general pathology lecture 5 inflammation & repair

INFLAMMATION AND REPAIR

Lecture 5

INFLAMMATION AND REPAIR

Lecture 5

INFLAMMATORY CELLSINFLAMMATORY CELLS

SIGNS OF INFLAMMATION• RUBOR- REDNESS DUE TO INCREASED BLOOD BLOW AND VASODILATION• CALOR- OR HEAT DUE TO INCREASE BLOOD FLOW TO THE PERIPHERY• TUMOR- SWELLING FROM INFLAMMATORY EDEMA• DOLOR-PAIN FROM SWELLING AND PRESENCE OF INFLAMMATORY

MEDIATORS• FUNCTIO LAESA-LOSS OF FUNCTION DUE

TO MAIN AND STRUCTURAL NECROSIS

Question

• Pain associated with acute inflammation is thought to be caused by

A. pressure effects of exudate fluid

B. histamine

C. serotonin

D. kinins

E. all of the above

Acute Inflammation• What is it?

– Series of reactions of

vascularized tissuevascularized tissue to injury

• What is its purpose?– Defend against foreign

substances (infection)

– Dispose of dead / dying

tissue

– Immobilize injured area

– Compartmentalize area

Acute Inflammation

• Events in Acute Inflammation– Neurologic events– Hemodynamic events– Cellular events

• Events Overlap and are related• Events are the same regardless of cause of

inflammation– Magnitude of events depends on:

• severity of injury• immune status• temperature

Acute Inflammation – Neurologic events

• Initial Vasoconstriction– Transatory & reflexive

– usually lasts up to 30 seconds

• Gradual Vasodilation– Relaxation of reflexive spasm

– Causes “bleeding” to start

Acute Inflammation – Hemodynamic Events

• Vasodilation– From relaxation of reflex & chemical mediators

• Slowing of bloodflow– Relationship of flow to diameter

• Margination of Leukocytes– ???? Nobel prize for Medicine

• Hemostasis• Permeability Changes

Acute Inflammation – Hemodynamic Events

• Permeability Changes– Mostly from inflammatory chemicals– Occurs in capillaries & small venules– Junctions between epithelial cells loosen– Fluid leaks (transudate exudate)– Leads to hemoconcentration– Makes margination easier

ACUTE INFLAMMATIONACUTE INFLAMMATION

Events in Acute Inflammation

• The order of the events in acute inflammation are

1. vascular dilatation 2. increased vascular permeability 3. local hemoconcentration and slowing of blood 4. margination of white blood cells 5. emigration of leukocytes

Acute Inflammation – Cellular Events• Circulating Leukocytes

– Marginated cells emmigrate from vasculature (diapedesis) – smaller first, larger later

– Basophils – release anti-coagulants– Neutrophils – vicious phagocytes

• Release many chemical mediators – chemotaxis• Primary job is to phagocytize bacteria• Magnifies inflammation above required level in musculoskeletal

injury

– Monocytes Macrophages• Arrive ~ 5h post-injury• Remove dead tissue debris (clean up the mess)

Acute Inflammation – Chemical events

• Over 180 different chemicals involved in acute inflammation

• Sources = damaged cells, inflammatory cells, platelets, plasma, etc.

• Histamine – 1st chemical, strong vasodilator & increases permeability

• Bradykinins – increases permeability & pain (especially with prostaglandins)

• Prostaglandins – made from released phospholipids (arachadonic acid cascade)– Target of NSAIDS & steroidal anti-inflammatories

Acute Inflammation – big picture

• First few seconds– Immediate vasoconstriction

• First Hour– Gradual vasodilation

– Hemostasis begins

– Mast Cell degranulation

– Margination of WBC’s

– Large scale neutrophil response begins

• After the first hour?– Hemoconcentration

from edema– Ischemia– Growing interaction of

chemical mediators– Emmigration of larger

WBC’s– Complement System

Question

• Of the following events that are part of the acute inflammatory response, which would occur THIRD in correct sequence?

