2. Inflammation

Qbank - 2. Inflammation


Inflammation is the response of vascularized connective tissue

  • Injury -> Response of Body
    • Change in Blood Vessels
    • Changes in Cells [Connective tissue]
  • This response is usually protective, but sometimes harmful
  • -itis denotes inflammation
  • Types
    • Purulent infl.
    • Serous infl.
    • Fibrinous
    • Cattarhal inflammation [Inflammation involving mucous membrane - discharge of watery + mucous Most common]
  • Acute Inflammation -> Neutrophils
  • Chronic Inflammation -> Mononuclear WBCs (lymphocytes with their round nucleus and monocytes with kidney shaped nucleus)

Cardinal signs of inflammation: [Described by Celsus]

  • Rubor
  • Dolor
  • Calor
  • Tumor
  • Funcio lassiea / Loss of function - Virchow

[[Pasted image 20210624232124.png]]

Acute Inflammation

Vascular changes

  • Vasoconstriction is the first/earliest change during inflammation
  • Vasodilation due to release of due to release of inflammatory mediators such as Histamine
    • Responsible for rubor due to hyperemia
    • Responsible for calor
  • Increased vascular permeability
    • This is primarily due to endothelial cell contraction and increased gap between endothelial cells from vasodilation due to chemical mediators
    • This leads to formation of exudate (protein and cell rich fluid)
      • Fluids
      • Cells
      • Proteins
    • Specific gravity of Exudate is greater than 1.020 -> This leads to swelling/edema [Tumor]
    • Small blood vessels such as below, can also be involved
      • Arterioles
      • Capillaries
      • Venules (most commonly involved)
  • Stasis
    • This is reduction in velocity of blood flow
    • This is due to increased vascular permeability which leads to hemoconcentration -> Viscosity increases
    • Due to stasis, there is inceased chances of thrombosis due to settling down of platelets and clotting factors
    • VIRCHO’S TRIAD - Associated with Thrombus formation

      [[Pasted image 20210624234922.png]]

      • Endothelial cell injury
      • Changes in blood flow -> if increased speed -> turbulence -> endothelial cell damage
      • Hypercoagulability

Mechanisms of Vascular permeability

  • This is the most characteristic change in inflammation
  • Endothelial cell contraction - MOST COMMON
    • due to action of histamine
    • immediate transient (lasting only for a short time; impermanent.)
    • e.g. thorn prick
  • Direct endothelial cell injury
    • Massive release of toxins causing damage to endothelial cells
    • Since repair of these endothelial cells take time, it is an immediate but sustained response
    • e.g: Septicemia, Severe burn
  • Endothelial cell retraction
    • It is mediated by cytokines (which are usually released after inflammation)
    • This is re-organization of ECs
    • Thus it is delayed transient change
    • e.g: bacterial infections
  • Endothelial cell Damage
    • Gradual damage occurs
    • Thus it is Delayed prolonged leakage
    • e.g: late sun burn
  • The extracellular fluid is drained by lymph

  • During exudate release, bacteria/toxins may also be released, thus this may enter the lymph

  • This causes lymphangitis (inflammation of lymph vessels)

    • Most common infection for lymphangitis: Streptococcus pyogenes

    [[Pasted image 20210624234404.png]]

    • Notice the thin red lines along the lymph vessels visible superficially

Cellular Changes

5 R’s

  • Recognition
  • Recruitment
  • Removal
  • Regulation
  • Repair

Intravascular Changes

[[Pasted image 20210627075405.png]]

  • Margination - WBCs start to move o margins when inflammation occurs
    • Neutrophils have 2 pools - 50% on margination pool, 50% in systemic circulation
    • Laminar Flow Theory: Cells tend to move in the center while fluid moves in the periphery
  • Rolling, a.k.a Loose Adhesion - slowing down of WBC
    • Endothelial cells express Selectins (CD62)
      • E -> expressed on surface of Endothelial cells | Induced by TNF and IL-1
      • P -> expressed on Platelets, and Endothelial cells - mediated by histamine
        • It is pressent in a low-energy state during non-inflammatory conditions as Weibel-Palade Body as an intracellular body
        • It is expressed during inflammation onto the surface of endothelial cell
        • It contains Willebrand factor and selectins
      • L -> expressed on Leukocytes (WBCs)
    • WBCs express Siayl-Lewis-X (sugar moiety/molecule)

