draft sooca case 8 carbuncle

8/13/2019 Draft Sooca Case 8 Carbuncle

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CASE 8

C RBUNCLEGeneral Pathology:

Cell Adaptation

Cell Injury and Death

Inflammation

Tissue Healing and Repair

Haemodynamic Disorder

Microscopic FeaturesImmunity Process

Infectious Disease

TIM AKADEMIK

DIVISI SOOCA

SPEKATRIA


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CASE REVIEWMr. Carbun, 20 years old

CC : Fever Since 2 Days Ago

History Taking :

Pain, swelling, andburning sensation in

buttock since 3 daysago

Lesion ruptured thismorning

Bloody pus come out

Physical Examination :

Body Temperature :38

0C

Head and Neck :Normal

Gluteal Region : Red Solitary

Nodule, 2 cm in

diameter

Ulcer (+), 0,5 cm indiameter

Discharge (+)bloody pus

Lab Examination :

Leukositosis

Diagnosis: Carbuncle

Treatment :

Pharmacology : Antibiotic

Non Pharmacology : Took blood for culture examination

Prognosis:

After 1 week : Lesion healed

After 4 weeks : Scar in buttock


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CONCEPT

MAP

Hyperemia Stimulate cyclic adonosine

monophosphate

Pain (Dolor)

Stimulate

Neurotransmitter

Homeostasis

Infection by Staphylococcus aureous

Failed cell adaptation

Cell injury

Inflammation (Acute)

Artery DilationStaphylococcus excrete exotoxinIncreased Vascular Permeability

Dolor

Blood into

Normal Tissue

Blood into

njury tissue

Tumor

Edema

Liquid to interstitial

Secrete Cytokine

Fever

Neutrophil fight the pathogen

Secretion of Prostaglandin

Producing of Leukocyte by

Bone Marrow

Burning Sensation

Local Calor

Scar Formation

Collagen in Wound Area

Tissue Repair

UlcerBloody Pus

Carbuncle

Pus

Compensanting Loss ofLeukocyte Cells

Leukocytosis

Leukocyte

Acceleration Release

of Leukocyte


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CELL ADAPTATION

Normal cell tends to maintain their steady state, called homeostasis. As cells encounter

physiologic stresses or pathologic stimuli, they can undergo adaptation, achieving a new

steady state and preserving viability and function. The principal adaptive responses are

hypertrophy, hyperplasia, atrophy, and metaplasia.

A.HYPERTROPHY Hypertrophy is an increase in the size of cells resulting in increase in the size

of the organ.The hypertrophied organ has no new cells, just larger cells.

Occurs in tissue whose cell are incapable to divide Hypertrophy can be physiologic or pathologic and is caused either by

increased functional demand or by specific hormonal stimulation.

Hypertrophy and hyperplasia can also occur together, and obviously both

result in an enlarged (hypertrophic) organ.

Mechanisms: Hypertrophy is the result of increased production of cellularproteins.

Example:


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o Physiologic hypertrophyof the uterus during pregnancy, occurs as aconsequence of estrogen-stimulated smooth muscle hypertrophy and

smooth muscle hyperplasia.

o Pathologic cellular hypertrophyof skeletal muscle and the heart canundergo only hypertrophy in response to increased demand because

in the adult they have limited capacity to divide.

B.ATROPHY Atrophy is reduced size of an organ or tissue resulting from a decrease in

cell size & number.It should be emphasized that although atrophic cells may

have diminished function, they are not dead.

Mechanisms: Atrophy results from decreased protein synthesis and increasedprotein degradation in cells. Protein synthesis decreases because of reduced

metabolic activity.

Example:o Physiologic atrophy is common during normal development

(notochord and thyroglossal duct).

o Pathologic atrophydepends on the underlying cause: Decreased workload (atrophy of disease) bedrest/plaster

cast on fractures bones

Loss of innervation(denervation atrophy) atrophy of musclefibers because of nerve damage

Diminished blood supply ischemia to a tissue may result inatrophy e.g. brain may undergo progressive atrophy because

of ischemia by atherosclerosis

Inadequate nutrition in marasmus Loss of endocrine stimulation e.g. loss of estrogen after

menopause

Pressure tissue compression for any length of time cancause atrophy


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C.HYPERPLASIA Hyperplasia is an adaptive response in cells capable of replication and

usuallyresulting in increased mass of tissue or organ.

Occurs in tissue whose cell are able to divide. Pathologic hyperplasia constitutes a fertile soil for cancer proliferation. Hyperplasia can be physiologic or pathologic.

Physiologic hyperplasia:

o Hormonal hyperplasia: increases the functional capacity of a tissuewhen needed e.g. proliferation of glandular epithelium of female

breast at puberty and during pregnancy accompaniedby hypertrophy

of glandular epithelial cells.

o Compensatory hyperplasia: increases tissue mass afterdamages/partial resection e.g. donating one lobe of liver remaining

cells proliferate so the organ soon grows back to its original size.

