Gen Pathology Exam 1 Section 1: Cell Injury, Cell Death, and Adaptations Flashcards
1
Q
Pathology
A
study of disease, “suffering”
pathos- meaning “experience” or “suffering”
-logia meaning the “study of”
2
Q
Homeostasis
A
tendency toward a relatively stable equilibrium optimal homeostasis is interchangable with optimal health
3
Q
Disease
A
structural and/or functional change in the body that is harmful to the organism; a deviation from optimal health
4
Q
What are the two observable clinical features?
A
sign and symptoms
5
Q
What is a sign?
A
objective and observable indication of disease; obtained via physical examination
Ex: increased body temp (fever)
6
Q
What is a symptom?
A
subjective evidence of disease or physical disturbance; patients experience; obtained via oral report from patient history
Ex: pain, blurry vision, and numbness
7
Q
Cellular Adaptation
A
cell’s attempt to preserve viability while overcoming stressful stimulus
8
Q
What are 2 factors that influence cell’s ability to overcome a harmful stimulus?
A
- the cell type
2. the nature of the cellular stress
9
Q
When will cell injury occur?
A
when cell is NO longer able to adapt to cellular stressors
10
Q
etiology
A
the cause, set of causes, or manner of cause of given pathology
11
Q
What is a “risk factor”?
A
used to label causation agent
Ex: smoking is a risk factor for lung cancer
12
Q
What two things lay at the core of most disease processes?
A
- Genetic susceptibilities (“nature”) Ex: Huntington Disease
- Environmental triggers (“nurture”) Ex: environmental role
13
Q
Huntington Disease
A
neurodegenerative disease; causes severe dementia during middle adult hood and develops via specific genetic mutation
14
Q
Mesothelioma
A
a cancer of pulmonary pleura; usually in people with history of exposure to asbestos (env. role)
15
Q
Pathogenesis
A
series of events involved in cellular and molecular changes involved with specific disease process
describes biological mechanisms that describe the structural and functional abnormalities of a disease process
16
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Physiological Adaptations
A
responses expected to occur with normal physiological changes
Ex: hormonal enlargement of uterus and breast during pregnancy
Ex: skeletal muscle hypertrophy following weight training
17
Q
Pathological Adaptations
A
responses to excessive cellular stress and indicate a loss of optimal structure and function; allow cells to avoid/delay injury
Ex: Cardiac Ventricular hypertrophy
Ex: heavy alcohol consumption
18
Q
What are non harmful stimuli?
A
changes in cell’s environment assisting it in maintaining homeostasis
19
Q
What are harmful stimuli?
A
changes in cell’s environment that are sources of cellular stress
20
Q
Are cellular adaptations reversible?
A
yes
21
Q
What are the 4 main adaptations to stress?
A
- Hypertrophy
- Hyperplasia
- Atrophy
- Metaplasia
22
Q
Hypertrophy
A
An increase in size of cell, and if severe may increase size of organ or enlarge area of organ.
Achieved due to increase in synthesis of intracellular proteins and organelles
Ex: ventricular hypertrophy
23
Q
Hyperplasia
A
an increase in the number of cells, due to cellular division; typically results in enlargement of tissue
Ex: Benign Prostatic hyperplasia
Ex: Wart (verruca)
24
Q
Atrophy
A
shrinkage of cell size, due to loss of cell’s structural proteins; overall size of tissue may decrease
Function is diminished, but it remains viable ( IS NOT DEAD)
Causes: immobilization, denervation, ischemia, malnutrition, aging
25
What two things does atrophy involve?
1. reduced protein synthesis
| 2. increase rate protein breakdown
26
Metaplasia
one cell type replaced by another cell type; one adult cell transitioning into a different adult cell type
Ex: Chronic smokers--ciliated columnar epithelia replaced by stratified squamous cells; leads to chronic bronchitis
Ex: Gastroesophageal reflux disease; leads to esophageal cancer
27
What are the 8 causes of cell injury and death?