[[Pasted image 20210627075611.png]]

* This reduces the speed of WBCs
  • Adhesion | Firm Adhesion
    • WBCs express Integrins, a.k.a CD11a / LFA1 (Lymphoctes), CD11b /Mac1 (Macrophages) - upregulated by LTB4 and C5a
    • Endothelial cells express:
      • ICAM: Inter Cellular Adhesion Molecule
      • VCAM: Vascular Cellular Adhesion Molecule
      • Upregulated by TNF and IL1

Leukocyte adhesion deficiency- Most commonly due to an autosomal recessive defect of integrins (CD18 subunit)

Presentation- Late separation (>30 days) of umbilical cord, absent pus, dysfunctional neutrophils, recurrent skin and mucosal bacterial infections. Finding - increased neutrophils in blood, Absence of neutrophils at infection sites, impaired wound healing LAD I - Malfunctioning of Integrins [CD11a/CD11b -3 LFA-1] - FIRM ADHENSION - DELAYED UMBLICAL CORD SEPERATION LAD II - malfunctioning of selectin receptors (Siayl-Lewis molecule) - LOOSE ADHESION > -Fucosyl trasferase defect -> Leads to defect of H-antigen and other sugar groups such as Siayl-Lewis molecule > - Decreased Growth (e.g. short stature), No H-Antigen at all -> Bombay Blood Group

[[Pasted image 20210627101852.png]]

  • Transmigration/Diapedesis
  • It requires CD31 [PECAM - Platelet Endotelial Cell Adhesion Molecule]
    • It is present on both the neutrophil and endothelial cell thus the interaction is homotypic interaction homotypic interaction
  • Predominant involvement of venules except Pulmonary Circulation (in capilaries)

[[Pasted image 20210627110756.png]]

  • An important component of Basement membrane called Laminin and Collagen IV ^9c610e

  • Collagenase is secreted by WBCs and is responsible for breaking of collagen of Basement Membrane

  • Normal transmigration of Neutrophil occur for 24 hrs followed by monocytes except:

    • In parasitic infections- eosinophils
    • In viral infections - lymphocyted
    • In Pseudomonas infection - Neutrophils transmigrate for 2-4 days

Extracellular Vascular Changes

  • Chemotaxis

    • Chemotaxis is the unidirectional movement of WBC towards bacteria
    • Chemicals responsible - exogenous (bacterial products) and Endogenous
      • C5a [Complement Protein]
      • IL-8 [Interleukin]
      • LT-B4 [Leukotriene]
    • Chemotaxis may damage tissue
    • Steroids inhibit Chemotaxis
  • Phagocytosis

    • Recognition of target cells
      • WBCs express Mannose-binding receptors [Binding to mannose on microbes]
      • Scavenger Receptors: [Binds to other practicals]
      • Process of phagocytosis is facilitated by OPSONIZATON
        • The bacteria is covered by opsonins (chemicals) -> leads to preferential killing of cells

          • Fc fragmennt of IgG
          • C3b
          • Fibrinogen
          • C-reactive protein

          [[Pasted image 20210627203200.png]]

          It leads to defective opsonization

          • C-Reactive Protein: reacts to C - Carbohydrate antigen of bacteria like streptococcus pneumonia
    • Engulfment
      • Pseudopod formation due to actin polymerization
      • The target is internalized and forms phagosome
    • Killing of bacteria
      • Phagosome is transferred to Lysosome
      • Transport is due to LYST - lysosomal transfer protein
      • Phagosome and lysosome is then fused


    • LysT protein is needed for Neutrophils, platelets, melanocytes, activity of Myelin (neurological)
    • Due to this defect, there are presence of granular phagosomes in the cells -> seen in peripheral smear

    [[Pasted image 20210627204435.png]]

    C - CNS HE - HEmorrhage D - Decrease I Immunity A - Albinism K

Oxygen Independent Killing

ACHIEVED WITH THE HELP OF Secondary granules of Leukocytes

  • CATHELICIDIN - Related to Vitamin D EJSEXPAND
  • LACTOFERRIN -> reason for lesser infections of infants
    • abundant in EOSINOPHILS
    • parasitic killing
  • Defensins - Arginine rich molecules with antibacterial action

