Pathology Of Cellular Adaptations/Injury/Death And Inflammation (MODULE 7A & 7B) Flashcards
Define pathology, etiology, pathogenesis.
Break it into word parts.
• Pathology
• Pathos= suffering
• -ology= study
• Study of disease- the causes of disease and the associated changes at the levels of cells, tissues, and organs
• Etiology
• Etio= cause
• -ology= study
• Study of the origin of disease, including causes and modifying factors
- Refers to why a disease occurs, and pathogenesis describes how a disease develops
• Pathogenesis
• Pathos= suffering
• -genesis= beginning, development, or production of something
Define morphology and clinical manifestations.
- Morphology
• Gross and microscopic appearance of cells and tissues - Clinical Manifestations
• End results of genetic, biochemical, structural changes in cells and tissues
that lead to physiological changes/impairment • Lead to signs and symptoms of disease
What are the 4 pathology disease processes?
Four Aspects of a Disease Process
- Etiology
• Causation of disease - Pathogenesis
• Biochemical and molecular mechanisms - Morphological Change s
• Associated structural changes - Clinical Manifestations
• Functional alterations in cells and organs, and the
resulting clinical consequences
**look at diagram on slide 5 (Draw?)
T or F
Adaptations are reversible functional and structural responses to changes in physiological states
T
Allow cells to survive and function
If limits of adaptive responses are exceeded or cells are exposed to further stress, loss of nutrients, compromised by mutations that affect cellular function- this leads to cell injury and…
A. Cell regeneration
B. Leads to irreversible injury and eventually cell
death
C. Leads to reversible responses from the cells
B
T or F
Cellular adaptations are irreversible
F
The adaptations are REVERSIBLE
What are the two categories of adaptations?
- Physiologic Adaptations
• Stimulation from hormones, chemical mediators - Pathologic Adaptations
• Responses to stress
• Cells adapt and change their structure and function
• “Escape” injury
The reason or causation of why a disease occurs is referred to:
• A) Clinical manifestations
• B) Pathology
• C) Pathogenesis
• D) Etiology
D
Cellular adaptations can be reversible if the stimulus is removed?
• A) True
• B) False
A
Stimulus in this case is the stressor
What are the 5 forms of cellular adaptions?
Hypertrophy
Hyperplasia
Atrophy
Metaplasia
Dysplasia
Clinically – patients will present with these cellular and tissue
adaptations
Define hypertrophy, physiological hypertrophy, photo logical hypertrophy.
Df - Increase in the size of cells resulting in increase in the size of the organ
- Not an increase in # of cells- an increase in the size of each individual cell
Physiological Hypertrophy
• Changes in the uterus, skeletal muscle
• Yo, have you been working out? Your lats got some nice hypertrophy.
Pathological Hypertrophy
• Changes in the myocardium due to HBP (high blood pressure), stenosis Becomes Hypertrophic
Define hyperplasia, physiological hyperplasia, pathological hyperplasia.
Differentiate between pathological hyperplasia and cancer.
Df - Adaptive response where cells capable of replication, undergo replication to increase in overall number of cells
• Can occur simultaneously with hypertrophic response
Physiological Hyperplasia
• Hormonal Hyperplasia: Normal growth of a tissue or during pregnancy • Compensatory Hyperplasia: Growth after a loss of part of an organ
Pathological Hyperplasia
• Most likely due to an excessive hormonal or growth factor • ***Important Note - if signals that initiate additional growth are removed, the hyperplasia is stopped
Differentiation between pathological hyperplasia and cancer = is the excessive hormonal leads to hyperplasia change; if the excessive part of it is removed and its normal then the hyperplasia is stopped; cancer involves aggressive growth and divide of the cells in size and numbers (never stops) nothing removed will stop that.
Define atrophy. What are causes of this?
Df - Cells shrinking in size due to loss of cell substance
• Tissue and organ could diminish in size if enough cells atrophy
• May have loss of cell function, but not dead
• Mainly pathological, but may be physiologic
— Causes Include: decreased workload, loss of innervation,
degradation
ischemia, malnutrition, loss of endocrine/chemical mediator stimulation, aging
• Combination of decreased protein synthesis and protein
Define metaplasia. Explain this cellular adaption. Is it reversible?
Df - Change in phenotype- one adult cell type is
replaced by another adult cell type
• It is reversible!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!
• Cell type sensitive to a particular stress is replaced by another cell type
— New cell phenotype has better capabilities to
withstand and adapt to stressor
Note the metaplasia change from columnar epithelium to squamous epithelium (still a normal cell) — WHY?
—> to provide more protective measure for the tissues
Explain and contrast cellular differentiation and cellular dedifferentiation.
*Cellular Differentiation
• Dividing cells change their function or phenotype
• Develop from one cell type to another
- Process where cells become more specialized (cellular growth)
*Cellular
Dedifferentiation
• Dividing cells transition to a lesser specialized state
• Loss certain function and/or phenotype • Going from a differentiated to a less differentiated state
What is dysplasia and how does this fit into cellular differentiation?
