Chapter 1: Cell adaptation, injury and death Flashcards
the reactions of cells and tissues to abnormal stimuli and to inherited defects
Systemic pathology
examines the alterations in specialized organs and tissues that are responsible for disorders that involve these organs
general pathology
four aspects of a disease process that form the core of pathology are:
- etiology
- pathogenesis
- molecular and morphologic changes
- clinical manifestations
two major classes of etiologic factors:
1 genetic
2 acquired
father of modern pathology
Rudolf Virchow
The reversible functional and structural responses to more severe physiologic stresses with new altered state that allows cell to survive and continue to function.
Adaptation
Refers to an increase in the size of cells, resulting in an increase in the size of the organ.
hypertrophy
is an increase in the number of cells in an organ or tissue, usually resulting in increased mass of the organ or tissue
hyperplasia
__________ is reduced size of an organ or tissue resulting from a decrease in cell size and number.
atrophy
Reversible change in which one differentiated cell type (epithelial or mesenchymal) is replaced by another cell type
metaplasia
What is/are the cellular adaptation in the ff:
Increased demand, increased stimulation (e.g., by growth factors, hormones)
Hyperplasia, hypertrophy
What is/are the cellular adaptation in the ff:
Decreased nutrients, decreased stimulation
Atrophy
What is/are the cellular adaptation in the ff: Chronic irritation (physical or chemical)
Metaplasia
Acute and transient cell injury leads to
Acute reversible injury and cellular swelling fatty change
Progressive and severe (including DNA damage) cell injury leads to
Irreversible injury ➙ cell death
Necrosis
Apoptosis
Metabolic alterations, genetic/ acquired and chronic cell injury leads to what cellular response?
Intracellular accumulation
Calcification
A cellular response due to cumulative sublethal injury over a span of years
Cellular aging
The end result of progressive cell injury, also a normal and essential process in embryogenesis and hemeostasis.
Cell death
Two principal pathways of cell death
1 necrosis
2 apoptosis
3 autophagy (nutrient deprivation)
Three other processes that affect cells and tissues:
1 Intracellular accumulation
2 pathologic calcification
3 cell aging
The most common stimulus for hypertrophy of muscle is
increased workload
The mechanism of hypertrophy is
the result of increased production of cellular proteins
Hypertrophy can be induced by:
1 mechanical sensors (by increased work load)
- integrins
2 growth factors
- TGF-β
- insulin-like growth factor-1 [IGF-1]
- fibroblast growth factor
3 vasoactive agents
- α-adrenergic agonists
- endothelin-1
- angiotensin IIThe two main biochemical pathways involved in muscle hypertrophy are:
1 phosphoinositide 3-kinase/Akt pathway
(physiologic hypertrophy i.e. exercise)
2 signaling downstream of G protein-coupled receptors
(induced by growth factors and vasoactive agents; pathologic hypertrophy)
During muscle hypertrophy the α isoform of myosin heavy chain is replaced by
the β isoform - has a slower, more energetically economical contraction
Cardiac hypertrophy is associated with reinduction of ___________ found in embryonic heart.
ANF gene expression
A peptide hormone that causes salt secretion by the kidney, decreases blood volume and pressure, and reduce hemodynamic load?
atrial natriuretic factor (ANF)
Pts treated with this drug may undergo subcellular organelle selective hypertrophy. It shows hypertrophy of the smooth endoplamic reticulum (ER) in hepatocytes, an adaptive response that increases the amount of enzymes cytochrome P-450 to detoxify the drugs.
barbiturates
Physiologic hyperplasia can be divided into:
1 hormonal hyperplasia
- increases the functional capacity of a tissue
- ex breast (glandular epithelial cells)
2 compensatory hyperplasia
- increases tissue mass after damage or partial resection
- liver regeneration
It is caused by excess of hormones or growth factors acting on target cells.
