INJURY AND ADAPTATION

PROCESSES

Department of Anatomic Pathology
Fac. of Medicine Gadjah Mada University
DEFINITION

Pathology is a discipline bridging clinical practice
and basic sciences

Identify changes in cells and tissues morphology
diagnoses and therapy

Focus of pathology:
etiology ( cause )
pathogenesis
pathways by which morphologic changes occurs
DEFINISI

Patologi adalah menjembatani disiplin praktek klinis dan
ilmu dasar

Identifikasi perubahan dalam jaringan sel dan morfologi -
diagnosis dan terapi

Fokus patologi:
etiologi (penyebab)
patogenesis
jalur dimana terjadi perubahan morfologi


CELLULAR RESPONSES AGAINST INJURY



Cells

Cellular adaptations
Physiologic stresses/ pathologic stimuli
Adaptive responses:
atrophy, hypertrophy, hyperplasia, metaplasia
Cellular injury
Adaptive capability is exceeded
Reversible injury
Irreversible injury
Dies: apoptosis and necrosis
Causes of cellular injury :




Hypoxia
Physical agents
Chemicals and drugs
Microbiologic agents
Immunologic agents
Genetic defects
Nutritional imbalances
Aging

Hipoksia
Agen fisik
Bahan kimia dan obat-obatan
Microbiologic agen
Kekebalan agen
Cacat genetik
Ketidakseimbangan gizi
Penuaan
Hypoxia
Diminish/ loss of blood supply
Constriction/ obstruction of blood vessel
Diminish of oxygen supply
Cardio-respiration failure
Heart failure
Lung diseases
Diminish / loss of oxygen carrying capacity
CO stable HbCO

Effect: depend on the grade of the stress
Hipoksia
Menghilangkan / kehilangan suplai darah
Penyempitan / penyumbatan pembuluh darah
Mengurangi pasokan oksigen
Kegagalan respirasi cardio -
Jantung
Penyakit paru-paru
Berkurang / hilangnya daya oksigen
HbCO stabil CO

Efek: tergantung pada derajat stres

DRUGS AND CHEMICAL SUBSTANCES

Toxic agent cellular death tissue death
Non toxic agent: glucosa high osmotic pressure
cellular injury

Specific target of chemical substance:
absorption, transportation, metabolism, excretion
- barbiturat liver damage due to degradation/
metabolism process
- mercurichlorida stomach (absorption), colon
and kidney ( excretion)
NARKOBA DAN KIMIA ZAT

Beracun agen jaringan seluler mati-
mati
Non toxic agent: glucosa - tekanan
osmotik tinggi cedera selular

Sasaran spesifik zat kimia:
penyerapan, transportasi,
metabolisme, ekskresi
- Barbiturat kerusakan hati akibat
degradasi / proses metabolisme
- mercurichlorida perut
(penyerapan), kolon dan ginjal
(ekskresi)
Microbiologic agents
Virus:
Cytolytic/cytophatic cellular death
Oncogenic ->>> proliferation -- neoplasm
Bacterie
Exotoxin
Endotoxin
Lecitinase damage of cell membrane
Hemolysin -> hemolysis
Fungi
actinomycosis
- Parasite
- Amoeba, malaria, toxoplasm
Worm
Filaria dll
Microbiologic agen
Virus:
Cytolytic / cytophatic kematian sel
Onkogenik ->>> proliferasi - neoplasma
Bacterie
Eksotoksin
Endotoksin
Lecitinase kerusakan membran sel
Hemolysin -> hemolisis
Jamur
actinomycosis
Parasit
Amuba, malaria, toxoplasm
Cacing
Filaria dll
Physical agent:
Cold
vasoconstriction blood supply << , intravascular
coagulation Crystalisasion of intravascular
substances

Hot
Hypermetabolism --- necroses due to burning
process
_ athmospher Caisson disease
_ electric -> burn ulcer cardiac arytmia

Fisik agen
Dingin
vasokonstriksi aliran darah <<, koagulasi
intravaskular - Crystalisasion dari zat
intravaskular

Panas
Hypermetabolism --- necroses akibat proses
pembakaran
Athmospher _ Caisson penyakit
_ Listrik -> membakar borok-jantung arytmia

Immunologic reaction
anaphylactic reaction
Genetic defects
Defect congenital
Hemoglobin S of sickle cell anemia
Nutritional imbalances
Protein calorie insufficiency, obesity
Atherosclerosis
Aging
acumulation of subletal injury -> decreased of
cellular responses

