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001-MBBS-05-Pathology
❖ "Amyloidosis"
"welcome to the one of the interesting topic that is amyloidosis so very small topic
let us see what is this amyloid what is the problems with the amyloid and how to
diagnose this amyloid amyloid is a name that has been read from a latin word a
mile um that means a starch like it is not described a very recently it is law as long
as mid 19th century itself Rudolf it sure has described these amyloid this is
abnormal pathological protein which is all due to the aggregation of the
undegraded protein fibrils because of the misc folding mechanisms so amyloid is all
because of the misc folding of the proteins that gets aggregated and they'll be
deposited between these cells it is not only one disease it is a group of disorders
where you see the diversion of this amirite so there is not only one condition
where you see deposition of amyloid there are so many conditions where you see
this abnormal pathological protein so the definition of amyloidosis goes like this it
is a pathological protein deposited between the cells in various tissues and organs
of the body in wide variety of clinical settings remember it is never physiological
proteins always pathological protein and it is between essence not with you this
else it's not intracellular protein it is extracellular so between the cells this
particular protein will gets accumulate in various tissues various organs in wide
variety of clinical disorders so let us have a look on the physical nature and
chemical nature of this amyloid it is made up of non-branching fibers of indefinite
length and of diameter of around seven point five to ten nanometers this
particular configuration you can easily make out with the special techniques like
what we call it as x-ray crystallography are infrared spectroscopy so these are the
two special techniques by which you can make out this non benching very long
verily in the fibers these amyloid fibers you can see very beautifully with this x-ray
crystallographic chemically it is composed around 95% by free proteins and
remaining 5% is made up of glycoproteins so predominantly it is a febrile protein
and with a small amount of glycoproteins so three important forms of amyloid are
al a a and a beta amyloid L stands for amyloid light chains it is there from mainly
plasma cells a is the amyloid associated protein which is mainly sacred by the liver
a beta amyloid is seen in cerebral lesions in patient data algae Mo's disease so we
have a classification of this amyloidosis as a systemic and a local systemic
importance being the multiple myeloma where you see the portion of the amyloid
light-chain proteins so we deal in detail about the multiple myeloma in the chapter

of hematology so multiple myeloma is the disorders of plasma cells it is a plasma
cell dyscrasia where the plasma cells will keep on secreting these light chain
proteins so these light chain proteins will keep on depositing in various organs and
responsible for so many complications reactive systemic amyloidosis AAA which is
seen in mainly in chronic inflammatory conditions hemodialysis associated
amyloidosis will have a beta microglobulin form so these are the different types of
for amyloid says such and in different conditions here in a tree amyloidosis
variables again CA a type of analysis family a minute Aryan fever again you see a
type of amyloidosis family amyloid or topic neuropathy is where you see a ATR
type of amyloid proteins system external amyloidosis again attr it will naturally
peptide Lake proteins have seen in mainly in the heart also they are seen localized
Nam analysis where only one are the to Arkansas get affected Inazuma this is for
example a beta type of amulet will be deposited between the neurons and they
are the one material responsible for the memory loss the medullary chasm of the
earth is very peculiarly showed a portion of the a Cal Cal stands for calcitonin so AG
care type of home already seen with the medullary carcinomas a lot of Langerhans
in bankers also show a I a ppm type of amyloid isolated atrial amyloidosis this is the
one which you need to remember and that is the one which is responsible for
suddenly cardiac death one of the important cause for sudden cardiac death is the
portion of the amyloidosis so this you need to take the multiple sections from the
heart of such a patients and if at all you see homogeneous material you have to
stain with a special stain for amyloid then you have to confirm that it is a amyloid
that is causing the arrhythmias and causing the death in these patients prioritises
again there is a biggie later for form white prpsc that's a type of formula and that is
seen with the prion disease so remember my friends there is a huge list of types of
amyloidosis and there are so many conditions where amyloidosis are seen every
year this particular chart is keep on you know modified every six months they will
three months three most six months they will discover a new type of amyloid and
they keep on adding so there are Amano projects who love to study and discover
these different pathological proteins so what is the pathogenesis of this amyloid
acid it is all because of the abnormal folding of the proteins so these misfolded
proteins are very highly unstable in their configuration and they will self associate
and such a misfolded proteins they will accumulate in the extrasolar matrix
thereby resulting in the arc anomaly initial will be there we are gana McCauley but
later on they results in the dysfunction of that particular arc on and finally it can
desert even in the pressure atrophy of the cells so all those will be are genomically
in initial event but later on if the patient surveys for long time then there can be

