inflammation reference: robbins basic pathology 9 th edition- 2013

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inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

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Page 1: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

inflammation

Reference: Robbins Basic Pathology9th edition- 2013

Page 2: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

یا خارجی آزاررسان عوامل حذف به بدن بقای . پاسخ ی وسیله به کار این است وابسته داخلی

نام با میزبان پیچیده های

Inflammationالتهاب یا

شود می .انجام

Page 3: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

یک کننده التهاب محافظت برای پاسخنیز و سلولی آزار اولیه عامل حذف

ناشی نکروتیک های بافتاست آسیب .از

اندازد می راه به را وقایعی سپس التهابمی بافت بازسازی و بهبود به منجر که

نام. با وقایع این “ شود خوانده ترمیم“شوند .می

Page 4: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

رسان آسیب عوامل سازی پاک به التهاب هرچندکند می آغاز را ترمیم فرایند و کرده هم کمک

زدن آسیب پتانسیل ترمیم هم و التهابدارند را بدن های بافت .به

التهابی اساس ها بیماری از بسیاری رو این از.دارند

Page 5: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

سلول انتقال التهابی واکنش هدفمیزبان دفاعی های مولکول و ها

پروتئین شامل و ها لکوسیتپالسما به های خون گردش از

است دیده آسیب بافت .محل

Page 6: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

التهابی پاسخ :اجزای

Page 7: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

Two basic patterns of inflammation:

Acute inflammation ( التهاب (حاد

Chronic inflammation ( التهاب (مزمن

Page 8: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

Characteristics of acute inflammation:

Rapid onset (minutes)

Relatively short duration, lasting up to a few days

Fluid and plasma protein leakage

Predominantly neutrophilic leukocyte accumulation

Page 9: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

Characteristics of chronic inflammation:

Longer duration(days to years)

Accumulation of lymphocytes and macrophages

Page 10: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

Neutrophils & Lymphocyte

Page 11: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

Monocyte

Page 12: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

Main manifestations of inflammation:

Redness (erythema) Swelling Heat Pain Loss of function

Page 13: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

شونده خودمحدود طبیعی طور به التهابسلول است. و التهاب شیمیایی های واسطه

به پاسخ در تنها التهاب در کننده شرکت هایطول و شوند می فعال رسان آسیب محرک

است کوتاه ها آن .عمرالتهابی ضد های مکانیسم التهاب جریان در عالوه به

را التهاب شدت تا شوند می فعال نیز مختلفکنند .کنترل

Page 14: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

به توان می را التهابی پاسخ کلی طور بهکرد تقسیم مرحله :پنج

رسان -1 آسیب عامل شناساییها -2 لکوسیت فراخوانیمضر -3 عامل برداشتالتهابی -4 پاسخ کنترل

بهبودی -5 و ترمیم

Page 15: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

Acute Inflammation

Page 16: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

Acute inflammation is a rapid response to injurious agent to deliver leukocytes and plasma proteins to the site of injury.

Page 17: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

Stimuli for acute inflammation:

Infections (e.g. bacterial) :the most common cause

Trauma Physical and chemical agents (e.g.

burns and frostbite, some chemicals) Tissue necrosis

Page 18: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

های سلول و ها میکروب شناساییرسان آسیب عوامل سایر و :نکروتیک

سلول بسیاری و دندریتیک های سلول و ها فاگوسیتاپیتلیال های سلول مانند دیگر هایی های گیرنده

و عفونی های پاتوژن حضور توانند می که دارندکنند حس را مرده های سلول از شده آزاد .مواد

ها گیرنده : اینPattern recognition receptors

الگو تشخیص های گیرنده یایا ساختارها توانند می که چرا شوند می نامیده

بین یا و ها میکروب بسیاری بین مشترک الگوهایدهند تشخیص را مرده های .سلول

Page 19: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

Pattern recognition receptors:

Toll- like receptors:ها پاتوژن سایر و ها ویروس و ها باکتری محصوالت

و. پالسمایی غشا در و کنند می شناسایی رادارند قرار ها .اندوزوم

Inflammasome:که است پروتئینی چند سیتوپالسمی ی مجموعه یک

محصوالت برخی و مرده های سلول محصوالتکند می شناسایی را .میکروبی

Page 20: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

حاد التهاب در عروقی های :واکنش

خون -1 جریان افزایش نتیجه در و عروق اتساععروق -2 نفوذپذیری افزایش

خونی های سلول رسیدن به واکنش دو این ) کمک) آسیب محل به ها پروتئین و ها لکوسیت

کنند .می

Page 21: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

Vascular changes occur in microcirculation:

Capillary bed

Page 22: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013
Page 23: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

Vasodilation is the earliest change in acute inflammation which first

involves arteioles:

Increased blood flow

Heat & redness

histamine

Page 24: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

Vasodilation

Page 25: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

Vasodilation causing “hyperemia and redness”

Page 26: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

Increased vascular permeability

Movement of protein-rich fluid from capillaries (exudate)

Page 27: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

What’s exudate?

Exudate is a fluid with high protein content.

Page 28: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

The final result is:

Fluid accumulation in extravascular

tissue “EDEMA”(swelling)

Page 29: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

What’s edema?

Edema is an excess of fluid in the interstitium or body

cavities.

