Inflammatory response(old)

Coordinated response to tissue damage goals

‒ Wall off injured area

‒ Prevent injury spread

‒ Bring defenses

local inflammation

response restricted to area of injury

Systemic inflammation

The inflammatory response affects the whole body

5 classic signs of inflammation

Redness

Swelling

Heat

Pain

Loss of function

5 classic signs of inflammation(latin)

Rubor

Tumor

Calor

Dolor

Functio laesa

Acute inflammation

• Rapid onset with quick termination

• Chemical mediators

2 phases of acute inflammation

Vascular

Cellular

Vascular phase

• Initial vasoconstriction

• Increased vascular permeability

Cellular phase

• Signal to attract WBCs

• WBCs move to area of injury

What are histamine and bradykinin?

Inflammatory mediators released during tissue injury that contribute to vasodilation and increased vascular permeability.

Vasodilation in context of inflammatory response

Widening of blood vessels, which increases blood flow to the injured area.

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 the difference between vasodilation and increased vascular permeability?

Vasodilation makes vessels wider; increased vascular permeability makes vessels leakier.

Why do WBCs travel to the site of injury during inflammation?

To eliminate pathogens and remove damaged cells and tissue debris.

What is extravasation?

The movement of fluid, WBCs, or other blood components out of the blood vessel and into surrounding tissue.

What is fluid extravasation during inflammation?

Movement of fluid from blood vessels into injured tissue due to increased vascular permeability.

What is one major consequence of fluid extravasation?

Edema (swelling) of the injured tissue.

What can the fluid entering injured tissue help do?

Dilute toxins and deliver proteins and other components involved in the inflammatory response.

What is phagocytosis in the context of the inflammatory response?

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

Why is WBC phagocytosis important during inflammation?

It removes pathogens and damaged tissue so the injured area can be cleaned up and begin healing.

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)

WBC chemotaxis

movement of WBCs toward a chemical signal

Leukocytosis

Increase in WBC number

Normal WBC count

4,000 to 10,000 cells mL = normal

Leukemoid reaction

extreme increase in WBCs caused by a severe reactive stimulus

Margination

When WBCs line up along the endothelium during inflammation

Neutrophils

The predominant WBC during the first 6–24 hours of acute inflammation.

Monocytes

• Replace neutrophils

• 24 to 48 hours change into macrophages

What are inflammatory mediators?

Chemical signals that coordinate and regulate the inflammatory response.

What releases inflammatory mediators?

Damaged tissues and white blood cells (WBCs)

Pro-inflammatory mediators

• TNF-alpha

• Interleukins (ILs)

• Histamine

• Prostaglandins

• Leukotrienes

Cytokines

Signaling proteins that communicate messages between cells and regulate immune and inflammatory responses.

What can cytokines trigger?

Can trigger:
Cellular processes

release of hormones and other substances.

Can cytokines promote or inhibit inflammation?

Yes. Different cytokines can either promote or inhibit inflammation.

How can medications affect inflammation?

Can modify inflammatory responses by altering inflammatory signaling or mediator activity.

WBC released cytokines examples

TNF-alpha, IL

Chemokines

Specialized signaling proteins

Attract WBC to endothelium

Move immune cells around

Autocrine

Same cell secretes and receives cytokine signal

Paracrine

Cytokine signal secreted to a nearby cell

Endocrine

Cytokine signal secreted to circulatory system, travels to distant cells

What are acute phase proteins?

Proteins produced by the liver in response to inflammation.

C-reactive protein (CRP)

An acute phase protein produced by the liver that increases during inflammation.

CRP function

marks foreign material for phagocytosis

activates the complement system

stimulates other inflammatory cytokines

What does it mean when CRP is elevated?

indicates active inflammation in the body

What is high-sensitivity CRP (hs-CRP)?

A more sensitive measurement of CRP used to help assess cardiovascular risk.

What does an elevated hs-CRP indicate?

Increased risk of myocardial infarction (heart attack).

What happens when fibrinogen binds to red blood cells (RBCs)?

RBCs stick together and form stacks called rouleaux.

What is rouleaux?

Stacking of red blood cells caused in part by increased fibrinogen during inflammation.

How does fibrinogen affect RBC sedimentation?

Fibrinogen promotes aggregation, causing RBCs to settle more rapidly in a blood sample.

