INFLAMMATION, INJURY, AND
REPAIR
REVIEW OF STRUCTURE AND FUNCTION
• THE BODY IS CAPABLE OF UNDERGOING DYNAMIC CHANGES TO
CARRY OUT BODY FUNCTIONS.
• EACH COMPONENT OF A CELL CARRIES OUT A SPECIFIC,
NECESSARY FUNCTION.
MAJOR CELL TYPES
• EPITHELIAL CELLS: FORMS GLANDS, LINES BLOOD VESSELS, HOLLOW
ORGANS, SUPERFICIAL SKIN AND PASSAGES THAT LEAD EXTERNALLY
• CONNECTIVE TISSUE CELLS: BINDING AND SUPPORTING
• NERVE CELLS:
• MUSCLE CELLS
WHAT IS INFLAMMATION?
• FUNDAMENTALLY PROTECTIVE REACTION AGAINST CELL INJURY
• OCCURS ONLY IN VASCULARIZED TISSUE
• MAY BE ACUTE OR CHRONIC
CAUSES OF INFLAMMATION:
• PHYSICAL: TRAUMA/HEAT
• CHEMICAL: CHEMOTHERAPY OR INDUSTRIAL ACCIDENTS
• IMMUNOLOGICAL AGENTS: ANTIGEN-ANTIBODY RESPONSE
• RADIATION: NON THERAPY EXPOSURE OR FOR THERAPEUTIC
• MICROBES: BACTERIA, VIRUSES, FUNGI
4 SIGNS OF INFLAMMATION
• HEAT
• REDNESS
• SWELLING
• PAIN
EVENTS FOLLOWING INJURY
• NECROSIS OR SUBLETHAL CELL INJURY
• DEATH OR DAMAGE OF CELLS DUE TO INJURY
• INFLAMMATION
• THE VASCULAR AND CELLULAR RESPONSE ATTEMPTING TO LIMIT
DAMAGE AND REMOVE NECROTIC TISSUE
EVENTS FOLLOWING INJURY
• REPAIR
• THE BODY’S ATTEMPT TO REPLACE DEAD CELLS
NECROSIS VS. SUBLETHAL
• NECROSIS IS THE IRREVERSIBLE DEATH OF THE CELL
• SUBLETHAL INJURY INDICATES THE CELL IS CAPABLE OF AT LEAST
SOME RECOVERY.
ACUTE INJURY AND NECROSIS
• THE MOST COMMON CAUSE OF ACUTE INJURY IS A REDUCED LEVEL
OF OXYGEN.
• CELLS THAT ARE VERY ACTIVE REQUIRE MORE OXYGEN, AND WILL
SUFFER ILL EFFECTS FIRST.
• LOCALIZED HYPOXIA DUE TO POOR BLOOD FLOW (NOT DECREASED
OXYGEN LEVELS) IS CALLED ISCHEMIA. IF THIS BECOMES MORE
SEVERE, ISCHEMIA PROGRESSES TO INFARCT.
CAUSES OF ISCHEMIA OR NECROSIS
• THROMBUS
• EMBOLUS
• TRAUMA
• INFECTIONS
CAUSES OF ISCHEMIA OR NECROSIS
• IMMUNOLOGIC REACTIONS
• COAGULATION, LIQUEFACTION, CASEOUS,
GANGRENOUS, AND ENZYMATIC FAT NECROSIS
CHRONIC INJURY
• CHRONIC INJURY MAY CAUSE ATROPHY OR
ACCUMULATION OF MATERIAL WITHIN CELLS.
