CH 2 Cellular Injury, Adaptation, and Maladaptive Changes Flashcards
1
Q
etiology
A
the original cause of a cellular alteration or disease
2
Q
Examples of different distinctive cellular changes from etiologic agents
A
- Exposure to extreme cold temperatures will cause localized frostbite and tissue necrosis.
- Exposure to electrical current can burn tissue and cause cardiac rhythm disturbances.
- Alcohol abuse can cause the liver to take on characteristic fatty changes.
3
Q
Cells can do one of two things
A
- Develop adaptive, compensatory changes in an attempt to maintain homeostasis
- Develop maladaptive changes, which are derangements of structure or function
In overwhelming insult cell death or injury can result
4
Q
Histology
A
the microscopic study of tissues and cells
5
Q
Biopsy
A
extracts a cell sample from an organ or mass of tissue for a histological examination
6
Q
pathognomonic changes
A
unique histological findings that represent distinct disease processes
Example: an inflamed, craterlike breach in the gastrointestinal mucosa, as seen on an endoscopic examination of the stomach and duodenum, is pathognomonic for peptic ulcer disease
7
Q
Atrophy
A
cellular adaption in which cells revert to a smaller size in response to changes in metabolic requirements or their environment
8
Q
Causes of cellular atrophy
A
- Disuse or diminished workload
- Lack of nerve stimulation (paralysis)
- Loss of hormonal stimulation
- Inadequate nutrition
- Decreased blood flow (ischemia)
- Aging
9
Q
Paralysis
A
lack of nerve stimulation
10
Q
ischemia
A
decreased blood flow
11
Q
Paralysis causes
A
lack of muscle contraction, loss of nerve stimulation, and decreased workload of the muscles
12
Q
Hypertrophy
A
increase in individuals cell size resulting in enlargement of functioning tissue mass.
13
Q
Angiogenesis
A
stimulated by exercise to the growth of new blood vessel branches
14
Q
Physiological Hypertrophy
A
the enlarged muscle is adequately perfused and supplied with blood flow, oxygen, and nutrients because of angiogenesis
15
Q
Pathological Hypertrophy
A
when there is an increase in cellular size but not an increase in supportive structures necessary for the enlarged cell’s increased metabolic needs
16
Q
Stimulus for hypertrophy increases the muscle cell’s:
A
- actin and myosin filaments
- enzymes
- mitochondria
- blood vessel growth
- ATP production
17
Q
Hyperplasia
A
the increase of number of cells in a tissue or organ, occurs only in cells capable of mitotic division
18
Q
Hyperplasia stimulated by:
A
hormonal or compensatory cellular mechanisms
19
Q
Keloid
A
maladaptive hyperplastic accumulation of epithelial tissues and connective tissue occurring in wound healing that creates an elevated, disfigured scar
20
Q
Stem Cells
A
self-renewing cells
21
Q
Benign Prostatic Hyperplasia (BPH)
A
prostate gland cells increase in number in the aging male caused by testosterone stimulation
22
Q
Metaplasia
A
Replacement of one type of cell by another type of cell, likely a result of the cell’s genetic programming to a change in environmental conditions, such as inflammation and the substitution of cells ensures the tissues survival
23
Q
GERD and Metaplasia
A
lower esophageal sphincter is weakened and allows stomach acid into the lower esophagus. The irritated cells inflame, and with prolonged irritation and no treatment, the cells turn from squamous epithelium to columnar stomach-like cells that have a greater tolerance for the acid
24
Q
Barret’s esophagus
A
the metaplastic change from squamous to columnar cells. It requires periodic examination and aggressive treatment because it can deteriorate into cancer of the esophagus
25
Dysplasia
deranged cellular growth within a specific tissue, often a result of chronic inflammation or a precancerous condition
26
Dysplasia Histologic View
Vary in size, shape, and architectural organization compared to the healthy cells
27
Neoplasia
"new growth", usually refers to disorganized, uncoordinated, uncontrolled proliferative cell growth that is cancerous. Neoplasm and tumor are often used interchangeably
28
Neoplasm classifications
benign or malignant, depends on differentiation of cells
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Differentiation
the process where newly growing cells acquire the specialized structure and function of the cells they replace
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Malignant neoplasm
contain poorly-differentiated cells which have a tendency to break away, enter the lymphatic or circulatory systems, and metastasize to distant sites to form secondary neoplasms.