Pathologic hyperplasia: caused by excess of hormones/growth factors acting

on target cells. For example:

o Disturbance of balance between estrogen and progesterone increase in amount of estrogen hyperplasia of endometrial gland

(abnormal menstrual bleeding)

o Hyperplasia is also an important response of connective tissue cells inwound healing, in which proliferating fibroblasts and blood vessels aid

in repair.

D.METAPLASIA Metaplasia is a reversible change in which one differentiated cell type

(epithelial or mesenchymal) is replaced by another cell type, which is better

able to withstand the adverse environment. The influences that predispose to

metaplasia, if persistent, may initiate malignant transformation of

metaplastic epithelium.

Example:


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o The normal ciliated columnar epithelial cells of the trachea andbronchi are widely replaced by stratified squamous epithelial cells (in

cigarette smokers).

o Vitamin A deficiency may also induce squamous metaplasia in therespiratory epithelium.

o In chronic gastric reflux, the normal stratified squamous epithelium ofthe lower esophagus may undergo metaplastic transformation to

gastric or intestinal-type columnar epithelium.


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CELL INJURY AND CELL DEATH

A.CELL INJURY

Cell injury results when cells are stressed so severelythat they are no longer able to adapt

or when cells are exposed to inherently damaging agents or suffer from intrinsic

abnormalities.

Injury may progress through a reversible stage and irreversible stage.

TYPE OF CELL INJURY

1. Reversible InjuryOccur in early stages or mild forms of injury. The functional and morphologic

changes are reversible if the damaging stimulus is removed.

The hallmarks of reversible injury :

a. Reduced oxidative phosphorylation with resultant depletion of energy stores in theform of adenosine triphosphate (ATP)


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b. Cellular swelling caused by changes in ion concentrations and water influxc. In addition, various intracellular organelles, such as mitochondria and the

cytoskeleton, may also show alterations

2. Irreversible InjuryWith continuing damage the injury becomes irreversible, at which time the cell cannot

recover and it dies (undergo cell death).

CAUSE OF CELL INJURY

a. Loss of blood supply or loss of oxygen-carrying capacity Oxygendeprivationreducing aerobic oxidative respiration

b. Physical agents : mechanical trauma, temperature, radiation, electric shockc. Chemical agents : Imbalanced concentration, poisond. Environment & air pollutant: social stimuli (alcohol & narcotics)e. Infectious agents : virus, worms, bacteria, fungif. Immunologic reactionsg. Genetic derangement : Chromosomal abnormality, point mutationh. Nutritional imbalances : deficiency and excess

MECHANISM OF CELL INJURY

Principle:

1. Depends on the type, duration, and severity of the injury2. Depends on the type, state, and adaptability of cell3. Results from functional and biomechanical abnormality


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B.CELL DEATHCell deathoccurs when the injury becomes irreversible due to continued damage, at which

time the cell cannot recover and it dies. Cell death is divided into two morphologic and

mechanism pattern, necrosis and apoptosis.

There are 2 principles of cell death:

a. NecrosisWhen damage to membranes is severe, lysosomal enzymes enter the cytoplasm and

digest the cell, and cellular contents leak out.

b. ApoptosisWhen the cell' s DNA or proteins are damaged beyond repair, the cell kill itself. A form

of cell death that is characterized by nuclear dissolution, fragmentation of the cell

without complete loss of membrane integrity, and rapid removal of the cellular debris.

Features of Necrosis and Apoptosis

Pyknosis : degenerasi sel dimana ukuran sel mengecil dan kromatin mengalamikondensasi menjadi massa yang padat serta tidak berbentuk

Karyorrhexis: pecahnya inti sel dimana kromatinnya hancur menjadi granul-granul yangtidak berbentuk, yang dikeluarkan dari sel.

Karyolysis: Terputusnya inti sel


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INFLAMMATION

Inflammationis a complex reaction in tissues that consists mainly of responsesof blood

vessels and leukocytes. Inflammation may be acute or chronic, depending on the nature of

the stimulus and the effectiveness of the initial reaction in eliminating the stimulus or the

damaged tissues.