• ATROPHY
• SENILE
• DISUSE
• PRESSURE
• DENERVATION
• ENDOCRINE
CHRONIC INJURY
• ACCUMULATION
• FATTY CHANGE
• ADIPOSITY
• GLYCOGEN STORAGE
• HYALINE
• METASTATIC CALCIFICATION
• HEMOSIDEROSIS
• HEMOCHROMATOSIS
INFLAMMATION
• FIRST RESPONSE IS REDNESS AND SWELLING AS CHANGES IN BLOOD
FLOW OCCUR
• SMOOTH MUSCLES RELAX AND BLOOD RUSHES INTO THE
CAPILLARIES
• INFLUX OF BLOOD ALSO ADDS HEAT AT INJURY SITE
• LEUKOCYTES RUSH TO THE SITE AND BECOME ATTACHED TO THE
ENDOTHELIUM
• ADHESION MOLECULES ARE ACTIVATED THROUGH CYTOKINES SUCH AS
INTERLEUKINS, TUMOR NECROSIS FACTOR (FROM NEARBY CONNECTIVE
TISSUE)
ACUTE INFLAMMATION
• LASTS FOR 8-10 DAYS
• CHARACTERIZED BY FORMATION AND LEAKAGE OF EXUDATE
• EXUDATE: INFLAMMATORY EXTRAVASCULAR FLUID WITH HIGH PROTEIN AND
CELLULAR DEBRIS CONTENT
• IN ADVANCED INFLAMMATION: EXUDATE BECOMES THICK
• LARGE # OF LEUKOCYTES = PUS
• LARGE # OF RBC’S DUE TO BLEEDING/CLOTTING= HEMORRHAGIC
ACUTE INFLAMMATION LOCAL VASCULAR CHANGES
• VASODILATION: ARTERIOLES AND CAPILLARY BEDS EXPAND TO INCREASE BLOOD FLOW TO
INJURY
• INCREASED VASCULAR PERMEABILITY: CONTRACTION OF ENDOTHELIAL CELLS
• ENDOTHELIAL CELLS MAY BE INJURED DIRECTLY OR BY LEUKOCYTES
• LEUKOCYTES ADHERE TO THE ENDOTHELIUM AND RELEASES DAMAGING ENZYMES.
• STASIS: CIRCULATION SLOWS DUE TO EXTRAVASATION OF FLUID INTO EXTRAVASCULAR SPACES
• LEADS TO INCREASE IN RBC’S IN SMALL VESSELS AND INCREASED VISCOSITY OF BLOOD.
ACUTE INFLAMMATION
• VASCULAR RESPONSE: INCREASED BLOOD FLOW TO THE INJURED AREA,
AND THE VASCULATURE BECOMES MORE PERMEABLE.
• CELLULAR RESPONSE: MOVEMENT OF LEUKOCYTES, PREDOMINANTLY
NEUTROPHILS AND MONOCYTES FROM THE BLOOD INTO THE TISSUE.
ACUTE INFLAMMATION: LOCAL CELLULAR EVENTS
• MIGRATION: LEUKOCYTES
• EMIGRATION: LEUKOCYTES MOVE FROM MICROCIRCULATION TO INJURY SITE
• CHEMOTAXIS: ONCE OUTSIDE THE BLOOD VESSEL, CELLS MIGRATE IN INTERSTITIAL TISSUE
TOWARDS THE CHEMOTACTIC STIMULUS IN THE INFLAMMATORY FOCUS
• HISTAMINE IS NOT A CHEMOTACTIC AGENT BUT FACILITATES THE PROCESS
• GRANULOCYTES (LEUKOCYTES, EOSINOPHILS, BASOPHILS) ALL RESPOND TO INFLAMMATION
• BACTERIAL INFECTIONS HAVE MORE NEUTROPHIL CHEMOTAXIS
• PHAGOCYTOSIS: DEFENSE MECHANISM
• POLYMORPHONUCLEAR LEUKOCYTES AND MACROPHAGES INGEST DEBRIS
CHEMICAL MEDIATORS
• THE INFLAMMATORY REACTION IS INITIATED BY LOCAL FACTORS IN THE
INJURED TISSUE
• HISTAMINE: RELEASED FROM PLATELETS AND MAST CELLS
• BRADYKININ: PLASMA PROTEIN THAT ACTIVATES HISTAMINE
• VASOACTIVE AMINES: FACILITATE CHEMOTAXIS AND PHAGOCYTOSIS
CHEMICAL SYSTEMS
• THERE ARE THREE CHEMICAL SYSTEMS AT WORK TOGETHER DURING THE
INFLAMMATORY REACTION
• KININ SYSTEM: ACTIVATES INFLAMMATION AND BRADYKININ
• COMPLEMENT SYSTEM: PLASMA PROTEINS, CLOTTING, THROMBOLYSIS
• MEMBRANE ATTACK COMPLEX: KILLS CELLS
• COAGULATION SYSTEM:
CHRONIC INFLAMMATION
• MAY BE PRIMARY OR FOLLOW ACUTE
• CHRONIC INFLAMMATION CAUSES HISTOLOGIC
CHANGES DIFFERENT FROM ACUTE INFLAMMATION.
