Chronic Inflammation Flashcards
(24 cards)
Granuloma 🦠
A nodular inflammatory lesion made up of macrophages, lymphocytes, and fibroblasts.
==> Forms in response to persistent irritants (e.g., tuberculosis bacteria, foreign bodies) to wall off and contain the threat.
Granulation Tissue ❤️🩹
Newly formed tissue containing macrophages, blood vessels, and fibroblasts.
==> Essential for wound healing—it fills in damaged areas, removes debris, and produces new connective tissue (fibrosis).
Fibrinogen
→ Fibrin 🩸
A glycoprotein made by the liver, converted into fibrin during clotting.
==> Forms clots and can help create a fibrin mesh in inflamed tissues.
Fibrosis 🏗️
Formation of fibrous connective tissue (scarring) as a part of healing.
==> Replaces damaged tissue but can also cause stiffening and loss of function in organs.
progression of acute inflammation
[little or no fibrin
deposition
or tissue damage]
1️⃣ Fibrin is first deposited to stabilize the injury and help with clotting & inflammation.
2️⃣ If the injury is mild, enzymes like plasmin break down the fibrin (this is called fibrinolysis).
3️⃣ The fluid, dead cells, and debris are cleared through lymphatic drainage.
4️⃣ The tissue returns to normal (resolution) with no scar formation.
progression of acute inflammation
[substantial fibrin
deposition
or tissue damage]
1️⃣ A lot of fibrin means more severe damage → it signals deeper injury, infection, or persistent irritation.
=> The body cannot simply remove the fibrin like it clears fluids.
Instead, it needs macrophages and fibroblasts to break it down and replace it with fibrous tissue (scar tissue).
This leads to long-term healing (fibrosis), abscess formation, or chronic inflammation.
If there’s too much damage, macrophages can’t remove everything quickly.
Fibrin stays longer → more fibroblasts arrive and start depositing collagen.
Over time, the area fills in with scar tissue (fibrosis) instead of normal tissue.
Why Does Fibrosis Take Longer?
Macrophages from the exudate are needed to clear debris & fibrin.
If the damage is big, this process takes longer because:
More fibrin to break down → macrophages work harder.
More tissue destruction → fibroblasts start depositing collagen to replace lost tissue.
Inflammation lasts longer → slows down healing, leading to scarring.
exudation
🔹 What is Exudation?
Exudation = The leakage of fluid, proteins, and immune cells from blood vessels into tissues.
It happens when blood vessels become more permeable (leaky) during inflammation.
🔹 Why Does Exudation Happen?
When you have an infection or injury, your body needs to send immune cells to the site quickly.
To do this, blood vessels widen (vasodilation) and become more leaky → allowing fluid, proteins, and immune cells to flow out into the tissue.
🔹 What’s in the Exudate (Leaked Fluid)?
The fluid contains:
✔️ Plasma proteins (like fibrinogen → forms fibrin for clotting).
✔️ Immune cells (neutrophils, macrophages → to fight infection).
✔️ Antibodies & complement proteins (to attack pathogens).
. What is Suppuration?
Suppuration = Formation of pus (neutrophils, dead cells, bacteria, debris).
Happens when neutrophils dominate the response but can’t fully clear the infection.
Seen in bacterial infections (“pyogenic” bacteria like Staphylococcus aureus).
Can form abscesses (localized pus collection) or ulcers (surface pus).
Neutrophils are great at killing bacteria, but they don’t repair tissue.
Pus is just dead neutrophils, bacteria, and debris—it doesn’t help healing.
Once neutrophils complete their job, they die
=Macrophages take over
–> Releasing signals to stop inflammation and start repair.
=Fibroblasts arrive → Lay down collagen for fibrosis/scarring.
✔ Acute suppuration (short-term pus formation) → Can sometimes heal if infection is controlled.
❌ If infection or damage persists, it becomes chronic → Chronic Suppurative Inflammation.
Chronic Suppurative Inflammation
(Neutrophil-Driven)
What If the Infection Persists?
If the infection stays (e.g., deep abscess, chronic wound), neutrophils keep coming → chronic suppurative inflammation.
This leads to more pus, more necrosis, and delayed healing.
Occurs when pus formation continues for a long time.
Neutrophils keep coming because the infection/injury isn’t resolved.
Leads to chronic abscesses or ongoing tissue destruction.
Key Difference Between Suppuration and Fibrosis
✔ Fibrosis (Scarring) → Macrophages + Fibroblasts Dominate
✔ Suppuration (Pus) → Neutrophils Dominate
Chronic Granulomatous Inflammation
(Macrophage-Driven)
If an infection or foreign body can’t be destroyed, the body walls it off with macrophages and lymphocytes.
These immune cells form granulomas to trap the pathogen.
This is different from suppuration, which is neutrophil-based.