even pressure a trophy of the argon and the cells can takes place so this all
remember it's because of the abnormal folding of the proteins so two categories of
the proteins whether they may be normal proteins but they are producing excess
quantity so much success that it out limits the capacity of the body to fold them so
they have inherent a tendency to food improperly and deform the fibers
sometimes they can be by birth itself defective mutant proteins that means they
are already structurally unstable hence they are very much both for miss folding
and B aggregation so remember either it would be novel proteins which are
produced in excess quantity or it could be mutant protein itself features very much
more for miss folding and aggregation so let us have a look on this primary
amyloidosis this is just very commonly seen with the multiple main my cases which
is a type of plasma cell disorder it is a light chain proteins al type of hominid that is
get deposited it is all because of the abnormal B cells that is plasma cell
proliferation not only multiple myeloma plasma cell Manama and even other
monoclonal b-cell lesions can result in the in diversion of this particular type of
amyloid there is increased and increased production of these light chain proteins
some of these later chain proteins are get excreted from the kidney in the form of
suppress Ben Jones proteins in the urine so demonstration of been John proteins
in the urine is one of the important diagnostic tests to further diagnosing the
multiple myeloma cases react or editors so this is a diaper form right which is
mainly secreted from the liver secondary to various chronic inflammatory lesions
like very commonly we see um reduces in a patient who suffered from tuberculosis
bronchiectasis osteomyelitis rheumatoid arthritis we see again sections of the
synovial joint they will send it for with a query that panas and it shows a diversion
of the amyloid inflammatory Boris's ankylosing spondylitis and even intravenous
drug abusers so these are all the chronic inflammatory disorders where you see
the portion of this reactive type of secondary addresses so remember costly
initially there will be a gurney Omega knee that is enlargement of the argon the
argon will appear as more of a waxy and firm because it's a starch like material and
there is one technique what we commonly use on cross section we have to paint
the cut surface of the argon with the IOD after applying the iodine it gives an aloe
color and that will be transferred to blue air it after application of these sulfuric
acid so this is a grass technique to demonstration of the am i right but anyway you
have to confirm it under microscopy using a special stain form light remember the
very commonly asked what are the special stain for a monoid is how to remember
it so this is a special stain for demonstration of former addresses and not only
conquer it there are so many other stains like a tea of Liberty and pas stains but