1. Ischemia
2. Hypoxia
3. Toxic Exposures
4. Infections
5. Immunological Reaction
6. Nutritional Imbalances
7. Trauma
8. Aging
28
Ischemia
insufficient blood supply to a tissue
| Ex: myocardial infarction (heart attack), cerebral infarction (stroke), ischemia bowel disease, gangrene
29
What does ischemia most commonly develop from?
atherosclerotic plaque formation, blood clots, reduced cardiac output (heart failure), compression of major arteries
30
Hypoxia
organ is NOT receiving adequate oxygen within blood supplying the organ
Ex: pneumonia, carbon monoxide poisoning, a disease inhibiting diaphragm (botulism, Guillain-Barre syndrome) or injury to phrenic nerve
31
Toxic Exposures
depends on how harmful (noxious) it is and concentration and duration of exposure
Examples of toxic poisonous substances:
air pollution, insecticides, asbestos, CO, smoke, alcohol
Examples of innocuous substances:
1. diabetes (hyperglycemia) causes peripheral vascular disease
2. water intoxication
3. retinopathy of prematurity
32
Infections
all forms of infectious microbes (bacteria, viruses, protoxoans, fungi) may injure cells
33
Immunological Reaction
over-activation of normal immune mechanisms may injure cells via autoimmunity or allergies
34
Nutritional Imbalances
deficiencies or excesses of dietary nutrients may inhibit homeostasis and result in pathology
35
Trauma
from mechanical (physical) trauma, thermal trauma, electrical injury, or injury from high-energy radiation (ionizing or irradiation)
36
Aging- Cellular Senescence
reduced capacity for cells to react to stress and maintain homeostasis
37
Reversible Cellular injury
may regain original form and function if stimulus removed
38
Two Types of Reversible Cellular Injury
1. Cellular Swelling
| 2. Fatty Change (Steatosis)
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Cellular Swelling
occurs because not enough ATP to "power" ATP-dependent pumps (Na-K Pump, Calcium Pump)
Results in accumulation of ions w.in cell and therefore accumulation of water in cell
40
"hydropic change" or "vacuolar degeneration"
names for microscopic findings of cellular swelling
41
Fatty Change (Steatosis)
accumulation of lipid (fat) vacuoles w/in a cell's cytoplasm; found commonly in cells normally involved with lipid metabolism
Ex: in liver
42
What will persistent or excessive cellular injury eventually cause?
it will cause a transition of injured cell from reversible injury to irreversible injury (DEATH)
43
What 3 things is Cellular Death Associated with?
1. significant mitochondrial damage or dysfunction
2. a damaged or dysfunctional plasma membrane
3. genetic or nuclear damage
44
What are the 2 Primary Pathways for cellular death (irreversible cellular injury)?
1. Apoptosis
| 2. Necrosis
45
Apoptosis
regulated cell death, controlled cellular breakdown; maintains outer plasma membrane and forms apoptotic bodies that fall away and are removed via phagocytes
(could be physiological or pathological)
46
Necrosis
destroys cell membrane and initiates prominent inflammatory response--> brings phagocytes to area to eliminate dead cellular debris and initiate healing
(always a pathological process)
47
What are the type types of morphological changes of necrosis?
1. cytoplasmic changes
| 2. nuclear changes
48
What 2 types of cytoplasmic changes can occur in necrosis?
1. eosinophilia
| 2. myelin figures
49
Eosinophilia
necrtotic cells manifest with an increase ink or red appearance with stranded hematoxylin and eosin (H&E) stain
50
myelin figures
necrotic cells contain membrane damage and myelin figures which = "rolled-up" or "scroll-like" area of lipid bilayer that is within a cell
51
What 3 types of Nuclear Changes can occur in necrosis?
1. Pyknosis
2. Karyorrhexis
3. Karyolysis
52
Pyknosis
nuclear shrinking and increase basophilia (blue-staining/darker appearance) due to nuclear DNA condensing
53
Karyorrhexis
after pyknosis, cell fragment/fall apart in the process
54
Karyolysis
after karyorrhexis; nucleus continues to degrade and basophilia fades. After 1-2 days, nucleus disappears
55
What are the 5 distinct patterns of necrosis?
1. Coagulative Necrosis (subcategory is Gangrenous Necrosis)
2. Liquefactive Necrosis
3. Caseous Necrosis
4. Fat Necrosis
5. Fibrinoid Necrosis
56
Coagulative Necrosis
most likely to manifest in solid organs that experience severe ischemia; maintains firm texture for a few days to weeks after tissue dies; once WBCs accumulate it will phagocytize necrotic tissue and cavity is left or scar tissue
57
Examples of Coagulative Necrosis
Sites of:
1. myocardial infarction (heart attack)
2. ischemia to a kidney or adrenal glands
58
Gangrenous Necrosis
it is coagulative necrosis in an extremity, occurs in hands and feet; mostly in foot/leg
59
Examples of Gangrenous Necrosis
peripheral vascular disease
frostbite
major trauma that obstructs blood supply
60
What are the 3 types of Gangrenous Necrosis?