Resolution Suppuration Granulomatous pathways
Resolution: Mild, sterile; Macrophages; Full healing
Suppuration: Bacterial infection; Neutrophils; Pus, then fibrosis (if resolved)
Granulomatous: Persistent pathogen/foreign body; Macrophages; Granuloma, then fibrosis
difference between reoslution and organisaion
resolution
mild injury, no signficnat tissue damage
little to no fibrin
macrophages clear fluid and debris quickly
fibroblasts not needed much (tissue regenerates on its own)
tissue retiurns to normal, no scar
organisation
Mild to moderate injury with significant fibrin deposition
copious fibrin deposition
In Organisation:
Macrophages try to clear fibrin but can’t remove all of it.
Fibroblasts step in and lay down collagen to “replace” the fibrin → forming a scar.
Once collagen is deposited, healing is complete → Even though a scar remains, there’s no more inflammation or new fibrin being deposited.
🔹 So even though the fibrin wasn’t 100% cleared, the tissue is stable and doesn’t keep worsening.
fibroblasts lay down collagen, scar tissue (fibrosis)
fibrosis tissue replaces damaged area (Scar)
Why Can’t Fibroblasts Fully Deposit Collagen in Chronic Fibrosis?
Macrophages Stay in “Inflammation Mode” Instead of “Healing Mode”
In acute healing, macrophages stop releasing inflammatory signals once fibroblasts take over.
In chronic fibrosis, macrophages remain active and keep producing pro-inflammatory cytokines (e.g., TNF-α, IL-1, IL-6).
These signals keep fibroblasts in an activated state but also prevent them from fully stabilizing the tissue.
four main features of chronic inflammation
1️⃣ Persistence (Chronicity)
✔ Chronic inflammation lasts for weeks, months, or even years instead of resolving quickly like acute inflammation.
✔ It happens when the cause of inflammation isn’t eliminated (e.g., persistent infections, autoimmune diseases, long-term irritants).
✔ Examples:
Tuberculosis (TB) → Mycobacterium tuberculosis survives inside macrophages, leading to chronic immune activation.
Rheumatoid arthritis → The immune system keeps attacking joint tissues.
2️⃣ Cellular Infiltration
✔ Unlike acute inflammation (which is mostly neutrophils), chronic inflammation involves:
Macrophages (clear debris but also drive fibrosis).
Lymphocytes (T-cells, B-cells) (especially in autoimmune diseases).
Plasma cells (produce antibodies that can contribute to tissue damage).
✔ These immune cells stay in the affected tissue, leading to constant immune activation.
3️⃣ Destruction of Normal Tissue
✔ Because inflammation lasts too long, immune cells can damage the body’s own tissues.
✔ Causes of tissue destruction:
Macrophages release proteases & reactive oxygen species (ROS) → Breakdown of healthy tissue.
Lymphocytes signal further immune attack (in autoimmune diseases).
Granulomas (macrophage clusters) can trap infections but also damage surrounding tissue.
✔ Examples:
Liver cirrhosis (chronic hepatitis) → Continuous inflammation destroys liver cells.
Chronic wounds (diabetic ulcers) → Inflammation prevents normal tissue repair.
4️⃣ Formation of Fibrous Connective Tissue (Fibrosis)
✔ When inflammation doesn’t resolve, the body replaces damaged tissue with fibrous tissue (scar tissue) instead of normal healing.
✔ Fibrosis happens because:
Macrophages release TGF-β, which stimulates fibroblasts.
Fibroblasts lay down collagen, leading to scar formation.
✔ Examples:
Pulmonary fibrosis (lungs become stiff due to chronic inflammation).
Chronic kidney disease (long-term inflammation leads to kidney scarring).
Types of Chronic Granulomatous Inflammation
- Foreign Body Granuloma : Non-degradable materials that the body can’t break down.
- Chronic Granulomatous Inflammation of Unknown Origin : No clear infection or foreign material, but the immune system still forms granulomas.
- Immune-Type Granulomatous Inflammation: Pathogens that survive inside macrophages.
Foreign Body Granuloma
✔ Cause:
Non-degradable materials that the body can’t break down.
Examples: Surgical sutures, splinters, asbestos fibers.
✔ Histopathology:
Giant cells (fusion of macrophages trying to engulf the foreign material).
Fibrosis (scar formation around the irritant).
✔ Why Does This Happen?
Macrophages can’t digest the material, so they surround it to isolate it from the body.
✔ Example:
A suture granuloma where leftover surgical sutures cause a persistent immune response.
Chronic Granulomatous Inflammation of Unknown Origin
✔ Cause:
No clear infection or foreign material, but the immune system still forms granulomas.
Example: Sarcoidosis (autoimmune-like response with no known pathogen).
✔ Histopathology:
Epithelioid cells (activated macrophages) and Langhans giant cells.
Lymphocytes (chronic immune activation).
Peripheral fibrosis (scarring around the granuloma).
✔ Why Does This Happen?
The immune system mistakenly forms granulomas even without a clear threat.
✔ Example:
Sarcoidosis (granulomas in the lungs, lymph nodes, or other organs without an obvious infection).
