that the artery is occluded enough so there is not enough blood
to keep the tissue alive even though there might be a trickle of blood.
d. In slide 31, there was still a little blood getting through, but it was such a small amount of blood that the heart
cells cannot stay alive.
e. When blood stops, the first thing that happens is an aberration in the mitochondria—the mitochondria don’t have
any oxygen so they can’t go through oxidization phosphorylation so ATP production is decreased.
f. The main problem with ischemia due to a myocardial infarction (or any infarction) is decreased ATP production
by the mitochondria because the oxygen is too low.
g. Once the ATP goes down, sodium pumping is decreased so there is an influx of Calcium, water, and sodium
into the cell and decreased efflux of potassium.
h. What happens if you get water in a cell? The cell gets full of water and eventually will explode—the cell
basically blows up.
i. When a cell realizes it does not have enough ATP, it increases anaerobic glycolysis. It tries to switch from
aerobic metabolism to anaerobic metabolism. This is a good thing because anaerobic metabolism uses up
glycogen to produce ATP—the cell needs ATP. The bad part is that the byproduct of anaerobic glycolysis is
lactic acid.
j. The cell becomes acidoitic. When the pH goes low enough, the low pH shuts off all the enzymes due to the
acidosis. One of the signs of this is the clumping of the nuclear chromatid.
k. Other things that happen:
i. Because of low ATP and acidosis, the ribosomes come off the endoplasmic reticulum so the cell cannot
make any new proteins. This decreases the cell’s ability to respond to stress and causes problems.
ii. Have to have proteins to bind to lipids to form lipoproteins because lipids are not soluble in cells. They
need the protein because they are hydrophilic. The proteins must bind onto the lipids to make them usable
in the cell.
iii. Without the protein, you just get globs of lipid bubbles floating around inside the cell.
iv. All of these things together lead to bad things happening to the cell.
l. [S34] Here’s the guy who had the heart attack.
m. [S35] Here is the thrombus in the coronary artery. (Arrows are pointing the thrombus.) Because of the
thrombus, he did not get any blood to this section of the heart. This is the area of myocardial infarction. It’s kind
of pale in the center and then has a red rim around it. The red rim around it is due to the fact that there is still
blood around the outside that sort of comes into the area that is dead and leaks out. This is leaking hemorrhage
from blood that is seeping in from adjacent tissues.
n. [S36] What happens when you first stop the oxygen to the tissues?
i. Morphologically, you can look for blebbing.
ii. As ATP is decreased the cell fills with water, the sodium can’t be pumped out (this sucks in water), the cell
begins to swell and you end up with “blebs” on the surface.
iii. The blebbing is an initial sign of injury—as long as they don’t burst the cell will still be okay.
iv. Get swelling of the endoplasmic reticulum and the ribosomes come off of the rough endoplasmic reticulum
and get clumping of chromatin within the nucleus and you get swelling of the mitochondria.
o. What happens if when that guy into the emergency room and into the cath lab and a cathedar was stuck into the
lesion in his coronary artery and a balloon was stuck in there and the balloon was inflated and then the balloon
was deflated and pulled out and blood went down there?
i. Some of the cells in the heart are now getting oxygen. All of these things seen here are examples of
reversible injury.
ii. If you oxygen back to the tissue, the cells can recover—it may take a while because the ribosomes have to
hook back on, etc. but eventually that cell can recover and go to a completely normal cell.
p. [S37] What does that look like in the real world? This is a section of that guy’s heart. (He did not live.)
i. Remember the hemorrhage around the outside? There is an area called the border zone. Around the
clump of dead tissue there is just enough blood to keep the cells alive.
FUN2: 10:00-11:00
Scribe: Maggie Law
Tuesday, November 18, 2008
Proof: Kallie Law
Dr. Anderson
Cell Adaption and Injury
Page 5 of 6
ii. This is a section that was taken right at the border zone region.
iii. On the left is the normal myocyte. These cells have gotten enough blood and oxygen—each of the cells
have nuclei, the cells stain okay and look fairly normal.
iv. On the far right, notice that there is not a single nucleus in the whole area—this is an example of a dead
cell. The cells lose their nuclei and the DNA goes away.
v. In the middle, these are cells that are reversibly injured. There are still nuclei in the cells; they look funny
and not totally normal, but there are still nuclei. The cells are swollen because there is so much water in
there that the cytoplasm is spread out—this gives a granular pink appearance. The cells aren’t healthy and
normal but they are still alive and still have cell membrane that is holding the cell together, are fairly
acidotic, and have used up all their glycogen. Still alive.
vi. If this coronary artery is opened up, these cells will eventually recover and look like the cells on the left.