you need also a special microscope for staining with the component you need a
wipe or razor so you need to stay in first sections with the carburetor stain then
you have to see the sections under polarizing microscopy using the polarizer then
only you can appreciate so far - apple green I have a green by a vengeance so this
is very commonly they will ask me mcq that what is the special strain for am light
what is a special microscope is useful for demonstration of amyloidosis how it
appear so remember my business can be demonstrated with the conga red stain
using a polarizing microscopy that use apple green birefringence but in the
ordinary light microscope it appears as if like a pink color or radicular but it is a
polarizer which use apple green birefringence so other special stains you need to
remember one is the Congo red second is the T of Levantine rarely we will use Van
Giessen stain that use the Kaka color for amyloidosis and PS / Erica 16 can also be
used so concrete is the one which use apple green diff birefringence that is said to
be the gold standard test for amyloidosis how would a percent of light microscopy
the actual dissections it appears as amorphous usana fake hylene extracellular
protein so remember it just appears homogeneous and ocean effect and when you
keep on saying this kind of material under these sections between the since then
you should think that it would be a case of am ready position with the progressive
accumulation of the amyloid in the more excessive quantity it produces pressure
or trophy of the adjacent cells so most of the organs that we get affected TP is the
one which is again get affected they be a focal or diffuse mesangial depression of
the amyloid there can be sometimes nodal our basement membrane deposits so
can deposit anyway that could mean the glomeruli are in the basement membrane
are within the tubular matrix are even in the blood vessels so it can be even
deposited within the capillary loose interstitial space and even in the one of the
blood vessels liver will show again hepatomegaly in the initial stages and it show
cut section shows waxy appearance heart very peculiar appearance of amyloidosis
is so called as do you drop like sub endocardial nodules so do you love a dew drop
like appearance will be there between the caudal fibers the tongue can be
enlarged so much that it may even hamper the speech of a patient we call it as
macro glass here sarire condition but very well-established condition macro class
they are due to the depression of the amyloid we call it as Emily DOMA oma no
more - more like condition so it can also present with the gingival swellings
sometimes it can deposit it within the carpal tunnel syndrome it can cause it can
compress the median nerve spleen you not remember what will happen to the
spleen in a more addresses very commonly asked and execuse on this inevitably
explained Omega will be there in most of the cases and the amyloid deposits in the

white bump in these clinic for equals it is so called as a cosplay because it appears
like as if typical like crannis on the grass examination if at all they already
deposited in the red bulb in the splenic sinuses then it is so Curtis law - is spleen
where there is map like large deposits of amulets are seen so remember sag was
plain in the white bulb Lord ish is playing in the red part of this brief so clinical
features of amyloidosis it all depends on which organ is getting what and what is
the extent of formality portion sometimes it could be a unexpected finding in
autopsy cases it can also lead to the serious organ dysfunction at certain times
most importantly if these are get affected it can lead to the nephrotic syndrome
remember it is one of the important cause of sudden cardiac death it can cause
conduction defects it can also cause restrictive cardiomyopathy so type of
cardiomyopathy where huge amount of form already will be get deposited
between the cardiac muscle fibers hepatosplenomegaly is again common with the
a portion of the amyloid so far a demonstration of amyloidosis you can take a
biopsy from different areas of the body depending on where it is get deposited if
it's a systemic de portion of amyloid you can take a biopsy from abdominal fat if
there's a macro class here you can take a biopsy from the tank if you feel that
involvement of the GI is there you can take even or if it is a system we come
analysis it can take a rectal mucosa PFC but the best biopsy is the renal perhaps
because most of time the kidneys will be getting bored in the amyloidosis so
whenever you feel that patient is having systemic amyloidosis and kidneys are
getting more so ren el-bee FC is the best because you can say I'm all right in any
portion of the kidney for that matter in the glow male in the interstitium in the
blood vessels so even in the tubules you can see the amyloid depression anywhere
in the kidney so Reynolds is the word standard technique again where do you can
take a biopsy to prove the diagnosis even you can take a bone marrow biopsies to
do the analysis so that is about interesting topic of amyloid read about it fuse
questions are invariably the last con the Amarok chapter thank you"
Summary Points
- Amyloidosis is the deposition of pathological protein between the cells in various tissues and
organs of the body in a wide variety of clinical settings
...

- Amyloid is made up of non-branching fibers of indefinite length and of a diameter of around 7
...


- There are different forms of amyloid, including AL, AA, and A beta amyloid
...


❖ "Apoptosis"

