General Pathology
Pathology of Organels I.
– Introduction
The Secretory
Process
and
Its DisordersInst. Pathol. ,1st Med. Faculty, Charles Univ. Prague
Jaroslava Dušková
http://pau.lf1.cuni.cz/en/texts-from-the-lectures-and-seminars-presentations
Pathology of Organels I - table of contents
Cell components & their function
Pathomorphology of the cell nucleus
quantitative
qualitative
Pathomorphology of the cytoplasm
cytosol
organelles
intracellular accumulations
water
proteins
lipids
glycogen
pigments,foreign bodies
Cellular secretion
types
organelles involved
sense
The Cell Components &Their Function
1. nucleus (incl. nucleolus and
nuclear envelope)
2. cytoplasm
cytoplasmic matrix
cytoplasmic organelles
3. plasma membranes
Main Cell
Organelles
The Cell Components &Their Function
The nucleus(incl. nucleolus and nuclear
envelope)
chromosomes
DNA, RNA, histones
Nuclear envelope
with pores
The Cell Components &Their Function
The nucleus functions
– cell division
– genetic information
transcription & control
Cell Nucleus Pathology (1)
Related to genom changes
quantitative:
– binucleation, multinucleation – regular
polyploidy (4n, 8n… 2nn) - reactive change eg.
in inflammation –adaptation
qualitative:
– translocations, deletions, amplifications –
aneuploidy – often in neoplasms
(DNA densitometry, FISH, CGH…)
Neoplasia (Tumour)
DNA disease
Stepwise accumulation
of genetic abnormalities
Escape of immunological
clearing systems
Neoplasia (Tumour)
DNA disease Stepwise accumulation of genetic abnormalities
self sufficiency in growth sighnals
insensitivity to anti-growth signals
limitless replicative potential
sustained angiogenesis
tissue invasion and metastasis
Escape of immunological clearing systems
evading apoptosis
L SIL
CIN I
p16INK4a protein
inhibitor of cyclin
dependent kinase
controled in healthy
cells – undetectable
overexpressed as a
result of HPV E7
protein
MARKER OF
DYSPLASTIC CELLS
Apoptotic bodies
ATM/p53 Signaling Pathway
Ca ovarii MIB1 (Ki67)
Ca ovarii p53
Lymphocyti &
mesothelia
Carcinosis
peritonei
Pleuritis
carcinomatosa
AgNOR
Alc. Blue pH2,5
CSF carcinosis
Cell Nucleus Pathology (2)
Related to nucleolemma
quantitative:
– invaginations - pseudoinclusions
qualitative:
– thickening (irregular)
– chromatin margination
Nuclear inclusions (real)
– viral, lipids, glycogen
Cytoplasmic nuclear pseudoinclusions
papillary ca of thyroid
grooves
HPV - koilocytes
Cytomegalovirus
Cowdry A inclusion – herpetic encephalitis
glycogen nuclei
The Cell Components &Their Function
ribosomes
endoplasmic
reticulum
Golgi complex
lysosomes
peroxisomes
mitochondria
cytoskeleton
caveolae
The cytoplasm (cytosol)cytoplasmic matrix
cytoplasmic organelles
The Cell Components &Their Function
The cytoplasm (cytosol)aqueous solution with enzymes
The Cell Components &Their Function
The cytoplasm function
– proteosynthesis (in coop. with organelles)
– storage unit (fat, carbohydrates and
secretory vesicles)
Intracellular Accumulations
water –hydropic degeneration
proteins – hyaline droplets
lipids – steatosis
glycogen – glycogenosis
pigments – melanin, ceroid, lipofuscin,
hemosiderin
foreign bodies, crystals
microorganisms
Hydropic Degeneration
intoxications
sepsis
anoxia
starvation
functional overload
autolysis
ENERGY DEFICIENCY
Intracellular Accumulations
water –hydropic degeneration
proteins – hyaline droplets
lipids – steatosis
glycogen – glycogenosis
pigments – melanin, ceroid, lipofuscin,
hemosiderin
foreign bodies, crystals
microorganisms
Intracellular Accumulations
water –hydropic degeneration
proteins – hyaline droplets
lipids – steatosis
glycogen – glycogenosis
pigments – melanin, ceroid, lipofuscin,
hemosiderin
foreign bodies, crystals
microorganisms
Steatosis myocardii (oil red)
Adenoma corticis glandulae suprarenalis
Intracellular Accumulations
water –hydropic degeneration
proteins – hyaline droplets
lipids – steatosis
glycogen – glycogenosis
pigments – melanin, ceroid, lipofuscin,
hemosiderin
foreign bodies, crystals
microorganisms
PAS
Intracellular Accumulations
water –hydropic degeneration
proteins – hyaline droplets
lipids – steatosis
glycogen – glycogenosis
pigments – melanin, ceroid, lipofuscin,
hemosiderin
foreign bodies, crystals
microorganisms
Melanoma
Ceroid - pseudomelanosis intestini crassi
HEHS
Haemosiderosis hepatis
Intracellular Accumulations
water –hydropic degeneration
proteins – hyaline droplets
lipids – steatosis
glycogen – glycogenosis
pigments – melanin, ceroid, lipofuscin,
hemosiderin
foreign bodies, crystals
microorganisms
Asbestosis
Sinus pilonides
Intracellular Accumulations
water –hydropic degeneration
proteins – hyaline droplets
lipids – steatosis
glycogen – glycogenosis
pigments – melanin, ceroid, lipofuscin,
hemosiderin
foreign bodies, crystals
microorganisms
Cytomegalovirus inclusions in the GER
Chlamydia
The Cell Components &Their Function
ribosomes
endoplasmic
reticulum
Golgi complex
lysosomes
peroxisomes
mitochondria
cytoskeleton
caveolae
vaults
The cytoplasm -cytoplasmic organelles
The Cytoplasmic Organelles Functions (1)
Organelle Composition Function
ribosomes RNA –protein
complexes
proteosynthesis
endoplasmic
reticulum
cisternae,tubular
channels
proteosynthesis
& transport
Golgi complex
(GC)
smooth
membranes &
vesicles
processing and
packaging
lysosomes sacklike GC
derived
digestion
GC
ER
N
Autophagosomes
The Cytoplasmic Organelles Functions (2)
Organelle Composition Function
peroxisomes lysosomes like
producing or
using H2O2
detoxication
mitochondria membrane
bound energy
production
Oxydative
fosforylation, cell
signaling, pH
control, Ca
homeostasis
Oncocytus
MGG
HE
Oncocytes
Oncocytes
The Biology and the Genetics of Hürthle Cell Tumors of the Thyroid
Máximo V et al, Endocrine-Related Cancer, 2012, 19, R131-R147
• Hürthle cell appearance - a phenotype superimposed on the
genotypic and conventional histopathologic features of the
tumors.