Physiological Response

Release of soluble mediators Vasodilation Increased blood flow Extravasation of fluid ( permeability) Cellular influx (chemotaxis) Elevated cellular metabolism

A.ACUTE INFLAMMATIONInvolves :

Hemodynamic changes Exudate formation Presence of granular leukocytes

Local Manifestations

Heat (calor) Redness (rubor) Swelling ( tumor) Pain (dolor) Loss Function (functio lesa)

Local Manifestation

Heat (Calor) Redness (Rubor) Swelling (Tumor) Pain (Dolor)


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Sistemic Manifestations

Fever Chills Malaise Myalgia

Stage of Acute Inflammation

1. Vasodilation2. Increased vascular permeability3. Movement of white blood cells (chemotaxis)

Process by which white blood cells are drawn to the site of inflammation. The process include :

1) Margination and Rolling Margination: blood leukocytes, predominantly neutrophils, accumulation at the

periphery of vessels [cytokines: tumor necrosis factor (TNF), interleukin-1 (IL-1),

chemokines]

Rolling: the leukocytes adhere transiently to the endothelium, detach and bind again,thus rolling on the vessel's wall. [selectins: L-selectin, E-selectin, P-selectin]

2) AdhesionRolling leukocytes are able to sense changes in the endothelium that initiate the next step in

the reaction of the leukocytes. The cells finally come to rest at some points where they

adhere firmly. [integrins]; [other mediators: histamine, thrombin, and platelet-activating

factor (PAF)]

3) Diapedesis or transmigrationMigration of leukocytes through the endothelium, squeezing between cells at intercellular

junction [chemokines] expressed on leukocyte and endothelial cells, mediates the binding

event needed for leukocytes to traverse the endothelium enable to pass through the

vascular basement membrane leukocyte secrete collagenase PECAM - 1

4) ChemotaxisMovement of leukocytes toward sites of infection or injury along a chemical gradients. Both

exogenous and endogenous substances can be chemotactic for leukocytes, including : (1)

bacterial products (2) cytokine, especially chemokine family [cytokines, C5a, leukotriene B4].


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4. Phagocytosis

Involves three steps:

a. Recognition & binding. Microorganism coated by opsonin that enhance phagocytosisefficiency by binding leukocyte receptors.

b. Engulfment by encircling pseudopods and enclosure of the particle within an intracellularphagosome

c. Killing & degradation of phagocytosed particles5. Termination

Development of inflammation process also trigger stop signal that actively terminate the

reaction.


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Morphology of Acute Inflammation

a. Serous InflammationClear, watery fluid appearance. Seen in viral infection and burns.

b. Fibrinous InflammationFinely particulate, thick fluid appearance. Seen in uremic and postmyocardial infarct pericarditis.

c. Purulent InflammationPus appearance. Seen in bacterial and fungal infection.

B.CHRONIC INFLAMMATIONChronic inflammation is prolonged process(weeks, months, even years).

Involve :

Presence of nongranular leukocytes Results in more extensive scarring

Local Manifestations

Heat (calor) Redness (rubor) Swelling ( tumor) Pain (dolor) Loss of Function


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DIFFERENCES BETWEEN ACUTE AND CHRONIC INFLAMMATION

STIMULI OF INFLAMMATION :


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TISSUE HEALING AND TISSUE REPAIR

Injury to cells and tissue sets in motion a series of event that contain the damage and

initiate the healing process, it can be separatedinto:

1. RegenerationProliferation of cells and tissues to replace lost structure. Type of regeneration depends

on tissue type :

A. LABILECapable of lifelong regeneration

B. STABLETissue can regenerate when stimulatedC. PERMANENTNo regenerative ability

2. RepairCombination of regeneration and scar formation by deposition of collagen.

3. HealingA process of cure, restoration of integrity to injured tissue.

I. First Intention

A. Minimal Tissue Loss

B. No Granulation Formation

II. Second Intention

A. Significant Tissue Loss

B. Granulation Tissue

C. Slow Healing

D. Scar Tissue

Healing is repair involving a combination of regeneration and connective tissue deposition.

Scarring occurs when tissues are intrinsically unable to regenerate.

Regeneration is cell or tissue growth that replaces lost structures


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STEM CELLS

Characterized byprolonged self renewal capacity and by asymmetric replication

Embryonic stem cellscapable to differentiate into any tissue typeThe functions are:

To identify signals required for normal tissue differentiation To generate animals congenitally deficient in specific genes by inactivating or

deleting gene in embryonic stem cells (ES) then incorporating the modified ES

to a developing blastocyst

Potentially of use in repopulating damaged organStem cell can also come from adult tissue, the example is bone marrow that contains

hematopoietic stemm cells.

