Cell Injury, Cell Death And Adaptations - Chapter 1

Front 1

Define the word "Etiology"

Back 1

The cause of diseases and pathologies.

Front 2

Define the word "pathogenesis".

Back 2

The underlying mechanisms that result in the presenting signs and symptoms of the patient.

Front 3

Name the principal adaptive responses.

Back 3

• Hypertrophy
• Hyperplasia
• Atrophy
• Metaplasia

Front 4

How do stresses affect cells?

Back 4

• Morphologically
• Functionally

Front 5

What type of changes are adaptations, reversible or irreversiblle?

Back 5

Reversible

Front 6

Into what categories can adaptations be subdivided?

Back 6

• Physiological adaptations
- Hormones etc.

• Pathological adaptations
- Cellular change in order to escape injury.

Front 7

Hypertrophy

• Definition?
• What happens with hypertrophic
cells?
• What type of cells undergo
hypertrophy?
• Is hypertrophy physiological or
pathological?
• Can hypertrophy occur together
with another adatpive response?
Give an example.
• Give an example of pathologic
cellular hypertrophy.

Back 7

• The increase in the SIZE of cells.
• They enlarge by an increased
amount of structural proteins and
organelles.
• Cells that cannot divide.
• It can be both.
• Yes, together with hyperplasia.
One example is the pregnant
uterus.
• Cardiac enlargement that occurs
with hypertension or aortic valve
disese.

Front 8

What are the mechanisms driving cardiac hypertrophy?

Back 8

• Mechanical triggers
- Stretch

• Trophic triggers
- Activation of α-adrenergic
receptors

• (Sometimes) Switch from adult
contractile protein forms to
neonatal.

Front 9

What happens to cardiac muscle when hypertrophy can no longer compensate for the increased burden?

What is the effect of this?

Back 9

• Fragmentation
• Loss of myofibrillar contractile
elements.

• The effect is ventricular dilation
and ultimately cardiac failure.

Front 10

What happens to cardiac muscle when hypertrophy can no longer compensate for the increased burden?

What is the effect of this?

Back 10

• Fragmentation
• Loss of myofibrillar contractile
elements.

• The effect is ventricular dilation
and ultimately cardiac failure.

Front 11

Hyperplasia

What type of cells undergo hyperplasia?

What other adaptive processes can occur together with hyperlasia?

Into what categories can hyperplasia be subdivided?

Back 11

• Cells capable of undergoing
replication.

• Hypertrophy - often in response to
the same stimuli

•Physiological
-Hormonal hyperplasia
+Prolif. in glandular epithelium of
the female breast at puberty
and during pregnancy
- Compensatory hyperplasia
+When a liver is partially
resected.
+Wound healing
• Pathologic hyperplasia
- Excessive hormonal or growth
factor stimulation (soemtimes
associated with viral infections
e.g. papillomaviruses ->warts
-

Front 12

What distinguishes hyperplasia from neoplasms?

Is there a connection between hyperplasia and neoplasms?

Back 12

In hyperplasia, the growth abates when the hormonal stimulation is removed. In cancer, the growth control mechanisms become dysregulated and ineffective.
Therefore, it can be said that it is the sensitivity to to normal regulatory control mechanisms that distinguishes benign pathologic hyperplasia from neoplasms.

Yes, there is. Pathologic hyperplasia constitutes a fertile soil in which neoplasmic prolif. may eventually arise.
-E.g. Patients with hyperplasia of
the endometrium are at
increased risk of developing
endometrial cancer.

Front 13

Atrophy

• Define "atrophy".

• What is the cellular mechanism of
atrophy?

• Are atrophic cells dead?

• What can be the cause of
atrophy?

• What categories can atrophy be
subdivided into?

Back 13

• Shrinkage in the size of the cell by
the loss of cell substance.

• Decreased protein synthesis
• Increased protein degradation
- Ubiquitin-proteasome pathway

• No, they are not dead, but they
are functionally unoptimized.

• Decreased workload (immob.)
• Loss of innervation
• Diminished blood supply
• Inadequate nutrition
• Loss of endocrine stimulation
• Aging (senile atrophy)

• Physiological and pathological,
but the fundamental cellular
changes are identical.

Front 14

Metaplasia

• Define "metaplasia".

• Why does metaplasia occur?

• How does metaplasia occur?

• Give 3 examples of metaplasia
and their etiology.

• Is metaplasia harmful?

Back 14

• A reversible change in which one
adult cell type (epithelial or
mesenchymal) is replaced by
another adult cell type.

• The new type of cells are better
able to withstand the adverse
environment.

• By genetic "reprogramming" of
stem cells. Not transdifferentiation
of already diffated cells.

1) Ciliated columnar epithelia --->
Stratified squamous epithelia
in the trachea and bronhi,
because of smoking
2) ---"--- because of vit. A deficiency
3) Stratified squamous epithelium
---> gastric columnar epithelium,
because of chronic gastric reflux. (Barret's esophagus)

• Yes, but inderectly. It has a
protective effect but it also
predisposes to malignant
transformation of epithelium.

