สาเหตุ[causative agents]

Transcription

สาเหตุ[causative agents]
Disturbances of Cellular Metabolism 1
Injury
พยาธิวิทยาของเซลล:
Pigments
การเปลี่ยนแปลงของเมตาบอลิสมของเซลล
(Cellular Pathology:
Disturbances of cellular metabolism )
ANIMAL
PLANT
Centriole
Plasma mem.
Cell wall
NECROSIS
PATHOLOGIC
Local
Sequestration
Calcification
Lysis (cyst, cavity)
Repair
2O infection
(abscess, gangrene)
Scar
รศ. น.สพ.ดร. วิจิตร บรรลุนารา
CU VET PATH: WB
สาเหตุ [causative agents]
CU VET PATH: WB
a
rn
te
In
[ชนิด & ปริมาณ]
CU VET PATH: WB
Cellular Pathology
External stimuli
2&3. External stimuli
•Oxygen deprivation
•Physic
•Chemicals& drug
•infectious agent
•Immune
•Nutrition
Cell death
APOPTOSIS
Somatic death
Vacuole
Agent
Oncosis
Pyroptosis,
Pyronecrosis
Diffuse
Chloroplast
mitochondria
DEGENRATION
Physiological
inducers
Normal
CU VET PATH: WB
time
uli
tim
S
l
Pathogenesis
REVERSIBLE
[Degeneration]
2. Internal Stimuli;
metabolism, DNA
IRREVERSIBLE
Cell death
1. ชนิดเซลล [Cell type]
Cell transformation
Metaplasia
Lesions
4. ชวงเวลา [Exposure time]
CU VET PATH: WB
Pathogenesis of cell injury & death
1) Ischemic & hypoxic injury
CU VET PATH: WB
General biochemical pathomechanisms
oxidative phosphorylation ในผนังชั้นในของไมโตคอนเดรีย STOP!
swollen
ATP depletion
- Ischemic/reperfusion injury
2) Free radical induced cell injury
3) Chemical induced cell injury
O 2-
Irreversible mitochondrial damage
Ca2+
Na+
Ca2+
Mg2+
K+
Defects in membrane permeability
Assoc. Prof. Dr. Wijit Banlunara
1
Disturbances of Cellular Metabolism 1
CU VET PATH: WB
O2
1) Ischemic & hypoxic injury
- Ischemic/reperfusion injury
Respiratory chain enz.
P450 oxidase
ATP
RER
oxidative phosphorylation STOP!
ATP
CU VET PATH: WB
2) Free radical induced cell injury
H2O + O2
RER
swollen
Anaerobic glycolysis
pH
O 2-
mitochondrial damage
Defects of membrane permea.
Ca2+
Na+
swollen
Peroxisome oxidase
NADPH oxidase
Cytosolic enz.
Ca2+
H2O2
Cell swollen
Catalase
Mg2+
RER
หลุด
H2O
Fenton reaction
GSH
Cell swollen
Na+
Ca2+
H2O
K+
H2O
O2- + OHSOD
Defects in membrane permea.
Lipid peroxidation
DNA & Protein damage
RER หลุด
CU VET PATH: WB
CU VET PATH: WB
3) Chemical induced cell injury
Respiratory chain enz.
P450 oxidase
ATP
RER
Virus induced cell injury
CCl4
swollen
Peroxisome oxidase
NADPH oxidase
Cytosolic enz.
Cytolytic virus
CCl3
+
Cl-
Inclusion body
Duplicate in cells
Virus
-
+ O2
Cell mediated immune response
H2O2
Free radical pathways
Cell swollen
Na+
Ca2+
Defects in membrane permea.
Lipid peroxidation
DNA & Protein damage
Ca2+
K+
RER หลุด
การเสื่อมของโปรตีน (Degeneration of proteins)
1. การเสื่อมของเซลลเนื้อแท
(Parenchymatous degeneration,
cloudy swelling, albuminous degeneration)
2. การเสื่อมของเซลลที่มีการสะสมน้ําในเซลล
3. การเสื่อมแบบไฮอลิน (Hyaline degeneration)
4. การเสื่อมแบบคลายไฟบริน (Fibrinoid degeneration)
5. การเสื่อมแบบเปนเมือก (Mucinous degeneration)
6. การเสื่อมแบบคลายเมือก (Mucoid degeneration)
7. การเสื่อมแบบคลายแปง (Amyloid degeneration)
8. กอนโปรตีนที่พบในไซโตพลาสม (Protein inclusion bodies)
Assoc. Prof. Dr. Wijit Banlunara
Cell lysis
Cytopathic virus
Mg2+
CU VET PATH: WB
(Hydropic degeneration)
Mg2+
K+
Ca2+
Virus
Phagocytosis, endocytosis,
fusion
Cell transform
Cell death
CU VET PATH: WB
1. การเสื่อมของเซลลเนื้อแท
(Parenchymatous degeneration,
cloudy swelling, albuminous degeneration)
อวัยวะบวมโต สีซีด หนาตัดนูน (bulgy)
Swollen cell
เซลลบวม
Cytoplasm -ground glass
ขุนเหมือนกระจกฝา
clumping of ill defined ribosome
(basophilic color) โปรตีนตกตะกอน
Lumen & sinusoid -แคบลง
Parenchymatous cells; liver, kidney
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Disturbances of Cellular Metabolism 1
Cloudy swelling- Parenchymatous swelling
2. การเสื่อมของเซลลที่มีการสะสมน้ําในเซลล
CU VET PATH: WB
(Hydropic degeneration)
Pox, โรคปากและเทาเปอ ย (Foot and mouth disease), น้ํารอนลวก
mild
Intracellular Na+
severe
GROSS --Vesicle
[HP] -Ballooning degeneration
Hydropic degeneration
Liver
H2O
Hydropic degeneration- Gross
Vesicles
Rupture
vesicles
Early vesicle
Swollen &
Fluid filled
[HP] = Severe hydropic degeneration
FMD, epithelium
FMD, pig
Histopath-Ballooning degeneration
FMD, epithelium
Ballooning d.