1. Dry Gangrene = uncomplicated gangrene
2. Wet Gangrene = when infected w/ opportunistic bacteria--it liquefies
3. Gas Gangrene = when bacteria infects and gas byproduct and is trapped w/in tissues Ex: Clostridium perfringens
61
Liquefactive necrosis
tissues liquify due to WBC's releasing enzymes that breakdown necrotic tissue; if survive, cavity left behind; usually ass. with bacterial infection, but could be do to deep fungal infections too
62
Examples of liquefactive necrosis
hypoxia to cells of CNS, therefore cerebral infarctions (strokes) lead to this
63
Caseous Necrosis
tuberculosis infections; produce "cheese-like" pattern; relates to crumbly (friable) cheeses-- blue cheese
64
Microscopically, what is caseous necrosis called?
"caseous granuloma"
| Granulomas = pattern of chronic inflammation that consists of collections of macrophages
65
Fat necrosis
(= enzyme necrosis); areas of fat destruction that result in saponification
66
What does Fat necrosis most likely result form?
a ruptured pancreas--the enyzmes cause tissue necrosis--> usually due to acute pancreatitis from chronic alcoholism
67
Examples of Fat necrosis
direct trauma via vehicle accident or trauma to breast tissue
(also ruptured pancreas due to chronic alcoholism)
68
Fibrinoid necrosis
requires microscope to visualize; typically occurs in vessel walls of patients with autoimmune disorder causing vasculitis
(manifests as eosinophilic appearance when biopsy taken)
69
Vasculitis
general term for inflammation within vessel walls
70
The two primary pathways for Apoptosis
1. Mitochondrial Pathway
| 2. Death Receptor Pathway
71
Mitochondrial Pathway of apoptosis
intrinsic apoptosis, increase in mitochondrial membrane permeability to cytochrome C and that leaks into cytosol, and increase levels of caspase 9
72
What stimulates Mitochondrial Pathway of apoptosis?
genetic damage, accumulation of misfolded proteins, or decease in GF
73
Death Receptor Pathway for apoptosis
extrinsic, surface of cell may bind with signaling molecule (like tumor necrosis factor--TNF or Fas ligand) and activate caspase 8
74
What stimulates Death Receptor Pathway of apoptosis?
autoreactive (self-reactive) WBC's that cause autoimmunity or virally-infected cells
75
What do both, Mitochondrial and Death Receptor apoptosis pathways form?
apoptotic bodies--> therefore membrane is NOT sig. disrupted
76
Autophagy
= "self-eating"; a survival mechanism for cell to avoid death @ time it's experiencing nutrient deprivation
- sequesters own organelles within autophagic vacuole; then cell's lysomomes release enzymes that break down the vacuole and use as a source of nutrients
*at a point cell will STOP eating itself and initiate apoptosis
77
5 Mechanisms of Cellular Injury
1. Hypoxia and Ischemia
2. Ishcemia-Reperfusion Injury
3. Oxidative Stress
4. Chemical (Toxis) Injury
5. Genetic Damage
78
Hypoxia and Ischemia (mechanisms of cellular injury)
inhibit cells ability to perform ATP production, via oxidative phosphorylation within mitochondria; ATP needed for protein synthesis and pumps; deprived ATP leads to membrane destruction and trigger necrosis
79
What cells are resistant to Hypoxia and ishcmeia?
cells that can switch to glycolysis (but that will increase lactic acid production and may decrease pH and cause injury
80
What cells are high susceptible to Hypoxia and Ischemia?
cardiac myocytes or CNS neurons b/c have inability to perform glycolysis; therefor myocardial infarction and cerebral infarction quickly develop during state of ischemia or hypoxia
81
Ischemia-Reperfusion Injury (mechanism of cellular injury)
reperfusion of blood to ischemic tissue may cause this injury; will deliver large amounts of WBC's that initiate inflammatory rxn and produce large amounts of reactive oxidative species (ROS) and further injuries ischemic tissue
82
Oxidative Stress (mechanism of cellular injury)
an increase in ROS; injuries variety of cellular componets like;
- proteins, lipids (lipid bilayer), or nuclear DNA
- -> may cause apoptosis or necrosis
83
What does oxidative stress occur in?