Front 15

What has normally not occured in reversible cell injury?

Back 15

• Severe membrane damage

• Nuclear dissolution

Front 16

• Is apoptosis a pathologic process?

• Is necrosis a pathologic process?

Back 16

• No, but it can be.

• Yes, always.

Front 17

• What is the difference between
"hypoxia" and "ischemia"?

• What process injures cells
faster, hypoxia or ischemia?

• Why does hypoxia damage cells?

Back 17

• Hypoxia = Oxygen deficiency
• Ischemia = Loss of blood supply
However, a hypoxic state still allows the generation of energy through the anaerobic pathway.
Ischemia, on the other hand, also compromises the delivery of substrates for glycolysis.

• Ischemia, because of the
lack of anaerobic
glycolysis.

• Because it interferes with
aerobic oxidative phosphorylation.

Front 18

How is cellular function, cell death and cell morphology related?
- Why?

Back 18

Cellular function may be lost lost long before cell death occurs and morphologic changes of cell injury (or death) lag far behind both.

Function>Death>>>Morphology

Because biochemical and molecular mechanism are the first to become affected.

Front 19

What two phenomena consistently characterize irreversibility?

Back 19

• The inability to reverse mitochondrial
dysfuntion (lack of oxidative phospho-
rylation and ATP generation).

• Profound disturbances in
membrane function.

Front 20

What are the two main correlates of reversible cell injury?
- What is their mechanism?

Back 20

• Cellular swelling
- Due to failure of energy-dependent
pumps in plasma membrane.
• Fatty change
- Mostly in hypoxic injury and
various forms of toxic or
metabolic injury.
- Occurs mainly in cells involved in
and dependent on fat metabol.

Front 21

What are the changes accompanied by necrosis linked to?

Back 21

• Largely to the degenerative action of enzymes on lethally injured cells.

The enzymes come from the lysosomes from the dying cell or from lysosomes of leukocytes that are recruited as part of the inflammatory reaction to dead cells.

• Protein denaturation

Front 22

• What are "myelin figures", and when
and where can they be found?

• What can happen to the myelin
figures?

Back 22

• They are phospholipid masses
derived from damaged cellular
membranes, from dead cells.

• They may be phagocytosed or
further degraded into fatty acids.
The fatty acids may then be
calcified.

Front 23

Explain the terms:

• Pyknosis
• Karyorrhexis
• Karyolysis

Back 23

• Nuclear shrinkage and increased
basophilia.

• The pyknotic nucleus undergoes
fragmentation.

• Basophilia of the chromatin may
fade.

Front 24

Coagulative Necrosis

How is the tissue architecture affected?
- Why?

Where, and due to what, is coagulative necrosis characteristic?

Back 24

Tissue architecture remains unchanged for at least several days.
- The theory is that the injury does not only denature structural proteins but also enzymes and so blocks the proteolysis of the dead cells.

Coagulative necrosis is characteristic of infarcts (ischemic necrosis) in all SOLID organs except the brain.

Front 25

Liquefactive necrosis

How is tissue architecture affected?

Where does it occur?
What may cause it?

Back 25

The dead cells are completely digested, and therefore, the tissue architecture is completely lost.

It can occur in any part of the body due to focal bacterial infections, sometimes fungal infections.
However, in the CNS, the response to hypoxic death often liquefactive necrosis.

Front 26

Gangrenous necrosis

What does it refer to?

What is "wet" gangrene?

Back 26

It refers to an ischemic limb where coagulative necrosis involving several tissue layers has occured.

When a bacterial infection is superimposed on the gangrenous necrosis, modifying it by the liquefactive actions of the bacteria and attrected leukocytes.

Front 27

Caseous Necrosis

How is the tissue architecture affected?

Where does it normally occur?

What is a "granuloma"?

Back 27

The tissue architecture is completely obliterated.

In foci of TBC infections.

An infection enclosed within a distinctive inflammatory border.

Front 28

Fat Necrosis

Definition?

What occurs?

What pathology may cause it?

What can be said about the gross morphology of fat necrosis?

Back 28

Focal areas of fat destruction.

Activated pancreatic lipases are released into the substance of the pancreas and peritoneal cavity. Resulting in breakdown of cell membranes and TG's.

Acute pancreatitis.

The FA's released by the breakdown may become calcified and form white chalky areas in/on the affected tissue.

Front 29

Fibrinoid Necrosis

Seen where?

Seen why?

What pathology may cause it?

Back 29

In blood vessels.

Immune reactions : antigen-antibody complexes are deposited in the walls of aa's.

Polyarteritis nodosa.

Front 30

What is the critical level in ATP depletion?

Back 30

5-10%

Front 31

How can damage to mitochondria lead to the death of a cell?

Back 31

Mitochondrial membrane damage may result in the formation of a high conductance channel that leads to the decrease in mitochondrial membrane potential, leading to the failure of oxidative phosphorylation.