Df - A term used to describe the presence of abnormal cells within a tissue or organ
• Cells/tissue partially lose morphological characteristics of mature cells
• Undergo dedifferentiation
- Dysplasia can be mild, moderate, or severe
- Cells lose morphological characteristics of normal healthy cells
***Dysplasia is not cancer, BUT it may become cancer (precancerous)
What is anaplasia?
Dr - Advanced form of dysplasia
• Dedifferentiation or total loss of structural and functional
differentiation of normal cells
• Do not look or act like original cells
• A term used to describe cancer cells that divide rapidly and have
little or no resemblance to normal cells
The term that refers to when a cell changes its phenotype and
even function is called:
• A) Atrophy
• B) Hyperplasia
• C) Metaplasia
• D) Dysplasia
C
Dysplasia can be a reversible process and sometimes is referred to
as pre-cancerous.
• A) True • B) False
A true
What are the two forms of cell injury? Describe each.
Which leads to cell death?
- Reversible Cell Injury
• Structure and functional changes are reversible
if damaging stimulus is removed (To an extent) - Irreversible Cell Injury
• If damaging stimulus is not removed-cell
damage and injury becomes irreversible
Cell Death
• Irreversible cell injury leads to cell death
—> Necrosis OR Apoptosis
What are the three relevant principles to most forms of cell injury?
Relevant Principles to Most Forms of Cell Injury
- The cellular response to injurious stimuli depends on the nature of
the injury, its duration, and its severity - The consequences of cell injury depend on the type, state, and
adaptability of the injured cell - Any injurious stimulus may simultaneously trigger multiple
interconnected mechanisms that damage cells
What are the types of oxygen deprivation?
Can you have hypoxia without ischemia? It is possible?
Ischemia
• Reduction of blood flow causing inadequate perfusion
• Ischemia is the most common cause of cell injury in clinical setting
Hypoxia
- reduction in O2 levels below metabolic needs
**you can have normal BF and reduced number of O2 levels (this would be Anemia); YOU ALWAYS have hypoxia with ischemia; BUT you can have hypoxia WITHOUT ischemia as well
What’s the most common cause of cell injury in clinical settings?
Ischemia
What is ischemia-repercussion injury?
Ischemia-Reperfusion Injury
• Restoration of blood flow to ischemic tissues can promote recovery of cells if they are reversibly injured but can also paradoxically exacerbate cell injury and cause cell death
What overview chemical agents, physical agents, and infectious agents-pathogens relate to cellular injury?
*Chemical Agents and Drugs
- Commonly affects the liver
• Chemicals induce cell injury by one of two general mechanisms:
- Direct toxicity
- Cyanide
- Conversion to toxic metabolites
• Acetaminophen is also converted to a toxic product during detoxification in the liver leading to cell injury
*Physical Agents
• Trauma- micro and macro
• Extreme temperatures
• Radiation
*Infectious Agents- Pathogens
• Bacteria, viruses, parasites, fungi
• Lead to cellular injury cellular infection or production of toxins
What immunological reactions can contribute to cellular injury?
*Immunological Reactions
• Autoimmune disorders
• Hypersensitivity reactions
Briefly explain genetic abnormalities, nutritional imbalances and aging contributing to cellular injury.
*Genetic Abnormalities
• Congenital or acquired due to exposed stress • Can be an entire chromosome or single gene • Leads to faulty protein production/function
*Nutritional Imbalances
• Increased or decreased caloric intake
• Obesity or loss of nutrients
*Aging
• Cellular senescence leads to less adaptability
• Senescence: Condition or process of deterioration with age
Briefly explain oxidative stress and reactive oxygen species (ROS) as cellular injury.
Oxidative Stress and Reactive Oxygen Species (ROS)
• Free radicals are chemical species that have a single unpaired electron in an outer orbit
• Body normally makes free radicals, but ”scavengers” degrade and
remove them
• Increased production or decreased scavenging of ROS may lead to
an excess of free radicals, a condition called oxidative stress
• Oxidative stress has been implicated in a wide variety of
pathologic processes
- Cell injury, cancer, aging, and Alzheimer disease
What is the role of antioxidants regarding free radicals?
Antioxidants to the Rescue!!
• Block production of free radicals and/or inactivate them (scavengers)
Where does cell damage occur? Irreversible cell injury
Mitochondria Damage (hypoxia/ischemia radiation and other injurious agents) = cells can’t make ATP efficiently; Incomplete phosphorylation; leakage of mitochondrial proteins
Membrane Damage (ROS/ Other injurious agents) = things can move in and out of the cell without filtration; impaired transport functions & leakage of cellular contents; Decreased phospholipid synthesis; increased phospholipid degradation; cytoskeleton abnormalities
Nucleus/DNA Damage (Radiation mutations/ chemotherapeutic (anti cancer) drugs, and ROS, or may occur spontaneously as part of aging) = short term or long term DNA damage leads to APOPTOSIS
T or F
Basically, a cell would rather kill itself than live with damaged DNA
T
How cellular romantic..
What is the difference between hypoxia and ischemia is?
