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Mona lisa – „la Gioconda”
Pathology – history continues
M.Bogdańska . 2015
Chair and Department of Pathology
• "la Gioconda", the laughing one. Painted in 15031507 by Leonardo da Vinci. In the present era it is
arguably the most famous painting in the world. Its
fame rests, in particular, on the elusive smile on the
woman's face, its mysterious quality brought about
perhaps by the fact that the artist has subtly
shadowed the corners of the mouth and eyes so
that the exact nature of the smile cannot be
determined
Pathology – what is it ?
(Greek); pathos – suffering, disease
logos – study, word
The study of disease or
Let’s talk about disease
„a discipline that bridges clinical practice and basic
science, involving causes and mechanisms of
disease that results in the presenting symptoms of
the patient” (by Robbins)
Rudolf
Virchow
•Born 1821 - died
1902
•Father of cellular
pathology
Rudolf Virchow
•Pathologist and statesman, one of the most
prominent physicians of the 19th century. He
pioneered the modern concept of pathological
processes by his application of the cell theory
to explain the effects of disease in the organs
and tissues of the body
•He was known for constantly urging his
students to 'think microscopically'
•A father of cellular pathology
History of the cell theory
• Until the 18th century, diseases were supposed to be
due to an imbalance of the four fluid humours of the
body (blood, phlegm, yellow bile, and black bile):
“humoral pathology” which dated back to the Greeks.
• In 1761 an Italian anatomist, Giovanni Battista
Morgagni, showed that diseases were due to lesions
in organs.
• Around 1800 a French anatomist, Xavier Bichat,
demonstrated that the body was made up of 21
different kinds of tissues.
• The later event in the complex history of the cell
theory : Virchow postulated that every cell originated
from a preexisting cell (Omnis cellula e cellula )
Virchows medical investigations
•He demonstrated that masses in the blood
vessels resulted from “thrombosis” (his term)
and that portions of a thrombus could
become detached to form an “embolus”
(also his term).
•Virchow's triad — 3 groups of factors
contributing toward thrombus formation.
The International Society on
Thrombosis and Haemostasis
(ISTH) has declared Oct 13 to
be World Thrombosis Day, to
be held annually from 2014
onwards
This date has been chosen
because it is the birthday of
Rudolf Virchow (1821–1902)
Virchows medical investigations
Virchows medical investigations
• He devoted great attention to the pathology of tumors. He is
cited as the first to recognize leukemia (1845).
• Virchow's node — the presence of metastatic cancer in a
lymph node in the left supraclavicular fossa
• Virchow shed new light on the
process of inflammation, though
he rejected the possibility of
migration of the leukocytes
• He described fatty
degeneration
• He introduced the modern
conception of amyloid
(starchy) degeneration
(After Encyclopedia Britannica)
Degeneration = accumulation
Rudolf Virchow
• Virchow's method of autopsy — A method of
autopsy where each organ is taken out one by one.
• Other methods are Letulle's method, where they
are taken out en bloc, Rokitansky's method, where
they are examined in situ, and Ghon's method
where they are usually taken out in three separate
blocks
Accumulation of water
•Intra- or
extracellular
accumulation of
substances which
under normal
condition are there
in small quantities
or are absent
Accumulation of water
• Tubular epithelial vacuolar
change, kidney
(enlargement of the
reticulum)
• This change can be seen in
hypokalemia, ischemia,
dextran and mannitol
administration
Accumulation of fat
Obesity – increase in size and number
of fat cells
Steatosis – accumulation of fat in
parenchymal cells = fatty degeneration
Protein degeneration
• Intracellular protein accumulations
• hyaline degeneration - Mallory bodies
(„alcoholic hyalin”) –aggregated intermediate
filaments in hepatocytes
• Mallory bodies are classically found in alcoholic
liver disease and were once thought to be specific
for that
• They are most common in alcoholic hepatitis
(prevalence of 65%) and alcoholic cirrhosis (51%)
• They are a recognized feature of Wilson's disease
(25%), primary biliary cirrhosis (24%), nonalcoholic cirrhosis (24%), hepatocellular
carcinoma and morbid obesity
Protein degeneration
Amyloidosis
•Extracellular accumulations
•collagen degeneration
•amyloidosis
• Amyloidosis is a group of diseases that are a
consequence of abnormal (inappropriately folded)
protein deposits. When proteins that are normally
soluble in water fold to become amyloids, they
become insoluble and deposit in organs
• Depending on the structure of the particular
amyloid, the protein can accumulate in an isolated
tissue or be widespread, affecting numerous organs
and tissues.