31
Benign Neoplasms
contain well-differentiated cells, or cells that resemble the healthy cells of the tissue of origin. the cells do not metastasize or break loose from the tissue of origin.
32
Cell injury occurs when:
cells are exposed to stress that no longer allows them to maintain homeostasis, resulting in structural and functional changes
33
Basic changes of cell injury
- dysfunction of sodium-potassium pump
- loss of plasma membrane integrity
- mitochondrial dysfunction
- defects in protein synthesis
- intracellular accumulations
- cellular swelling
- DNA damage
34
Dysfunction of the Sodium Potassium Pump, when it's not working: these things can happen
- intracellular sodium increased because it can't be adequately pumped out of the cell, leading to cellular swelling
- lack of ATP, energy-dependent calcium pump becomes dysfunctional, calcium accumulates in cell and disrupts numerous biochemical processes
35
Calcium issues from dysfunction of sodium-potassium pump
Buildup of calcium activates a number of enzymes that further deplete ATP, damage the plasma membrane, disrupt DNA, and induce cell degeneration.
36
Pathological Calcification
the deposition of calcium and other minerals within tissues, occurs in a variety of conditions. Calcifications often accumulate in areas of cell injury and cell death
37
Conditions that cause pathological calcification (Box 2-2)
* In arteriosclerosis, calcifications accumulate within long-standing plaque. Calcified plaque is hardened, fragile, and likely to break apart into small pieces that can travel in the bloodstream.
* Aortic sclerosis, a common disorder in elderly individuals, involves a calcified aortic heart valve. Calcification causes thickening and narrowing of the heart valve with consequent blood disruption.
* On mammography, a breast lesion containing microcalcifications is often indicative of a malignancy. Calcium deposits are seen within the nutrient-deprived cells of a malignant tumor in the breast.
38
Loss of Plasma Membrane Integrity - Cellular injury
- injurious agents can affect any of the organelles
- water can enter the intracellular compartment causing intracellular swelling
- mitochondria can be damaged, halting the cell's ability to produce energy
- organelles can swell and deteriorate
- nucleus can be left vulnerable to injury and the cell would then be left without the ability to regenerate
39
Defects in Protein synthesis ability- cellular injury
With dwindling ATP availability, the critical cellular process of protein synthesis begins to fail. The cells cannot manufacture proteins, which are crucial constituents for their own regeneration and many different kinds of body processes. Lack of protein synthesis can begin the process of cell degeneration or cell death.
40
Intracellular Accumulations - Cellular Injury
Can accumulate excessive amounts of various substances:
-cellular constituents
-environmentally acquired substances
-cell breakdown products
Due to abnormal metabolic function, these may be harmless or toxic to the cell and may be transient or become permanently embedded in the cell
41
Intracellular accumulation example - excessive alcohol
hepatocytes, involved in lipid metabolism, can sustain toxic injury from alcohol and accumulate large quantities of fat causing fatty liver
42
Fatty Liver
a distinct histological change associated with alcoholism causing the liver to enlarge and be dysfunctional in part due to intracellular accumulation
43
Familial Hypercholesterolemia - Intracellular Accumulation
Condition that causes defective cholesterol metabolism
| -causes yellow, raised skin lesions from intracellular accumulation of excess cholesterol in epithelial cells
44
Xanthomas and xanthelasma
yellow, raised lesions from intracellular accumulation of cholesterol in epithelial cells
45
Anthracosis
Coal Miner's Lung Disease
-environmentally derived from chronically inhaling coal dust, leads to cellular accumulation in respiratory tract epithelial cells leading to blackened lung tissue
46
Jaundice
the yellow hue of skin and sclera, from the cellular accumulation of bilirubin in the bloodstream. If excess RBC breakdown or liver dysfunction occurs, bilirubin accumulates in bloodstream.
47
Bilirubin
A yellow, pigmented substance, a breakdown product of hemoglobin. Constitutes of bile, synthesized by the liver, with a high affinity for elastin, a component of skin and sclera of the eye.