Adult stem cellsare numbers of reservoir cells in normal adult tissues located inniches unique to each tissue.Ex:

Bone marrow contain hematopoietic stem cells (HSCs) Mesodermal lineage cells are capable of differentiating into neuron,

hepatocytes

Fuse with host cells, transfering genetic material and giving the falseimpression of transdifferentiation

Multipotent adult progenitor cells which are have broad developmentalcapacity

The role of stem cellin tissue homeostatis are:

Epithelium; most epithelial surfaces are constantly maintained by stem cells with adiscrete set of differentiation lineages. After injury stem cells can repopulate the

tissue

Liver; liver stem cells reside in the canals of Hering with capacity to formhepatocytes or biliary epithelium

Brain; neural stem cells exist and can even be integrated into neural circuit


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GROWTH FACTORS

Function:

Stimulating proliferating Affect cells movement, contractility, differentiation, angiogenesis

Major growth factors are :

EGF (Epidermal Growth Factor), TGF-(Transforming Growth Factor) HGF (Hepatocytes Growth Factor) is produced by fibroblast, endothelial cells

and hepatocytes

VEGF (Vascular Endothelial Growth Factor) play role in vasculogenesis andangiogenesis

PDGF (Platelet-derived Growth Factor) FGFs (Fibroblast Growth Factors) TGF-is a growth inhibitor for most epithelial cells and has potent anti

inflammatory effects

SIGNALING MECHANISM IN CELL GROWTH

Autocrine: cells respond to signaling substances produced by themselves Paracrine: a cell produce substances that affect target cells inclose proximity Endocrine: cells synthesize hormones that circulate in the blood to act on distant

targets

MECHANISM OF TISSUE REGENERATION

Mammals lack this capacity & regeneration in damaged tissues is largely just

compensatory growth involving cell hypertrophy ad hyperplasia. This will restore the

functional capacity but doesnt reconstitute the original anatomy. This ascribed to a

rapid fibropoliferative response and scar formation after wounding.


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REGENERATION, HEALING AND FIBROSIS

The main healing process is repair by deposition of collagen and other ECM

components, causing the formation of a scar. Repair by connective tisue deposition

includes:

Inflammation

Angiogenesis (blood vessel formation in adults)

Migration and proliferation of fibroblast

Scar formation

Connective tissue remodelling

Mechanism of Angiogenesis

From Preexisting Vessels

Vasodilation in response to nitric oxide and VEGF-induced increasedpermeability of vessels


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Proteolytic degradation of basement membrane of parent vessel byMMPs

Disruption of cell to cell contact between endothelial cells byplasminogen activators

Migration of endothelial cell towards the angiogenic stimulus Proliferation of endothelial cells behind the leading front of

migrating cells

Maturation of endothelial cells (inhibition of growth) Recruitment of periendothelial cells (vascular smooth muscle cells

to form the mature vessels)

From Endothelial Percusor Cells (EPC)

EPCs can be recruited from the bone marrow into tissues Migrate to a site of injury or tumor growth EPCs differentiate and form a mature network by linking to existing

vessels. EPCs express some markers of hematopoietic stem cells as

well as VEGR-2 and VE-catherin. The growth factor and receptor in

angiogenesis are VEGF (vascular endothelial growth factor), and

bFGF(base fibroblast growth factor)

Regulator of Angiogenesis: ECM proteins

Integrins (V3): for the formation and maintenance of newlyformed blood vessels

Matricellular proteins (thrombospondin 1, SPARC, tenascin C):destabilize cell-matrix interactin and promote angiogenesis

Proteinase (plasminogen activator and MMPs): remodelling duringendothelial invasion,

cleave extracellular protein, release inhibitor such as endostatin

Cutaneous Wound Healing

1.

Inflammation

Initial injury causes platelet adhesion and aggegation, blood clotting


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2. ProliferationFormation of granulation tissue, proliferation and migration of connective tissue

cells, re-epithelization of wound surface

3. MaturationECM deposition, tissue remodelling, wound contraction

Healing by First or Second Intention

First intentionMinimal tissue loss and no granulation formation

Second intention significant tissue loss granulation tissue slow healing scar tissue

Sequence of events

1) Formation of blood clot The clot serves to stop bleeding and also as scaffold for migrating cells Within 24 hours, neutrophils appear at margin of the incision Neutrophils release proteolytic enzymes that clean out debris and

invading bacteria

2) Formation of granulation tissue Its characteristic histology feature is the presence of the new small blood

vessel (angiogenesis) and the proliferation of fibroblast

Fibroblast and vascular endothelial cells proliferate in the first 24-72hours forming specialized type of tissue called granulation tissue

Amount of granulation tissue depends on the size of the tissue deficit andintensity of inflammation

By 5-7 days, granulation tissue fills the wound area andneovascularization is maximal

3) Cell proliferation and collagen deposition Neutrophils are replaced by macrophages by 48-96 hours


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Migration of fibroblast is driven by chemokines, TNF, PDGF, TGF-, andFGF. Their proliferation is triggered by TNF, PDGF, TGF-. FGF, IL-1, and

TNF. Macrophages are the main sources of these factors.