• A) Hypoxia is reduced blood flow and ischemia is reduced oxygen levels
• B) Ischemia is reduced blood flow and hypoxia is reduced oxygen levels
• C) Hypoxia is increased oxygen levels and ischemia is reduction in blood flow
• D) Hypoxia is when a cell is injured due to ischemia which is a reduction in
blood flow
B
Define reversible cellular injury.
Df - Reversible cellular injury is when abnormal
function and morphology of the injured cells can
return to normal if the damaging stimulus is
removed
What are the 2 major morphological changes with reversible injury?
- Cellular Swelling
• Cell injury associated with increased permeability of the plasma membrane - Fatty Change
• Triglyceride containing lipid vacuoles in the cytoplasm
• Mainly the liver
What leads to irreversible cellular injury?
- Inability to restore mitochondrial function
• Even after resolution of the original injury - Loss of structure and functions of the plasma membrane and
intracellular membranes - Loss of DNA and chromatin structural integrity
What are the two distinct features seen in cells with reversible cell
injury?
Generalized swelling and fatty changes
All of the following are characterizations of irreversible cell injury,
except?
injury?
A. Loss of DNA integrity
B. Loss of function and structure of plasma membrane
C. Increased lysosome function
D. Inability to restore mitochondrial function
C
What needs to occur to move from reversible to irreversible cell injury?
Expose to persistent or excessive damaging stimuli
What is cellular death and what are the two categories of cell death?
• If damaging stimulus is not removed-cell damage and
injury becomes irreversible and leads to cell death
Two categories of Cell Death
1. Necrosis
2. Apoptosis
Differentiate necrosis and apoptosis.
- Inflammation
• Necrosis causes inflammation
• Apoptosis does not cause inflammation - Cellular Leakage
• Necrosis leads to leakage of cellular content
• Apoptosis leads to leakage of apoptotic bodies
Overview of the process of necrosis and apoptosis.
*Necrosis cell process
—> normal cell —> small blobs form; the structure of the nucleus changes —> the blobs fuse and become larger; no organelles are located in the blebs —> the cell membrane ruptures and releases that cell’s content; the organelles are not functional
*Apoptosis cell process
—> small blebs form —> the nucleus begins to break apart, and the DNA breaks into small pieces. The organelles are also located in the blebs. —> the cell breaks into the several apoptosis bodies; the organelles are still functional
——> gets packed into bubbles
**Look at the diagram on slide 63 to compare and contrast necrosis and apoptosis
Necrosis overview:
Think of it as the “accidental” death of cells
- The result of severe injury
• Leads to local inflammation due to cellular leakage
• Necrosis is characterized by denaturation of cellular proteins,
leakage of cellular contents through damaged membranes, local inflammation, and enzymatic digestion of the lethally injured cell
***NECROSIS is loss of membrane integrity which leads to leakage of cellular contents and enzymatic digestion that then CAUSES INFLAMMATION!!!
Necrosis: Pathogenesis
Reversible to irreversible injury- point of no return?
• Inability to reverse mitochondrial dysfunction
• Profound disturbances in membrane function
• Loss of DNA/chromatin structural integrity
Can be caused by a lot of various cellular damage
• Ischemia, toxins, chemical/physical injury
But it all leads to??? MEMBRANE DAMAGE!!!!
What involves membrane damage and DAMPS?
Membrane Damage & DAMPS
• Cellular contents leak through damaged plasma membrane into ECF
This cellular content leakage is referred to as DAMPS
• DAMPs: Damaged Associated Molecular Patterns
• ATP, uric acid, proteins, and other intercellular organelles and compounds
DAMPs recognized and phagocytized by macrophages in ECF leads to INFLAMMATION!!
What is the importance of DAMPs?
DAMPS are the reason necrosis cell death leads to inflammation
DAMPs ultimately get into blood circulation
- Can be detected by blood work
What entails cardiac troponin DAMPs?
Can be detected in blood as soon as 2 hours after myocardial cell necrosis
If someone is feeling as though they will have a heart attack we can test the blood and can detect troponin DAMPs in the blood and this represents that the heart has undergone necrosis due to ischemia (lack of O2).
DAMPs is that internal cellular component that is getting released into the blood.
All of the statements are true, except?
• A. DAMPS are released when mitochondria break down with necrosis
• B. Cellular components are released when necrosis occurs
• C. Apoptosis doesn’t cause inflammation, but necrosis does
• D. Necrosis
A
When a cell is undergoing necrosis it will shrink in size.
• A. True
• B. False
B
Apoptosis Overview:
— Cell suicide- “ programmed cell death” • Necrosis- trauma induced and leads to
inflammatory response
• Apoptosis is a type of cell death that is
induced by a tightly regulated suicide
program in which cells destined to die
activate intrinsic enzymes that degrade the
cells’ genomic DNA and nuclear and
cytoplasmic proteins
T or F
Apoptosis is Controlled by regulatory genes and is a normal process for certain processes
T
What are caspases?
Specific enzymes that break down protiens.
These enzymes must become activated for cell to undergo apoptosis. (Pro enzymes must be activated)
What are the two pathways to an activate caspases?
Briefly explain these processes.