ABSCESS FORMATION
• ABSCESS: COLLECTION OF PUS IN TISSUES OR ORGANS
• USUALLY CAUSED BY BACTERIAL INFECTIONS
• BEGINS WITH CELLULITIS, HYPEREMIA, LEUKOCYTOSIS AND EDEMA WITHOUT NECROSIS
• MAY BE FOLLOWED BY NECROSIS, LIQUIDIFICATION AND PYROGENIC MEMBRANE
SURROUNDING PUS
GRANULOMATOUS INFLAMMATION
• CHARACTERIZED BY FOCAL COLLECTIONS OF CLOSELY
PACKED, PLUMP MACROPHAGES, IT IS IN RESPONSE TO
INDIGESTIBLE ORGANISMS.
• THE OBJECT IS TOO LARGE TO BE BROKEN DOWN, SO
MACROPHAGES ENGULF THE OFFENDER TO KEEP IT
FROM MOVING ELSEWHERE.
• EXAMPLES INCLUDE: TB, FUNGAL INFECTIONS, AND
SARCOIDOSIS
TRANSUDATES AND EXUDATES
• TRANSUDATE
• CAUSED BY INCREASED HYDROSTATIC PRESSURE OR DECREASED OSMOTIC
PRESSURE
• THESE HAVE A LOW PROTEIN COUNT
• EXUDATE
• CAUSED BY INCREASED ONCOTIC PRESSURE
• THESE HAVE A HIGH PROTEIN COUNT
3 SYSTEMIC CHANGES THAT OCCUR
• LEUKOCYTOSIS (INCREASE IN WBC’S)
• FEVER (FEBRILE RESPONSE DUE TO PYROGENS)
• INCREASE IN PLASMA PROTEINS DUE TO STIMULATION OF THE LIVER TO RELEASE
ANTI-INFLAMMATORY AGENTS.
REPAIR
• REGENERATION
• THIS IS THE DESIRED REPAIR, AS REPLACEMENT OF DESTROYED TISSUE
IS WITH SIMILAR TISSUE, AND NORMAL FUNCTION IS RESTORED.
REPAIR
• FIBROUS CONNECTIVE TISSUE REPAIR
• THIS IS LESS DESIRED, AS THE DAMAGED AREA IS REPLACED WITH
FIBROUS TISSUE, AND NORMAL FUNCTION IS NOT RESTORED.
• COLLAGEN ACCUMULATES TO FORM A SCAR
• THE GOAL OF THIS REPAIR IS TO PROVIDE A BRIDGE ACROSS THE
DAMAGED AREA.
BLEEDING DISORDERS
• NORMAL HEMOSTASIS DEPENDS ON:
• VASCULAR FACTORS
• PLATELET FACTORS
• COAGULATION FACTORS
VASCULAR DISORDERS:
• MECHANICAL TRAUMA: SMALL BRUISES, MINOR WOUNDS, OR MAJOR INJURIES
THAT CAUSE HEMORRHAGE
• VESSEL WALL WEAKNESS: WEAKER CONNECTIVE TISSUE WILL TEAR EASIER
WITH MINOR INJURIES
• ALSO OCCURS WITH CUSHING'S SYNDROME, CONGENITAL DISORDERS, AND SCURVY
• IMMUNE MECHANISMS:
• IMMUNE MECHANISMS DAMAGE THE BLOOD VESSELS AND CAUSE HEMORRHAGE
• ALLERGIC REACTIONS IN WHICH THE SKIN TURNS PINK AND BUMPY
PLATELET DISORDERS
• MAY BE CAUSED BY A DECREASE IN NUMBER, OR A CHANGE IN CELL
STRUCTURE AND FUNCTION
• BLEEDING TENDENCIES ONLY DEVELOP WITH SEVERE THROMBOCYTOPENIA
• APLASTIC ANEMIA, LEUKEMIA, DRUGS, INFECTIONS SUCH AS RUBELLA,
AUTOIMMUNE DISEASES
• PT MAY REQUIRE BLOOD OR PLATELET TRANSFUSIONS, OR BONE
MARROW TRANSPLANTS