Vesicle
Fluid-filled= vesicle
Ballooning d.
Assoc. Prof. Dr. Wijit Banlunara
3
Disturbances of Cellular Metabolism 1
CU VET PATH: WB
Hyaline degeneration
Zenker’s degeneration
3. การเสื่อมแบบไฮอลิน (Hyaline degeneration)
ไฮอลินกลามเนื้อ (Muscle hyaline)
Zenker's degeneration
หรือ Waxy D.
ไฮอลินเยื่อเกี่ยวพัน (Connective tissue hyaline D.)
ไฮอลินเยื่อบุ (Epithelial hyaline D.)
Equine azoturia
White muscle disease (Calf)
Stift lamb disease
Captive myopathy
Gross : สีซีด บวมโต
[HP]: ชมพูสด เนื้อเดียว ลายหายไป
Hyaline degeneration
CU VET PATH: WB
ไฮอลินเยื่อเกี่ยวพัน (CNT
hyaline degeneration)
Artheriosclerosis
Chronic inflammation
Scar tissue
ไฮอลินเยื่อบุ (Epithelial hyaline degeneration)
Keratin
Epidermis
Hyperkeratosis -Zn deficiency
Vitamin A deficiency
ไฮอลินเยื่อบุ (Epithelial hyaline degeneration)
CU VET PATH: WB
4. การเสื่อมแบบคลายไฟบริน (Fibrinoid degeneration)
Fibrinoid degeneration
Exudate
Hyaline granules
Assoc. Prof. Dr. Wijit Banlunara
Permeability failure
Malignant catarrhal fever (MCF)-ruminant
Feline infectious peritonitis (FIP)
Swine erysipelas
Uremia
Human-collagen disease group; SLE, Rheumatoid
4
Disturbances of Cellular Metabolism 1
Fibrinoid degeneration
CU VET PATH: WB
5.
การเสื่อมแบบเปนเมือก (Mucinous degeneration)
Mucin
Globlet cell
Bronchial epithelium
Acute rhinitis
Bovine viral diarrhoea
Canine distemper
ยอมสี
H&E-
น้ําเงินจาง
PAS- ชมพูสด
6. การเสื่อมแบบคลายเมือก (Mucoid degeneration)
Mucoid
Myxosarcoma
Myxoma
Myxedema
MCF-ruminant
Mucinous degeneration
Mucoid
degeneration
Myxosarcoma
in Rabbit
Sarcoma cells
Mucoid
Trachea
Bronchi, PAS
Mucoid / mucin degeneration
CU VET PATH: WB
การเสื่อมแบบคลายแปง (Amyloid degeneration)
Amylon- แปง
Amyloidosis-progressive process
โปรตีนเสนใยที่ไมมีกิ่งกานสาขา (non-branching fibrillar protein)
Amyloid light chain (AL) protein
Amyloid associated (AA) protein
Apolipoprotein (AI)
Islet amyloid polypeptide (IAPP) amylin
β-amyloid precursor protein (APP)
ไกลโคโปรตีน P-components
Myxosarcoma
Assoc. Prof. Dr. Wijit Banlunara
Alcian blue
Transthyretin ชนิด mutant form
β2- microglobulin
β2- amyloid protein (A4)
Hormone precusors (procalcitonin, proinsulin)
Prion protein
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Disturbances of Cellular Metabolism 1
CU VET PATH: WB
Special stains -Amyloid
โปรตีนเสนใยที่ไมมีกิ่งกานสาขา (non-branching fibrillar protein)
AL
Light chain
+
BV
Serum AA
lipoprotein (apo E, HDL3)
AA
Blood vessel wall
AI
Islet amyloid polypeptide (IAPP) amylin
long chain break down (37 amino acid)
Amylin
Secretory granules
pancreatic beta cell
Neuron
1% Iodine solution
Methyl violet
Plasma cells
Toluidine blue
Congo red
KMno4 + Congo red
AA
AL & transthyretin
β-amyloid precursor protein (APP)
long chain break down (40, 42 amino acid)
βA
Thioflavin -T หรือ -S
CU VET PATH: WB
ชนิด
LIVER
นํ้าเงิน
แดง (metachromatic)
โพลาไรส -แดง
แดง
โพลาไรส -เขียวแอปเปล
ผลลบ
ผลบวก (แดง)
โพลาไรส -เขียวแอปเปล
LIVER AMYLOIDOSIS
Primary amyloidosis --- AL
Secondary amyloidosis --- AA AI Amylin
Senile amyloidosis --- βA
อวัยวะ ตับ มาม ไต ตับออน
CU VET PATH: WB
ตอมน้ําเหลือง ตอมหมวกไต ลําไส
Space of Disse
ตับโต เปราะแตกงาย สีจาง
sinusoid แคบลง เซลลตับฝอลีบ
SEVERE LIVER AMYLOIDOSIS, duck
H&E
Spleen
Sago
spleen
Congo red
CU VET PATH: WB
Bacon spleen
red pulp
white pulp
Assoc. Prof. Dr. Wijit Banlunara
6
Disturbances of Cellular Metabolism 1
Kidney
AMYLOIDOSIS, Ruminant, Kidney
Glomeruli
Basement mem. of endothelium & epithelium
Interstitial tissue
ผล = Blood vessel damage
RENAL FAILURE
CU VET PATH: WB
Pancreas
Pancreas
Islet of Langerhans’
-Basement mem. of capillary
endothelium
Islet of Langerhans’
-Basement mem. of capillary
endothelium
ผล = Insulin
Diabetes
Congo red
β-A
Meningeal artery-amyloidosis
Brain
-Basement mem. of capillary
endothelium
- Senile plaque
Amyloid core
glia
on
ur
ne
PAM
ผล
= Hemorrhage
Neuronal cell death
Assoc. Prof. Dr. Wijit Banlunara
-amyloid
β
H&E
Congo red
7
Disturbances of Cellular Metabolism 1
Protein inclusion bodies