Collagen fibers are now present at the margins of incision, but at firstthese are vertically oriented and do not bridge the incision In the 24-48

hours, spours of epithelial cells move from the wound edge along the cut

margins of the dermis, depositing basement membrance component as

they move. They fuse in the midline beneath the surface scab, producing

a thin, continuous epithelial layer that closes the wound

4) Scar formation The leukocytic infiltrate, Edema, and increased vascularity largely

disappear during the second week

Blanching begins, accomplished by the increased occumulation ofcollagen within the wound area and regression of vascular channel

5) Wound contraction Generally occur in large surface of wounds The contraction helps to close the wound by decreasing the gap between

its dermal edge and by reducing the wounds surface area

6) Connective tissue remodelling The replacement of granulation tissue with a scar involves transitions in

the composition of the ECM. Some of the growth factors that stimulate

synthesis of collagen and other concetive tissue molecules also modulate

the synthesis and activation of metalloproteinase, enzymes that degrade

these ECM components

The balance between ECM synthesis and degradation results inremodelling of the connective tissue framework-an important feature of

both chronic inflammation and wound repair

7) Recovery of tensile strength Scar tissue may achieve may achieve 70-80% of the tensile strength of

unwounded skin

Result from excess of collagen synthesis over collagen degradation duringthe first 2 months of healing


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Factors Influencing Wound Healing

a. Systemic factor: nutrition, metabolic status, circulatory system, hormoneb. Local factor:infection, mechanical factor, foreign bodies, size, location, and type of

wound

Fibrosis

Fibrosis is emigration and proliferation of fibroblast in the site of injury anddeposition of ECM in the fibroblast. The proliferation of fibroblast is:

i. Migration of fibroblast and their proliferation are triggered bymultiple GF ( TGF-, PDGF, EGF, FGF, Fibrogenic cytokines, IL-1, TNF-

)

ii. TGF- : Fibroblast migration and proliferation, increasing of thesynthesis of collagen and fibronectin and degradation of ECM

Extracellular atrix deposition are: decreasing of fibroblast, increasing of deposit ofECM, synthesis and accumulation of collagen, and collagen synthesis is enhanced by

(PDGF, FGF, TGF-) and cytokines (IL-1, IL-4)

EXTRACELLULAR MATRIX & CELL MATRIX INTERACTIONS

ECM is dynamic, constantly remodellingmacromoleculer complex synthesizedlocally and constituting a significant proportion of any tissue.

ECM supplies a substratum for cell adhesion and critically regulates the growth,movement, and differentiattionof the cells living within it.

ECM occurs in two basic form:1. Interstitiel matrix

2. Basement membrane


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ROLES OF EXTRACELLULAR MATRIX

- Mechanical support for cell anchorage

- Determination of cell orientation (polarity)

- Control of cell growth

- Maintenance of cell differentiation

- Scaffolding for tissue renewal

- Establishment of tissue microenvironments

- Storage and presentation of regulatory molecules

COMPONENTS OF THE EXTRACELLULER MATRIX

1. Collagen and elastin2. Proteoglycans and hyaluronan3. Adhesive glycoprotein and integrin

REPAIR BY HEALING, SCAR FORMATION AND FIBROSIS

After injury, tissues may regenerate or heal Regeneration involves restitution of tissue identical to that lost by injury Healing is a fibro proliferative responses that patches rather than restores a tissue

For tissue incapable of regeneration, repair is accomplished by ECM deposition, producing a

scar.

The Sequence of Healing

Inflammatory response to eliminate the initial stimulus, remove injured tissue,initiate ECM deposition

Proliferation & migration of parenchymal & connective tissue cells Formation of new blood vessels (angiogenesis) Migration and proliferation of fibroblast

Deposition of ECM Maturation and organization of fibrous tissue


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HAEMODYNAMIC DISORDER

A.EDEMA

Edema signifies increased fluid in the interstitial tissue spaces. Depending on the site,

fluid collections are variously designated hydrothorax, hydropericardium, and

hydroperitoneum(ascites).

Types of Edema

Transdate - protein poor(1.020 resultsfrom endothelial damage and alteration of vasular permeability e.g.

inflammatory and immunologic pathology.

Process of Edema


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B.HYPEREMIA & CONGESTIONHyperemiais an active processresulting from tissue inflowbecause of arteriolar

dilation, e.g. skeletal muscle during exercise or at sites of inflammation. The affected

tissue is redder because of the engorgement of vessels with oxygenated blood.

Congestionis a passive processresulting from impaired outflowfrom a tissue. It

may be systemic e.g. cardiac failure, or local e.g. an isolated venous obstruction. The

tissue has a blue-red color (cyanosis), due to accumulation of deoxygenated hemoglobin

in the affected tissues.

C. SHOCKShock, or cardiovascular collapse,is the final common pathway for a number of

potentially lethal clinical events, including severe hemorrhage, extensive trauma or

burns, large myocardial infarction, massive pulmonary embolism, and microbial sepsis.

The type of shock:

Cardiogenic shockresults from myocardial pump failure e.g intrinsic myocardialinfarction, ventricular arrhythmias.

