Pathology of Organels I. Introductionpau.lf1.cuni.cz/file/6372/3pathorganels-introduction.pdf ·...

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

o

ll

a

g

e

n

p

r

o

d

u

c

ti

o

n

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