Oxygen dependent

  • This is more efficient in killing
  • Killing of bacteria -> Lysosomal formaion -> O2 for killing -> respiratory burst
  • NO -> Peroxynitrate Mechanism
    • Most important in macrophage, esp. myocobacterral infections
    • Oxidized by superoxide
  • NADPH oxidase mechanism
    • NADPH oxudase Converts O2 to Superoxide
    • Superoxide converts to hydrogen peroxide
      • H202 is acted upon by Myeloperoxidase Enzyme in presence of halide -> hypohalus radical

        • MPO-Halide system is the most bactericidal way utilized by neutrophils
        • If MPO deficiency occurs, hydroxyl radicals are formed -> Not very severe
          • It increases susceptibility to Candida infections, however, it is asymptomatic
      • H202 may be converted OH- radical

    • Hypochlorous radical -> destructive
    • Thus WBCs require more O2 during inflammation -> thus named Respiratory Burst Oxidase and Phagocyte Oxidase

Chronic granulomatous disease

  • It is due to deficiency of NADPH Oxidase defect
    • X-linked Recessive (more common)
      • Membrane bound component is defective | GP91 PHOX (PhagocyteOxidase)
    • Autosomal Recessive
      • Cytosomal component defect
      • gp47 PHOX defect
      • gp67 PHOX defect
  • Granulomas are formed in different organs (lungs, liver, lymph nodes, GIT)
  • Recurrent Infections, especially by catalase positive organisms e.g: * Staph. aureus * Aspergillious * Pseudomonas cepacia * Candida * Nocardia

[[Pasted image 20210628150733.png]]


[[Pasted image 20210628145559.png]]

[[Pasted image 20210629234837.png]]

Nitro-blue Tetrazolium POSITIVE is for normal individuals

  • DHR test - Flow cytometry
  • Cyt-C reduction assay test - quantitative test


  • Bone Marrow Transplant
  • IFN-gamma -> activates macrophages
  • Broad spectrum antibiotics & antifungals

Neutrophil Extracellular Trap

  • Extracellular fibrillary network

  • Stimuli

    • Infectious pathogens
      • TLRs of Platelets are activated by microbes -> activation of neutrophils/macrophages
    • Inflamatory mediators
      • Activation of neutrophils
  • ROS activates Arginine Deiminase, converting Arginine to Citroline

[[Pasted image 20210628183909.png]]

  • Chromatin decondensation in neutrophils during sepsis (large bacterial load) and some fungal infections,
    • This is due to overwhelmed presence since engulfment will not work
    • Chromatin comes out of nucleus and act as trap for bacteria
    • However death of neutrophil occurs
    • Risk of Autoimmune diseases (due to formation of antinuclear antibodies due to release of chromatin), e.g, SLE

Chemical Mediators

Preformed (cellular)Freshly formed (cellular)Plasma
HistamineNitric OxideKinin System
SerotoninCytokinesCoagulatary system
Lysosomal enzymesArachidonic acid metabolitesComplementary system

Preformed Chemical Mediators


  • Histidine derived chemical

  • Present in

    • mast cells [richest source],
    • basophils,
    • platelets
  • Functions:

    • Vasodilation
    • Increasing vascular permeability
    • Intense Itching
    • Bronchospasm
  • Mast cells have a receptor for IgE

    • igE crosslinking leads to release of histamine release ^a7504d
    • [[Pasted image 20210628185226.png]]

Toulidine blue is a basic dye which binds to acidic proteoglycans and granules help in detection of histamine

[[Pasted image 20210628185328.png]]


  • Temperature : Cold temperature | High temperature -> Solar urticaria
  • Infectious organs [ like Viruses]
  • Anaphylotoxins - [Toxins that generate mast cell degranulations]
    • Complement proteins
      • C2a/C3a/C4a/C5a
      • Bee sting - Mellitin
      • Insect venom
      • Drugs
        • Morphine [Asthmatics - caution]
        • D-tuborcuraraine
        • Vancomycin [Antibiotic]
          • Red man syndrome -> due to degranulation of mast cells