Hypovolemic shockresults from loss of blood or plasma volume e.g. hemorrhage,fluid loss from severe burns, or trauma.

Septic shockis caused by systemic microbial infection. Most commonly due togram-negative infections (endotoxic shock),but it can also occur with gram-

positive and fungal infections.

Neurogenic shock:anesthetic accident or spinal cord injury can lead to loss ofvascular tone and peripheral pooling of blood.

Anaphylactic shock: initiated by a generalized IgE-mediated hypersensitivityresponse, is associated with systemic vasodilation and increased vascular

permeability.


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MICROSCOPIC FEATURE OF CERTAIN ABNORMALITIES

(LAB ACT)

1. Cell Injury : Cellular Injury2. Tissue Repair : Cirrhosis3. Metaplasia : Cervix4. Infectious : Lymphadenitis Tuberculosa

Reactive Hyperplasia Of The Lymph Node

5. Inflammation : Acute AppendicitisChronic Cholecystitis

6. Haemodynamic : Hemorrhoid

Abnormality Microscopic

Cellular Injury Small nuclear vacuoles may beseen within the cytoplasm

Represent distended andpinched-off segments of the ER

Cirrhosis Of The

Liver

Diffuse hepatic fibrosis withreplacement of normal nobular

architecture by parenchymal

nodules separated by fibrous

tissue

Portal-central septa linking portaltracts and central vein are the c

omponent of cirrosis


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Metaplasia Columnar cell lining theendocervix is replaced by

squamous cells

Lymphadenitis

Tuberculosa

The appearance range from

multiple small epitheloid granuloma

to huge caseous masses surronded

by langerhans giant cells,

epitheloid cells, and lymphocyte

Reactive

Hyperplasia

The margins of reactive folliclesare sharply defined and

surrounded by a mantle of smalllympocites often arranged

circumferencially with onion-skin

pattern

The follicles are composed of anadmixture of small and large

lymphoid cell with irregular

nuclei


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Acute

Appendicitis

Acute inflammatory cells arescattered throughtout the

mucosa, submucosa, and

muscularis propia.

Usually seen in serous layer The abnormality is indicated by

PMN

Chronic

Cholecystitis

In mildest cases, only scatteredlymphocyte, plasma cell and

macrophages.

Hemorrhoid The lesion consist of thin walleddilated submucosal varices thatprotude beneath the anl/ rectal

mucosa.

Thrombosis of these dilated veinis frequent.


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IMMUNITY PROCESS

Figure 6-1 Innate and adaptive immunity. The principal mechanisms of innate immunity and

adaptive immunity are shown.

A. INNATE IMMUNITYInnate immunity also called natural or native immunity, refers to defense

mechanismsthat are present even before infection and have evolved to specifically

recognize microbes and protect multicellular organisms against infections.

The major components of innate immunity are epithelial barriersthat block

entry of environmental microbes, phagocytic cells (mainly neutrophils and

macrophages), natural killer (NK) cells, and several plasma proteins, including the

proteins of the complement system. Phagocytes are recruited to sites of infection,

resulting in inflammation, and here the cells ingest the microbes and are then

activated to destroy the ingested pathogens. Phagocytes recognize microbes by

several membrane receptors.


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1. Macrophages

Macrophages are a part of the mononuclear phagocyte system. Macrophages

play important roles both in the induction and in the effector phase of immune

responses.

2. Dendritic Cells

a. Interdigitating dendritic cells (dendritic cells)

These cells are the most important antigen-presenting cells for

initiating primary immune responses against protein antigens. Several

features of dendritic cells account for their key role in antigen presentation.

First,these cells are located at the right place to capture antigens

under epithelia, the common site of entry of microbes and foreign antigens,

and in the interstitia of all tissues, where antigens may be produced.

Immature dendritic cells within the epidermis are called Langerhans cells.

Second, dendritic cells express many receptors for capturing and

responding to microbes (and other antigens), including TLRs and mannose

receptors.

Third, in response to microbes, dendritic cells express the same

chemokine receptor as do naive T cells and are thus recruited to the T-cell

zones of lymphoid organs, where they are ideally located to present antigens

to recirculating T cells.

Fourth, dendritic cells express high levels of MHC class II molecules

as well as the costimulatory molecules B7-1 and B7-2. Thus, they possess all

the machinery needed for presenting antigens to and activating CD4+ T cells.

b. Follicular dendritic cells

These cells present in the germinal centers of lymphoid follicles in thespleen and lymph nodes.


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These cells bear Fc receptors for IgG and receptors for C3b and can

trap antigen bound to antibodies or complement proteins .Such cells play a

role in ongoing immune responses by presenting antigens to B cells and

selecting the B cells that have the highest affinity for the antigen , thus

improving the quality of the humoral immune response. Follicular dendritic

cells also play a role in the pathogenesis of the acquired immunodeficiency

syndrome (AIDS).