Intrinsic: mitochondrial pathway
—> responsible for apoptosis in most physiologic and pathological situations (DNA damage; Oxidative stress; growth factor withdrawal)
—> Increased permeability of mitochondrial outer membrane
—> causes release of DEATH-INDUCING (pro-apoptosis) molecules from mitochondrial outer membrane intermembrane space.
*Cytochrome c (this is one wild protein)
— Inside the mitochondria- essential for making ATP
— Outside of the mitochondria- initiates apoptosis
Extrinsic: death receptor pathway
—> Initiated by engagement of plasma membrane death receptors
• Death domain on plasma membrane
What is autophagy?
• Autophagy is a process in which a cell eats its own contents • It involves the delivery of cytoplasmic materials to the lysosome
for degradation • Physiological responses- exercise, aging • Pathological responses- stress situations
• Adaptive response- during nutrient deprivation • Complex process that includes a sequence of protein activation • Ultimately form autophagosomes
• Cytoplasmic autophagic vacuoles • Autophagosomes bind to lysosomes and contents are degraded
What statement is TRUE?
• A) Cytochrome C found within the mitochondria will lead to apoptosis
• B) The mitochondrial pathway of apoptosis has FADD activate the caspases
• C) A cell undergoing apoptosis will undergo swelling
• D) With the lack of survival signals, stimulation of synthesis of BAX/BAK
occurs
D
Describe how apoptosis occurs?
Mitochondrial pathway - caspases enzymes - leading to packing of intracellular components and released into the cell to be phagocytosized
Define morphology and necrotic morphology.
Morphology
Df- Gross and microscopic appearance of cells and tissues
Necrotic morphology can be at a cellular and tissue/organ level. Cellular Swelling
*Cytoplasmic Changes
• Breakdown of organelle membranes
What are the three types of nuclear changes? Explain each.
(Common boards question)
Nuclear Changes
1. Pyknosis
• Nucleus shrinks and chromatin solidifies
2. Karyorrhexis
• Nucleus fragments and chromatin disintegrates into granules
3. Karyolysis
• Swelling of nucleus and fading of chromatin
What is the most common type of necrosis?
(Boards question)
Coagulation necrosis,
• Primarily caused by ischemia/hypoxia
conditions (lack of BF)
• Solid mass that turns pale or discolored
compared to surrounding tissue
• Localized area of coagulative necrosis is called infarct
• Infarct
• Necrosis of tissue due to inadequate blood supply
to the affected area
What is liquefaction necrosis?
• Digestion of dead cells • Cells/tissue is completely digested by enzymes • Lesion is soft and even viscous
What is gangrenous necrosis? What are the two types?
Refers to when there is a loss of blood supply and coagulative necrosis occurs in
multiple tissue layers
1) Dry Gangrene
• Occurs when the blood supply is slowly reduced to an area • Commonly due to blood vessel damage from medical conditions
• Medical conditions like diabetes or atherosclerosis • The affected tissues become hard, black, and purplish • THERE IS NO BACTERIAL INFECTION
2) Wet Gangrene
• Occurs when there is a sudden reduction in blood to the affected tissues
• Commonly due to a traumatic event or situation
• Frostbite or a blood clot • BACTERIAL INFECTION is present and exotoxins can get into the blood • Leads to pus formation- reason why it is called wet gangrene
What is caseous necrosis?
- Necrotic tissue enclosed within a distinct
inflammatory border
—“Seal off the infection”
• Commonly seen with chronic inflammation
• Forms a granuloma
—> “A mass or nodule of chronically inflamed tissue
with granulations that is usually associated with an infective process” – Merriam-Webster Dictionary
• Associated with specific disorders such as
Tuberculosis
What is fat necrosis?
Fibrinoid necrosis?
*Fat Necrosis
• Focal areas of fat destruction- release of
activated pancreatic lipases
*Fibrinoid Necrosis
• Vascular (endothelial) damage seen in
immune reactions involving blood vessels • Antigen-antibody complexes deposited
into the walls of the blood vessels
• Makes a fibrinoid appearance of vessel wall
What is the cellular morphology associated with apoptosis?
• Cell Shrinkage
• Cytoplasm becomes dense and cell shrinks
• Necrosis you see what???? • Chromatin Condensation
• Most characteristic morphology feature
• Chromatin of DNA condenses • Formation of Cytoplasmic Blebs/Apoptotic Bodies
• Cells starts to break apart into smaller droplets • Phagocytosis of Apoptotic Cells
• Apoptotic bodies are phagocytized
What are the types of intracellular accumulations?
• Lipids
—> Steatosis (fatty change)- abnormal accumulations of triglycerides in cell or organ
• Cholesterol
—> Accumulation of cholesterol- LDL
—> Think atherosclerosis
• Proteins
—> Can be caused by variety of reasons
—> Commonly an aggregation of abnormal proteins (denatured = loses its shape and loses its function)
• Glycogen
—> Excessive amounts of glycogen
—-> Due to glucose or glycogen metabolism abnormalities
• Pigments: Carbon
—> Most common- leads to a black color
• Pigments: Lipofuscin
—> Insoluble brownish-yellow granular intracellular material that accumulates in a variety of
tissues with aging or atrophy
—> “Wear-and-Tear pigment”
• Pigments: Melanin
—> Keratinocytes in the skin can accumulate the pigment- freckles
• Pigments: Hemosiderin
—>A hemoglobin-derived granular pigment
—>Golden yellow to brown
—>Accumulates in tissues when there is a local or systemic excess of iron
What are the four mechanisms leading to abnormal accumulations within intracellular accumulations?