normal redox rxns, exposure to harmful chemicals; hypoxia; ionizing radiation, excessive inflam. rxns, or ischemia-reperfusion injury
84
Chemical (toxic) injury-- 2 Main Mechanisms (mechanism of cellular injury)
1. Direct-Injury
| 2. Latent-Injury
85
Direct-injury mechanism of chemical injury
chemical becomes bound to cell and directly kills cell and interferes with fxn --> "cytotoxicity"
occurs--> with anti-cancer chemotherapy medications; exposure to naturally-occurring toxins like Cholera toxin (deadly diarrhea disease)
86
Latent-injury mechanism of chemical injury
substance ingested and does NOT cause direct-injury, BUT is converted into a harmful substance via activity of normal metabolism; occurs in SER of liver via cytochrome P-450 system
87
Example of Latent-injury
consume toxic levels of Tylenol (acetaminophen) which puts oxidative stress on hepatocytes (liver cells) and damages membranes--> creating acute liver necrosis and liver failure
88
Genetic Damage (mechanism of cellular injury)
damage to cell's DNA will produce mutations that increase risk of cancer formation (carcinogenesis), BUT may also trigger apoptosis via mitochondria pathway
89
Sources of Genetic Damgae
ionizing radiation, viral infections, or various chemical like chemotherapeutic medicaitons
90
Intracellular Accumulations definition and causes
when abnormal or excessive substances accumulate in a cell due to:
1. abnormal metabolism
2. defective protein folding or cellular transportation
3. lack of an enzyme
4. ingestion of an indigestible substance
- some accumulations indicate cell injury or pathology; while others are relatively normal
91
8 Intracellular Accumulations
1. Fatty change (steatosis)
2. cholesterol
3. Glycogen
4. Lipofusion
5. Melanin
6. Hemosiderin
7. Carbon
8. Tattoo pigment
92
Fatty Change (steatosis) (intracellulaar accumulations)
when fat accumulates in cell it is direct evidence of cellular injury; most likely to occur in liver; but also occurs in skeletal muscle, heart, or kidneys
93
Causes of Fatty Change
toxic exposure, obesity, protein malnutrition, diabetes mellitus, or ischemia/hypoxia
94
Cholesterols (intracellulaar accumulations)
needed for cell membranes; BUT hypercholesterolemia may overload phagocytes and can injury inner lining or arterial walls, specifically endothelial cells and increase onset of atherosclerotic plagues
95
Reasons for abnormally high cholesterol:
- high intake of fats (trans or sat.)
| - or decrease cholesterol catabolism
96
Glycogen (intracellulaar accumulations)
stores glucose in liver and skeletal muscle tissues; glycogen storage disease is conditions that produce elevated intracellular glycogen (abnormal)
97
Lipofusion (intracellulaar accumulations)
normal age-related finding in elderly or cells at end of their life; composed on lipids and proteins; "wear and tear" pigment
98
Melanin (intracellulaar accumulations)
normal pigment to skin and produced by melaocytes;; brownish-black pigment; protect vs UV radiation; excessive = freckles (ephelis); UVB stimulates melanocytes to produce melanin
99
Hemosiderin (intracellulaar accumulations)
major iron-storage complex within blood and tissues (macrophages in bone marrow, spleen, liver); accumulates at risky levels--> means site has had some bleeding (hemmorrhage) --> such as a bruise OR cells contain excess iron (hemosiderosis)
100
Hemosiderosis
= formation of iron overloading and ass. with repetitive blood transfusions
(when iron in excess, viewed with "Prussian Blue" stain)
101
Carbon (intracellulaar accumulations)
(coal dust); MOST COMMON exogenous pigment in humans; more likely in inds. living in high populated areas, coal miners, and smokers
- anthracosis
102
anthracosis
blackening of the lungs
103
Tattoo Pigments (intracellulaar accumulations)
composed of metal salts (iron oxide)
| pigment phagotosized by macrophages within dermis and retained for life
104
What are the two main forms of Fatty Liver Disease?
1. Alcoholic Liver Disease
| 2. Non-alcoholic Fatty Liver Disease
105
Alcoholic Liver Disease
alcohol = most common cause of hepatic injury like
1. hepatic steatosis (fatty liver disease)
2. hepatitis (inflammation of liver)
3. cirrhosis (scarring of liver)
106
Excessive alcohol intake is _____all chronic liver disease in US and nearly half of all _____ cases.