  • Enterochromaffin cells - GIT
  • Platelets
  • CNS


  • Same as histamine
  • Responsible for
    • Vasoconstriction in small blood vessels
    • Vasodilation in large blood vessels
    • serotonin is a derivative 09 tryptophan
    • serotonin syndrome is caused by any drug that increases 5-HT.
    • It includes Psychiatric drugs: MAOIs,SSRIs, SNRls, TCAs, vilazodone, vortioxetine, buspirone and Nonpsychiatric drugs: Ondansetron, Triptans. Tnamadol,linezolid, MDMA (ecstasy). dextromethorphan, meperidine, St. Sohn’s wort Serotonin is decreased in Anxiety, Depression and parkinson disease.
    • Carcinoid syndrome Carcinoid tumors arise (from neuroendocrine cells most comnonly in the intestine or lung. Neuroendocrine cells secrete 5-HT


  • Primary granules and secondary granules are present

  • Phospholipase A2 is present in both

  • Primary granules

    • A.k.a Azurophilic granules
  • Secondary granule

    • Alkaline phosphatase is present
    • LAP score -> leukocyte alkaline phosphate score
      • There is an increase in mature WBC count
      • This LAP score staining technique is used to detect this
      • e.g: in benign infections, leukemoid reaction (leukemia like reaction)

Freshly formed

Arachidonic Acid

  • Phospholipids present on the cell membrane at time of inflammation -> Arachadonic Acid [Essential fatty acid - dietary absorption]
    • Other Essential FA:
      • Linoleic Acid
      • Linolenic Acid
      • DHA [Ducosa Hexaenoic Acid] present in breast milk essential for development of brain
  • This is by the enzyme Phospholipase A2 - [ which is a Rate limiting enzyme]
    • inhibited by Steroids
  • AA -> [Cyclooxygensase COX] -> PGG2 <-> PGH2
    • COX 1 - Constitutive -> prostaglandins are protective in function in gastric epithelia
    • COX 2 - Inflammation
      • Physiological function in kidney
      • Aspirin - irreversible both COX1 and COX2 ->Gastritis ADR or ulcer
  • PGG2 converts into
    • PGI2/Prostacyclin
      • Vasodilation Endothelial cells
      • Inhibition of Platelets
    • Other PGs - PGD2, PGE2, PGF2
      • Pain - PGE2
      • Pyrexia - PGE2
      • Vasodilation
      • Increased permeability -> Swelling
      • Increased secretion in lungs by PGD2
    • ThrombaxaneA2 [TXA2]
      • Aggregation of plateltes
      • Vasoconstriction
  • Inflammation is a protective response, but beyond certain point -> discomfort

PGI2 analog— Epoprostenol, iloprost.- used in Pulmonary arterial hypertension PGEl analog- Alprostadil PGE2 (increased uterine tone )- Dinoprostone PGFZ alpha ( increased uterine tone)- Carboprost

AA -> [5-LOX] -> LTA4 (unstable) LTA4 ->

  • LTB4
    • Chemotaxis
    • Binds with endothelial cells and WBC binding
  • LTC4/D4/E4 - Slow reacting substance of anaphylaxis - SRS-A
    • Bronchospasm - most power bronchospasm
    • Increased permeability of blood vessels


  • Phospolipase inhibition
  • 5-LOX -> Zileuton
  • LT Receptor antagoinst - Monteleukast


[[Pasted image 20210629075828.png]]

Nitric Oxide

  • L-Argininge - [Nitric Oxide Synthase] -> NO -> Increased Guanyl Cyclase -> Increased CGMP -> smooth muscle relaxation -> vasodilation
  • functions: vasodilation, platelet inhibitory actions
  • eNOS - endothelial
  • nNOS - induce/inflammation
  • iNOS - neurons


