Introduction to pathology

Question 1

What are the 3 primary morfologic classifications of disease?

Answer 1

Degenerative

Inflammatory

Neoplastic

Question 2

What are the 2 primary morphologic classifications of inflammation?

Answer 2

Acute

and

Chronic

Question 3

What are the 2 types of neoplasmas?

Answer 3

benign(non-infiltrative)

and

malignant(infiltrive)

Question 4

What are degenerative diseases?

Answer 4

degenerative diseases are generally characterized by loss of normal histologic structures, without significant infiltration of inflamatory cellsor proliferation of indigenous cells

Question 5

What are some primary processes associated with degeneration?

Answer 5

Aging

atrophy

hypoplasia

hormonal involution

Question 6

Define cell injury.

Answer 6

Normal cells are in a state of homeostasis (i.e., an equilibrium with their environment). Injury is
defined as a set of biochemical and/or morphologic changes that occur when the state of
homeostasis is perturbed by adverse influences. Cell injury may be reversible or irreversible.

Question 7

What is the difference between reversible and irreversible cell injury?

Answer 7

The differences are mostly quantitative. Reversible injury is usually mild, and, following the
removal of the adverse influences, the cell reverts to its normal steady state. If the cell cannot
recover, the injury is considered to be irreversible.

Question 8

What could cause cell injury?

Answer 8

The causes of cell injury are classified as exogenous or endogenous. In principle, cell injury can
occur due to the following factors:
- Excessive or overly prolonged normal stimuli
- Action of toxins and other adverse influences that could inhibit the vital cell functions (e.g.,
oxidative phosphorylation or protein synthesis)
- Deficiency of oxygen and/or essential nutrients and metabolites

Question 9

Some key points to cell injury

Answer 9

1. Cell injury can be reversible or irreversible.
2. Hypoxia is the most important cause of cell injury.
3. Irreversible cell injury can be recognized by changes in the appearance of the nucleus and
   rupture of the cell membrane.

Question 10

Name some exogenous causes of cell injury.

Answer 10

Exogenous causes include physical, chemical, and biological factors, such as heat and cold,
toxins and drugs, and viruses and bacteria.

Question 11

Name some endogenous causes of cell injury.

Answer 11

Endogenous causes include genetic defects, metabolites, hormones, cytokines, and other
‘‘bioactive’’ substances.

Question 12

What is hypoxia?

Answer 12

Hypoxia is a relative deficiency of oxygen recognizable as a disproportion between the need
for oxygen and its availability. It may result from a reduced supply or increased demand
that cannot be satisfied. Complete block in the oxygen supply is called anoxia.

Question 13

What could cause hypoxia or anoxia?

Answer 13

Hypoxia and anoxia can result from the following:
- Inadequate supply of oxygen (e.g., low concentration of oxygen in air at high altitude)
- Obstruction of airways (e.g., strangulation and drowning)
- Inadequate oxygenation of blood in the lungs (e.g., lung diseases)
- Inadequate oxygen transport in blood (e.g., anemia)
- Inadequate perfusion of blood in the tissues (ischemia resulting from heart failure)
- Inhibition of cellular respiration—that is, blocked utilization of oxygen (e.g., cyanide
poisoning of respiratory enzymes)

Question 14

How does hypoxia cause cell injury?

Answer 14

Oxygen is essential for aerobic respiration. Hypoxia prevents normal oxidative phosphorylation,
thus reducing the capacity of mitochondria to generate adenosine triphosphate (ATP). Without
ATP, the cell cannot maintain its vital functions. Hypoxic cells swell. This change is called
hydropic or vacuolar change and is typically reversible.

Question 15

How does ATP deficiency cause cell swelling?

Answer 15

The cell volume depends on the proper functioning of the plasma membrane, which remains
semipermeable only if properly energized with ATP. ATP provides fuel for the Na/K ATPase, which
acts as a pump, keeping the high concentration of sodium in the intercellular fluid and the high
concentration of potassium inside the cell. If this ATPase malfunctions because of an energy
deficiency, an uncontrolled influx of sodium and water from the extracellular space occurs.
A consequent net increase of the total fluid content in the cytoplasm results in cell swelling. The
intracellular concentration of potassium declines because potassium leaks out of the cell.