60%
| cirrhosis
107
____ percent of heavy drinkers develop _____. Of these ____ develop ______. Of these ____ develop ____.
90-100%; hepatic steatosis
25%; hepatitis
15%; cirrhosis
108
About ____ years of heavy drinking is required to develop cirrhosis
20 years
109
______ of heavy drinking required to develop hepatitis
few weeks
110
___ and ___ are reversible if stop drinking, and ____ is NOT reversible.
hepatic steatosis and hepatitis; cirrhosis
111
Ascitis
(ass. with advanced liver disease)
occurs when peritoreal cavity of abdomen accumulates excessive fluid (edema); liver = main source of protein production and when injured it cannot do that --> so decrease proteins in blood results in fluid from blood leaving circulation and accumulate in body tissues
112
Caput Medusae
(ass. with advanced liver disease)
when superficial epigastric veins become engorged
advanced liver disease cirrhosis prevents blood from flowing through liver, therefore shunts venous blood from liver to epigastric veins and it occurs as dilated and tortuous superficial abdominal veins
113
Mallory bodies
(ass. with advanced liver disease)
| intracellular inclusion that are accumulated in liver cells of patients who have alcoholic liver disease
114
Nonalcoholic Fatty Liver Disease
degree of inflammation (hepatitis) is less severe; most commonly asymptomatic and need liver biopsy
Stimulated by:
- obesity, Type II diabetes, dyslipidemia (high LDL's and low HDL's), and chronic hypertension
115
Hepatocellular carcinoma
= MOST COMMON form of primary liver cancer
116
Primary liver cancer vs Secondary Liver cancer
```
Primary = liver cells give rise to liver cancer
Secondary = liver cells are site for cancer metastasis
```
117
Viral Infections and Liver Cancer
areas with high rates of hepatitis viral infections have higher rates of liver cancer (Africa and Asia when compared to US)
- Africa and Asia--> liver cancer 20-40 years due to HBV (mom to baby)
- US ---> HCV
118
Do males or females have increased risk of liver cancer?
males are 3x more likely than females to develop hepatocellular carcinoma
119
Aflatoxin and liver cancer
Aflatoxin = carcinogen produced by certain molds (Aspergillus species); most likely to grow in improperly stored grains, like peanuts
is a "risk factor" for liver cancer
120
Pathological Calcification
calcium always in blood
- some pathological situations may cause Ca+ to be deposited intracellular or in ECM
- "white granules or clumps" or "gritty deposits"
- asymptomatic or could be lethal
121
Degree of dysfunction of pathological calcification depends on what 2 things
1. severity of calcification
| 2. organ or organs involved with calcification
122
Two Primary Categories of Pathological Calcificaiton
1. Dystrophic Calcification
| 2. Metastatic Calcification
123
Dystrophic Calcification
occurs at areas of tissue injury or in response to tissue death; very common and ass. with age related pathologies (like atherosclerosis)
Ex: aortic calcification or Tuberculosis (causes caseous necrosis--> cavities in lungs--> calcification on x-ray)
124
Metastatic Calcificaiton
occurs in presence of hypercalcemia = elevated blood calcium levels; and deposits Ca salts into normal tissues
- likely to occur throughout body!!
125
What does Metastatic Calcification commonly originate from?
1. Destruction of bone
2. renal failure
3. increase PTH
4. hyervitaminosis D (Vit. D toxicity)
126
Telomeres
short sequences of DNA at ends of chromosomes, protect material during cellular division
- once shorted to point, triggers "replication senescence"
127
Telomerase
enzyme; adds nucleotides to ends
- germ cells = contain high levels
- stem cells = contain low levels
- somatic cells = is absent
128
Progeria
like Blood Syndrome or Werner Syndrome--> born with rare genetic disorders that accelerate aging
129
Cellular senescence
Hayflick limit = cell's pre-programmed # of cellular divisions; once reach this limit, cell can NO longer divide
130
Defective Protein Homeostasis
increase age; decrease synthesis of proteins and increase possibility proteins misfold--> which triggers apoptosis
- disrupts cell's ability to fxn or survive
131
Inflammation of age
due to cellular stress on older cells--> may trigger persistent low-level inflammation
- plays role in development of atherosclerosis and Type II diabetes
132
Blue Zone Project
factors ass. with living a long healthy life
