Inflammation and Repair Gen Path Exam 1

Steps of inflammation

1. kills and eliminates microbes

2. removes debris

3. initiates repair

What are sentinel cells?

cells already in the tissue

What are white blood cells?

cells that are in circulation

Mast cells function in inflammation

release of histamine

What is the function of macrophages in inflammation

perform phagocytosis

present antigens to T-cells

Release cytokines

What is the function of neutrophils in inflammation

perform phagocytosis

MOST ABUNDANT

response to bacteria

What are examples of stimulus that cause inflammation?

1. tissue damage

2. injuries

3. infections

4. inappropriate immune response

Where does heat and redness come from?

Vasodilation

Where does the swelling in inflammation come from?

increased vascular permeability

What are the 5 Rs of inflammation?

1. Recognize injury/microbe

2. Recruit leukocytes

3. Remove Agent

4. Regulate response

5. Resolution

What is acute inflammation?

Rapid onset within minutes

has a short duration

Cardinal Signs-local and systemic signs, no fibrosis

What is the dominant cell type of acute inflammation?

neutrophils

What is chronic inflammation?

insidious onset (multiple days)

longer duration

few signs- angiogenesis, fibrosis

What is the dominant cell type in chronic inflammation?

macrophages

What is angiogenesis?

new blood vessel formation and new vessels have immature (leaky) endothelia

When does acute inflammation peak?

peaks day two

When does chronic inflammation take affect?

begins to build up after day two

What are the stimuli for acute inflammation?

1. Infection

2. Trauma

3. Ischemia

4. Necrosis

5. Foreign bodies

6. Hypersensitivity reactions

How does the body recognize the acute inflammation stimuli?

Immune cell recognition of non self

Immune cell recognition of damage

What is recognition of non self?

recognition of harmful molecular patterns

What is PAMP?

Pathogen Associated Molecular Patterns

What are examples of PAMP?

Lipopolysaccharides, Lipoteichoic Acid and Viral RNA/DNA

What is recognition of damage?

recognition of damaged cells

What is DAMP?

Damage Associated Molecular Patterns

What are examples of DAMP?

Uric Acid, ATP, K+, DNA

What stimulates the release of IL-1?

PAMP and DAMP

What is IL-1?

proinflammatory cytokine that induces inflammation and recruits inflammatory cells to the area

What is the second step in the inflammatory process?

Vascular Change

What are the 2 things associated with Vascular Change?

Vasodilation which would increase the blood flow and cause erythema and warmth

Increase vessel permeability which would cause edema (exudate)

Mechanisms of increased permeability

1. Endothelial contraction

2. endothelial necrosis

3. Angiogenesis

What is endothelial contraction?

gaps in postcapillary venules

What induces endothelial contraction?

Histamine

What is endothelial necrosis?

leaky (until repaired)

What causes endothelial necrosis?

burns, severe infections, irradiation

Why does angiogenesis occur?

to help with tissue repair by creating new blood vessels to provide blood flow to the damaged tissue

What are the two types of edema?

exudate

transudate

What is exudate (inflammatory)?

protein- rich due to the increase in vessel permeability during localized inflammatory changes (creates push back)

What is transudate edema?

protein-poor due to lack of permeability change in conditions that are not inflammatory (no push back)

What is lymphadenopathy?

disorder of lymph nodes

What is lymphadenitis?

inflamed nodes, increase size and pain

What is lymphangitis?

inflamed lymphatic channel, red streak

Steps of Leukocyte Recruitment

1. Margination and rolling

2. firm adhesion

3. diapedesis

4. chemotaxis

What role does selectins play in rolling?

slow the white blood cells down

What role does integrin play in firm adhesion?

adheres cells to blood vessel wall

What is diapedesis?

passage of white blood cells through intact capillary walls

What is chemotaxis?

movement towards the site of injury/infection guided by chemcial signs from the damaged tissue 

What activates leukocytes?

PAMPS

cytokines

complement proteins

What is the lifespan of a neutrophil?

killed within 48 hours via apoptosis

What are the neutrophils replaced by?

macrophages and lymphocytes

What stimulates leukocyte activation?

microbes (PAMPS), necrotic tissues (DAMPS), or foreign bodies

What is acute-phase reaction?

early generalized response by immune system to infection which causes liver to produce acute- phase proteins

When might back pain be from an infection?

if they have an infected disc

unrelieved pain with rest

fever, localized pain with spinal percussion

recent infection

history of I.V. drug abuse

What is the normal leukocyte count?

4500 to 10000 cells per microliter of blood

What is leukocytosis? What’s the count?

increase in leukocytes in blood

15,000 to 30000 cells per microliter of blood

What causes leukocytosis?

Infections

What will leukocytosis due to a bacterial infection cause?

increase in neutrophils

What will leukocytosis due to a viral infection cause?

increase in lymphocytes

What is leukemoid reactions?

extreme leukocytosis with a leukocyte counts of 40000 to 100000

What are the symptoms of leukemoid reactions?

mimics leukemia symptoms such as fatigue, weight loss, and bruising

How does chronic inflammation cause a leukemoid reaction?

stimulation of bone marrow that produces/releases more WBC’s (neutrophils) in response to inflammatory stimuli.