  • Pleotropy - more than one action by one cytokine

  • Reduncancy - Multiple cytokines having common effects

  • Local affects

  • Systemic effects

    • acts on IL1
    • IL6
    • TNF-alpha
    • On Brain:
      • Decreased appetite
      • Increased sleep
      • Upregulate COX -> Increased PGs -> Fever
    • Bone Marrow
      • Total leukocyte count increased -> Leukocytosis
        • Neutrophils in bacterial infection
        • Lymphocytes in viral infection
        • Eosinophil in parasitic infection
        • immature cells [band cells I slab cell] are also seen in Peripheral Blood Smear known as “shift to left”
        • Leukomoid reaction : [When TLC is high 40k - 60k]
    • Liver
      • Acute Phase Reactants
        • CRP [Normal level - 0.2 mg/dl]
          • Carbohydrate-antigen
          • During Sepsis -> increased levels
          • Pro-calcitonin - Also involved in sepsis [recent marker for sepisis]
        • Hepcidin
          • Hepatic iron inhibitory protein - Negative regulator
          • Inflammation associated with anemia
        • Ferritin
        • Fibrinogen
          • ESR [Erythrocyte Sedimentation Rate] increases as sedimentation increases
        • Serum Amyloid A protien
          • Elevated levels lead to secondary amyloidosis
        • Thrombopoeitin
          • -> Increased number of platelets
      • Negative Acute Phase Reactants
        • Albumin
        • Anti-thrombin
        • TTR [Transthyretin]
        • Transferrin
  • Dual role
    • Systemic effects
      • Severe suppression of appetite (cachexia)
      • Thus chronic conditions like cancer leads to significant weight loss
    • Macrophage activation -> Block killing
      • TNF-alpha blocker therapy may kead to higher risk to Tuberculosis
        • Thus TB must be ruled out before it is given
  • Exogenous
    • Bacterial toxins
  • Endogenous
    • IL-1 - macrophage prod
    • TNF-alpha - macrophage prod
    • IL-6
    • CNTF - Ciliary neurotrophic factor
    • PGE2

Most cytokines cause inflammation except

  • IL-10
  • TGF-Beta Dual action in some conditions where they may act inflammatory or ant-inflammatory
  • IL-4
  • IL-6
  • Adiponectin



  • IL1 - Systemic effects of inflammation
  • IL2 - Autocrine action (stimulates the cell that produced it (T-Cell))
  • IL3 - Hemopoeitic precursor
  • IL4 & IL5 - Increase B-Cell proliferation and differentiation
  • IL-6 - Systemic Effects of Inflammation
  • IL-7 - Normal functioning of B/T-Cell -> Causes SCID [Severe combined ImmunoDisorder]
  • IL-8 Continued acute inflammation - produced by macrophage to call in neutrophil
  • IL - 10 Resolution and healing
  • IL-11 - Increased platelets
  • IL-13 - Activation of M2 Macrophages (along with IL4)
  • IL-17 - Secreted by Th17 cells | Responsible for recruitment of Neutrophils | e.g: in hepatitis, kaposis sarcoma


  • Small proteins (kines) that are present during chemotaxis

Types: based on cysteine residues

  • Alpha chemokines

    • CXC
    • IL-8 is an example. A.k.a CXCL-8
      • Chemotactic agent of neutrophil
    • CXCR4 receptor
  • Beta-chemokines

    • CC
    • Lesser actions on neutrophil, more on monocytes
    • MCP-2 - Monocytes chemotaxis
    • EOTAXIN - Eosinophil chemotaxis
    • RANTES - attracts T-Cells
    • CCR5 receptor
  • Gamma-chemokines

    • C
    • Lymphotactin - attracts Lymphocytes
  • Fractalkine

    • CXXXC
    • Dual function
      • Cell bound form: Present on endothelial cells -> Adhesion of monocytes
      • Soluble form: Chemotaxis during

CCR5 and CXCR4 are required for entry of HIV into host cells. Blocking of these receptors leads to inhibition of infection caused by HIV

  • Maraviroc blocks CCR5 receptor
SourceActionClinical Use
LeukocytesAntiviralViral infections
FibroblastsImmunomodulataryMultiple Sclerosis
T-Cells (TH1) and CD8 cellsMacrophage activationChronic Granulatmous disease


Chemical mediators in Plasma

Kinin System

Injury to blood vessel -> XII ->XIIa Pre-Kallikrein -> [XIIa] ->Kallikrein

  • Activation of Bradykinin
  • Activation of Complement system
  • Activation of Plasminogen - Plasmin