Immune-Type Granulomatous Inflammation
✔ Cause:
Pathogens that survive inside macrophages.
Examples: Tuberculosis (Mycobacterium tuberculosis), Leprosy (Mycobacterium leprae).
✔ Histopathology:
Caseous necrosis (cheese-like dead tissue in TB).
Epithelioid cells and Langhans-type giant cells (specialized macrophages).
Lymphocytes (chronic immune response).
Peripheral fibrosis (scar tissue around granulomas).
✔ Why Does This Happen?
Some bacteria can hide inside macrophages.
The immune system traps them in granulomas to stop their spread.
✔ Example:
Tuberculosis (TB) → The body walls off TB bacteria in lung granulomas, but the bacteria can remain alive inside for years.
Roles of Granulomas
✔ Containment of Microorganisms/Irritants
The body traps infections or foreign particles to prevent them from spreading.
Example: TB granulomas keep Mycobacterium tuberculosis localized.
✔ Focus the Immune Response
Instead of widespread inflammation, granulomas localize the attack.
This helps concentrate macrophages, lymphocytes, and fibroblasts at the site of infection.
How Granulomas Form
1️⃣ A foreign particle or pathogen enters the body (e.g., TB bacteria, fungal spores, or surgical sutures).
2️⃣ Macrophages try to engulf & digest it, but fail (some pathogens resist destruction).
3️⃣ The immune system activates → T-cells release cytokines (like TNF-α, IFN-γ) to attract more immune cells.
4️⃣ More monocytes are recruited & differentiate into macrophages.
5️⃣ Macrophages fuse into giant cells or become epithelioid cells (modified macrophages).
6️⃣ Fibroblasts are activated → Lay down fibrous tissue, leading to scarring (fibrosis).
🔹 Outcome: A granuloma forms, creating a physical barrier between the irritant and the rest of the body.
Role of TNF-α in Granuloma Formation (Second Image)
✔ TNF-α (Tumor Necrosis Factor-alpha) is pro-inflammatory cytokine produced by macrophages, T-cells, and other immune cells.
✔ It is a key regulator of inflammation and helps coordinate immune responses against infections.
[1️⃣ Activate Macrophages → Keeps them in an “angry” state, so they stay at the infection site.
2️⃣ Recruit More Immune Cells → Attracts monocytes, which become macrophages, strengthening the granuloma structure.
3️⃣ Promote Cell Fusion → Encourages macrophages to merge into giant cells, forming the granuloma’s core.
4️⃣ Induce Fibrosis → Signals fibroblasts to produce collagen, stabilizing the granuloma.]
==> crucial for granuloma maintenance.
If TNF is blocked, granulomas break down → This shows that TNF is essential for keeping granulomas stable.
✔ Why is this important?
Patients on anti-TNF drugs (e.g., for rheumatoid arthritis) are at risk for TB reactivation because granulomas can’t be maintained.
Components of the Inflammatory Pathway
1️⃣ Inducers:
Infection (bacteria, viruses, fungi).
Tissue damage (physical injury, toxins, or autoimmune attacks).
2️⃣ Sensors (Detection of Threats):
Toll-like receptors (TLRs) on mast cells, dendritic cells, and macrophages recognize microbial invaders or damaged tissue.
3️⃣ Mediators (Inflammatory Signals):
Cytokines (TNF, IL-1, IL-6): Amplify inflammation.
Chemokines (CCL2, CXCL8): Attract more immune cells to the site.
Histamine & Bradykinin: Increase blood flow and permeability.
Eicosanoids (e.g., prostaglandins): Contribute to pain and fever.
4️⃣ Target Tissues (Response & Healing):
Blood vessels (increase permeability, allowing immune cells in).
Liver (produces acute-phase proteins for defense).
Damaged tissues (initiate healing).
✔ Final Outcome: Killing of microorganisms & initiation of healing.
Chronic Inflammation of “Mixed Type”
It means the inflammation involves both neutrophils (acute) and macrophages/lymphocytes (chronic) together in the same disease process.
🔹 How Does This Happen?
1️⃣ Neutrophils are usually found in acute inflammation.
They arrive quickly to kill bacteria and clear debris.
But in chronic inflammation, they usually disappear.
==> In “mixed-type” chronic inflammation, neutrophils remain present along with macrophages and lymphocytes.
✔ Key Features:
Neutrophils (acute response) + Macrophages/Lymphocytes (chronic response).
Can persist for long periods.
The initiating cause is often unknown.
✔ Example: Rheumatoid Arthritis (RA)
✔ Key Players in RA:
In the joint synovial fluid, neutrophils are present → Acute inflammation feature.
In the pannus (thickened synovial tissue), macrophages & lymphocytes dominate → Chronic inflammation feature.
Most chronic inflammation (e.g., TB granulomas) doesn’t have neutrophils—just macrophages and lymphocytes.
In RA, neutrophils stay active, constantly releasing enzymes & ROS, causing tissue destruction.