- Inadequate removal
- Defects in folding, packaging, transporting or secretion
- Failure to degrade a metabolite
- Accumulation of abnormal exogenous substance
This type necrosis morphology is associated with a granuloma
• A. Caseous
• B. Liquefactive
• C. Coagulative
• D. Fibrinoid
A
This type of nuclear changes involves the nucleus fragments and chromatin
disintegrates into granules?
• A. Pyknosis
• B. Karyolysis
• C. Karyorrhexis
• D. Paryolysis
C
Which option is the most common type of tissue necrosis morphology?
• A. Caseous
• B. Liquefactive
• C. Coagulative
• D. Fibrinoid
C
This term is given for insoluble brownish-yellow granular intracellular material
that accumulates in a variety of tissues with aging or atrophy?
• A) Senescence • B) Lipofuscin • C) Hemosiderin • D) Dystrophic calcification
B
Steatosis is when there is an accumulation of cholesterol in a cell or organ.
• A) True • B) False
B
This type of cellular accumulation is due to excessive amounts of iron?
• A) Melanin • B) Lipofuscin • C) Hemosiderin • D) Dystrophic calcification
C
C
All of the options are true regarding cell death, except?
A. Necrosis leads to cellular components leaking out of the cell.
, Not Selected
B. The production of cytochrome c inside the mitochondrial leads to mitochondrial damage and apoptosis.
C. Apoptosis is ultimately caused by the activation of caspases.
, Not Selected
D. Apoptosis can be a normal physiological process that occurs in healthy physiological processes.
B
All of the options are primary sites for cellular injury, except?
A. Mitochondria damage/dysfunction.
B. DNA damage.
C. Lyosome damage.
D. Plasma membrane damage.
C
What type of necrosis has necrotic tissue enclosed within a distinct inflammatory border?
A. Liquefactive necrosis.
B. Gangrenous necrosis.
C. Fibrinoid necrosis.
D. Caseous necrosis.
D
This type of pigmentation is associated with systemic excess of iron.
A. Lysosomal vesicles.
B. Senescence.
C. Lipofuscin.
D. Hemosiderin.
D
An individual who is a lifelong smoker could see this type of cellular adaption occur where tracheal columnar epithelial tissue transitions into stratified squamous epithelial tissue?
A. Atrophy.
B. Hypertrophy.
C. Hyperplasia.
D. Metaplasia.
D
All of the options are true regarding irreversible cell injury and death, except ?
A. Irreversible cell injury always leads to cell death.
B. Severe membrane disturbances is one of the pathways that leads to irreversible cell injury.
C. Apoptosis cell death does not cause inflammation.
D. One of the characteristics of irreversible cell death is increased lysosomal activity.
D
What is the most common type of morphology of necrotic tissue?
A. Caseous necrosis.
B. Coagulative necrosis.
C. Liquefactive necrosis.
D. Gangrenous necrosis
B
What statement is TRUE?
A. Pathological derived apoptosis can lead to localized inflammation.
B. None of the options are true.
C. Cellular swelling is an early manifestation of reversible cell injury.
D. Metaplasia can be a reversible process, but dysplasia cannot.
C
All of the following statements are true regarding cellular adaptations, except?
A. Anaplastic cells are also referred to as precancerous cells.
B. Dysplasia and anaplasia both undergo cellular dedifferentiation.
C. Both metaplasia and dysplasia can be reversible.
D. A tissue can undergo hyperplasia and hypertrophy at the same time.
A
What term is associated with swelling of nucleus and fading of chromatin?
A. Karyolysis..
B. Metahexis.
C. Karyorrhexis.
D. Pyknosis.
A
Define the term inflammation.
Inflammation is a protective response involving host cells, blood vessels,
and proteins and other mediators.
Intended to eliminate the initial cause of cell injury, as well as the necrotic
cells and tissues resulting from the original insult • When damaging stimulus is removed, it initiates the process of repair • Inflammation is a response of vascularized tissues that delivers leukocytes
and molecules of host defense from the circulation to the sites of infection
and cell damage in order to eliminate the offending agents • Considered part of our innate immunity
T or F
Inflammatory reactions can become the cause of disease
T
The damage it produces becomes its dominant feature
What are the two main causes of inflammation?
What are the three main functions of inflammation?
Causes:
1. Trauma (micro or macro trauma)
2. Infection
Functions:
1. Limit the spread of pathogens/damaged tissue
2. Remove cellular debris and foreign substances
3. Initiate tissue repair
Name some causes of inflammation.