Kininogen -> [Kallikrein] -> Bradykinin

  • Venular permeability (postcapillary venules) - incresased

  • Pain

  • Vasodilation

  • Bronchospasm

  • drycough is due to vasospasm caused by increased bradykinin

    • Angioedema

Complement System

  • These are a group of more than 20 proteins
  • Responsible for immunity
    • Activated by both innate and adaptive
  • Regulates normal function
Classical Pathway

GM Manufactures Classic Cars - IgG and IgM ^0c3b7d

  • Adaptive Immunity

  • IgM is more important

    • IgG1 IgG2 Ig3 can activate complement system
      • IgG4 cannot - LOW-YIELD
  • C1 -> [Immunoglobulin] -> Activated C1

    • C2a + C4b -> [Activated C1] -> C4b2a (C3 Convertase)
    • C3b -> [C3 Convertase - C4b2a] -> C4b2a3b (C5 Convertase)
    • C5 -> [C5 Convertase] -> C5b + C6-C9 Membrane Attack Complex
Lectin pathway


  • Mannose-binding lectin -> Activating C4
  • C1-like complex instead of C1
  • C4 is the first component that’s activated
  • Rest is similar to Classical Pathway
Alternate Pathway
  • Innate immunity
  • Activated by
    • Endotoxins (LPS)
    • Venom
    • IgA IgD very rarely
  • C3 -> [Hydrolysis] -> C3b
    • C3b + Bb -> [Factor D] -> C3Bb [C3 convertase]
    • 3b -> [C3 convertase - C3bBb] -> C3bBb3b (C5 Convertase)

Pathway that is activated can be diagnosed by assessing Complement proteins levels and mark those that have decreased

C5bMembrane Attack Complex
Complement Protein DeficiencyAssosciated Defect
C1/C2/C4 [Early Proteins]Autoimmune Disorders (SLE)
C3Pyogenic infections
C5/C6/C7/C8 [Late Proteinas]Increased susceptibility to Neisseria - Toxoplasmosis
C9No significant effect
  • C1 Inhibitor

    • Blocks activation of C1
    • Deficiency leads to:
      • Increased C1 Activation
      • Release of C3a/C5a
      • Hereditary Angioneurotic Edema
      • Females are more susceptible
      • Edema - Non pitting -> in face/cutaneous tissue
      • Laryngeal edema/GIT -> Emergency
  • CD46/Factor H Factor

    • Controls the alternate pathway
    • Deficiency leads to increased complement system activation
      • -> Endothelial Cell Damage -> Atypical Hemolytic Uremic Syndrome [HUS]
      • Age Related Macular Degeneration is also associated
  • CD55/CD59

    • present on normal blood cell: prevent RBC/WBC/platelets from damage by Complement system
    • Deficiency occurs -> Decreased RBC/WBC/Platelets
      • -> Pancytopenia -> Paroxysmal Nocturnal Hemoglobinuria

Chronic Inflammation

  • This is an ongoing prolonged inflammation
  • It is more specific (adaptive immunity)
  • Associated with tissue destruction

Hallmark: Tissue Destruction

  • Associated with repair/healing

Monoblast -> Monocyte -> Macrophage Bone -> Blood -> Tissue

  • Macrophage survives for a much longer duration

[[Pasted image 20210701093452.png]]


  • M1: Activated by Interferon-gamma - secreted by CD8 T Cells and Th1 -> Pro-inflammatory
  • M2: Activated by IL-4, IL13 - secreted by Th2 -> Anti-inflammatory

Granulmatous inflammation

Granuloma - Inflammatory core with a Macrophage and giant cells surrounded by a rim of lymphocytes

  • Epitheloid histocytes (macrophages with abundant pink cytoplasm)