CU VET PATH: WB
Hyaline droplets
Hyaline casts
Absorption inclusions
-hyaline cast
- hyaline droplets
Renal tubular cell
Secretory inclusions
- Corpora amylacea
- Psammoma bodies
Mammary gland cell
Keratin perls
Calcification
Meningioma
Mammary gland tumor, Copora amylacea
Brain inclusions-Copora amylacea
Axon degeneration
Hippocampus
Protein inclusion bodies
CU VET PATH: WB
Viral inclusion bodies
Inclusions of toxic injury
-Eosinophilic brick-shaped intranuclear
-inclusion bodies
Eosinophilic ICIB
Cowdry A INIB
Brick/block INIB
Chronic lead poisoning
Pox
Inclusions of protein
aggregation disorders
Papilloma
CU VET PATH: WB
การเปลี่ยนแปลงทางเสื่อมของคารโบไฮเดรต
(Glycogen degeneration)
ไกลโคเจน (Glycogen) ในตับและกลามเนื้อ & กลูโคส (Glucose) ในเลือด
glycogen inspissation
ตับ ไต white blood cell, heart muscle
glycogen storage diseases (glycogenoses)-congenital
steroid-induced hepatopathy
diabetes mellitus
ขอบของ vacuole ไมเรียบ
มี glycogen granule ติดอยู
ยอมติดสี PAS
-Neurofibrillary tangles (NFTs)
Assoc. Prof. Dr. Wijit Banlunara
8
Disturbances of Cellular Metabolism 1
Glycogen degeneration
Mild
Glycogen degeneration
การเปลี่ยนแปลงทางเสื่อมของไขมัน
CU VET PATH: WB
(Disturbances in fat metabolism)
neutral fat 3/4
สวนถูกดูดซึมเขาสู
1/4 สวน ดูดซึมผาน portal vein -->
thoracic duct &
ตับ
CU VET PATH: WB
Pathogenesis of fatty change
Excessive lipid metabolism --Fatty liver syndrome, lipidosis
การปลอยไขมันอิสระจากแหลงมากเกินไป
Excessive release of fatty acid) --Serous atrophy
(depot fat)
subcutis, Brisket, perirenal fat, Jowl, coronary fat,
omentum, orbital fat, mesentery, bone marrow
lipotrophic factor
เชน choline
Severe, steroid, Liver, PAS
Severe, steroid, Liver
phosphorylation
phospholipid
การลดการใชหรือการออกซิเดชั่นของกรดไขมัน
Decreased utilization or oxidation of fatty acid
-centrolobular zone
การขาด cofactor เชน choline & methionine
กรดไขมันถูกเหนี่ยวนําใหเกิดการ esterified เปน triglycerides
เกิดจากการเพิ่มระดับของ α-glycerophosphate
ความบกพรองของการสังเคราะห apoprotein
ความบกพรองของการหลั่ง lipoprotein จากตับ
CU VET PATH: WB
Fatty change, fatty degeneration,lipidosis
Gross
Fatty change
อวัยวะบวม
ลายสีเหลือง-กลามเนื้อหัวใจ = "thrush breast”
Yellow-tan, เปราะ
Serous atrophy
– fat replaced by fluid
Histopathology
Fatty degeneration
Fat droplets ใน epithelial cells;
proximal convuluted tubules
ascending loops of Henle
except; ไต & adrenal cortex ของ
แมว เสือ สิงโต และสุนัขปา
Fatty infiltration
Stromal fatty infiltrationl
อวน!
Lipocyte แทรกตามเนื้อเยื่อ
หัวใจ ตับออน กลามเนือ้
มักพบชัดเจนที่ coronary fat
& bone marrow (depot fat)
Assoc. Prof. Dr. Wijit Banlunara
9
Disturbances of Cellular Metabolism 1
CU VET PATH: WB
Severe centrolobular
fatty change
Pattern of Fatty degeneration
Portal triad
Centrolobular fatty degeneration;
CV
hypoxia, anemia, heart failure
NUT MEG LIVER
Peripheral fatty degeneration;
stravation, mild toxic
Panlobular fatty degeneratio;
toxemia, strong toxic, pregnancy toxemia,
bacterial toxin , hepatic lipidosis
Severe panlobular fatty change
Severe panlobular fatty change
Severe panlobular fatty degeneration
Special stain for fat
*OIL RED O
Sudan III &IV
Scharlach R
Osmic acid
Nile blue sulfate
CU VET PATH: WB
RED
BLACK
Effect of fatty change
Spontaneous rupture cell death
Liver enzyme (ALT, AST) increased
Assoc. Prof. Dr. Wijit Banlunara
10
Disturbances of Cellular Metabolism 1
คีโตซีส (Ketosis) ในวัว
CU VET PATH: WB
CU VET PATH: WB
การสะสมแคลเซียม (Calcification)
Normal blood Ca 2+ = 9-11 mg%, P=4-6 mg%
Parathomone
Ca 2+
Blood
Calcitonin
Kidney
Bone
Ketone bodies = acetone, di-acetic acid, β-hydroxy butyric acid
เปนสาร intermediate ในการสันดาปของไขมัน (Kreb's cycle)
Over release of fatty acid
Blood glucose decreased
(Stravation)
Lack of Co-enzyme A
Cobalt deficiency
Stress
Thyroid hormone reduced
Liver damage
Gluconeogenesis
Fatty acid
การสะสมของแคลเซียมเฉพาะที่หรือเฉพาะแหง
(Dystrophic or local calcification)
KETONE
Ca 2+
Glucose
Liver -fatty change
Tubercle (in T.B.)