What other diseases can cause leukemoid reactions?

TB and clostridium difficile

What is leukopenia?

decrease in blood leukocyte count (<4000/microliter)

What can cause leukopenia?

HIV/AIDS

chemotherapy

radiation therapy

What are the six patterns of inflammation?

1. serous

2. fibrinous

3. purulent/suppurative

4. ulcerative

5. pseudomembranous

6. granulomatous

What is the serous pattern of inflammation?

serum accumulates within or below epidermis, watery effusion (“blister”)

exudate that is low in cell content

What is an example of serous pattern of inflammation?

burns, viral infections, autoimmunity

What is the fibrinous pattern of inflammation?

severe injury which results in increased vessel permeability

large molecules out of circulation

fibrin rich exudate

What are examples of fibrinous patterns of inflammation?

severe fibrosis

pericarditis and pleuritis

What is the suppurative pattern of inflammation?

local infection with pus forming organism (Staph)

What’s the difference between pus and abscess?

pus= neutrophils, necrotic cells (liquefactive necrosis), and edema

abscess= area of pus accumulation

What is the ulcerative pattern of inflammation?

superficial area of tissue necrosis

superficial layer is sloughed off

What’s an example of ulcerative pattern of inflammation?

peptic ulcers, aphthous ulcer (canker sore)

What is the pseudomembranous pattern of inflammation?

false membrane on mucosal surface (GI and GU)

made up of necrotic cells, exudate, and fibrin

What is an example of pseudomembranous pattern of inflammation?

corynebacterium diphtheriae and clostridium difficile

What is granulomatous inflammation?

granuloma=pattern of chronic inflammation

collection of macrophages aka epithelioid cells, giant cells due to persistent infection

What are some conditions that produce granulomas?

Tuberculosis= caseating granulomas

fungal infections

leprosy

syphilis

cat-scratch disease

crohn disease

sarcoidosis

foreign bodies

What are the outcomes of acute inflammation?

Resolution- minimal injury in cells that can replicate

Chronic inflammation- little capacity for replication and frequent scarring

Scarring (fibrosis)- tissues can’t replicate which alters structure and decreases function

What are the unresolved inflammatory reactions for chronic inflammation?

1. persistent infection/injury- TB and repetitive overuse

2. immunosuppression- AIDS

3. hypersensitivity reactions- lupus

What are some features of chronic inflammation?

1. mononuclear leukocytes

2. tissue destruction

3. Angiogenesis and fibrosis

What are classically activated macrophages (M1)?

promote inflammation and host defense against pathogens

What are alternatively activated macrophages (M2)?

promote anti-inflammatory effects and focus on tissue repair/fibrosis

secrete growth factors that recruit fibroblasts= scarring and angiogenesis

When does tissue repair begin?

Begins before inflammation is eliminated

What are the mechanisms of tissue repair?

1. Regeneration-replaces damaged cells

2. Scarring- deposition of fibrotic tissue when regeneration isn’t possible

What is regeneration dependent on?

ability to replace injured tissues is variable

cell’s inherent growth capacity

nature of injury

What type of cells are associated with regenration?

Labile cells- constant division (skin, epithelia, bone marrow)

Stable cells- capacity to repair, but aren’t constantly actively dividing (endocrine cells and proximal tubules of kidney)

When does fibrosis occur?

1. chronic inflammation

2. death of terminally diferentiated cells

What are examples of when fibrosis would occur?

Myocardium (MI), lungs (ARDS), liver (cirrhosis)

What is the site that will result in fibrosis?

Infarct

Why does scar formation occur?

tissues can’t regenerate due to severe damage, prolonged injury, and injury to terminally differentiated cells

What is scar formation a combo of?

regeneration and fibrosis

What are the steps of scar formation?

1. Angiogenesis

2. Fibroblast migration and proliferation

3. Collagen deposition= scar

4. remodeling

What is granulation tissue and when will it develop?

Granulation tissue is new connective tissue that develops at wound site within 3-5 days

What is built onto granulation tissue?

macrophages secrete GF’s that recruit fibroblasts

fibroblasts migrate/proliferate and irregular collagen (ECM) deposits

Are scars initially vascular?

yes, but later become progressively avascular which give the pale scar

What are keloids

excessive granulation tissue formation, leading to over-abundant scarring

What is an example of persistent infection/injury?

tuberculosis, silicosis, repetitive overuse

What is an example of immunosuppression?

AIDS, transplant recipients

What is an example of hypersensitivity reactions?

Rheumatoid Arthritis, lupus

What factors lead to scarring?

Larger injury, chronic recurring injury, or the cells can’t divide

What factors lead to regeneration?

Cells are able to proliferate and the injury isn’t severe