A. vascular dilatation

B. local hemoconcentration and slowing

of blood

C. margination of WBC’s

D. emigration of WBC’s

E. increased vascular permeability

TYPES OF INFLAMMATION BASED ON SITE AFFECTED

• ABSCESS

• ULCER

• CELLULITIS or PHLEGMON

• PSEUDOMEMBRANOUS INFLAMMATION

Chronic Inflammation

• Immunologists define as period when macrophages predominate

• Clinicians define as recurrent inflammation prior to completion of repair or resolution

• Cellular Aspects– Leukocytes during early post-acute phase

• CD8+ (T- killer) & CD4+ (delayed hypersensitivity)

CHRONIC OSTEOMYELITIS-BRODIE’S ABSCESS

CHRONIC OSTEOMYELITIS-BRODIE’S ABSCESS

Chronic Inflammation

• Easy to re-start inflammation– Clinically, must control activity level & protect

injury site

• Leads to hypertrophic scarring– Additional infiltration of fibroblasts– Abundance of stimulating chemicals

Question

• The features, monocytes, giant cells, fibroblasts and lymphocytes, are characteristics of

A. acute inflammation

B. granulation tissue

C. wound healing

D. chronic inflammation

E. suppuration

ABSCESS-HEARTABSCESS-HEART

Question Which of the following inflammation commonly

is characterized by collections of dead and dying polymorphs, dead and dying bacteria, and necrosis of tissue, all of which form a turbid or thick fluid in tissues?

A. catarrhal inflammation

B. phlegmonous inflammation

C. cellulitis

D. abscess formation

E. granulomatous inflammation

ULCER-GASTRIC MUCOSAULCER-GASTRIC MUCOSA

PEPTIC ULCERPEPTIC ULCER

CELLULITISCELLULITIS

PSEUDOMEMBRANOUS INFLAMMATION - DIPTHERIA

PSEUDOMEMBRANOUS INFLAMMATION - DIPTHERIA

TYPES OF INFLAMMATION BASED ON THE NATURE OF EXUDATES

• SEROUS INFLAMMATION

• MUCOUS INFLAMMATION

• FIBRINOUS INFLAMMATION

• CATARRHAL INFLAMMATION

• HEMORRHAGIC INFLAMMATION

• PURULENT OR SUPPURATIVE

FIBRINOUS INFLAMMATION-PERICARDIUM

FIBRINOUS INFLAMMATION-PERICARDIUM

HEMMORRHAGIC INFLAMMATION-RIGHTHEMMORRHAGIC INFLAMMATION-RIGHT

GRANULOMATOUS INFLAMMATION

• Granulomatous inflammation occurs after the acute-phase response and consists of epithelioid and giant cells.

• Two types of granuloma:

1. Foreign Body granuloma-formed in response to indigestible materials

2. Allergic granuloma-formed in delayed hypersensitivity reactions

Question

Which of the following findings is an invariably histologic feature of granulomatous inflammation?

A. caseous necrosis

B. multinucleated giant cells

C. positive acid-fast staining of causative

organism

D. surrounding cuff of lymphocytes

E. epithelioid cells

GRANULOMATOUS INFLAMMATION-LUNGSTHYROIDITIS WITH GRANULOMA

GRANULOMATOUS INFLAMMATION-LUNGSTHYROIDITIS WITH GRANULOMA

GRANULOMATOUS INFLAMMATION WITH SPHERULES

GRANULOMATOUS INFLAMMATION WITH SPHERULES

LANGHAN’S GIANT CELLS FOREIGN BODY GIANT CELL- IN SUTURE LINELANGHAN’S GIANT CELLS FOREIGN BODY GIANT CELL- IN SUTURE LINE

SYNCYTHIAL GIANT CELLSSYNCYTHIAL GIANT CELLS

REED-STERNBERG GIANT CELLREED-STERNBERG GIANT CELL

TOUTON GIANT CELLWARTHIN-FINKELDEY GIANT CELL

TOUTON GIANT CELLWARTHIN-FINKELDEY GIANT CELL

PRIMARY SKIN LESIONSPRIMARY SKIN LESIONS

PRIMARY SKIN LESIONS

MACULE

• MACULE IS A CIRCUMSCRIBED FLAT AREA LESS THAN 1 CM OF DISCOLORATION WITHOUT ELEVATION OR DEPRESSION OF SURFACE RELATIVE TO SURROUNDING SKIN

