Cell Injury, Inflammation, Tissue Healing Flashcards
What are morphological changes?
The structural alterations of a cell
What are the morphological changes divided into?
Gross or macroscopic appearance
Microscopic appearance
Which type of stain is used in routine pathology?
Hematoxylin & Eosin
Why is the H&E stain useful in pathology?
Hematoxylin is positively charged so it would helpful to identify the nucleus since it is negative
Eosin is negatively charged so it would help identify the enzymes in the cytoplasm which are positively charged
What colour does the cytoplasm become under the H&E stain?
Pink
What colour does the nucleus become under the H&E stain?
Blue
What is cell injury and when does it occur?
When a stress exceeds the cell’s ability to adapt
What might cause cell injury?
Infectious agents
Immunological reactions (autoimmune)
Physical agents
Genetic defects
Hypoxia (lack of oxygen)
Drugs (overdose)
Nutritional imbalance
Thermal sources (burns)
Chemical agents
What are the two types of cell injury?
Reversible (sub-lethal)
Irreversible (lethal)
What is reversible cell injury?
Short duration
Reversible effects
What is an example of short duration cell injury?
Hypoxia
What are the changes that occur inside the cell during reversible cell injury?
Partial damage to the Na+ pump
Swelling of cell and organelles
What is irreversible cell injury?
Long duration
Irreversible effects leading to necrosis
What are some changes in the cell during irreversible cell injury?
Cell membrane damage
Cytoplasmic leakage
Nuclear changes
What are the kinds of changes that the nucleus might experience during irreversible cell injury?
Pyknosis, Karyorrhexix and karyolysis
What happens to the nucleus during pyknosis?
Nucleus shrinks in size and condenses
What is the nuclear pattern in necrosis called where the nucleus breaks down into small fragments?
Karyorrhexis
What happens to the nucleus during karyolysis?
Nucleus looks fade
Why does the nucleus look fade during karyolysis?
Chromatin lysed and DNA is lost
Where is coagulative necrosis usually seen?
In hypoxic environments, for instance ischemia and infraction
What kind of tissues is coagulative necrosis usually seen in?
Kidney, heart, and adrenal glands
What would coagulative necrosis look like under a microscope?
The affected part would be more pale compared to normal tissue
What usually causes coagulative necrosis?
A blockage
What is liquefactive necrosis?
Digestion of dead cells resulting in transformation of the tissue into a liquid viscous
Which kind of necrosis is associated with pus or abscess?
Liquefactive necrosis
What usually causes liquefactive necrosis?
Bacterial and sometimes fungal infections
What is the difference between pus and abscess?
Pus is a discharge
Abscess is a pocket of pus; accumulated pus
What is gangrenous necrosis?
It is a type of coagulative necrosis
Where does gangrenous necrosis usually occur?
Lower limbs, affects mainly diabetic patients, and the GI tracts
When is gangrenous necrosis considered as liquefactive necrosis?
If a superimposed infection occurs, it causes wet gangrene
What is caseous necrosis?
It is considered as a combination of coagulative and liquefactive necrosis
What is the appearance of caseous necrosis?
Dead cells look like large granules since they are not completely digested, giving the appearance of clumped cheese.
What usually causes caseous necrosis?
Mycobacteria such as Tuberculosis
What is seen microscopically for caseous necrosis?
Giant cells that are formed by the fusion of epithelioid cells (macrophages)
What is fat necrosis?
Appears as yellowish-whitened firm deposits
Where does fat necrosis usually occur?
In organs with adipose tissue, such as the pancreas
What is seen microscopically for fat necrosis?
The necrotic cells have a cloudy appearance
What is the process of fat necrosis occurring?
Triglycerides –> fat acids (lipase)
Fat acids –> fat acids + Ca+
Fat acids + Ca+ –> White chalky deposits
What is fibrinoid necrosis>
Occurs in smooth muscle cells which allow fibrins to deposit in the area of necrosis
Where does fibrinoid necrosis occur?
In the arterial wall, for instance vasculitis
What does fibrinoid necrosis look like microscopically?
The wall of the artery is bright pink with dark neutrophils
What is apoptosis?
Programmed cell death to eliminate the unwanted cells
What is the process of apoptosis?