การสะสมของแคลเซียมเฉพาะทีห่ รือเฉพาะแหง
Skin
Calcinosis circumscripta
การสะสมของแคลเซียมเฉพาะทีห่ รือเฉพาะแหง
(Dystrophic or local calcification)
(Dystrophic or local calcification)
Skin
Calcinosis
circumscripta
CU VET PATH: WB
“Osteorenal syndrome”
การสะสมของแคลเซียม แพรกระจายทั่วรางกาย
(Metastatic or generalized calcification)
Hypercalcemia
Blood
P Ca
P
Hypervitaminosis-D
Parathyroid tumor/hyperplasia
Bone tumor ; osteosarcoma
Plants; Solanum, Cestrum และ Trisetum
Calcium-sequestering bacterias
Chronic interstitial nephritis;
renal failure (uremia)
“Osteorenal syndrome”
Assoc. Prof. Dr. Wijit Banlunara
Parathyroid gland
CU VET PATH: WB
Bone
Ca
Contracted kidney
Generalized/metastatic calcification
Kidney- renal tubule
Lung- elastic fiber of alveoli, bronchial cartilage
Costal pleura- intercostal muscle & elastic fibers
Blood vessel- subintema
Stomach- submucosa & mucosa
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Disturbances of Cellular Metabolism 1
Osteorenal syndrome
erosion
Osteorenal syndrome
Hyaline degeneration
Contracted kidney
Gastric hemorrhage
Osteorenal syndrome
Generalized/metastatic calcification
Zenker’s degeneration hemorrhage
Generalized/metastatic calcification
Assoc. Prof. Dr. Wijit Banlunara
Generalized/metastatic calcification
12
Disturbances of Cellular Metabolism 1
การสะสมของเกลือยูเรทและกรดยูริค
CU VET PATH: WB
(Deposition of urate and uric acid)
(LIVER) purine: uric acid, urate
uricase
allantoin
เกาต (Gout) -สัตวปก งู สัตวเลี้ยงลูกดวยนม-คน ลิง ชะนี สุนัขพันธุดัลเมเชี่ยน
สัตวเลี้ยงลูกดวยนม
1) มีกรดยูริคมากเพราะกินโปรตีนมาก
2) ขาดเอนไซมยูริเคทที่ตับ
3) ถูกขับออกนอยเนื่องจากไตเสียหาย
สัตวปก
1) กินอาหารโปรตีนเพิ่มขึน้
2) การขาดไวตามินเอ
3) กรรมพันธุ
Articular gout (ที่ขอ) -foot, hock ขอบวมโต แข็ง เดินกระเพลก
Visceral gout (อวัยวะภายใน) -ไต ตับ ถุงหุมหัวใจ
Tophus- articular gout
CU VET PATH: WB
Gross = "Tophus" เกลือยูเรทสีขาวคลายชอลก
[HP] urate-พัดจีน (fan shaped)
มาโครฟาจ foreign body giant cells
foreign body giant cells
มาโครฟาจ
urate
Chronic foreign body inflammation -- granuloma
Pseudogout หรือ chondrocalcinosis
calcium pyrophosphate dihydrate & hydroxyapatite
Articular pseudogout สุนัขและลิงแสม
ในสุนัขมักพบที่ขอตอของนิ้ว
Visceral gout- kidney
เอาไกชนใสแทน
Visceral gout- kidney
Giant cells
foreign body giant cells
macrophage
urate
Tuberculosis-tubercle
Caseous necrosis
Dystrophic calcification Ca
2+
Langhans’ giant cells
Urate-FAN shaped-like
Foreign body giant cells
Gout granuloma
Assoc. Prof. Dr. Wijit Banlunara
Touton giant cells in Xanthomatous lesion
13
Disturbances of Cellular Metabolism 1
CELL DEATH
CU VET PATH: WB
1842 Carl Vogt
1858 KH Schultz in Lecture XV of Virchow’s
Cellular Pathology “Necrobiosis”
1879 Karyorhexis & Karyolysis
1890 Pyknosis
1877 Weigert C. & Cohnheim J. Coagulative necrosis
1900 Klebs E. “Autolysis”
……… Chromatopyknosis….
1972 Kerr JFR, Wyllie AH., Currie AR
= the first published research document-Apoptosis
Apoptosis (Greek); Apo- & -ptosis
dropping off -falling leaves
2005 Pyroptosis
2007 Pyronecrosis
CU VET PATH: WB
CELL DEATH
PCD
CELL DEATH
1. Apoptosis
Necrobiosis
Physiological cell death
-inducers
Programmed cell death -time dependent (clock)
-embryo
3. Pyroptosis - caspase 1 dying pathway
4. Pyronecrosis – caspase independent
2. Necrosis (Greek)= make death เนื้อตาย
“Inflammation=ขบวนการอักเสบ”
Oncosis -Onkos = swelling
Comparison of cell death pathways
CU VET PATH: WB
Oncosis
Pyroptosis
APOPTOSIS
CU VET PATH: WB
NECROSIS
Pyronecrosis
Nature reviews | immunology | May 2008 V.8;372-379
RECENT CELL DEATH 2008
CU VET PATH: WB
Normal cell
Caspases
Mitochondria
Lysosome
NECROSIS
APOPTOSIS
Caspases family
1972
1858
2005
2007
Shrinkage
PYROPTOSIS
Caspase‐1 activation
PYRONECROSIS
ASC activation
Cathepsin B
Oncosis
Chromatolysis
Pyronecrosis
Caspaseindependent
ASC
Condensation
Fragmentation
Budding
Nuclear hyperchromatosis
DNA damage
Release inflammatory cytokines
Karyopyknosis
Lysosome rupture
Karyorhexis
DNA damage
Release inflammatory cytokines
Lysosome rupture
Karyorhexis
Apoptotic body
Karyorhexis
Release inflammatory content
Cell rupture
Release inflammatory content
Cell rupture
Karyolysis
Infect. Immun
2005, 73(4):
1907-1916.