• There are over 30 different amyloid proteins.
Amyloid
Amyloidosis
• At the time of the first description (Virchow,1854)
..it was thought to be starchlike, hence the term
amyloidosis (amylum=starch), because of staining
properties (it is stained with iodine which in
chemistry is used to indicate starch)
HE – amyloid deposits
between myocardiocytes
• Despite variety of different precursor proteins and
types of resulting amyloid, various types share
common features:
• Identical light microscopic appearance
• Selective staining with Congo red dye, with
resulting diagnostic bright green fluorescence
under polarized light.
The most common forms of
amyloid
Amyloidosis
•Note the amyloid
deposits stain red
with Congo red stain
and exhibit an apple
green birefringence
with polarized light
1/ AL (amyloid light chain, primary amyloid)- light
chains of immunoglobulins: associated with
multiple myeloma or macroglobulinemia of
Waldenström.
Myeloma - neoplastic plasma cells secrete
different immunoglobulins or only light chains
Macroglobulinemia (B-cell lymphoma) - cells
secrete only IgM
The most common forms of
amyloid
2/ AA (amyloid-associated, secondary
amyloid),
nonimmunoglobulin
protein
synthesized by the liver; associated with
chronic debilitating diseases, running with
the breakdown of tissues, e.g. infectious (TB),
neoplastic (Hodgkins disease), autoimmune
diseases (rheumatoid arthritis, Crohn’s
disease).
The most common forms of
amyloid
3/ Aß – found in the cerebral lesions of Alzheimer’s
disease (a common form of dementia)
brain deposits are composed of an abnormally
folded proteolytic fragment of amyloid precursor
protein.
Alzheimer’s disease is not a „pure” amyloidosis, as it
is characterized not only by abnormal protein
processing but also by intracellular accumulation of
another protein – microtubule stabilizing tau
protein in neuronal cells
Diagnosis
Amyloid deposition must be identified in tissue
sections. Identification of the type of amyloid
deposited is important with respect to treatment
and prognosis.
Diagnostic methods:
• Pathological examination of an involved site
showing Congo red-positive amyloid deposits,
• Positive reaction with an anti-LC antibody by
immunohistochemistry and/or
• immunofluorescence
Diagnosis
• Due to the systemic nature of the disease, non-invasive
biopsies such as abdominal fat aspiration/oral mucosa
biopsy should be considered before taking biopsies from
involved organs, in order to reduce the risk of bleeding
complications
Tissue processing
•Tissues from the body removed at surgery
and/or taken for diagnosis are processed in
the laboratory to produce microscopic slides
that are viewed under the microscope by
pathologists.
•The persons who do the tissue processing
and make the glass microscopic slides are
histotechnologists.
Specimen processing
Aquiring specimens
1. Gross examination and dissection
2. Fixation
3. Tissue processing (dehydration,
clearing)
4. Paraffin embedding
5. Cutting sections on microtome
6. Staining
7. Coverslipping
Fixation
Fixation
Serves to:
•Preserve tissue, prevent autolysis
•Harden tissue to allow thin sectioning
•Devitalize or inactivate infectious agents
•Stabilize tissue components
•Enhance avidity for dyes
•Fixation should be carried out as soon
as possible after removal of the tissues
(in the case of surgical pathology) or
soon after death (with autopsy) to
prevent autolysis !
An adequate amount of fixative is usually considered 15 to 20 times
the volume of the tissue!
Fixatives penetrate approx. 0,1 cm per hour.
Fixation
Type of fixatives:
•10% phosphate-buffered formalin – used for
routine fixation of all specimens
•Alcohol
•Bouin’s solution
•Glutaraldehyde
•…
Gross examination &
dissection
Describing:
•Localization of lesion
•Size
•Gross appearance
•Distance from surgical
margins
•Relation to adjacent
tissues/organs
Inking margins
Sectioning and taking
samples.