Page 30: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013
Page 31: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

Cellulitis (“itis” is the suffix for inflammation):

Erythema &

Swelling

Page 32: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

Acute meningitis(exudate on the brain surface)

Page 33: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

Loss of fluid from intravascular space

Concentration of RBCs in small vessels

Dilated small vessels packed with RBCs with slower blood flow

(STASIS)

Page 34: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

STASIS

Accumulation of WBCs along the vascular endothelium

Page 35: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

Mechanisms of increased vascular permeability

1. Endothelial contraction

The most common mechanism Rapid onset & short duration

Page 36: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

Mechanisms of increased vascular permeability

2. direct endothelial injury

Endothelial cell necrosis and detachment

Severe injuries (burns)

Page 37: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

Mechanisms of increased vascular permeability

3. leukocyte- mediated endothelial injury

By toxic mediators released from leukocytes

Page 38: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

Mechanisms of increased vascular permeability

4. increased transcytosis

Intracellular pathway

Mediator: Vascular Endothelial Growth Factor (VEGF)

Page 39: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013
Page 40: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

LEUKOCYTE EVENTS:

EXTRAVASATION &

LEUKOCYTE ACTIVATION

Page 41: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

Sequence of events in the extravasation of leukocytes:

-Margination -Rolling -Adhesion -Transmigration -Chemotaxis

Page 42: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013
Page 43: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013
Page 44: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

margination

Page 45: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

Leukocyte emigration

Page 46: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

Leukocyte emigration

Page 47: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

Rolling, adhesion, and transmigration are mediated by binding of complementary molecules on leukocytes and endothelial surfaces.

Page 48: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

ROLLING

Relatively loose and transient adhesion of leukocytes to endothelial surfaces mediated by:

SELECTIN family of molecules

E- selectin: on endothelial cells P- selectin: on endothelial cells

Page 49: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

ROLLING

Selectins bind to oligosaccharides:

E- selectin: sialyl- Lewis X P- selectin: sialyl- Lewis X

Page 50: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

ROLLING

Page 51: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

ADHESION

In adhesion, leukocytes firmly stick to endothelial surfaces.

Adhesion is mediated by:

Integrins: on leukocytes Integrin ligands: on

endothelial cells

Page 52: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

Integrin ligands on endothelial cells

ICAM-1: Intercellular Adhesion Molecule- 1

VCAM- 1: Vascular Cell Adhesion

Molecule- 1

Page 53: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

Integrins:

Integrin family consists of a group of cell surface proteins that promote cell- cell or cell- matrix interactions.

Page 54: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

Rolling & Adhesion

Page 55: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

Transmigration

Transmigration is mediated by :

PECAM- 1 (CD31): Platelet Endothelial Cell Adhesion Molecule- 1

Page 56: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

Transmigration

collagenase

Page 57: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

The sequence of leukocyte recruitment in inflammation

Page 58: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

Chemotaxis After extravasation, leukocytes

emigrate in tissues towards the site of injury oriented along a chemical gradient.

Examples of chemotactic agents: Bacterial soluble products

Page 59: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

Chemotaxis

Chemotactic agents bind to their specific receptors on surface of leukocytes. This

results in actin polymerization and formation

of filopodia.

Page 60: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

Leukocyte with filopodia

Page 61: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

Leukocyte recruitment also induces

leukocyte activation:

Production of active metabolites

Secretion of cytokines

Phagocytosis

Page 62: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

The type of emigrating leukocyte depends on the age of the inflammatory response:

First 6- 24 hours: neutrophils

After that: monocytes

Page 63: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

Myocardial infarction (early neutrophilic infiltrate):

Page 64: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

Myocardial infarction (later mononuclear infiltrate):

Page 65: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

The sequence of events in acute inflammation:

Page 66: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

Phagocytosis:

Three steps of phagocytosis:• Recognition and attachment of

the particle to the leukocyte• Engulfment with formation of

phagocytic vacuole• Killing and degradation of the

ingested particle

Page 67: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

Recognition & attachment:

Recognition of microbes is mediated by serum proteins called

opsonins.

Opsonins bind to microbes on one hand and have specific receptors on leukocytes on the other.

Page 68: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

Recognition, attachment & engulfment:

Page 69: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

Opsonins Opsonin receptors

IgG FcR

C3b CR1

Page 70: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

Engulfment & phagolysosome formation:

Page 71: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

Killing & degradation:

Reactive oxygen species are responsible for microbial killing.

Page 72: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

NADPH oxidase (phagocyte oxidase) begins the oxidative burst in

leukocyte.

HOCL

Page 73: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

Hypochlorite (HOCL)is a potent antimicrobial agent

that destroys microbes by halogenation or

by oxidation of proteins and lipids.

Page 74: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

After killing, lysosomal acid hydrolases

degrade the microbes within phagolysosome.

Page 75: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

Neutrophilic Extracellular Traps (NETs):

نوتروفیلی سلولی خارج های شبکه تلهبه پاسخ در که هستند سلولی خارج های

می آزاد التهابی های واسطه و عفونی عوامل.شوند

ها تله ای این هسته کروماتین از دارند چارچوبیها که آنزیم و میکروبی ضد آن پپتیدهای در

اند گرفته .قرار

Page 76: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

Neutrophilic Extracellular Traps (NETs):

NET

Microbe

Page 77: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

Neutrophilic Extracellular Traps (NETs):

نوتروفیلی سلولی خارج های غلظت تلهمحل در را میکروبی ضد مواد از باالیی

انداختن دام به با و کنند می فراهم عفونتمی جلوگیری ها آن گسترش از ها میکروب

.کنند

و رفته بین از نوتروفیل هسته فرآیند این طی درمیرد می .سلول

Page 78: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013
Page 79: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

Lymphatics & lymph nodes in inflammation:

Page 80: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

Lymphatics & lymph nodes in inflammation:

During inflammation, lymphatic flow increases

Regional lymph nodes

Lymphangitis

Reactive lymphadenitis

Page 81: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

Lymphatic drainage of the hand

Page 82: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

Lymphangitis

Page 83: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

Structure of lymph node(afferent vessels)

Page 84: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013

Lymphadenitis

Page 85: Inflammation Reference: Robbins Basic Pathology 9 th edition- 2013