- Infections
• Bacterial, viral, fungal, parasitic, and microbial toxins
• Outcomes are determined by pathogen and host response • Tissue Necrosis
• Cellular necrotic death elicits inflammation
• What causes cell death? Does apoptosis cause inflammation? • Foreign Bodies
• Splinters or endogenous substances deposited into tissues • Immune Reactions
• Hypersensitivity reactions • Basically- Infection and/or Trauma
What are the 5 signs/symptoms of inflammation?
Cardinal Signs of Inflammation
Cardinal Signs of Inflammation
• Redness (rubor)
• Warmth/Heat (calor)
• Edema/Swelling (tumor)
• Pain (dolor)
• Loss of function (functio laesa)
What are the 5 steps of inflammatory sequence? Simplified.
Inflammatory sequence/steps (5 R’s)
• Recognition
- Noxious agent/stimulus
• Recruitment (Mobilization)
- Leukocytes and plasma proteins
• Removal
- Of the stimulus
• Regulation
- Stop inflammatory process when finished
• Resolution
- Heal, repair, or replace damaged tissue
Compare acute vs Chronic inflammation
Acute Inflammation
• Rapid, self-limiting, and noxious agents are readily eliminated • Main components of acute inflammation are:
• Vascular reaction
• Cellular response
Chronic Inflammation
• Slower response to agents that are difficult to eliminate
• May not be able to eliminate provoking stimulus- Osteoarthritis
• Associated with more tissue damage- Fibrosis
What is the order of acute inflammatory morphology?
• 1. Infiltration of neutrophils
-Primarily neutrophils (first)
-Then macrophages (second)
• 2. Cardinal Signs
-The 5 cardinal signs of inflammation are present
• 3. Repair
-Tissue regeneration
-Fibrosis- scarring!
T or F
Chronic inflammation involves a short response and duration
F
Response of prolonged duration
• Weeks or months
Chronic inflammation is commonly caused by?
• 1. Persistent infections
• 2. Hypersensitivity diseases
• 3. Prolonged exposure to a damaging stimuli
- Endogenous and/or exogenous
What is the order of chronic inflammatory morphology?
- Infiltration of mononuclear cells
• Predominately macrophages (sustain inflammatory process)
• Lymphocytes and plasma cells too - Tissue destruction
• Predominately caused by ongoing inflammatory processes and cells
• The area of inflammation becomes damaged
-Osteoarthritis -Hepitatis - Repair
• Angiogenesis
• Fibrosis- scarring!
All of the following options are signs of inflammation, except…?
• A. Swelling
• B. Heat
• C. Pain
• D. Fever
• E. Redness
• F. All of the options are signs of inflammation
D
The ability to initiate tissue repair is part of the inflammatory process.
• A. True
• B. False
A
Fibrosis is commonly seen with acute inflammation.
• A. True
• B. False
B
Edema associated with acute inflammation is primarily due to:
• A. Broken blood vessels
• B. Vasodilation
• C. Leukocyte activation
• D. Increased vascular permeability
• E. Two of the answers are correct
E (b and d)
All of the options are true regarding inflammation, except?
• A. Acute inflammation can happen within minutes
• B. Chronic inflammation primarily has neutrophil infiltration
• C. Chronic inflammation does not have as prominent local and systemic signs
• D. Hypersensitivity disorders can lead to chronic inflammation
• E. Acute inflammation has increased vascular permeability
B
What are chemical mediators? What 4 common characteristics do they have?
Df: Chemical Mediators of inflammation are the substances that
initiate and regulate inflammatory reactions
Chemical Mediators Have Four Common Characteristics:
1. Active mediators are produced only in response to various
molecules that stimulate inflammation
• Include microbial products and substances released from necrotic cells
- Mediators can stimulate the release of other mediators
• Provides mechanisms for amplifying or counteracting the initial action of a
mediator - Mediators may be produced:
• A. Specific cells at the site of inflammation
• Maybe stored in granules or synthesized upon stimulation • Major Cells: Macrophages, dendritic cells, and mast cells
• B. Derived from circulating inactive precursors that are activated at the site of
inflammation
- Plasma Derived Mediators- Present in the circulation as inactive precursors that must be activated
- Complement proteins
- Mediators are short-lived
• Quickly decay or are inactivated by enzymes
What are the 5 major categories of chemical mediators? Briefly explain each.
- Vasoactive Amines
—Are named vasoactive because of effects on blood vessels
• Among the first mediators to be released during inflammation - Serotonin
-Found in platelets
-Part of the inflammation and coagulation process
—>Causes vasoconstriction - Histamine
-Stored in mast cells and is a stored in granules
- THINK VASODILATOR and INCREASED VASCULAR PERMEABILITY (ability for blood cells or others to squeeze through BV wall)
- Considered the principal initial mediator of inflammation
A) Vasodilator
B) Increased vascular permeability - Cytokines and Chemokines
Cytokines
• Proteins secreted by many cells
• Mediate and regulate immune and inflammatory reactions
Chemokines
• Smaller proteins that act as chemo-attractants for specific types of
leukocytes
• “Guide” leukocytes to sites of infection or tissue damage outside of blood vessels
- Kinins
Kinins are vasoactive peptides derived from plasma proteins
• Most influential kinin is Bradykinin
• Bradykinin
• Increases vascular permeability
• Vasodilation
• Similar to the effects of histamine - Arachidonic Acid Metabolites
—> on its owe slide - Complement System Proteins (more on further slides)
• Collection of soluble proteins and their membrane receptors that
function mainly in host defense against microbes and in pathologic
inflammatory reactions
• More than 20 complement proteins
• Complement proteins are present in inactive forms in the plasma
• Once activated- become proteolytic enzymes that degrade other
complement proteins
• Lead to immunological and inflammatory responses
Arachidonic acid metabolite overview. What is it? And what substances does it produce?