Damage to the membrane may also lead to the realease of apoptosis-inducing molecules, such as cytochrome c. The result is unwanted death by apoptosis.

Front 32

Fatty change (steatosis)

Definition?

In what organs does it occur?

What are its largest causes?

What effect does it have on cellular funtion?

Back 32

The accumulation of TG's within parenchymal tissue.

Mostly the LIVER, but also in the heart, skeletal m, kidneys and other organs.

Alcohol abuse, obesity and diabetes.

If mild; no effect.
If intermediate; reversible effect
If severe; cell death

Front 33

Fatty change of the liver

Macroscopically, what happens to the liver?

Back 33

It increases in size and weight.

It may become yellow and greasy.

Front 34

What are "Mallory bodies"?

Back 34

Accumulations of intracellular proteins in liver cells. They are characteristic of ALCOHOLIC LIVER DISEASE.

Front 35

Pigments

Where do they come from?

Back 35

They may be exogenous or endogenous.

Front 36

Anthracosis

Definition?

Is anthracosis dangerous?

Back 36

Blackened tracheobronchial lymph nodes. The pigment is CARBON and its way to the lymph nodes is via alveolar macrophages.

Yes. Heavy accumulations may induce emphysema or a fibroblastic reaction that can result in a serious lung disease called coal workers' pneumoconiosis.

Front 37

Lipofuscin

What does it represent?

Where can it be found?

What is "brown atrophy"?

Back 37

It represent previous damage to polyunsaturated lipids of subcellular membranes by ROS'es.

Mostly in heart, liver and brain. The older tha patient the more lipofuscin. It's intracellular location is often perinuclear.

Brown atrophy is used to describe large amounts of lipofuscin accumulations in a tissue. The tissue itself becomes brownish.

Front 38

Hemosiderin

Where does it come from?

What is hemosiderin?

Are hemosiderin accumulations pathologic?

Back 38

It is HEMOGLOBIN-derived.

It is a large collection of ferritin micelles, which consist of iron and apoferritin (a proteinto which iron binds).

It is usually pathologic but small amounts are normal in macrophages in tissues where there is extensive RBC breakdown.
e.g. Spleen, liver, bone marrow.

Front 39

Hemosiderosis

Defintion?

Causes?

Is hemosiderosis harmful?

Back 39

The deposition of large amounts of hemosiderin in many organs and tissues due to a systemic overload of iron.

Increased iron absorption
Decreased iron utilization
Hemolytic anemias
Blood transfusions

No. However, with very large accumulations, such as encountered in hereditary hemochromatosis, there is tissue injury resulting in:
Liver fibrosis
HF
Diabetes mellitus

Front 40

Calcification

Into what categories can calcification be subdivided?
-In which ways do the subdivisions differ?

What may cause hypercalcemia?

Back 40

DYSTROPHIC calcification
-Occurs in the absence of calcium metabolic derangements
-Related to injury or necrosis.

METASTATIC calcification
-Can occur in normal tissues whenever there is hypercalcemia

1) Increased secretion of parathyroid hormone.
2) Destruction of bone due to the effects of accelerated turnover
3) Vitamin D-related disorders
4) Renal failure.

Front 41

What cells are most capable of hypertrophy?

Back 41

Striated m. cells in both skeletal and heart m.

Front 42

What are the most common causes of hypertrophy of the heart?

Back 42

• Hypertension
• Faulty valves
- Both create chronic hemodynamic overload/increased afterload.

Front 43

What is normal thickness of the left ventricular wall?

Back 43

1-1.5 cm

Front 44

What is Reye's syndrome?

Back 44

It is a potentially fatal disease that causes numerous detrimental effects to many organs, especially the brain and liver. It is associated with aspirin consumption by children with viral diseases such as chickenpox.

Causes fatty liver.

Front 45

Name 3 intracellular protein accumulation pathologies, and 1 extracellular.

Back 45

• Intracellular
-Reabsorption droplets in proximal convoluted tubules. Associated with proteinuria.
-Immunoglobulin in plasma cells (Russell bodies)
-α1-antitrypsin in ER of liver cells due to point mutation in α1-antitrypsin gene.

• Extracellular
-Amyloidosis - Fundamentally a disorder of protein misfolding.

Front 46

How is amyloidosis visualized hitsologically?

Back 46

Congo red dye

Front 47

When does myocardial necrosis become histologically visible?

Back 47

4-12h after the event

Front 48

What are "Councilman bodies"?

Back 48

Apoptotic cells in the liver due to viral hepatitis.

Front 49

Can it be said that certain injurious stimuli cause necrosis while others cause apoptosis?

Back 49

No. The same types of injurious stimuli may cause both necrosis and apoptosis. However, mild insult by a certain stimulus may lead to apotoptosis, while a larger insult by the same stimulus leads to necrosis.

Front 50

What is the most characteristic morphological feature of apoptosis?

Back 50

Chromatin condensation.