Assoc. Prof. Dr. Wijit Banlunara
Phagocyted by adjacent cells, eg.; macrophages
Cell death
Inflammation
14
Disturbances of Cellular Metabolism 1
Sculping;
Programmed cell death
CU VET PATH: WB
wing web, intestinal lumen
Deleting structures
; tapode tail,
sex organs(Mullerian/ Wallerian duct)
Adjusting cell numbers; brain
กลไกการเกิดอะพอฟโตซิส
CU VET PATH: WB
(Pathomechanism of apoptosis)
Eliminating dangerous,
non-functional, misplaced,
injured cells; abnormal cells
CU VET PATH: WB
1) ระยะกระตุนเซลล (Signaling pathways)
TNF-TNFR family
[ Fas-Fas ligand (CD95-CD95L), TNF-TNFR ]
2) ระยะควบคุมและประสานงานภายในเซลล
(Control and integration stages)
Cytochrome-C
Pro-apoptotic protease activating
factors (Apaf-1)
Caspase
3) ระยะเปลี่ยนแปลงรูปรางของเซลล (The execution phase)
Caspase 8,9
enzyme activation
“Apoptotic body”
4) ขั้นตอนการเก็บกอนอะพอฟโตซิสออกไป
(removal of apoptotic bodies)
phosphatidylserine, thrombospodin, adhesive glycoprotein
macrophages (phagocytosis)
CU VET PATH: WB
APOPTOSIS & NECROSIS
APOPTOSIS
NECROSIS
Mechanism & induction
Active
Physiological death
Passive
Pathological death
Activation signals
Intracellular communication
Cell destruction
Cell injury
Biochemical event
Completed apoptosis mechanism
APOPTOSIS & NECROSIS 2
Cell shrinkage
Membrane bleb
Cell frag. to APOPTOTIC bodies*
Lysosome intact
Mitochondria intact
Nucleus
Early chromatin
condensation
Chromatin fragmentation
Loss membrane integrity
DNA fragmentation
* ใน
NO
NO
NO
NO
Random DNA digestion
CU VET PATH: WB
APOPTOSIS
NECROSIS
Cellular morphology
Cytoplasm
Require protein/nucleic a. synthesis
Require new gene expression
Requires energy -ATP
Regulation of process/homeostasis
Non-random DNA fragment (cut)
Swelling
Loss cell mem. integrity
Efflux intracellular content
Lysosome- leak
Mitochondria swelling
Late nuclear dissociation
Clump, ill-defined aggregation of
chromatin
CU VET PATH: WB
APOPTOSIS & NECROSIS 3
APOPTOSIS
NECROSIS
Pathologic results
Deletion of single cell
Death of cell groups
No inflammation response
Significant inflam.
Apoptotic cells phagocyted
by neighbouring cells
“ Schwesterzellen”
Cellular cannibalism
Bystender cell death
Tissue lesions
Scaring
Hepatocytes เรียก Councilman bodies
Assoc. Prof. Dr. Wijit Banlunara
15
Disturbances of Cellular Metabolism 1
CU VET PATH: WB
How a Cell Commits Suicide: graphics
CU VET PATH: WB
Method : DNA fragmentation (biochemistry)
(Agarose gel electrophoresis)
T-2 toxin induced mouse-thymic apoptosis experiment
http://www.critpath.org/aric/library/img007.htm
CU VET PATH: WB
Electron microscopy:TEM
CU VET PATH: WB
Electron microscopy: SEM
DNA fragmentation & Budding
Apoptotic body
Normal
Cytoplasmic blebing
Necrosis
5-Azacytidine induced brain cell apoptosis; dose dependent
T-2 toxin induced apoptosis in mouse thymus
CU VET PATH: WB
T-2 toxin induced apoptosis
CU VET PATH: WB
Method for detection of the DNA fragmentation in situ;
(DNA nick-translation, TUNEL method)
Cortex
Mice , thymus
Assoc. Prof. Dr. Wijit Banlunara
16
Disturbances of Cellular Metabolism 1
CU VET PATH: WB
Apoptosis of thymic lymphocytes
Apoptosis of thymic lymphocytes
CU VET PATH: WB
MØ phagocyted apoptotic bodies
Apoptotic bodies phagocyted by MØ
Apoptosis in tumor
Councilman body
NECROSIS
CU VET PATH: WB
Fumonisin, mouse liver
CU VET PATH: WB
PCV-2 viral infection, pig liver
CU VET PATH: WB
CU VET PATH: WB
1. Coagulative necrosis เนื้อตายแบบแข็งตัว
2
1
3. Normal
2. Demarkation zone
Hyperremia; RBC WBC
1. Necrotic zone
3
embolism
Anemic infarct ; kidney
TUNEL
1
2
3
embolism
Hemorrhagic infarct
Blood riched tissue;spleen
Eosinophilic globules; smaller with peripheral clear zone
American Pathologist: William T. Councilman (1854-1933): Yellow fever
Assoc. Prof. Dr. Wijit Banlunara
17
Disturbances of Cellular Metabolism 1
Multifocal white foci; Salmonellosis, pig liver
CU VET PATH: WB
CU VET PATH: WB
Karyopyknosis
Karyorhexis
Karyolysis
Coagulative necrosis
Hemorrhagic infarct
Anemic Infarction
CU VET PATH: WB
CU VET PATH: WB
Coagulative necrosis
Coagulative necrosis
CU VET PATH: WB
CU VET PATH: WB
Thrombus in blood vessel
[HP]=Coagulative necrosis; kidney
Assoc. Prof. Dr. Wijit Banlunara
18
Disturbances of Cellular Metabolism 1
NECROSIS
NECROSIS
CU VET PATH: WB
2. Liquefactive necrosis เนื้อตายแบบเหลวตัว
ENCEPHALOMALACIA
CU VET PATH: WB
Phospholipid rich tissue; Brain
ENCEPHALOMALACIA
Mφ engulfed debri called : GITTER CELL
FOAM CELL
ENCEPHALOMALACIA
CU VET PATH: WB
Liquefactive necrosis
NECROSIS
NECROSIS
CU VET PATH: WB
3. Caseous necrosis เนื้อตายแบบเนยแข็ง
3
2
1
Calcium deposit
(Dystrophic calcification)
CU VET PATH: WB
Gitter cell (foam cell)
Caseous necrosis
CU VET PATH: WB
3. Fibrous tissue
2. Proliferative zone
Giant cells, Mφ, plasma cell,
lymphocytes
1. Necrotic zone
Mycobacteriosis: Mycobacterium sp.