Normal cell shrinks, chromatin condenses
Membrane starts blabbing, organelles disintegrate
Nucleus and organelles collapse, and the membrane continues to bleb
Apoptotic bodies form
Macrophages phagocytose apoptotic bodies
No inflammation
What happens to the size of the cell during necrosis and apoptosis?
Necrosis: swelling (enlarges)
Apoptosis: shrinkage (reduces)
What happens to the nucleus during necrosis and apoptosis?
Necrosis: pyknosis, karyorrhexis, karyolysis
Apoptosis: fragmentation around nucleosome (in apoptotic bodies)
What happens to the plasma membrane during necrosis and apoptosis ?
Necrosis: disrupted
Apoptosis: intact
What happens to the cellular contents during necrosis and apoptosis?
Necrosis: enzymatic digestion, Amy leak out of cells
Apoptosis: intact; may be release in apoptotic bodies
Is there adjacent inflammation during necrosis and apoptosis?
Necrosis: frequent
Apoptosis: no
Are necrosis and apoptosis of a physiologic or pathologic role?
Necrosis: pathologic only
Apoptosis: pathologic or physiologic
What is inflammation?
It is a non-specific immune (part of the innate immune system) that helps the body fight infection and heal tissue damage
How is inflammation clinically denoted?
By the suffix -itis
What are the signs of inflammation?
Pain
Redness
Immobility
Swelling
Heat
What is pathogenesis?
Mechanism of development of disease
What is the top layer of the skin?
Keratinized stratified squamous cells
What happens in the first seconds of a foreign object creating a wound?
Vasoconstriction
What is the arachidonic acid cascade?
Prostaglandin is released from the damaged cells. Role in pain
What is the role of mast cells after the pathogen enters through the wound?
Source of mediators, histamine causes vasodilation and leakiness of vessels.
Why does vasodilation occur?
So that more white blood cells can flow to the site of injury
What is the role of macrophages after the pathogen has entered the wound?
Elimination of microbes, dead tissue
Source of mediators, cytokines
Play a role in immune response
What is the role of neutrophils after the pathogen has entered the wound?
Elimination of microbes, dead tissue
What is the role of the endothelium after the pathogen has entered the wound?
Source of mediators, nitric oxide and cytokines.
What is extravasation?
Diapedesis, the transmigration of leukocytes from the vessel lumen into interstitium
What is the role of plasma proteins after the pathogen has entered the wound?
Complement: mediators of inflammation, elimination of microbe
Clotting factors and kininogens: mediators of inflammation
What causes the contraction of endothelial cells?
Histamine, white blood cells transmigrate from the cell wall and accumulate in the affected area.
What causes the production of an edema?
The increase of osmotic pressure and the transmigrating cells
What causes a transudate?
Disturbances of hydrostatic forces
What does inflammation cause?
Exudate
What do the transudate and the exudate contain?
Transudate: just fluid
Exudate: plasma proteins & leukocytes
What do transudates and exudates look like?
Transudate: clear appearance
Exudate: cloudy appearance
What is the specific gravity of a transudate?
Less than 1.01
What is the specific gravity of an exudate?
More than 1.02
What are the vascular changes of inflammation?
Vasoconstriction for a few seconds
Vasodilation with increased vascular permeability
What are the cellular events during inflammation?
Cellular recruitment and activation: emigration of WBC from intravascular (lumen of vessel) to extravascular (interstitial fluid)
What are the mediators during inflammation?
Cellular (inflammatory mediators)
Plasma (inflammatory mediators)
What happens during extravasation of leukocytes?
Margination
Rolling
Adhesion
Transmigration
What happens during margination of leukocytes?
Polymorphonuclear leukocytes move toward the wall of blood vessels
What are polymorphonuclear leukocytes?
Neutrophils
What are the systemic effects of inflammation?
Fever
Leukocytosis
Acute phase protein
What are the effects of fever?
Increased pulse and blood pressure
Loss of appetite (anorexia)
What can occur during leukocytosis?
Neutrophilia
Eosinophilia
Lympohocytosis
What is leukocytosis?
The elevated number of white blood cells in the blood
What indicates a bacterial infection?
Neutrophilia
What does eosinophilia indicate?
Allergy or parasitic infection
What indicates a viral infection?
Lymphocytosis
What are the effects of acute phase protein?
Increased erythrocyte sedimentation rate
Increased C-reactive protein
What are the two kinds of inflammation?
Acute and chronic
What are the characteristics of acute inflammation?