Noncaseating granulomas - Lack Central necrosis

Examples of granulomatous infections

InfectionType of Granuloma
TuberculosisCaseating Granuloma/Soft Granuloma (more frequently)
Sarcoidosis and Beryllium exposureNon-Caesating Granuloma/Hard Granuloma/Naked Granuloma
SyphilisGumma -> Caseating Granuloma
Cerebral MalariaDurck Granuloma (CNS)
Q FeverDonut granuloma
Inflammatory Bowel DiseaseSeen in Crohn’s subtype only
Cat scratch diseaseNon-caseating Stellate Shaped Granuloma
  • Macrophage -> [Antigen] Presented on MHC II -> CD4+ T cells
  • Macrophage -> secretes IL 12 -> Induced CD4+ Helper cells to differentiate into TH1 Subtype
  • Th1 subtype secretes-> IFN-Gamma -> Macrophage -> Epitheloid cells (Activated macrophage)
    • Epitheloid cells are secretory | Do not have phagocytic
    • Epitheloid cells fuse to form Giant Cells
Giant CellDisease
Langhans Giant CellsTuberculosis (Inverted U pattern/Horseshoe)
Foreign Body Giant CellsSeen with sutures/talc granuloma (foreign bodies)
Warthin-Finkeldey Giant CellsMeasles (Have eosinophilic inclusions)
Reed-Sternberg Cell/Tumor Giant CellHodgkin Lymphoma (Owl-eye appearance)
Touton Giant CellXanthoma (Fat droplets)


  • Giant cells per se are not diagnostic
  • For example, owl-eye appearance are seen in cytomegalovirus due to owl eye inclusions
  • Clinical history is important to determine diagnostic assets

Wound Healing

  • Occurs via regeneration and repair
  • Regeneration depends upon regenerative capacity
  • Labile Tissues
    • Continuously cycle to regenerate tissue
    • e.g: Small and large bowel (stem cells in mucosal crypt), Skin (stem cells in the basal layer), Bone marrow (hematopoeitic stem cells )
  • Stable tissues
    • These are quiescent, but can re-enter the cell cycle
    • e.g: hepatocytes undergo compensatory hyperplasia -> additional cells are produced -> reentry into quiescence
    • e.g: proximal renal tubule
  • Permanent tissues
    • Lack significant regenerative potential
    • e.g: myocardium, neurons, skeletal muscle
    • These undergo repair -> replacement with fibrous scar
  • Repair is seen when regenerative stem cells are lost or when tissue lacks regenerative capacity
  • Mediated by paracrine signaling via growth
    • Interaction of growth factors with receptors leads to regeneration
    • TGF-Beta: Important fibr
0Blood Clot
1Blood Clot + Neutrophilic Infiltration
2Day 1 + Thin Epithelial Layer
3Granulation tissue
3- Macrophages
3- Fibrous Tissues
3- Angiogenesis
4/5Granulation tissue + Collagen Deposition Type 3
14Increased collagen deposition

Collagen Remodelling

  • Type I : Bone
  • Type II : Cartilage
  • Type III : Pliable
  • Type IV: Basement Membrane
  • The collagen type III deposited is replaced by collagen Type 1
  • This happens with the help of Matrix Metalloproteases [MMPs]
    • MMPs such as collagenase require Zinc to function. Therefore when Zn deficiency is present, there’s decreased collagen remodelling -> Improper wound healing

Primary Union

  • This type of wound healing is seen in injuries caused by Sharp Objects
  • Less loss of connective tissue is present
  • Clean edges
  • Due to above reasons, it heals faster

Secondary Union

  • It is seen in Blunt Object Injury
  • Relatively, higher loss of connective tissue
  • More chance of scar formation is seen
  • Irregular surface edges are present
  • Longer healing
  • Granulation tissue fills in the defect
    • Myofibroblasts contract the wound

Fibroblasts -> Myofibroblast [Due to confluence of chemical factors]

  • Has contractile property
  • Thus the size of the scar decreases due to Scar contraction/Wound contraction due to contraction of myofibroblasts

Delayed Wound Healing

Foreign BodyDecreased immunity
Persistent InfectionsDiabetes mellitus
RadiationDrugs such as steroids

Excessive/Abnormal Healing

  • Keloid
    • Due to extra deposition of granulation tissue beyond margins
    • African-Americans have genetic predisposition
    • Characterized by Type III
    • Classically seen in earlobes
  • Hypertrophic Scar
    • Extra deposition of granulation is only vertical


  • Steroid Injections -> reduced fibroblast proliferation -> Decreased scar size