vii. This change is called hydropic degeneration because the cells are hydrated and full of fluid. Sometimes
this is also called vacuolar degeneration due to all the vacuoles within the cells. All the empty clear spaces
are called vacuoles.—THIS IS AN EXAMPLE OF REVERISBLE CELL INJURY.
viii. ARS Question: 40:55
IX. [S38] Necrosis—go past reversible cell injury and get cell death. This is called necrosis in pathology. Tissues go
through necrosis.
a. [S39] Get to a point where there is a straw that breaks the camel’s back—the cell reacts to the ischemia and
holds on as long as it can and finally gives up.
i. One of the main features that tells you the cell is irreversibly injured is when the membranes break—even
when the Na/K pump is shut off and the cell is full of water, as long as the membrane is still intact, you can
get ATP back to pump sodium out and pump water out and go back to normal.
ii. If there is a hole in the membrane, recovery is bad. If a cell goes past the point of reversible injury, the
main issue is that the membranes break. The membranes that line the lysosome also break too.
Lysosome are bags of enzymes designed to kill bacteria and break down foreign material—when this
breaks open, the enzymes from the lysosome start to digest the cell—basically going through auto
digestion. The cells digests itself.
iii. Also get continued blebbing, more breaks in the membrane, the endoplasmic reticulum breaks up, and go
from condensation and clumping of chromatin.
iv. When chromatin compresses it’s called pyknosis. Pyknosis is when all the chromatin compresses into a
ball. If it breaks into pieces, that is called karyorrhexis. If it’s totally compressed and the enzymes start
chewing it up and it all gets dissolved, this is called karyolysis.
v. In the heart tissue that was shown, it was an example of karyolysis because all of the nuclei were gone.
X. [S40] Types of Necrosis---once you have all this dead tissue, it can be classified according to its type of necrosis.
a. Coagulative necrosis, liquefaction necrosis, fat necrosis, caseous necrosis, fibrinoid necrosis, and gangrenous
necrosis.
b. [S41] Coagulative necrosis: coagulate the cells.
i. You get dissolution of nucleus (karyolysis) with preservation of cellular shape and tissue architecture.
ii. How can everything be dissolved and still tell what it is? –it’s like a hardboiled egg—it looks like an egg
even though it’s in a clump.
iii. The cells aren’t normal and don’t run all over the place, they aren’t like a regular egg but a hardboiled egg.
All the proteins are coagulated and don’t work anymore but you can still see the cell outline and what the
cell looked like.
iv. [S42] Classic example of coagulative necrosis—a myocardial infarction. To be different, we will be looking
at a kidney infarction.
1. Here is the pale area in the center with the red rim around it just like what was shown in the heart.
2. There was a thrombus in blood vessel so no blood reached the tissue—that is the area of renal
necrosis due to ischemia.
v. [S43] Histological section in the middle of the necrotic region—
1. Glomerulus in the lower right corner
2. The blue dots are inflammatory cells, not nuclei.
3. All the cells of the glomerulous have lost their nucleus and are now coagulated. All the proteins are
coagulated.
4. The circular things are proximal tubules in the cortex of the kidney that go around and back up and
then you have distal tubules. The proximal tubules don’t look normal because they lack nuclei and
are a brighter red than you would normally expect. When cells die, the red dye used for histology,
eosin, tends to stick to the cells better. They also have a granular appearance.
5. It’s hard to pick out individual cells, but you can tell there are proximal tubules lined by cells and now
all the cells are dead and this is what is called coagulative necrosis.
FUN2: 10:00-11:00
Scribe: Maggie Law
Tuesday, November 18, 2008
Proof: Kallie Law
Dr. Anderson
Cell Adaption and Injury
Page 6 of 6
6. What is this over here?—distal collecting duct—look white in appearance (urine goes through
proximal tubules, distal tubule then out the collecting duct.) All of those cells have nuclei and look
okay? Why are these cells alive and right next door the cells look dead?—ischemia is a decrease in
blood flow low enough so the tissue can’t stay alive. What’s a necessary corollary to that? Tissues
that need lots of oxygen die soon, and tissues that don’t need much oxygen stay alive.
a. In the infarct, there was a little bit of blood getting into the tissue.
b. Proximal tubular cells are full of mitochondria and pump ions all day long—this is how you
concentrate you urine. These cells need lots of oxygen and ATP. A little decrease in blood
flow will cause the cells to die because of lack of oxygen.
c. Distal tubular cells just sit there and the urine washes by—they don’t have to do anything and
have very few mitochondria and have a very low oxygen requirement.
d. The oxygen demand of the tissues is important to determine whether the cells die or not
when blood flow is decreased.
[end 51:20]