48
Genetic Damage - Cellular Injury
Injury to the DNA causes mutations, changing the cell's structure and function. Mutated DNA makes mutated RNA, instructs ribosomes to make abnormal proteins and manufacture abnormal secretions.
Often incompatible with life and will initiate change to bring about apoptosis (cell death)
49
Apoptosis
programmed cell degeneration - death
50
Oncoproteins
cancerous proteins manufactured by cancerous cells
51
DNA mutations - Radiation
With exposure to high doses of radiation, it can damage the DNA in the genes and mutate them to oncogenes, triggering cancerous cell changes
52
Causes of cell injury:
* Hypoxic cell injury
* Free radical injury (oxidative stress)
* Physical agents of injury
* Chemical injury
* Infectious agent injury
* Injurious immunological reactions
* Genetic defects
* Nutritional imbalances
53
Hypoxia
oxygen deprivation, most common cause of cell injury
54
Most common cause of cellular hypoxia
ischemia: diminished circulation
55
Ischemia occurs most often from:
obstruction of arterial blood flow
56
Most common arterial obstruction:
atherosclerotic plaque and clot formation blocking downstream circulation from the clot
57
Xanthelasma
intracellular accumulation of cholesterol in skin cells around the eyelids
58
Anemia and Hypoxia
in anemia blood lacks sufficient hemoglobin resulting in insufficient transport of oxygen by hemoglobin, cells not receiving fully oxygenated blood leads to cellular hypoxia
59
Hypoxia and Anaerobic Metabolism
enter anaerobic conditions, creating only 2 ATP and pyruvic acid. Pyruvic acid turns to lactic acid which alters cellular biochemical activity. Anaerobic metabolism cannot sustained life for a prolonged time
60
Causes of cellular hypoxia
- Anemia
- Ischemia
- exposure to low concentrations of oxygen in the environment, such as occurs at high altitudes;
- inadequate oxygen diffusion at the alveoli, as in pneumonia;
- suffocation injury;
- airway obstruction caused by a foreign body
- inflammation of oropharyngeal tissues.
61
Oxidative Phosphorylation
the process of cells generating energy in the mitochondria.
62
Free Radicals are made by:
during oxidative phosphorylation, described as a respiratory burst, small amounts of reactive oxygen molecules are produced as by-products. The reactive oxygen molecules are free radicals
63
Free Radical Make-Up
have a single unpaired electron in an outer orbit creating instability and reactivity with adjacent molecules
64
Free Radicals are:
oxidizing agents with the ability to penetrate the cell’s plasma membrane, disrupt internal organelles, and damage the nucleus and its DNA.
65
Free Radicals react with:
constituents of cell's plasma membrane and organelle membranes causing causing oxidative degradation
66
Oxidative Stress
when free radical generation overwhelms the mechanism s of removal causing cell injury
67
superoxide dismutases
a series of enzymes, a cell's multiple mechanisms to remove free radicals and minimize injury
68
Individuals can counteract free radical injury by:
consumption of antioxidants such as vitamins A, E, C, and beta-carotene
69
Ischemic-reperfusion injury
transient ischemia with subsequent resumption of circulation. Depending on the ischemic insult intensity and duration, variable numbers of cells die after blood flow is restored.
70
Cells die from ischemic-reperfusion because
new damaging forces are activated by free-radicals during reperfusion casing cell death in cells that may have recovered
71
A disease that commonly involves ischemic-reperfusion injury
heart disease. IR occurs when a blood clot obstructs coronary artery and causes cardiac muscle ischemia. Reperfusion happens with blood clot dissolution. by-products from mitochondria's oxidative phosphorylation from temporary hypoxia, is free radicals. Those free radicals cause injury to surrounding tissue.
72
Physical Agents of Injury
- Mechanical trauma (laceration, gunshot, fall, etc.)
- Temperature extremes
- Electric shock
- radiation
- extreme changes in environmental pressure
- excessive noise
73
Physiological responses to physical trauma
often include initiation of the inflammatory response, leading to healing or further cell damage.
74
Hypertension - cell injury
Constant high pressure on endothelial lining of arteries and vasculature causes shearing injury on endothelial lining. Also creates weakened integrity of smooth muscle in artery walls.