Rapid onset and short duration
What usually causes acute inflammation?
Trauma
Foreign body
Infection
Physical or chemical agents
Which cell is predominant in the acute inflammation?
Neutrophils
What are the characteristics of chronic inflammation?
Slow onset and long duration
What are usually the causes of chronic inflammation?
Persistent infection (TB)
Persistent exposure to toxic agents (Silicosis)
Autoimmunity
Which cells are predominant in chronic inflammation?
Lymphocytes and macrophages
What are the three types of exudates?
Serous exudate
Serosanguineous exudate
Suppurative exudate (pus)
Which exudate has a lower cellular amount and is yellow in colour?
Serous exudate
What are the characteristics of serosanguineous exudate?
Contains erythrocytes so it has a more red colour
Which exudate is creamy yellow with liquefactive necrosis?
Suppurative exudate (pus)
What are the outcomes of acute inflammation?
Complete resolution
Abscess formation
Fibrosis
Progression to chronic inflammation
What is the histologic examination of a serous or serosanguineous exudate?
Accumulation of fluid between layers of skin and the interstitial layer causing the bump.
What are the outcomes of chronic inflammation?
Cirrhosis
Chronic organ insufficiency
What causes chronic inflammation?
Bacterial
Fungal
Parasitic
Inorganic metals and dusts
Miscellaneous
What is seen microscopically if chronic inflammation is present?
Central necrosis with Giant cells
Examples of bacterial infections that can cause chronic inflammation?
Leprosy
TB
Syphilis
Granuloma inguinale
Cat scratch disease
Actinomycosis and blastomycosis are what kind of infections?
Fungal
What is an example of parasitic infection that leads to chronic inflammation?
Schistosomiasis
What inorganic metals and dusts can lead to chronic inflammation?
Silicosis
Asbestosis
What is considered miscellaneous but can also lead to chronic inflammation?
Sarcoidosis
Crohn’s disease
What are the two process that occur during healing?
Regeneration
Repair
What happens during regeneration?
Necrotic cells are replaced by new ones
What occurs during repair?
Proliferation of connective tissue (fibrous tissue and collagen) resulting in fibrosis and scarring
What happens during the initial minutes of healing?
Reduction of wound gap (vasoconstriction),
Haemostasis
Fibrin clot
What happens during the first 24 ours of healing?
Reduction of wound gap (vasoconstriction),
Clot formation
Migration of neutrophils
Increased mitotic activity of basal cells
What happens between 48 and 72 hours of healing?
Surface is intact, new basement membrane
Epithelial cells proliferate from both edge and meet in midline
What happens 3 days into the healing process?
Macrophages instead of neutrophils
Invasion of incision space by granulation
Collagen start to appear
Epithelial cells continue to proliferate
What is granulation?
Area of collagen deposit
What happens 5 days into healing process?
Neovascularization
Collagen bridge incision
Epidermis recovers
What happens 2 weeks into healing process?
Collagen accumulate and fibroblast proliferate
Leukocyte infiltration and edema are diminished
What are the different types of healing?
1st intention healing (primary)
2nd intention healing (secondary)
tertiary healing
What are the characteristics of primary healing?
Clean & uninfected
Not much loss of cells and tissue
Surgically incised
Edges of the wound are approximated and surgically sutured
What are the characteristics of secondary healing?
Open and may be infected
Extensive loss of cells and tissue
The wounds are not approximated by surgical sutures but left open
What is tertiary healing?
Surgeon combines primary and secondary
Contaminated wound is allowed to granulate and heal (5 to 7 days)
When risk of infection is lower, wound is sutured
What factors influence wound healing?
Local factors and systemic factors
What are local factors?
Infection
Poor blood supply
Foreign bodies
Less movement
Type, size and location of injury
What are systemic factors?
Age
Nutrition
History of glucocorticoids
Uncontrolled diabetes
Hematologic abnormalities
How does a history of glucocorticoids affect healing?
If steroids have been taken, healing will be slower
How does uncontrolled diabetes affect healing?
Less blood supply so slower healing
What are some complications of wound healing?
Infection of wound
Deficient scar formation
Pigmentation
Keloid
Dupuytren;s contracture
What causes deficient scar formation?
Inadequate granulation tissue
What is Dupuytren’s contracture?
Fibrous tissue over-proliferates in the tendon of the palm (4th and 5th digit)