• It is a polyunsaturated fatty acid found in phospholipids
• Released when phospholipids (in plasma membrane) are hydrolyzed
Prostaglandins and Leukotrienes are produced from arachidonic acid
• Present in membrane phospholipids
What are the lipid mediators that regulate vascular and cellular inflammatory reactions?
Prostaglandins and Leudotrienes
Once arachidonic acid is removed from the membrane it is rapidly converted to bioactive chemical mediators by enzymes. These mediators are called ____________
EICOSANOIDs
Phopholipase, Cox-1 and 2, and lipocygenase are what ? How do they tie into the process of chemical mediation?
• Phospholipase
- Metabolize cell membrane
phospholipids into Arachidonic Acid
• COX-1 & COX-2 (Cyclooxygenase)
- Metabolize AA into prostaglandins and
thromboxane A2
• Lipoxygenase
- Metabolize AA into leukotrienes
*look at diagram on written notes.
Briefly explain the complement system and pathways involved.
— Critical step in the activation and outcomes of the complement system:
• Proteolysis of C3
• 1. Inflammation: C3a and C5a
• Stimulate histamine release from mast cells
• Increase vascular permeability and vasodilation • Recruitment and activation of leukocytes
- Opsonization: C3b
• C3b on the membrane of pathogen becomes an opsonin • Opsonin: an antibody or other substance which binds to foreign microorganisms
or cells making them more susceptible to phagocytosis - Cell Lysis: C5b
• C5b activates other complement proteins to form MAC
• Membrane Attack Complex (MAC)
• Puncture hole through the cell membrane
C5b leads to the development of _____
MAC
All of the options are true regarding histamine, except….?
• A. It causes vasodilation
• B. Released from mast cells
• C. Cyclooxygenase enzyme activity creates histamine
• D. It leads to vascular permeability
C
NSAIDs block the production of arachidonic acid.
• A. True
• B. False
B
Both C3b and C5b are necessary for the MAC process to occur?
• A. True
• B. False
A
All of the options are true of opsonization, except?
• A. It is part of the complement system
• B. It is dependent upon the complement protein C3b
• C. Leads to a puncture in the cell membrane
• D. Causes phagocytosis of cell
C
All of the following options are outcomes of complement proteins, except?
• A. Opsonization
• B. Vasodilation
• C. Increased vascular permeability
• D. Phagocytosis
• E. All of the above are outcomes
E
What are PAMPs and DAMPs? What are they involved in?
Involved in acute inflammation: Recognition
PAMPs
• Pathogen Associated Molecular Patterns
• A molecular or portion of a pathogen that will be recognized PRRs
- Especially TLR
DAMPs
• Damaged Associated Molecular Patterns
• Derived from damaged cells
• Released extracellularly after tissue injury
• Recognized by PRRs located on cell surfaces and intracellularly
What are PRRs and what do they do?
Pattern Recognition Receptors (PRR; not PBR)
• Types of receptors found in various inflammation and immune
cells that detect PAMPs and DAMPs
This initiates release of chemical mediators and inflammation response
- All of the options are stimuli for recognition within inflammation,
except _____.
• A. Plasma proteins recognition of microbes and cell damage • B. Increase leukocytes • C. Cell receptors for necrosis • D. Cell receptors for microbes
B
Pattern recognition receptors (PRR) recognize PAMPs and DAMPs
to initiate the inflammatory process.
• A. True
• B. False
A
What is involved with Acute inflammation Recruitment? (Major components of acute inflammation recruitment)
• We have recognized PAMPs and DAMPs via PRRs
• Time to get the leukocytes to the area that PAMPs and DAMPs were detected!
• In the blood vessels AND in the tissue space
1- vascular changes (vasodilation, increased vascular permeability, adhesion of leukocytes)
2- Cellular changes (leukocytes): migration of leukocytes; activation of leukocytes = primarily neutrophils
Chemical mediators lead to _______ and increased _________ ________
Vasodilation and increased vascular permeability
With increased vessel diameter and loss of fluid-it leads to slower BF (stasis)
What is stasis of BF?
Stasis of blood flow
• Referred to vascular congestion
• Leads to prolonged redness of the involved tissue due to RBC congestion
What is the different between non-inflammatory edema/swelling and inflammatory edema/swelling?
Non-Inflammatory Edema/Swelling
• Fluid has a LOW protein and cellular content (bc no vascular permeability; fluid is pushed out of vessel bc of pressure)
• Fluid referred to as TRANSUDATE
Inflammatory Edema/Swelling
• Fluid has a HIGH protein and cellular content
• Fluid referred to as EXUDATE
What is edema, exudation, exudate, transudate, pus?