• large deletions of mitochondrial DNA (mtDNA), mutations of
mtDNA genes and nuclear genes coding for OXPHOS proteins
• energy production defects in Hürthle cell tumors;
• the increased proliferation of mitochondria a compensatory
mechanism
• predisposition for necrosis instead of apoptosis which seems to
be blocked in most Hürthle cell tumors.
The biology and the genetics of Hürthle cell tumors of the thyroid
Máximo V et al, Endocrine-Related Cancer, 2012, 19, R131-R147
Peroxisomes - microbodiesup to 2 microns - catalase
FunctionDegradation: substrate oxidation
(etanol)
Anabolism: synthesis of
prostaglandin , cholesterol,
billiary acids, plasmalogens,
gluconeogenesis,
transamination
The Cytoplasmic Organelles Functions (3)
Organelle Composition Function
Cytoskeleton Microtubules & actin
microfilaments
Microvilli, cilia,
flagella
Caveolae Membrane
indentationsShuttling
material
Vaults Octagonal barrrels
like
ribonucleoproteins
Shuttling
molecules
Trichomonas vaginalis
carcinoma
Mesothelioma
Mesothelioma
Cilia
The Cell Components &Their Function
The plasma membranes– cell surrounding
– organelles enclosing
– bilayer of lipids and proteins
alc. blue pH2,5
Cell
mechanismMembrane function
Structure Compartmentalization, cytoskeleton & ER
contacts, fluid & electrolyte balance
Protection Barrier to toxins & foreign organisms/cells
Activation of
cell
Hormones, mitogens, antigens, growth
&proliferation factors
Storage Receptors, transport, diffusion, exocytosis,
endocytosis
Cell to cell
interaction
Communication & attachment –junctional
complexes, nutritive relationship, enzymes
and antibody release
Estrogen
receptors
Carcinoma mammae ductale invasivum IDC
HE PRER
MIB1 e-cadherin c-erbB2 / Her2-neu
Secretion
– exocrine (apical pole of the cell lumen, duct)
– endocrine (basal pole of the cell blood)
– paracrine influencing neighbouring cells
– autocrine self influencing
Organelles Involved in Secretion
membrane type
maternal origin (ovum cytoplasm)
autoreplicative
– granular (rough) endoplasmic reticulum
– Golgi apparatus
– lysosomes
Exocytosis and Its Disorders
protein secretion on the granular
endoplasmic reticulum
cis Golgi network
trans Golgi network (signal molecules
attachment)
Golgi Endoplasmic Reticulum
Lysosomes
Secretion
continual - permanent -unregulated
pulsatory - regulated
Secretion
continual - permanent– unregulated vesicle transport
– protocolagen, proteoglycans, viral
particles
Targetting:immunoglobulins without and after stimulation
C
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Secretion pulsatory - regulated
– exocrine mucin or zymogen granules secretion
– endocrine cells– neurons– T-lymphocytes– heparinocytes– thrombocytes– granulocytes
– endothelia
membrane budding
coating proteins
Secretion Disordersdefects of synthesis product itself
auxilliary proteins
retention in GER(inborn endoplasmic reticulum storage
diseases)
hyaline droplets (Russel bodies)
Sinusitis chronica
Autophagosomes
Neuroendocrine
Secretion Disorders
defects of synthesis product itself
auxilliary proteins
regulation disorders on the receptor level
Neuroendocrine Secretion
dense core granules
secretory vesicles
(small synaptic vesicles)
Membrane Componentsof Secretory Granules and Vesicles
– Synaptophysin (synaptic vesicle protein)
– Neuron Specific Enolase
– S-100 protein
identification of neuroendocrine
neoplasms
calcitonin
chromogranin
Carcinoma medullare gl. thyeoideae
Juxtacrine Secretion (?) /Signaling
contact (- dependent) signalling
cell adhesion (inflammatory cells… neoplastic cells…
transmitted via oligosaccharide, lipid, or protein
components of a cell membrane
Unlike other types of cell signaling (such as paracrine
and endocrine), juxtacrine signaling requires physical
contact between the two cells involved.
Juxtacrine signaling has been observed for some
growth factors, cytokine and chemokine cellular
signals.
pathology of INFLAMMATION,
TUMOURS