Question 16

Where does water accumulate during hydropic change?

Answer 16

Water accumulates in the hyaloplasm but also in the invaginations of the plasma membrane
(hypoxic vacuoles), mitochondria, and the cisterns of rough endoplasmic reticulum (RER),
causing their malfunction. Swollen mitochondria produce less energy, and the detachment of
ribosomes from membranes of dilated RER results in reduced protein synthesis

Question 17

What is the role of calcium in acute cell injury?

Answer 17

Cell injury is accompanied by an increased concentration of free calcium ions in the hyaloplasm
(cytosol). These calcium ions are derived from the extracellular fluid, from the mitochondrial compartment, and from the cisterns of RER. Ionized calcium amplifies the adverse effects of hypoxia by activating several enzymes: - Lytic ATPase - Phospholipases -Proteases -Endonucleases All of these changes are initially reversible, but if prolonged or intensified they may lead to irreversible cell injury

Question 18

Ionized calcium amplifies the adverse effects of hypoxia by activating several enzymes:

Answer 18

• Lytic ATPase: Degrades ATP and further reduces the energy stores.
• Phospholipases: These enzymes remove phospholipids from the plasma or mitochondrial
  membranes, further impairing their function.
• Proteases: These enzymes degrade cell membrane or cytoskeletal proteins.
• Endonucleases: These enzymes act on the RNA and DNA.
  All of these changes are initially reversible, but if prolonged or intensified they may lead to
  irreversible cell injury

Question 19

How does the cell compensate for the loss of aerobic respiration?

Answer 19

Breakdown of ATP is accompanied by an increase in adenosine monophosphate (AMP), which
activates enzymes involved in anaerobic glycolysis. This leads to depletion of glycogen stored in the
cytoplasm.

Question 20

Is the cytoplasm of injured cells acidic or alkaline? and why?

Answer 20

Cell injury is accompanied by the lowering of intracellular pH from the normal neutral to the acidic
range. For example, the inhibition of oxidative phosphorylation promotes anaerobic glycolysis,
which is accompanied by accumulation of lactic acid in the cytoplasm. Phosphates released from
phospholipids and ATP contribute further to the acidification of the cytoplasm. Acidic milieu inhibits
the activity of most enzymes except those in the lysosomes, which function most efficiently in the
acid pH. The release of acid hydrolases from the lysosomes may further contribute to cell injury.

Question 21

How does the reversible cell injury become irreversible?

Answer 21

The transition from reversible to irreversible cell injury is gradual and occurs when the adaptive
mechanisms have been exhausted. A theoretical ‘‘point of no return’’ separating the reversible from
irreversible injury cannot be precisely defined even under tightly controlled experimental conditions.

Question 22

What are the signs of irreversible cell injury?

Answer 22

Initially, the differences between the reversible and irreversible cell injury are only quantitative.
For example, the hypoxic vacuoles become more numerous and larger. The mitochondria are
swollen, and many are even ruptured. However, many of these changes are still reversible, and it
is only when the plasma membrane ruptures and the nuclear changes ensue that one can be
certain that an injury is irreversible and the cell is dead.

Question 23

Which mitochondrial changes are irreversible?

Answer 23

Swelling of mitochondria represents a reversible change. Irreversible changes include the
following:
- Rupture of double membrane
- Fragmentation
&-Myelin figures (concentric curling up of damaged membranes)
- Calcification
Damaged mitochondria are taken up into autophagosomes and digested

Question 24

What are myelin figures?

Answer 24

Myelin figures are cytoplasmic bodies seen in damaged cells by electron microscopy. They
are composed of concentric whorls of membranes derived from damaged cytoplasmic organelles,
such as mitochondria, or RER. Myelin figures are prominent in neurons in Tay-Sachs disease
and other inborn errors of metabolism damaging the cytoplasmic membranes. Like other
remnants of damaged organelles, myelin figures are taken up into autophagosomes.

Question 25

Which nuclear changes are signs of cell death?