• Edema
-Excess of fluid in the interstitial tissue or serous cavities
• Can be exudate or transudate
-Exudation
-Escape of fluid, proteins, and blood cells from the vascular system into the interstitial tissue or body cavities
• Exudate
-Extravascular fluid that has a HIGH protein concentration and contains cellular debris
-Implies the existence of an inflammatory process that has increased the permeability of small blood vessels
-Transudate
• Extravascular fluid with LOW protein content with little or no cellular material
• Osmotic or hydrostatic imbalance across the vessel wall without an increase in vascular permeability
• Pus
-Purulent exudate due to the effects of inflammation
-Rich in leukocytes, debris of dead cells, and microbes
What is TRUE regarding vascular changes within inflammation?
• A. Serotonin release stimulates vascular changes
• B. Diapedesis is an outcome of vascular changes
• C. Monocytes are the primary leukocyte associated with recruitment
• D. Vascular changes cause redness, heat, and swelling symptoms
C
An exudate has a high protein content.
• A. True
• B. False
A
Describe how edema can occur due to inflammation.
Histamine leading to vasodilation and increased vascular
permeability
Vascular changes lead to vasodilation and loss of fluid from blood vessels… this leads to?
This leads to a condition called stasis (blood congestion)
Acute Inflammation Main Leukocytes
Neutrophils and macrophages
Neutrophils and Macrophages phagocytize bacteria, microbes, necrotic
tissue, and foreign substances
• These leukocytes are in the blood stream and need to get to the
damaged tissue
• Neutrophils, macrophages, and endothelial cells undergo CELLULAR
CHANGES that allow these processes to occur
Define extravasation
Discharge or escape of blood or some other fluid normally found in a vessel or tube, into the
surrounding tissue
What are the four major process phases involved in acute inflammation (recruitment cellular changes)
Th is Process is Divided Up Into 4 Phases:
• 1) Margination
• 2) Rolling and adhesion to the endothelium
• 3) Transmigration between endothelial cells
-Diapedesis
• 4) Migration into the interstitial tissues toward a chemotactic stimulus
-Chemokines
-Migration into the tissues by chemotaxis
What are the two main leukocytes within acute inflammation?
• A. Macrophages and Monocytes
• B. Neutrophils and Macrophages
• C. Eosinophils and Neutrophils
• D. Neutrophils and Monocytes
B
What is the process of the leukocytes squeezing between two endothelial
cells?
• A. Chemotaxis
• B. Diapedesis
• C. Cellular adhesions
• D. Stasis
B
Chemotaxis is the process of leukocytes migrating to the source of injury.
• A. True
• B. False
A
What can cause leukocyte activation?
Recognition of microbes, dead cells, or certain chemical mediators induce
several responses in leukocytes that activate them
We have the leukocytes to the area of damage/infection, now
what?
• We have to activate the leukocytes
• Have the leukocytes remove the damaged cells/tissues and pathogens
• Regulate this process so it isn’t too intense
Phagocytosis involves three sequential steps:
• 1) Recognition and attachment of the particle to be ingested
* Opsonin
• Complement proteins or antibodies that binds to antigens and induces their ability to be phagocytized by macrophages and neutrophils
• Dorland’s Medical Dictionary
*Opsonization
• The rendering of bacteria and other cells subject to phagocytosis by the action of an opsonin
• Dorland’s Medical Dictionary
• 2) Engulfment- formation of a phagocytic vacuole
-Leukocytes express receptors for opsonins
• Binding of opsonized particles to these receptors triggers engulfment and induces cellular activation that enhances degradation of ingested microbes
• 3) Killing or degradation of the ingested material
Phagolysosome now destroy the ingested foreign molecule or particle
• Through Lysosomes
Inflammation declines after the offending agents are removed. With this being said…
Chemical mediators are produced in short, rapid bursts as long as the stimulus persists
The inflammation process itself triggers the production of anti- inflammatory mediators
Acute inflammation has one of three outcomes
• Resolution
• Scar tissue formation
• Chronic Inflammation
Two Types of Tissue Repair:
- Regeneration
• Regain normal function of injured tissue - Scar formation
• Deposition of connective tissue
• Loss function of tissue
• Scarring/Fibrosis
Which option defines the role of opsonins in acute inflammation?
• A. Provides digestive enzymes to break down foreign and dead materials and substances
• B. Allows for the chemotactic process to occur
• C. Provides an increased ability for a substance to be phagocytized
• D. Creates the pathway for apoptosis to occur in foreign substances
C
Opsonization can occur from the complement system and/or antibodies?
• A. True
• B. False
A
Commonly, chemical mediators are still secreted after the offending agent is
removed?
• A. True
• B. False
B
What cardinal signs of inflammation are directly due to increased
blood flow and vascular permeability? (Select all that apply)
• A. Heat
• B. Pain
• C. Edema
• D. Redness
• E. Loss of function
A, C, D
Acute inflammation can lead to chronic inflammation when the
offending stimuli cannot be removed.
• A. True
• B. False
A