Tissue processing
Tissue processing
• Automated tissue processors
• Once the tissue has been fixed, it must be
processed into a form in which it can be made into
thin microscopic sections.
• Usuallly this is done is with paraffin. Tissues
embedded in paraffin, which is similar in density to
tissue, can be sectioned from 3 to 10 microns, 6-8
routinely.
• Specimens are placed into a small plastic cassettes
Paraffin embedding
Cutting sections
Procesor tkankowy (3-4)
Staining
Staining slides
Hematoxylin & eosin stain (HE stain) – most widely used
• Hematoxylin - dark blue or violet, basis, binds to
basophilic substances (DNA/RNA)
• Eosin – red or pink, acidic, binds to amino acids and
proteins
Regressive lesions
Special stains
• PAS – demonstrates glycogen, basement membranes,
mucins, colloid and fungi
• Trichrome Masson – demontrates collagen
• Ziehl-Neelsen – identification of mycobacteria
•…
Changes in the structure of normally developed cells, tissues or
organs, which usually interfere with their function
•
Cellular adaptation to injury
• atrophy
• intracellular accumulations (degeneration)
•cell death (necrosis)
• inborn abnormalities
Developmental abnormalities (organ-specific
malformations)
Developmental abnormalities -hypoplastic kidney
• agenesia (a lack of organ anlage)
• aplasia
• hypoplasia (incomplete development)
• atresia (complete failure of development of the
intestinal/duct lumen)
• double organs
• ectopy (abnormally located tissue)
• Hepinstall’s Pathology of the Kidney
Developmental abnormalities
Developmental abnormalities
atresia
atresia
• Duodenal atresia frequently associated with Down's
syndrome or other anomalies
• Presents relatively early in life with vomiting
• Treated surgically
Developmental abnormalities
Ectopy
double organs
• Ureteral duplication
• Lat. ectopia
• Gr. εκτοπία
• A developmental anomaly characterized by organ parenchyma
located outside of the normal anatomic location
note the two ureters (arrows)
from the right kidney.
• Termin używany w przypadku występowania narządu/tkanki w
miejscu innym niż fizjologiczne
Ectopy
Ectopy (pancreas)
• Lat. ectopia
• Gr. εκτοπία
• Ang.: aberrant pancreas, accessory pancreas,
ectopic pancreas, panreatic rest
• A developmental anomaly characterized by organ
parenchyma located outside of the normal
anatomic location
• Termin używany w przypadku występowania
narządu/tkanki w miejscu innym niż fizjologiczne
Development of the pancreas
Histologic classification of heterotopic
pancreatic tissue by Heinrich
• Typ I – normal
pancreatic tissue
(preserved lobular
structure, visible islets
and pancreatic ducts)
• Typ II – abnormal
structure, no islets
• Typ III – lesion
composed only of
pancreatic ducts
Medical eponyms used during this
lecture
• Virchow triad, Virchow node, Virchow method of
autopsy
• Crohn’s disease,
• Mallory bodies
• Hodgkin disease, macroglobulinemia of
Waldenström.
• Alzheimer disease ………
• in possessive or nonpossessive form
Eponyms
• By definition, the term „eponym” derives from Greek:
eponymos
• epi- upon, onyma – name
• Eponym indicates the name of a person after whom a
disease is named to commemorate the importance of
his/her contribution
• Most are derived from the names of those who first
described a disease
• Along with eponyms derived from names, there are
the names of mythical or biblical heroes, as well;
some eponyms came from paintings
Should eponyms be abandoned ? A recent
debate evoked strong responses both in favour
and against the motion:
Eponyms lack accuracy
Their main function is to
lead to confusions
immortalize the greats of the
are not descriptive
profession
sometimes are even misleading
They add color to medical
communication
Enrich our dry medical
language
Extend our knowledge
beyond pure medicine
Embed medical tradition in
BMJ 2007
our history
•Mona Lisa sydrome – the facial muscle
contracture which develops after facial
nerve palsy