Pathologic hyperplasia
ex endometrial hyperplasia (estrogen)
BPH (androgen)
Hyperplasia is a characteristic response to certain viral infections, such as papillomaviruses that cause?
skin warts and several mucosal lesions composed of masses of hyperplastic epithelium
Mechanism of hyperplasia
the result of growth factor–driven proliferation of mature cells and, in some cases, by increased output of new cells from tissue stem cells
Examples of physiologic atrophy:
1 notochord and thyroglossal duct
2 thymus
3 uterus decreases in size after parturition
The common causes of atrophy are:
1 Decreased workload (atrophy of disuse)
- fractured bone
2 Loss of innervation (denervation atrophy)
3 Diminished blood supply
4 Inadequate nutrition
- marasmus
5 Loss of endocrine stimulation
- menopause
6 Pressure
- tissue compression by tumorresults from decreased protein synthesis (reduce metabolic activity) and increased protein degradation in cells
Mechanisms of Atrophy
The degradation of cellular proteins occurs mainly by ________ triggered by nutrient deficiency and disuse.
the ubiquitin-proteasome pathway
Cellular proteins are degraded in
proteasomes
the process in which the starved cell eats its own components in an attempt to find nutrients and survive forming autophagic vacuoles and associated in atrophy.
Autophagy (“self eating”)
Residual bodies that impart a brown discoloration to the tissue (brown atrophy)
Lipofuscin granules
The most common epithelial metaplasia is ________ as occurs in the respiratory tract in response to chronic irritation
columnar to squamous
Metaplasia from squamous to columnar type in which the esophageal squamous epithelium is replaced by intestinal-like columnar cells under the influence of refluxed gastric acid and may lead to glandular (adeno)carcinomas.
Barrett esophagus
the formation of cartilage, bone, or adipose tissue (mesenchymal tissues) in tissues that normally do not contain these elements. Example, bone formation in muscle (myositis ossificans).
Connective tissue metaplasia
the result of a reprogramming of stem cells that are known to exist in normal tissues, or of undifferentiated mesenchymal cells present in connective tissue forming a new pathway.
Mechanisms of Metaplasia
The differentiation of stem cells to a particular lineage is brought about by signals generated by
1 cytokines
2 growth factors
3 extracellular matrix components in the cells’ environment
It regulates gene transcription directly through nuclear retinoid receptors which can influence the differentiation of progenitors derived from tissue stem cells
Vitamin A (retinoic acid)
early stages or mild forms of injury, the functional and morphologic changes are reversible if the damaging stimulus is removed
Reversible cell injury
The hallmarks of reversible injury with the resultant depletion of energy stores in the form of adenosine triphosphate (ATP) and changes in ion concentrations and water influx are?
1 reduced oxidative phosphorylation
2 cellular swelling
two principal types of cell death, which differ in their morphology, mechanisms, and roles in physiology and disease
1 necrosis
2 apoptosis
When damage to membranes is severe, lysosomal enzymes enter the cytoplasm and digest the cell, and cellular contents leak out, resulting in
necrosis (always a pathologic process)
When the cell’s DNA or proteins are damaged beyond repair, the cell kills itself by
apoptosis
is a deficiency of oxygen, which causes cell injury by reducing aerobic oxidative respiration
Hypoxia
Causes of Cell Injury
1 Oxygen Deprivation 2 Physical Agents 3 Chemical Agents and Drugs 4 Infectious Agents 5 Immunologic Reactions 6 Genetic Derangements 7 Nutritional Imbalances
Causes of hypoxia include
1 reduced blood flow (celled ischemia)
2 inadequate oxygenation
3 decreased oxygen-carrying capacity (anemia)
4 severe blood loss
Physical agents capable of causing cell injury include
1 mechanical trauma 2 extremes of temperature (burns and deep cold) 3 changes in atmospheric pressure 4 radiation 5 electric shock
the study (logos) of disease (pathos)
Pathology