What is erythrocyte sedimentation rate (ESR)?

The rate at which red blood cells settle to the bottom of a blood sample.

What does an elevated ESR indicate?

It is a nonspecific indicator of active inflammation.

What is the relationship between fibrinogen and ESR?

Inflammation increases fibrinogen, which promotes RBC aggregation (rouleaux), which increases the ESR.

Serum Amyloid A

acute phase protein that increases during inflammation.

What can prolonged elevation of serum amyloid A cause?

can contribute to amyloidosis, in which abnormal amyloid proteins accumulate in tissues.

What is hepcidin?

A hormone produced by the liver that regulates iron availability in the body.

What happens to hepcidin during chronic inflammation?

Hepcidin increases, causing iron to become less available for use in red blood cell production.

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.

What breaks down the clot/scab as part of the clean up process

macrophages

What do fibroblasts do during wound healing?

move into the injured area and produce collagen and other connective tissue fibers.

What is the purpose of collagen in wound healing?

Collagen strengthens the healing tissue and provides structural support.

What happens to connective tissue during wound healing?

Damaged connective tissue is gradually replaced and rebuilt with new connective tissue.

Wound healing stage 1

Hemostasis

Wound healing stage 2

Inflammation stage

Wound healing stage 3

Proliferative stage

Wound healing stage 4

Remodeling stage

Leukocytes

WBCs
Granulocytes and agranulocytes

Granulocytes

‒ Neutrophil

‒ Basophil

‒ Eosinophil

Agranulocytes

‒ Lymphocyte

‒ Monocyte (become macrophages)

Neutrophil lifespan

Short lifespan – hours to days

What is the main function of neutrophils?

They rapidly phagocytose and destroy pathogens and cellular debris.

Respiratory burst

A process in which neutrophils rapidly produce reactive oxygen species to help kill engulfed pathogens.

What does PMN stand for?

Polymorphonuclear cell, a term commonly used for neutrophils because of their segmented, multilobed nuclei.

What does the nucleus of a mature neutrophil look like?

It is segmented into multiple lobes.

What are “segs”?

A common term for mature neutrophils because they have segmented nuclei.

What are “bands”?

Immature neutrophils that have not yet developed the segmented nucleus of mature neutrophils.

What does an increased number of bands usually indicate?

An acute infection or significant inflammatory response.

What is a “shift to the left”?

An increase in immature neutrophils (bands) in the bloodstream, usually because the bone marrow is releasing neutrophils rapidly to meet demand.

Why does a shift to the left occur during acute infection?

The body rapidly produces and releases neutrophils, causing more immature bands to enter the bloodstream than usual

What is the difference between bands and segs?

Bands are immature neutrophils with an unsegmented/band-shaped nucleus; segs are mature neutrophils with segmented nuclei.

White Blood Cell Differential

part of complete blood count

% of each type of WBC within total WBC population

Types of WBCs

Monocytes(turn into macrophages)

Eosinophils

lymphocytes

basophils

neutrophils

What are systemic responses to acute inflammation?

Whole-body effects that occur when inflammatory mediators circulate beyond the local site of injury.

What are examples of chemical mediators involved in systemic inflammation?

TNF-alpha, prostaglandins, and interleukins.

What is the role of TNF-alpha in systemic inflammation?

It promotes systemic inflammatory responses, including fever, fatigue, loss of appetite, and lethargy

What is the role of prostaglandins in systemic inflammation?

They contribute to fever and other inflammatory responses.

What is the role of interleukins in systemic inflammation?

They act as signaling molecules that coordinate immune and inflammatory responses.

What are common systemic symptoms of acute inflammation?

Fever, lymphadenopathy, anorexia, sleepiness, lethargy, anemia, and weight loss.

Lymphadenopathy

Enlargement of lymph nodes

Pyrogens

Substances that cause fever by causing prostaglandins to increase the hypothalamus's temperature set point.

Why do chills occur at the onset of a fever?

The hypothalamic set point has increased, so the body feels cold relative to the new set point and responds by generating and conserving heat.

Higher temp and WBCs

Higher temp increases WBC efficiency

Anti-prostaglandins

Reduce fevers

Fever “breaks”

Return body temperature to normal

Lymphocytes

B and T cells

Mature in lymph nodes