MACULEMACULE

PAPULE

• PAPULE IS A CIRCUMSCRIBED, ELEVATED, SOLID LESION LESS THAN 1 CM IN DIAMETER, SUCH AS THE LESIONS OF LICHEN PLANUS AND NONPUSTULAR ACNE

PAPULEPAPULE

PATCH AND BULLA

• PATCH IS A CIRCUMSCRIBED AREA OF DISCOLORATION, GREATER THAN 1CM WHICH IS NEITHER ELEVATED OR DEPRESSED RELATIVE TO THE SURROUNDING SKIN

• BULLAE ARE RAISED, CIRCUMSCRIBED LESION GREATER THAN 0.5 CM THAT CONTAIN SEROUS FLUID

PATCH and BULLAEPATCH and BULLAE

PLAQUE AND PUSTULE

• PLAQUE IS A WELL-CIRCUMCRIBED, ELEVATED, SUPERFICIAL, SOLID LESION, GREATER THAN 1 CM IN DIAMETER

• PUSTULE IS A SMALL (1CM IN DIAMETER) CIRCUMSCRIBED SUPERFICIAL ELEVATION OF THE SKIN THAT IS FILLED WITH PURULENT MATERIAL

PLAQUE and PUSTULEPLAQUE and PUSTULE

TUMOR and VESICLE

• TUMOR – is a solid, firm lesion about 1 cm in diameter that can be above, level with or beneath the skin surface. It is also called a mass.

• VESICLE – is a small , superficial elevation of the skin, less than 0.5 cm, that contains serous fluid.

TUMOR and VESICLETUMOR and VESICLE

WHEAL OR PLAQUES ARE TRANSIENT,

CIRCUMSCRIBED, ELEVATED

PAPULES OFTEN WITH

ERYTHEMATOUS BORDERS AND PALE CENTERS

WHEAL OR PLAQUES ARE TRANSIENT,

CIRCUMSCRIBED, ELEVATED

PAPULES OFTEN WITH

ERYTHEMATOUS BORDERS AND PALE CENTERS

REPAIR, REGENERATION AND FIBROSIS

• Cell types and regenerative ability: 1. Labile cells- cells with short life span that

constantly proliferate. Excellent regeneration. (Ex. skin, gut, hemopoietic cells)

2. Stable cells-normally with little proliferation but remain capable of more raid cell division following injury. Good regeneration. (Ex. liver, renal PCT)

3. Permanent cell- are not capable of proliferation. No regeneration. Healed by scarring (Ex. Brain, heart)

Tissue Repair

• Fibroplasia – fibrous repair– Formulation of Granulation tissue

• Capillary budding results from mitogens– PDGF most important, hypoxia contributes

• Forms meshlike framework for scar development

– Infiltration of fibroblasts– Collagen laid down in random pattern

• Structure can be manipulated!!!!!

– Scar tissues excessive if inflammation re-initiated

Tissue Repair

• Maturation & Remodeling– Initial scar formation takes weeks– Scar matures

• Longest part of inflammation (over 1 yr)• Re-absorb temporary vasculature

– Scar shrinks (contraction) & changes color

– Scar remodels• Collagen fibers re-align with stress (SAID)• Less tensile strength than tissue it replaces

GRANULATION TISSUE IN HEALED SCAR

GRANULATION TISSUE IN HEALED SCAR

SURGICAL WOUNDS

• HEALING BY PRIMARY INTENTION – is letting a surgical wound heal without a big scar, where the wound hasneatly apposed edges

• HEALING BY SECONDARY INTENTION- is letting a surgical wound heal and leave a big scar, called granulation tissue that is formed from the bottom up, with the edges not neatly apposed.

GRANULATION TISSUE IN MYOCARDIAL INFARCT

GRANULATION TISSUE IN MYOCARDIAL INFARCT

KELOIDSKELOIDS