Reaksi kekebalan
reaksi anafilaksis
Cacat genetik
Cacat bawaan
Hemoglobin S dari anemia sel sabit
Ketidakseimbangan gizi
Kekurangan kalori protein, obesitas
Aterosklerosis
Penuaan
acumulation dari cedera subletal -> penurunan
dari tanggapan selular

Mechanisms of cell injury
Most forms of cell injury to ultimate cell death have
proved difficult to dissect, because:

* not all of injuries invariably fatal

* it is difficult to distinguish the primary target of
injury from any secondary ripple effects

* no precise cut-off point to establish cause and effect
Sebagian besar bentuk cedera sel utama
kematian sel memiliki
terbukti sulit untuk membedah, karena:

* Tidak semua luka selalu fatal

* Sulit untuk membedakan target utama
cedera dari setiap sekunder efek riak

* Tidak tepat cut-off point untuk menentukan
sebab dan akibat

There are a number of generalizations

The cellular responses to injurious depends on the type
of injury, its duration, and its severity
The consequences of injury are also dependent on the
type of cell, its current status, and its adaptability
Four intracellular systems are vulnerable:
1. cell membrane integrity
2. aerobic respiration
3. protein synthesis
4. the integrity of genetic aparatus
. Oxygen , oxygen derived free radicals and failure of
intracellular calcium homeostasis
Tanggapan selular untuk merugikan tergantung pada
jenis cedera, dengan durasi, dan tingkat keparahan
Konsekuensi dari cedera juga tergantung pada jenis sel,
status saat ini, dan kemampuan beradaptasi
Empat sistem intraselular yang rentan:
1. integritas membran sel
2. respirasi aerobik
3. sintesis protein
4. integritas aparatus genetik
. Oksigen, oksigen radikal bebas yang berasal dan
kegagalan homeostasis kalsium intraselular

Irreversible cell injury
Mechanisms of irreversible injury:
Inability to reverse mitochondrial dysfunction causing
marked ATP depletion
Development of profound disturbances in membrane
function
Several biochemical mechanisms may contribute to
membrane damage:
1. Loss of membrane phospholipids
2. Mitochondrial dysfunction
3. Cytoskeleton abnormalities
4. reactive oxygen species
5. Lipid breakdown products
6. Loss of intracellular amino acids
Mekanisme dari cedera ireversibel:
Ketidakmampuan untuk membalikkan disfungsi
mitokondria menyebabkan ATP ditandai penipisan
Pengembangan mendalam gangguan dalam fungsi
membran
Beberapa mekanisme biokimia dapat menyebabkan
kerusakan membran:
1. Hilangnya fosfolipid membran
2. Disfungsi mitokondria
3. Sitoskeleton kelainan
4. spesies oksigen reaktif
5. Produk pemecahan lipid
6. Kehilangan asam amino intraselular


Oxygen free radicals:
Superokside : O
2
-
Hidrogenperoksida : H
2
O
2
Ion hidroksil : OH *
Hydrogen peroxide
O
2
-
+ O
2
-
+ 2 H
+

SOD
H
2
O
2
+ O
2
Superoksid { O
2
-
} + enzym ( xanthine oxidase,
cytochrome P-450, dll )
Hidroksil [OH *]
- water hydrolysis due to ion radiation
H
2
O H
*
+ OH
*
- Fenton reaction:
Fe
++
+ H
2
O
2 ---
Fe
+++
+ OH * + OH

- Haber-Weiss reaction:
H
2
O
2
+ O
2
- ---
OH * + OH

+ O
2

Free radical injuced cell injury
Chemicals injury
Mercuri chloride + sulfidril of cellular membrane
Cyanide --- destruction of mitochondria
CCl
4 --
CCL
3
--- ( lipid peroxydase) fatty changes
Acetaminophen [ tylenol ) : toxic metabolite to the
liver
Chemicals cedera
Mercuri klorida + sulfidril dari membran
selular
--- Penghancuran sianida mitokondria
CCl4 - CCL3 --- (lipid peroxydase) - lemak
perubahan
Acetaminophen [Tylenol): metabolit
beracun ke hati

Sub-lethal injury [ reversible injury ]
Hydropic change = cellular swelling , hydropic change
Cellular edema : pale , vacuolated and edema of
cytoplasms
Causa: toxic agent, hypoxia
Reversible
irreversible, in a persistent causa ( mola hidatidosa,
adamantinoma )
Microscopic
membrane = blebbing, blunting
ME :
mikrovilli = distortion
mitokondria = fosfolipid amrof mass , clumping
RE = dilatation, disagregation of polisom
nuclear= disintegration of fibriler element


