Inflammatory Response Study Guide Cut

Coordinated response to tissue damage goals

‒ Wall off injured area

‒ Prevent injury spread

‒ Bring defenses

Five Classic Signs of Inflammation

Redness

Swelling

Heat

Pain

Loss of Function

Five Classic Signs of Inflammation(Latin)

Rubor

Tumor

Calor

Dolor

Functio Laesa

Acute Inflammation

• Rapid onset with quick termination

• Chemical mediators

Acute Inflammation Phases

Vascular

Cellular

Vascular phase

• Initial vasoconstriction

• Increased vascular permeability

Cellular phase

• Signal to attract WBCs

• WBCs to area of injury

5 Inflammatory Mediators

• TNF-alpha

• Interleukins (ILs)

• Histamine

• Prostaglandins

• Leukotrienes

Histamine and Bradykinin

Inflammatory mediators that promote vasodilation and vascular permeability

Extravasation

Movement of fluid, WBCs, and blood components from the vessels to surrounding tissue

What are two effects of vasodilation during inflammation?

Increased blood flow to the injured area(which produces redness and warmth)

Delivery of immune defenses

What does increased vascular permeability mean?

Blood vessels become more permeable (leaky), allowing:

fluid

proteins

and immune components to move from the blood into surrounding tissue.

What is one major consequence of fluid extravasation?

Edema

WBC phagocytosis

process by which certain WBCs engulf and destroy pathogens, dead cells, and cellular debris.

What is the basic sequence of vascular changes during inflammation?

Injury

inflammatory mediators such as histamine/bradykinin

vasodilation and increased vascular permeability

fluid and WBCs enter tissue

WBCs remove pathogens/debris.

Purulent exudate

Pus

White-green discharge containing proteins and microbes

Transudate

Watery, clear

Ex: Blister

Abscess

Localized, walled-off

Purulent exudate

Effusion

Accumulation of fluid in Body cavities (example: pericardial effusion)

Steps in the white blood cell response

1. Margination
2. Rolling
3. Adhesion
4. Diapedesis
5. Chemotaxis
6. Phagocytosis

Margination

WBCs move toward the endothelium

Rolling

WBCs roll along the endothelial wall

Adhesion

WBCs stick firmly to the endothelium

Diapedesis

WBCs squeeze through the vessel wall into the tissue

Chemotaxis

WBCs follow chemical signals toward the injury

Leukocytosis(1) and leukomoid reaction(2)

1) Increase in WBC number

2) extreme increase in wbc count due to severe reactive stimulus

Normal WBC count

4,000 to 10,000 cells mL = normal

Cytokine

signaling protein that communicates messages between cells and coordinates the inflammatory and immune responses

Chemokine

Specialized signaling proteins

Attract wbcs to endothelium

move immune cells

Acute Phase Proteins

Proteins produced by the liver in response to inflammation

Lecture acute phase proteins

CRP
Fibrinogen

Serum Amyloid A

Hepcidin

C-reactive protein(CRP)

• Marks foreign material for phagocytosis

• Activates complement system

• Stimulates other inflammatory cytokines

What does elevated CRP mean?

Elevation indicates active inflammation

Elevated High sensitivity CRP (hs-CRP)

Marker for increased risk of myocardial infarction

Fibrinogen

acute phase protein that causes RBCs to stick together and form stacks called rouleaux

ESR

Rate at which RBCs settle to the bottom of a blood sample

Fibrinogen and ESR connection

Inflammation increases fibrinogen, Fibrinogen promotes aggregation of RBCS(rouleaux), aggregation increases ESR

Elevated ESR

indicator of active inflammation

What can prolonged serum amyloid A secretion cause?

Amyloidosis

Amyloidosis

Accumulation of abnormal amyloid proteins in tissues, chronic inflammation

Hepcidin

acute phase protein/hormone produced by the liver that regulates iron availability in the body.

What happens to hepcidin during chronic inflammation?

Hepcidin increases

How can chronic inflammation contribute to anemia?

Increased hepcidin decreases iron availability, contributing to anemia

What does elevated hepcidin indicate in the context of chronic inflammation?

Diminished iron availability/storage for red blood cell production, potential active inflammation

What breaks down the clot/scab

macrophages

Fibroblasts and inflammation

Move into the injured area and secrete collagen and other connective tissue fibers

Collagen and the healing process

Collagen strengthens the area as it heals, and replaces the damaged connective tissue with new connective tissue

Stages of wound healing

Hemostasis

Inflammation

Proliferative

Remodeling

Systemic Responses in Acute Inflammation Mediators

• TNF-alpha

• Prostaglandins

• Interleukins

Systemic Responses in Acute Inflammation Examples

Fever

Lymphadenopathy

Anorexia

Sleepiness

Lethargy

Anemia

Weight Loss

What releases pyrogens

WBCs and microorgs

Pyrogens

Influence the hypothalamus to increase body temperature via prostaglandins, causing fever

Why are chills felt at the onset of a fever

Chills are felt as the body adjusts to a new higher set temp

Anti-prostaglandins

Reduce fever

Fever “breaks”

Return body temperature to normal

Lymphadenopathy

Enlargement of lymph nodes due to inflammatory processes

Lymphocytes

B and T cells

Lymphatic fluid

• Circulates throughout the body

• Injurious agents in lymph system can invade other tissues

What produces histamine

Basophils, platelets, mast cells

Systemic effects of histamine

• Arteriolar vasodilation

• Large artery vasoconstriction

• Increased permeability of venules

Example responses to histamine

Sneezing, runny nose, pharyngeal irritation

Phospholipase

Enzyme that breaks down phospholipids, forms Arachidonic acid

Cyclooxygenase produces _______

Prostaglandins

Lipoxygenase produces _____

leukotrienes

COX 1 products

Helpful PGs

Gastric mucus

Platelet adhesion

COX 2 products

Harmful PGs

Inflammation

Pain

Fever

Lipoxygenase pathway result

Bronchiole inflammation/constriction induced by leukotrienes(produced by the pathway)

What is the role of arachidonic acid in the COX-1, COX-2, and lipoxygenase pathways?

Arachidonic acid is the precursor that is metabolized by COX-1/COX-2/LIPO to produce the end products

What produces TNF-alpha and ILs

produced by macrophages

General effects of TNF-alpha and ILs

Induce fever, loss of appetite, and lethargy

TNF-alpha other effects

‒ Weight loss and cachexia

‒ Promotes endogenous corticosteroids

Angiogenesis

process by which new capillary blood vessels grow from pre-existing blood vessels, VEGF

Factors That Affect Wound Healing

Nutrition

Oxygen
Immune Strength

Infection(most important factor)

Foreign Bodies

Mechanical Factors

Laboratory results – Inflammation

C-RP, ESR, fibrinogen, hepcidin

Elevate with inflammation

Clinical Concepts: Fever

Beneficial effects(increases immune system efficiency)

High levels can be dangerous (>104 can be accompanied by severe side effects, such as delirium)

Clinical Concepts: Sepsis

Large amounts of TNF-alpha and ILs

May result in shock

Clinical Concepts: Pressure ulcers and severe burns

WBCs may increase. Secondary and tertiary intention healing required