Introduction to pathology Flashcards
What are the 3 primary morfologic classifications of disease?
Degenerative
Inflammatory
Neoplastic
What are the 2 primary morphologic classifications of inflammation?
Acute
and
Chronic
What are the 2 types of neoplasmas?
benign(non-infiltrative)
and
malignant(infiltrive)
What are degenerative diseases?
degenerative diseases are generally characterized by loss of normal histologic structures, without significant infiltration of inflamatory cellsor proliferation of indigenous cells
What are some primary processes associated with degeneration?
Aging
atrophy
hypoplasia
hormonal involution
Define cell injury.
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.
What is the difference between reversible and irreversible cell injury?
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.
What could cause cell injury?
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
Some key points to cell injury
- Cell injury can be reversible or irreversible.
- Hypoxia is the most important cause of cell injury.
- Irreversible cell injury can be recognized by changes in the appearance of the nucleus and
rupture of the cell membrane.
Name some exogenous causes of cell injury.
Exogenous causes include physical, chemical, and biological factors, such as heat and cold,
toxins and drugs, and viruses and bacteria.
Name some endogenous causes of cell injury.
Endogenous causes include genetic defects, metabolites, hormones, cytokines, and other
‘‘bioactive’’ substances.
What is hypoxia?
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.
What could cause hypoxia or anoxia?
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)
How does hypoxia cause cell injury?
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.
How does ATP deficiency cause cell swelling?
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.
Where does water accumulate during hydropic change?
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
What is the role of calcium in acute cell injury?
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
Ionized calcium amplifies the adverse effects of hypoxia by activating several enzymes:
- 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
How does the cell compensate for the loss of aerobic respiration?
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.
Is the cytoplasm of injured cells acidic or alkaline? and why?
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.
How does the reversible cell injury become irreversible?
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.
What are the signs of irreversible cell injury?
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.
Which mitochondrial changes are irreversible?
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
What are myelin figures?
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.
Which nuclear changes are signs of cell death?
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.’’
What are the clinical signs of irreversible cell injury?
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
Are there any clinically useful diagnostic laboratory signs of cell injury?
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
Can cell injury caused by hypoxia or anoxia be reversed or repaired by providing
the cells with adequate oxygen?
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.
What are free radicals?
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)
How are oxygen radicals formed?
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.
How are free oxygen radicals neutralized?
Superoxide is inactivated by superoxide dismutase and hydrogen peroxide by catalase and
glutathione peroxidase. Vitamin E and vitamin C also have antioxidant activity.
How do free radicals damage cells?
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.
What is necrosis?
Necrosis (from the Greek term necros, ‘‘dead’’) is localized death of cells, tissues, organs, or
parts of the body in a living organism.
What are the histologic signs of necrosis?
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.
What are the main forms of necrosis?
The main forms of necrosis are:
- Coagulative necrosis
- Liquefactive necrosis
- Caseous necrosis
- Fat necrosis
- Fibrinoid necrosis
What is the most common form of necrosis?
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.
What are the four things a disease should have to be called a disease?
Etiology
Pathogenesis
Morphology
Clinical Expression
What is pathogenesis
Sequence of eventsfrom the initial stimulus to the ultimate expression of the disease