Sub-mematikan cedera [dibalik cedera]
Hidropik perubahan = selular pembengkakan, perubahan hidropik
Seluler edema: pucat, edema vacuolated dan cytoplasms
Causa: beracun agen, hipoksia
Reversibel
ireversibel, dalam sebuah gigih causa (mola hidatidosa,
adamantinoma)
Mikroskopis
membran = blebbing, menumpulkan
ME:
mikrovilli = distorsi
mitokondria = fosfolipid amrof massa, penggumpalan
RE = dilatasi, disagregation dari polisom
nuklir = disintegrasi fibriler elemen

Hydropic change
Hydropic change in liver tissue
Hydropic change in hydatid mole
Musin degeneration / accumulation
Hialin degeneration of the uterus tumor
Intracell accumulations :

Accumulation of normal cellular materials:
water, lipid, protein dan charbohydrat
Accumulation of abnormal materials:
exogenous and endogenous materials ---
Mineral , metabolism metabolite
Pigmen


Intracell akumulasi:

Akumulasi bahan seluler normal:
air, lemak, protein dan charbohydrat
Akumulasi bahan abnormal:
eksogen dan endogen bahan ---
Mineral, metabolisme metabolit
Pigmen

Fatty accumulation, Fatty change :

Fatty drops accumulation
due to abnormal of ribosomes function
>> liver

Causa : Hypoxia, alcohol

Microscopic:
Fatty drops - vacuola nuclear expanded to
the one side of the cell
Reversible : mild- moderate grade
Irreversible : severe grade

Lemak akumulasi, perubahan Fatty:

Tetes akumulasi lemak
karena abnormal fungsi ribosom
>> Hati

Causa: Hipoksia, alkohol

Mikroskopis:
Lemak tetes - vacuola - nuklir diperluas ke satu sisi sel
Reversibel: ringan-sedang kelas
Ireversibel: kelas berat

Fatty changes
Fatty accumulation of the liver normal liver tissue
Liver, Mallory hialin, alcoholism
Hemosiderin pigmen ( HE stain ) Prusian blue stain
Pigment carbon in the lung tissue
Lung tissue
Skin tissue Melanin pigment in the skin tissue
Bilirubin pigment in the skin and sclera of the eye
Lipofuchsin pigmen ( wear tear pigmen )
Calcification
Calsium accumulation in the organ/ tissues
Dhystrophic calcification :
Locally Calcification in nonviable/ dying tissue
Lithopedion, arteriosclerosis, calcification in
neoplastic processes, necrosis
- metastatic calcification :
Calcification in disturbance of calcium metabolism
Hyper parathyroid hormone, destruction of bone
tissue ( plasmacytoma ), vit. D related disorder, renal
failure

Pengapuran
Calsium akumulasi pada organ / jaringan
Dhystrophic kalsifikasi:
Pengapuran lokal di nonviable / sekarat jaringan
Lithopedion, arteriosclerosis, kalsifikasi dalam proses
neoplastik, nekrosis
- Kalsifikasi metastatik:
Pengapuran dalam gangguan metabolisme kalsium
Hyper paratiroid hormon, kerusakan jaringan tulang
(plasmacytoma), vit. D terkait disorder, gagal ginjal

Disthropic calcification
Calcification in breast cancer
Necrosis :
Morphological changes in the cellular death

Type of necrosis:
enzymatic dygestion liquifaction necrosis
protein denaturation coagulative necrosis

Microscopic : nuclear picnosis, caryorexis, cariolysis
Necrosis:
Morfologis perubahan dalam kematian
selular
Jenis Nekrosis:
dygestion enzimatik liquifaction nekrosis
denaturasi protein nekrosis coagulative

Mikroskopis: picnosis nuklir, caryorexis,
cariolysis
Necrotic tissue
Necrosis:

Coagulative necrosis
Liquefaction necrosis
Caseous necrosis
fat necrosis
Fibrinoid necrosis
gangrenous necrosis

Liquefaction necrosis coagulative necrosis
Coagulative necrosis liquefaction necrosis
Fat necrosis
Fibrinoid necrosis
Caseous necrosis
Gangrenous necrosis
Apoptosis :
Programmed cell death
- Destruction of cells during embriogenesis:
implantation, organogenesis
- homeostasis mechanism: normal cells
population
- Protection : immunologic reaction
- Ageing processes

Apoptosis:
Kematian sel terprogram
- Penghancuran sel selama
embriogenesis: implantasi, organogenesis
- Mekanisme homeostasis: populasi sel-
sel normal
- Perlindungan: reaksi kekebalan
- Penuaan proses