Endothelial injury initiates development of atherosclerosis in arterial system and developments of aneurysm
75
Chemical injury caused by:
caused by endogenous biological substances like
- hypernatremia
- hyperglycemia
or exogenous synthetic substances like
-drugs
76
Hypernatremia
high sodium levels in blood stream
77
Advanced Glycation End Products
produced when high levels of blood glucose react with endothelial membrane consituents. These damage coronary and kidney arteries, and vessels of lower extremity, and retina of the eyes
78
Infectious Agents of Injury
- bacteria
- fungi
- viruses
- parasites
- other varieties of microorganisms
79
Allergies
adverse immune reactions in response to environmental substances called antigens
80
Rheumatoid Arthritis
immune cells are triggered by an unknown antigen to attack own body's joints
81
Genetic Defects - Cell Injury
genetic disorders damage and mutate DNA, initiating disease
82
Malnutrition
inadequate daily intake of carbs, fats, proteins, vitamins, and minerals. Adversely affects cell function
83
Fat soluble vitamins
A, D, E, K
84
Endothelium Secretes:
- vascular endothelial growth factor (VEGF)
- nitric oxide (NO)
- endothelin
85
Vascular Endothelial Growth Factor (VEGF)
also called angiogenesis growth factor
| -stimulates synthesis of collateral blood vessel branches
86
Nitric Oxide from endothelium does what
vasodilates
87
Endothelin secreted by endothelium does what?
Vasoconstricts
88
Blood constituents that acts on endothelium are:
- glucose
- lipids
- platelets
- norepinephrine
- epinephrine
- acetylcholine
- vasopressin
- natriuretic peptides
- angiotensin II
89
Considered the body's largest organ
endothelium
90
Endothelial Injury acts as an initiate of ________ and is the fundamental cell change that causes
______ ______
arteriosclerosis, cardiovascular disease
91
Most significant injurious agents of endothelial cells
- hypertension
- diabetic hyperglycemia
- free radicals
- persistent angiotensin II secretion
- LDL - C
92
Aneurysm
weakened area in an arterial wall
93
circle of willis
arterial network within the brain, where a berry aneurysm takes place.
94
Angiotensin II
product of renin-angiotensin-aldosterone cacade. Vasoconstrictor, raises BP.
95
Atherogenesis Definition
gradual and progressive development of atherosclerotic plaque in arteries initiated by endothelial injury
96
Steps of atherogenesis
1. Areas of endothelial injury undergo inflammation, attracting WBCs and platelets to the region.
2. Inflammatory changes cause diminished vasodilatory capacity, setting up conditions for LDL-C deposits and clot formation
3. LDL-C accumulates in macrophages to form foam cells, the foundation for large spans of atherosclerotic plaque along artery walls
4. During atherosclerotic formation, endothelial nitric oxide (NO) is depleted, inhibiting vasodilatory capacity of arteries.
5. Depletion of NO and changes of endothelium and LDL deposition cause arterial vasoconstriction and atherosclerosis, detrimental combination for coronary arteries: atherogenesis
97
Types of cell death
Apoptosis
| Necrosis
98
Apoptosis
Programmed cell death. Cells degenerate at a specific time with no adverse effects on the body
99
Necrosis
Cell death caused by injury. Cell is overcome by insult, cannot maintain homeostasis, before severely dysfunctional, and may adversely affect neighboring tissues or the organ as a whole.
100
Examples of Physiological Apoptosis
- hand's embryonic development in the womb
| - female ovaries in menopause
101
What happens when cells fail to undergo apoptosis
cells survive for an abnormally long amount of time and give rise to certain cancers, tumors, and detrimental hyperplastic cell changes
102
Increased cellular apoptosis, what is it and what diseases are linked to it
excessive cell rate death, spinal muscular atrophy and hashimotos thyroiditis
103
Infarction
ischemic necrosis, the death of tissue as a consequence of prolonged ischemia
104
Elevated levels of _____ and ____ confirm death of myocardial tissue
CPKmb (lysosmal enzyme), troponin (cardiac protein)
105
Gangrene occurs when
tissues endure prolonged ischemia, undergo infarction, and necrosis, then are exposed to bacteria that thrive on decaying tissue
106
Bacteria associated with Gangrene
Clostridium perfringens
107
Gangrene is most often seen in:
Patients with peripheral arterial disease of the lower extremities