Tuberculosis: M. tuberculosis
Pseudotuberculosis:
Corynebacterium pseudotuberculosis
Melloidosis:
Burkholderia pseudomallei
(Pseudomonas)
Assoc. Prof. Dr. Wijit Banlunara
Liquefactive necrosis
LN, TB, Cow
19
Disturbances of Cellular Metabolism 1
Caseous necrosis
CU VET PATH: WB
CU VET PATH: WB
Caseous necrosis
Melloidosis:
Burkholderia pseudomallei
Caseous necrosis
LN, TB, Pig
CU VET PATH: WB
Lung, TB, Cow
Lung, TB, Deer
Granuloma; caseous necrosis
CU VET PATH: WB
LN, TB, Deer
Granuloma; caseous necrosis
CU VET PATH: WB
NECROSIS
NECROSIS
CU VET PATH: WB
4. Necrosis of fat เนื้อตายของไขมัน
Traumatic fat necrosis
Enzymatic fat necrosis (pancreatic necrosis of fat)
FAT
Fatty acid + glycerol
lipase
Exocrine pancreas
+ Na 2+, Ca 2+, K +
Saponification = soap
Liver, TB, Gecko
Assoc. Prof. Dr. Wijit Banlunara
20
Disturbances of Cellular Metabolism 1
Necrosis of fat
CU VET PATH: WB
ชองทอง,
Enzymatic fat necrosis
(Pancreatic necrosis of fat)
CU VET PATH: WB
pancreas, Dog & cat
NECROSIS
NECROSIS
CU VET PATH: WB
5. Zenker’s necrosis การตายของกลามเนื้อลาย
Zenker’s necrosis
CU VET PATH: WB
Hyaline degeneration
Zenker’s necrosis
Dystrophic calcification
Cause;
Trauma
Drug; Monensin
Diseases; FMD, Parvovirus
Zenker’s degeneration
NECROSIS
NECROSIS
CU VET PATH: WB
6. Gangrene เนื้อตายแกงกรีน
Coagulative necrosis
+ pertrefaction (การเนา)
Zenker’s necrosis
Moist Gangrene
CU VET PATH: WB
Sapremia/ toxemia
Moist Gangrene เนื้อตายแกงกรีนแบบเปยก
ปอด ลําไส (intussusception, volvulus) เตานม
Dry Gangrene เนื้อตายแกงกรีนแบบแหง
ปลายอวัยวะ
Gas Gangrene เนื้อตายแกงกรีนแบบแกซ
Anaerobic bacterias (Clostridium)
Malignant edema, Black leg
Assoc. Prof. Dr. Wijit Banlunara
21
Disturbances of Cellular Metabolism 1
Dry Gangrene
NECROSIS
NECROSIS
CU VET PATH: WB
Dry Gangrene
CU VET PATH: WB
ผลที่ตามมาจาก necrosis
CU VET PATH: WB
CU VET PATH: WB
Cholesterol cleft in mammary
gland tumor
SCAR
Liquefaction
Cyst-like accumulation
Encapsulation without liquefaction
desquamation or sloughing
Replacing by scar/ regeneration
Calcification
Atrophy/somatic death
Cholesterol clefts
DEATH
Pigments
Artifact pigment
Formalin pigment
Mercury pigment
Chrome pigment
Non-artifact pigment
Exogeneous pigment
Endogeneous pigment
EX. Carbon = Anthracosis
Metal ; Silicosis, Asbestosis, Berylliosis
Plant fibers
Lead
EN. Heme derivatives
Hemosiderin
Aposiderin
Ferritin
Bile pigment
Parasitic pigment
Hamatin
Porphyrin
Assoc. Prof. Dr. Wijit Banlunara
CU VET PATH: WB
Phenolic
Phenolic derivatives
derivatives
Melanin
Melanin
Adenochrome
Adenochrome
Onchronosis
Onchronosis
Lipid
Lipid derivatives
derivatives
Ceroid
Ceroid
Lipofuscin
Lipofuscin
Carotenoid
Carotenoid
Dust, clay
Tatto ink
Drugs (Tetracycline)
Artifact pigment
CU VET PATH: WB
On the top of or between cells อยูบนหรือระหวางเซลล
Some fixative solution
เกิดจากสารแชเปนสวนใหญ
1) Formalin pigment
Dark brown crystalline ผลึกน้ําตาลเขม
acidic formaldehyde solution =Blood rich tissues
remove with alcoholic picric acid
22
Disturbances of Cellular Metabolism 1
1) Formalin pigment
Artifact
Artifact pigment
pigment
CU VET PATH: WB
2) Mercury pigment
• browm or gray-black granular เม็ดสีน้ําตาล-เทาดํา
• used mercurial fixative
สารปรอท
ตามดวย sodium thiosulfate
• กําจัดโดยแช alcoholic picric acid
3) Chrome pigment
• Chromate fixative; Zenker’s or Helly’s
• Brownish-black granules เม็ดสีน้ําตาลดําหยาบ
• Prevent by running in water (2-3hr) before
dehydration in alcohol
Exogenous Pigments
Anthracosis
CU VET PATH: WB
Carbon = Anthracosis
Dust, clay= kaolinosis
Metal ; Silicosis, Asbestosis, Berylliosis
[ Pneumoconiosis]
Granulomatous Pneumonia
Plant fibers, oxalate =oxalosis
Tatto ink
Lead (Plumbish,lead line)
Silver (Argyria)
Drugs (Tetracycline)
Sulfonamide crystal
Anthracosis
Endogeneous P. : Phenolic pigments
CU VET PATH: WB
A. Melanin (1)
Melanocytes
(melanosome)
Melanophages
(melanophore)
Aromatic amino acids; Phenyl-alanine, tyrosine,
Dihydroxyphenyl-alanine (DOPA)
DOPA oxidase