Regulation of cell death
Morphology of apoptosis:
Cellular shrinkage , denses organella
Condensation of chromatin, chromatin
aggregation, nuclear fragmented
apoptotic bodies
Phagocytosis of apoptotic bodies by
macrophages / cellular nearby

Morfologi apoptosis:
Cellular penyusutan, denses organella
Kondensasi kromatin, kromatin agregasi,
terfragmentasi nuklir
apoptotic tubuh
Apoptotic fagositosis dari badan oleh
makrofag / seluler di dekatnya

Adaptation processes:
Hypertrophy
Hyperplasia
Atrophy
Metaplsi
Dysplasi
Morfologi apoptosis:
Cellular penyusutan, denses organella
Kondensasi kromatin, kromatin agregasi,
terfragmentasi nuklir
apoptotic tubuh
Apoptotic fagositosis dari badan oleh
makrofag / seluler di dekatnya

Hyperplasia
Increase of cells number in an organ/ tissue
In an active DNA-synthesizing cells or cells mitoses
Physiologic hyperplasi
hormonal hyperplasi:
Glandular breast proliferation ( puberty,
pregnancy)
Uterus in pregnancy
Compensatoir hyperplasi
Partial hepatectomy
Pathologic hyperplasi:
Endometrial hyperplasi ( hormonal )
growth factor effect on target cells


Peningkatan jumlah sel dalam suatu organ / jaringan
Dalam aktif sintesis DNA sel atau mitosis sel
Fisiologis hyperplasi
hormon hyperplasi:
Kelenjar payudara proliferasi (pubertas, kehamilan)
Kehamilan rahim
Compensatoir hyperplasi
Partial hepatectomy
Patologis hyperplasi:
Endometrium hyperplasi (hormonal)
efek faktor pertumbuhan sel-sel sasaran

Endometrial hyperplasi
endometrium
miometrium
Hypertrophy
Increase in the size of cells - increase in the size of
tissue / organ
No new cells
Increase of cellular syntesis ( not edema )

Hypertrophy :
physiologic: uterus / breast during pregnancy ( hormonal
stimulation )
pathologic : muscular enlargement of the heart / sceletal
muscle ( >>> functional demand )
Peningkatan ukuran sel - peningkatan
ukuran jaringan / organ
Tidak ada sel-sel baru
Kenaikan syntesis selular (tidak edema)

Hipertrofi:
fisiologis: rahim / payudara selama
kehamilan (hormon stimulasi)
patologis: pembesaran otot jantung /
sceletal otot (>>> fungsional permintaan)


Hyperthropy of the heart
Atrophy
Shrinkage in the size of cells by loss of substances
Physiologic atrophy:
- embryogenic structure: thyroglossal duct
- decreased of uterus/ breast size after parturition
Pathologic atrophy:
1. Decreased workload / disuse atrophy
2. loss of inervation
3. diminished blood suply
4. inadequate nutrition
5. loss of endocrine stimulation
6. ageing process
7. pressure


Penyusutan dalam ukuran sel oleh hilangnya zat
Fisiologis atrofi:
- Embryogenic struktur: thyroglossal saluran
- Penurunan dari rahim / ukuran payudara setelah
kelahiran
Patologis atrofi:
1. Penurunan beban kerja / tidak digunakan atrofi
2. kehilangan inervation
3. SUPLY darah berkurang
4. nutrisi yang tidak mencukupi
5. hilangnya stimulasi endokrin
6. proses penuaan
7. tekanan

Testis atrophy Kidney atrophy
Metaplasi
Reversible changes in which one adult cell
type is replaced by another adult cell type
Exp: - columner epithel squamous epithel
( heavy smoker , chronic cervicitis)
- Squamous ep --- columner ep
( Barrets esophagus )
- columner ep --- apocrine ep
( fibrocystic changes of the breast )
- connective tissue metaplasia
Reversibel perubahan di mana satu tipe
sel dewasa digantikan oleh jenis sel
dewasa lain
Exp: - columner epithel - epithel squamous
(Perokok berat, cervicitis kronis)
- Skuamosa ep ep --- columner
(Barrets kerongkongan)
- Apokrin --- columner ep ep
(fibrokistik perubahan dari payudara)
- Metaplasia jaringan ikat


Barets esophagus ( squamous cell --- glandular cells )

Apocrine metaplasia of the breast
Dysplasi
mild moderate severe
Basal cell pro 1/3 2/3- all
liferation

Maturity yes / no yes / no no
Mitosis no/ mild moderate many
Cells atypi mild moderate severe