CR1 KCP1 Chronic Inflammation

Define Chronic Inflammation and state its 3 simultaneous hallmark processes.

A prolonged inflammatory response lasting weeks to months/years in which: 1. Persistent active inflammation; 2. Tissue destruction; and 3. Attempts at repair (fibrosis/angiogenesis) occur simultaneously.

Describe how acute inflammation progresses to chronic inflammation.

Occurs when the offending stimulus cannot be eliminated during the acute phase. Short-lived neutrophils die off and are replaced by persistent mononuclear cells (macrophages, lymphocytes, plasma cells).

3 main causes of chronic inflammation with examples for each.

1. Persistent Infections (e.g., M. tuberculosis, persistent fungi); 2. Hypersensitivity Diseases (Autoimmune like RA, Allergic like asthma); 3. Prolonged Toxic Exposure (Silicosis from silica, Atherosclerosis from lipids).

What triad of histological features defines chronic inflammation under the microscope?

1. Mononuclear cell infiltration (macrophages, lymphocytes, plasma cells); 2. Parenchymal tissue destruction; 3. Repair attempts (angiogenesis and fibrosis).

What is the dominant effector cell of chronic inflammation? Name its 4 primary functions.

Macrophages. Functions: 1. Phagocytosis; 2. Secretion of cytokines (TNF, IL-1); 3. Antigen presentation to T cells; 4. Initiation of repair/fibrosis via growth factors (TGF-β).

Differentiate between Classically Activated (M1) and Alternatively Activated (M2) Macrophages by inducers, products, and roles.

M1: Induced by IFN-γ/TLRs; produces ROS, NO, IL-1, TNF; promotes microbicidal killing and inflammation. M2: Induced by IL-4, IL-13; produces IL-10, TGF-β; promotes tissue repair, wound healing, and fibrosis.

Describe the bidirectional feedback loop between Macrophages and T Lymphocytes.

Activated macrophages present antigens to T cells and secrete IL-12 to activate them; activated T cells secrete IFN-γ (which activates M1 macrophages) and TNF/IL-17 (which recruits leukocytes), sustaining inflammation.

What are the roles of TH1, TH2, and TH17 helper T-cell subsets in chronic inflammation?

TH1: Secretes IFN-γ (activates M1 macrophages). TH2: Secretes IL-4, IL-5, IL-13 (recruits eosinophils, activates M2 macrophages). TH17: Secretes IL-17 (recruits neutrophils/monocytes).

In what specific clinical scenarios are Eosinophils predominantly recruited, and what toxin do they release?

Recruited in IgE-mediated allergic reactions (asthma) and parasitic infections; release Major Basic Protein (MBP).

Define Granulomatous Inflammation and describe its core microscopic architecture.

A specialized form of chronic inflammation characterized by focal collections of activated epithelioid macrophages surrounded by a collar of T lymphocytes, plasma cells, and multinucleated giant cells.

Epithelioid Cells and Multinucleated Giant Cells?

Epithelioid Cells: Activated macrophages with abundant pink/eosinophilic cytoplasm resembling epithelial cells. Giant Cells: Large cells formed by the fusion of multiple epithelioid macrophages.

Compare Immune (Hypersensitivity) Granulomas vs. Foreign Body Granulomas by cause, immune mechanism, and giant cell type.

Immune: Caused by persistent antigens; T-cell mediated (Type IV); features Langhans giant cells (horseshoe nuclei). Foreign Body: Caused by inert materials (sutures, talc); no T-cell response; features Foreign Body giant cells (scattered nuclei).

State the etiologic agent and key histologic hallmark for Tuberculosis (TB).

Etiology: Mycobacterium tuberculosis; Hallmark: Caseating granulomas with central cheesy necrosis, Langhans giant cells, and Acid-Fast Bacilli (AFB).

4 granulomatous diseases that typically feature non-caseating granulomas.

1. Sarcoidosis; 2. Crohn disease; 3. Leprosy (M. leprae); 4. Beryllium toxicity.

What distinct granuloma morphology is seen in Cat-Scratch Disease and Syphilis?

Cat-Scratch Disease: Stellate (star-shaped) necrotizing granuloma filled with neutrophils. Syphilis: Gumma (central necrosis surrounded by plasma cells).

What cytokines drive the Systemic Acute-Phase Response?

TNF, IL-1, and IL-6.

Explain the mechanism by which Pyrogens induce Fever in the hypothalamus.

Pyrogens (exogenous like LPS, endogenous like IL-1/TNF) stimulate perivascular cells in the hypothalamus to produce Prostaglandin PGE2, resetting the temperature set-point higher.

Name 3 acute-phase proteins synthesized by the liver and their clinical significance.

1. C-Reactive Protein (CRP); 2. Serum Amyloid A (SAA); 3. Fibrinogen (causes RBC rouleaux, increasing ESR).

What acute-phase peptide causes Anemia of Chronic Inflammation, and what is its mechanism?

Hepcidin; it reduces the systemic availability of iron for red blood cell production.

Define "Left Shift" and list the diagnostic WBC patterns for Bacterial, Viral, and Parasitic/Allergic conditions.

Left Shift: Increased immature neutrophils in blood. Bacterial = Neutrophilia; Viral = Lymphocytosis; Parasitic/Allergic = Eosinophilia.

What 3 severe pathological conditions characterize Septic Shock induced by massive systemic TNF/IL-1 levels?

1. Hypotension / Cardiovascular collapse; 2. Disseminated Intravascular Coagulation (DIC); 3. Metabolic disturbances (hypoglycemia).