MELANIN
การทดสอบ
Lung
Assoc. Prof. Dr. Wijit Banlunara
Lymph node
1. DOPA reaction DOPA buffer
2. Masson Fontana stain, Gomori’s Methanamine stain
brownish black granule
3. Warthin -Starry pH 3.2 stain
23
Disturbances of Cellular Metabolism 1
Endogeneous P. : Phenolic pigments
CU VET PATH: WB
A. Melanin (2)
Malignant Melanoma
ตําแหนงที่พบ
Skin, retina, uveal tract, leptomeninge,
CNS (Substantia nigra; neuromelanin)
ปญหาของ melanin
Melanosis
Melanoma
Pregnant -black nipple
Addison’s disease
Acanthosis nigricans
Hyperpigmentation of skin (Hormonal imbalance)
Neck, Dog
Malignant Melanoma
Malignant
Malignant Melanoma
Melanoma
Tail, horse
Malignant Melanoma
Melanosis- Brain - Cattle
Masson Fontana
Assoc. Prof. Dr. Wijit Banlunara
24
Disturbances of Cellular Metabolism 1
Melanosis-
Liver – Aldabra tortoise
Endogeneous P. : Phenolic pigments
CU VET PATH: WB
B. Adenochrome, Noradenochrome
Adrenal gland fixed in Potassium dichromate
Quinone - brown granules in adrenal medulla
C. Chromatophore pigment
Amphibian & reptile
Xanthrophore (แดง)
refractile irridophore
Endogeneous P. : Hematogeneous pigments
CU VET PATH: WB
A. Hemoglobin
Endogeneous P. : Hematogeneous pigments
CU VET PATH: WB
Endogeneous P. : Hematogeneous pigments
CU VET PATH: WB
A. Hemoglobin
In mononuclear phagocytes, renal tubules
other tissues (hemorrhage)- yellow color
การทดสอบ
1. Benzidine method
Peroxidase activity of hemoglobin and its derivatives
oxidize
Benzidine (blue)
Blue quinhydrone (brown)
2. Dunn-Thomson hemoglobin stain
ยอมดวย Hematoxylin + picrifuscin
Hemoglobin, RBC
emerald green
3. Okajima’s stain Hemoglobin
orange red
Endogeneous P. : Hematogeneous pigments
CU VET PATH: WB
B. Hemosiderin
= Ferric hydroxide (Fe(OH)3) + ferritin
Shiny granules ; yellow-brown & golden brown
(เหลืองแกมน้ําตาล - น้ําตาลทอง)
RBC, hemoglobin
Hemosiderin (Fe+)
B. Hemosiderin (2)
HEMOSIDEROSIS
= hemosiderin in Mφ - ปอด ตับ มาม (Gandy-gamma spleen)
สาเหตุ = chronic hemolytic anemia, Congestive heart failure
lung edema
RBC hemolysis
เก็บกิน by PAMs “HEART
HEART FAILURE CELLS”
CELLS
Mφ = ปอด ตับ มาม ไต ตอมน้ําเหลือง & hematoma
HEMOCHROMATOSIS
การสะสม Hemosiderin-like pigment ในเซลลตับ
MAN-- พบในตับ กรณี Cirrhosis
HORSE--Kidney “Equine infectious anemia” EIAs
Assoc. Prof. Dr. Wijit Banlunara
25
Disturbances of Cellular Metabolism 1
Endogeneous P. : Hematogeneous pigments
การทดสอบ
CU VET PATH: WB
B. Hemosiderin (3)
Endogeneous P. : Hematogeneous pigments
CU VET PATH: WB
B. Hemosiderin (2)
HEMOSIDEROSIS
1. Perl’s prussian blue reaction
Inorganic iron + potassium ferrocyanide in acid soln
Fe2+
Gandy-gamma spleen
Ferric ferrocyanide (Prussian blue)
2. Turnbull blue reaction
Ferrous iron + potassium ferricyanide
Ferrous ferricyanide (turnbull blue)
3. Quincke-Tirmann-Schmeizer method
Ferrous ferricyanide (turnbull blue)
4. Malloy’s method
Hemosiderotic plaque
Blue-black น้ําเงินใส = copper
SpleenSpleen-HEMOSIDERIN
H&E
Renal tubule
Hyaline cast
Assoc. Prof. Dr. Wijit Banlunara
Perl’s prussian blue
LUNG
Heart failure cells
HEMOSIDEROSIS in LN
H&E
RENAL TUBULAR CELLSCELLS-HEMOSIDERIN
Perl’
Perl’s stain
26
Disturbances of Cellular Metabolism 1
Endogeneous P. : Hematogeneous pigments
PancreasPancreas-HEMOSIDERIN
CU VET PATH: WB
C. Aposiderin
Brown granules
-ve for ALL hemosiderin test
in kidney tubule
D. Ferritin
Iron-apoferritin complex
storage form of iron
not hemosiderin
Endogeneous P. : Hematogeneous pigments
CU VET PATH: WB
E. Bile pigment (1)
Iron
Hemoglobin
Endogeneous P. : Hematogeneous pigments
E. Bile pigment (2)
globin
Bile pigment =bilirubin
Bright yellow
straight chain tetrapyrrole
Biliverdin
Free bilirubin in plasma
Liver
Kidney
Bilirubin glucoronide
Enterohepatic
circulation
glucoronic acid
Bile duct
conjugated bilirubin
urobilinogen
intestine
Urine urobilinogen
urobilin
Free bilirubin ไมละลายน้ํา ไมกรองผานไต Hemolytic Jaundice : free bilirubin
Conjugated bilirubin ละลายน้ํา กรองผานไต Obstructive Jaundice: conjugated b.