3. Natural Killer Cells

NK cells make up approximately

10% to 15% of the peripheral blood

lymphocytes and do not bear T-cell

receptors or cell surface

immunoglobulins. Morphologically, NK

cells are somewhat larger than small

lymphocytes, and they contain

abundant azurophilic granules. Hence,

they are also called large granular

lymphocytes. NK cells are endowed with

an innate ability to kill a variety of


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tumor cells, virally infected cells, and some normal cells, without previous

sensitizat ion. These cells are part of the innate immune system, and they may

be the first line of defense against viral infections and, perhaps, some tumors.

NK cells do not rearrange T-cell receptor genes and are CD3 negative. Two cell

surface molecules, CD16 and CD56, are widely used to identify NK cells. CD16 is

the Fc receptor for IgG and it endows NK cells with another function, the ability

to lyse IgG-coated target cells. This phenomenon, known as antibody-dependent

cell-mediated cytotoxicity.

The functional activityof NK cells is regulated by a balance between signals

from activating and inhibitory receptors. The activatingreceptors stimulate NK

cell killing by recognizing ill-defined molecules on target cells, some of which

may be viral products; the inhibitoryreceptors inhibit the activation of NK cells

by recognition of self-class I MHC molecules. The class I MHC-recognizing

inhibitory receptors on NK cells are aptly called killer inhibitory receptors.

NK cells also secrete cytokines, such as IFN-, TNF, and granulocyte

macrophage colony-stimulating factor (GM-CSF).

B.ADAPTIVE IMMUNITYAdaptive immunity (also called acquired, or specific, immunity) consists of

mechanisms that are stimulated by (adapt to) microbes and are capable of also

recognizing nonmicrobial substances, called antigens. Innate immunity is the first

line of defense, because it is always ready to prevent and eradicate infections.

Adaptive immunity develops later after exposure to microbes and is even more

powerful in combating infections. By convention, the term "immune response"

refers to adaptive immunity.

The adaptive immune system consists of lymphocytes and their products,

including antibodies. The receptors of lymphocytes are much more diverse than

those of the innate immune system, but lymphocytes are not inherently specific for

microbes, and they are capable of recognizing a vast array of foreign substances. In


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the remainder of this introductory section we focus on lymphocytes and the

reactions of the adaptive immune system.

1. T LymphocytesT lymphocytes are generated from immature precursors in the thymus.

Mature, naive T cells are found in the blood, where they constitute 60% to 70%

of lymphocytes, and in T-cell zones of peripheral lymphoid organs, such as the

paracortical areas of lymph nodes and periarteriolar sheaths of the spleen. The

segregation of naive T cells to these anatomic sites is because the cells express

receptors for chemoattractant cytokines (chemokines) that are produced only

in these regions of lymphoid organs. Each T cell is genetically programmed to

recognize a specific cell-bound antigen by means of an antigen-specific T-cell

receptor (TCR). In approximately 95% of T cells, the TCR consists of a disulfide-

linked heterodimer made up of an and a polypeptide chain , each having a

variable (antigen-binding) and a constant region. The TCR recognizes peptide

antigens that are displayed by major histocompatibility complex (MHC)

molecules on the surfaces of antigen-pressenting cells. T cells (in contrast to B

cells) cannot be activated by soluble antigens; therefore, presentation of

processed, membrane-bound antigens by antigen-presenting cells is required for

induction of cell-mediated immunity.

2. B Lymphocytes

B lymphocytes develop from immature precursors in the bone marrow.

Mature B cells constitute 10% to 20% of the circulating peripheral lymphocyte

population and are also present in peripheral lymphoid tissues such as lymph

nodes, spleen, or tonsils and extralymphatic organs such as the

gastrointestinal tract.

In lymph nodes, they are found in the superficial cortex. In the spleen, they

are found in the white pulp. At both sites, they are aggregated in the form oflymphoid follicles, which on activation develop pale-staining germinal centers. B


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cells are located in follicles, the B-cell zones of lymphoid organs, because the

cells express receptors for a chemokine that is produced in follicles.

B cells recognize antigen via the B-cell antigen receptor complex.

Immunoglobulin M (IgM) and IgD, present on the surface of all naive B cells,

constitute the antigen-binding component of the B-cell receptor complex. As

with T cells, each B-cell receptor has unique antigen specificity, derived in part

from somatic rearrangements of immunoglobulin genes. After antigenic

stimulation, B cells form plasma cells that secrete immunoglobulins, which are

the mediators of humoral immunity. In addition to membrane immunoglobulin,

the B-cell antigen receptor complex contains a heterodimer of nonpolymorphic

transmembrane proteins Ig and Ig. Similar to the CD3 proteins of the TCR, Ig

and Ig do not bind antigen but are essential for signal transduction through the

antigen receptor. B cells also express several other nonpolymorphic molecules

that are essential for B-cell function.