Answer 25

Dead cells show typical nuclear changes - Pyknosis: This term is derived from the Greek word pyknos meaning ‘‘dense,’’ and it denotes condensation of chromatin. - Karyolysis: This change results from the lysis of chromatin due to the action of endonucleases. - Karyorrhexis: This term is derived from the Greek word rhexis meaning ‘‘tearing apart’’ and denotes fragmentation of nuclear material. Colloquially, it is described as formation of ‘‘nuclear dust.’’

Question 26

What are the clinical signs of irreversible cell injury?

Answer 26

Irreversible cell injury results in a loss of cell functions. For example:

• Myocardial cell injury: loss of heart contraction
• Motor neuron: muscle paralysis
• Islets of Langerhans: diabetes

Question 27

Are there any clinically useful diagnostic laboratory signs of cell injury?

Answer 27

Severe cell injury is typically associated with a release of cytoplasmic enzymes into the blood.
For example:
- Creatine kinase may indicate cardiac or skeletal muscle cell injury.
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) are released from
damaged liver cells.
- Lactate dehydrogenase (LDH) is released from ruptured red blood cells and many other cells

Question 28

Can cell injury caused by hypoxia or anoxia be reversed or repaired by providing
the cells with adequate oxygen?

Answer 28

Irreversibly damaged cells cannot be revived by oxygen. On the other hand, the function of reversibly
injured cells that are still living can be improved by oxygen. The reoxygenation must be performed
carefully because if overly zealous, it may cause so-called reperfusion injury. This type of injury is
caused by oxygen-derived free radicals that may form under such conditions. For example,
reestablished blood flow to a myocardium made hypoxic by coronary obstruction may cause
reperfusion injury of still-living myocardial cells at the marginal zone of a myocardial infarction.

Question 29

What are free radicals?

Answer 29

Free radicals are unstable, highly reactive atoms or molecules that have an unpaired electron
in their outer orbit. After they are formed, they tend to self-propagate, forming new radicals in an autocatalytic sequence of reactions. The best-known free radicals are derived from oxygen and include the following:

• Superoxide (O2)
• Hydrogen peroxide (H2O2)
• Hydroxyl radical (OH1)

Question 30

How are oxygen radicals formed?

Answer 30

Oxygen radicals are formed in small quantities during normal cellular respiration. These oxygen
radicals are neutralized by natural antioxidants and degraded by protective enzymes. If these
normal defense mechanisms do not work, the free radicals may accumulate in toxic quantities.
Oxygen radicals are also formed by leukocytes, which use these reactive molecules to kill
bacteria.

Question 31

How are free oxygen radicals neutralized?

Answer 31

Superoxide is inactivated by superoxide dismutase and hydrogen peroxide by catalase and
glutathione peroxidase. Vitamin E and vitamin C also have antioxidant activity.

Question 32

How do free radicals damage cells?

Answer 32

Free radicals damage cells through a variety of mechanisms, most notably by the following:

• Lipid peroxidation: This process leads to membrane damage.
• Cross-linking of proteins: This leads to inactivation of enzymes.
• DNA breaks: This injury may block DNA transcription and cause mutations.

Question 33

What is necrosis?

Answer 33

Necrosis (from the Greek term necros, ‘‘dead’’) is localized death of cells, tissues, organs, or
parts of the body in a living organism.

Question 34

What are the histologic signs of necrosis?

Answer 34

The signs of necrosis are the same as those of irreversible cell injury—that is, cell membrane
rupture and nuclear changes, such as pyknosis, karyolysis, and karyorrhexis.

Question 35

What are the main forms of necrosis?

Answer 35

The main forms of necrosis are:

• Coagulative necrosis
• Liquefactive necrosis
• Caseous necrosis
• Fat necrosis
• Fibrinoid necrosis

Question 36

What is the most common form of necrosis?

Answer 36

The most common form of necrosis is coagulative necrosis. It is typically found in
myocardial infarction, as well as in infarcts of the kidney, the spleen, and many other organs.
Even the infarcted tumors may undergo coagulative necrosis.

Question 37

What are the four things a disease should have to be called a disease?

Answer 37

Etiology

Pathogenesis

Morphology

Clinical Expression

Question 38

What is pathogenesis

Answer 38

Sequence of eventsfrom the initial stimulus to the ultimate expression of the disease