Bile obstruction-Icterus
obstruction
obstruction-Icterus
Assoc. Prof. Dr. Wijit Banlunara
CU VET PATH: WB
การทดสอบ
Oxidation of bilirubin
biliverdin (blue-green)
Stein’s bile stain
Gmelin reaction
Hall’s technique
Hematoidin Yellow brown crystals
site of old hemorrhage
Bile obstructionobstruction-Icterus
27
Disturbances of Cellular Metabolism 1
Bile obstructionobstruction-Icterus
Endogeneous P. : Hematogeneous pigments
CU VET PATH: WB
F. Hematin (1)
Formalin pigment
•Hemoglobin +acid in fixative (reaction)
•Fine granular, anisotropic dark-brown pigment
้ ใน tissue ที่ไมแชใน buffered formalin
•ACID FORMALIN HEMATIN -เกิดขึน
•พบมากใน blood-rich tissues
Parasitic pigments
Malarial pigment
dark brown granules , iron test -ve , ไมสะทอนแสง
Pneumonyssus simicola pigment
brown or colorless needle like and fine brown granule
สะทอนแสง
Endogeneous P. : Hematogeneous pigments
CU VET PATH: WB
F. Hematin (2)
Fluke pigment, liver
Fluke pigment
Fasciola magna, F. hepatica
in macrophages in liver and LN
not well-characterized
Schistosomal pigment
similar to malarial pigments
Schistosoma sp.
Endogeneous P. : Hematogeneous pigments
CU VET PATH: WB
Endogeneous P. : Hematogeneous pigments
G. Porphyrin
Photosensitizing pigment
•Product of hemoglobin or Chlorophil
•blood, tissue เรียก PORPHYRIA
face, head, back ,ear (มีขนนอย)
CU VET PATH: WB
G.1) Primary Porphyria, I
Normal liver
Eat Chlorophyll -Photosensitization pigment
Plant; Helianthrones, Furocoumarins
Drugs; Phenothiazine (ยาถายพยาธิ์ )
Photosensitizing dermatitis
แกะ
Porphyria 3 types;
Congenital Porphyria, II
Primary Porphyria, I
Hepatotoxic Porphyria, III
Assoc. Prof. Dr. Wijit Banlunara
Acquired Porphyria
FACIAL ECZEMA (NZ)
Geeldikhop / Bighead (SA)
ลักษณะ --หู หนาบวม คางบวม ผิวหนังอักเสบแดง
28
Disturbances of Cellular Metabolism 1
Endogeneous P. : Hematogeneous pigments
CU VET PATH: WB
G.2) Congenital Porphyria, II
Metabolic defect of breakdown
Endogeneous P. : Hematogeneous pigments
CU VET PATH: WB
G.3) Hepatotoxic Porphyria, III
Acute / chronic hepatic diseases
Uroporphyrin III & Coproporphyrin III
Accumulation of Chlorophyll metabolite;
Phylloerythrin
face, head, back ,ear (มีขนนอย)
Photosensitizing dermatitis
face, head, back ,ear (มีขนนอย)
Cattle, Swine, Cat
•Teeth
PINK TOOTH (Osteohemochromatosis)
•UV Lamp
red fluorescent
•Urine
Porphyrinuria
G.2) Congenital Porphyria, II
Endogeneous P. : lipogenic pigments
CU VET PATH: WB
1) Lipofuscin
Unsaturated lipids
Peroxidation/
polymerization
Photosensitizing dermatitis
G.2) Congenital Porphyria, II
Ceroid-lipofuscinosis
Lipofuscin
Aging pigment Wear and tear pigment
Brown pigment Waste pigment
•Lipoprotein/ iron (-) in lysosome
•Yellow brown granules
•Brownish-flourescence (UV)
•Neurons, muscle, liver, testicular cells, Adrenal gland
•Steatorrhoea ( smooth muscle of intestine)
•black kidney (cow)
1. Periodic acid Shiff’s reaction (PAS) = + (PINK)
TEST 2. Acid fast = + (PINK)
3. Schmorl’s reaction = + (pale blue)
Assoc. Prof. Dr. Wijit Banlunara
Dog Brain,18Y,H&E
Dog Brain,18Y,PAS
29
Disturbances of Cellular Metabolism 1
Ceroid-lipofuscinosis
Endogeneous P. : lipogenic pigments
CU VET PATH: WB
2) Ceroid
•Yellow-brown pigment
•Mixture of lipofuscin-like substance
(early stage of lipofuscin?)
•Neurons, muscle, liver, testicular cells, Adrenal gland
•Cirrhosis
•Yellow fat disease/brown dog gut (Vitamin E deficiency)
• Choline deficiency
•Ceroid-lipofuscinosis (res.gene)
• Hepatic ceroidosis in salmon (red-brown)
•Sudan, Acid fast
Dog Brain,18Y,LFB
Dog Brain,18Y,PAS
Yellow fat disease/brown dog gut
Cat, visceral
Ceroidosis
Dog Int.,H&E
Assoc. Prof. Dr. Wijit Banlunara
= positive
•PAS, Prussian blue =varible
•Greenish-yellow-flourescence (UV)
Yellow fat disease/brown dog gut
Omentum, H&E
Acid fast
Ceroidosis
Dog Int.,PAS
30
Disturbances of Cellular Metabolism 1
Endogeneous P. : lipogenic pigments
CU VET PATH: WB
3.) Carotenoids
HP conclusion
Pigments
Location
H&E
Spec. stain
CU VET PATH: WB
Remark
Carbon
Mφ , LN, LU
Black
-
Formalin
crystal on top
Dark brown
wash-picric acid Artifact
•Yellowish to yellowish red tissue
Hemosiderin
Mφ , Sp, LN
Gloden brown
•Corpus lutea, Adrenal cortex
Bile
Liver, Kidney
bright yellow
Prussian blue Hemosiderosis
Heart failure cell
Stein’s/ Gmelin Jaundice/icterus
•Greenish flourescence (UV)
Porphyrin
Lipid derivatives of color hydrocarbon
•Strong acid: blue green or violet color
Melanin
Lipofuscin
& Ceroid
Skin etc.
-
yellow-brown
to black
CNS, muscle etc. yellow to brown
Anthracosis
UV-red
Porphyria
Masson fontana Melanosis
Melanoma
PAS, Acid fast
Wear& tear
pigment
Note; Mφ-macrophage, LN-lymph node, Lu-lung, Sp-spleen
Assoc. Prof. Dr. Wijit Banlunara
31

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