CYTOKINESmessenger molecules of the immune system

Many such interactions depend on cell-to-cell contact; however, many

interactions and effector functions are mediated by short-acting soluble mediators,

called cytokines. This term includes the previously designated lymphokines

(lymphocyte-derived), monokines (monocyte-derived), and several other

polypeptides that regulate immunologic, inflammatory, and reparative host

responses. Molecularly defined cytokines are called interleukins, implying that they

mediate communications between leukocytes. Most cytokines have a wide spectrum

of effects, and some are produced by several different cell types.

1. Cytokines that mediate innate (natural) immunity.Included in this group are IL-1, TNF (tumor necrosis factor, also called

TNF-), type 1 interferons, and IL-6. Some cytokines, such as IL-12 and

IFN-, are involved in both innate and adaptive immunity against

intracellular microbes. Certain of these cytokines (e.g., the interferons)


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protect against viral infections, whereas others (e.g., IL-1 and TNF)

promote leukocyte recruitment and acute inflammatory responses.

2. Cytokines that regulate lymphocyte growth, activation, anddifferentiation.

Within this category are IL-2, IL-4, IL-12, IL-15, and transforming growth

factor- (TGF-). IL-2 is an important growth factor for T-cells, IL-4

stimulates differentiation to the TH2 pathway and acts on B cells as well,

IL-12 stimulates differentiation to the TH1 pathway, and IL-15 stimulates

the growth and activity of NK cells. Other cytokines in this group, such as

IL-10 and TGF-, down-regulate immune responses.

3. Cytokines that activate inflammatory cellsIn this category are IFN-, which activates macrophages; IL-5, which

activates eosinophils; and TNF and lymphotoxin (also called TNF-),

which induce acute inflammation by acting on neutrophils and

endothelial cells.

4. Cytokines that affect leukocyte movement are also called chemokinesThe C-X-C chemokines are produced mainly by activated macrophages

and tissue cells (e.g., endothelium), whereas the C-C chemokines are

produced largely by T cells. Different chemokines recruit different types

of leukocytes to sites of inflammation. Chemokines are also normally

produced in tissues and are responsible for the anatomic localization of

different cell types, for example, the location of T and B cells in distinct

regions of lymphoid organs.

5. Cytokines that stimulate hematopoiesis.Many cytokines derived from lymphocytes or stromal cells stimulate the

growth and production of new blood cells by acting on hematopoietic

progenitor cells. Several members of this family are called colony-

stimulating factors (CSFs) because they were initially detected by their

ability to promote the in vitro growth of hematopoietic cell colonies from

the bone marrow. Some members of this group (e.g., GM-CSF and G-CSF)

act on committed progenitor cells, whereas others, exemplified by stemcell factor (c-kit ligand), act on pluripotent stem cells.


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INFECTIOUS DISEASE

CATEGORIES OF INFECTIOUS AGENTS

BACTERIAL INFECTION

Optional: untuk SOOCA saja.


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ROUTES OF ENTRY, DISSEMINATION, AND RELEASE OF MICROBES

FROM THE BODY

HOW MICROORGANISMS CAUSE DISEASE

Infectious agents establish infection and damage tissues in three ways:

They can contact or enter host cells and directly cause cell death.

They may release toxins that kill cells at a distance, release enzymes that degrade tissuecomponents, or damage blood vessels and cause ischemic necrosis.

They can induce host cellular responses that, although directed against the invader,cause additional tissue damage, usually by immune-mediated mechanisms. Thus, as we

The defensive responses of the host are a two-edged sword: They are necessary to

overcome the infectionbut at the same time may directly contribute to tissue damage.


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Pada kasus ini, bakteri yang terlibat adalah Staphylococcus aureousyang merupakan

bakteri aerob. Sebenarnya, bakteri ini banyak terdapat di permukaan kulit (ini adalah hal

yang normal). Tetapi, apabila terjadi luka pada kulit, maka bakteri tersebut akan masuk ke

dalam kulit sehingga menyebabkan infeksi dan dapat menyebabkan carbuncle.

The final common pathway of many infections is chronic inflammation, which can lead to

extensive scarring.


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BHP

Doctor should give complete information with right attitude Respect for patients privacy (confidentiality) Ask for permition to do physical examination (gluteal region) Informed consent about culture examination Giving right antibiotic type and dosage then give explanation about drugs administration Follow up the patient Explain to patient the scra that will be formed

PHOP

Educate the patients about healthy life (personal hygiene) Education about carbuncle Education about environment sanitary Explain about control of communicable disease

draft sooca case 8 carbuncle

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