"welcome to the one of the complex topic that is a pertussis as I told the
cells will take by two types of cell death one is necrosis are the third type is the
pertussis necrosis is the far most common type of cell death a pertussis occurs
who need a rare phenomena so let us see the what is the conditions where
apathetic figures are seen and what is the chemical mechanism that is involved
with the upper ptosis so let us see the topic under the following headings
definition what are the causes for up ptosis what is the clinical significance of a
pertussis how to identify the apathetic bodies the morphological findings the
mechanism the complex one and the clinical significance of the upper ptosis the
definition of up ptosis goes in a simple way it is a program to cell death it is
internally programmed cell death so it's actually cells suicide you can say it as
cell suicide so the word has been derived from a Greek so it means like falling
off a leaf from a tree so single leaf when it comes down so it is a falling off a leaf
whereas necrosis you can say it's a huge number of cells that are going to die so
it's a bunch of you know the tree one bunch itself is broken down that necrosis
once a leaf falls down that's a pertussis so in that we can compare but the that
definition of a photo sis goes in this way it is a form of cell death designed to
eliminate unwanted cells in the body through activated coordinated and
internally programmed series of events that is affected by dedicated set of gene
products so this is a wonderful definition of ptosis it is a process where
unwanted cells that what the body trying to eliminate from the body so they
are going to be removed by activation of coordinated internally programmed
series of cascade of events affected by dedicated set of genes so there are
plenty of genes that will control this opportunity phenomena necrosis
remember it's obvious pathological whereas upper ptosis can be both
physiological as well as pathological sociological examples that occurs in Korea

one of us is during embryogenesis starting from implantation of an embryo in
the uterus ingrediences organ audiences there also that process will takes place
hormone-dependent inhalation of the uterus that's an example of the up ptosis
cell deletion in a proliferating population for example cells in the skin cells in
the GI tract they are continuously dividing unwanted cells are removed by
Epidaurus phenomena said that by cytotoxic t-lymphocytes elimination of
harmful cell free activity impulses that's what happens in a thymus gland the
auto react to T lymphocytes unwanted cells that are removed by a process of
hypnosis if these cells react until you four cells are not removed then person
will suffer from diseases called as autoimmune reactions autoimmune disorders
even disorders a huge subset of a disease where self reactivity lymphocytes will
not be removed by a central tolerance what we call it as by the thymus gland
and these perfect two T lymphocytes will persist in the circulation and such a
person will suffer from autoimmune disorders then buffer forces that serve the
the useful purpose they'll be removed they will be eliminated from the body by
a process of apoptosis so these are the few examples of physiological a
pertussis pathological conditions like any after these severe injuries process cell
injury viral diseases like wile appetite is the hepatocytes which are infected by
the viral particles they will be removed by the process of mitosis classically in
viral apparatus we see a pathetic bodies under liver sections methodological at
Brophy in apparent kill organs which are after the oxygen for example SAR
every clan that if it is obstructed by a stone formation so the that a slave will
undergo atrophy and they'll be removed else will be removed by a process of
apoptosis and cell that occurs in tumors by a processor ah pertussis so
measurement of operatic index itself is in a good indicator of we can predict the
prognosis of the tumors how to identify the upper tonic bodies morphologically
so remember operatic forties always the cells will be shrunken it will be
condensed social shrinkage will occurs chromatic will undergo condensation
and it will broken down into multiple fragments so that is carry or exists so
most of that the operatic bodies will appears more intensely intensely uses and

the nucleus nucleus will undergo five men - so you see fragmented nucleus like
this but finding a processor is very tough under microscope because there will
be no inflammation the Apertura bodies why because the cellular contents will
not leak outside so there is no information around the area of opportunity
figures so there so the opportunity bodies you have to search a lot if they are
less in number it is very difficult to diagnose so by these morphological findings
that yes intensely your snowflake with the condensation of the nucleus
fragmentation of a nucleus you will see these apathetic bodies as single cell
death so HN is the one which can be used for identifying these opportunity
figures they appears as round or masses intensely use Netflix structures with a
dense nuclear fragments so let us see the complex mechanism which initiates
the upper ptosis so the biochemical mechanism is under four steps the intrinsic
pathway the extrinsic pathway in the execution pathway and the Faygo
psychosis the intrinsic pathway it's mainly mitochondrial pathway so imagine
this is a cell so whenever there is an induced stimulus for example radio
radiation so this say El Cid the intrinsic pathway pair mitochondrial enzyme
circuit activated so these mitochondrial enzymes mainly there is the activation
and release of the mitochondrial permeability transition in the outer membrane
of the mitochondria so mitochondria contains cytochrome C cytochrome C is a
proper Attica enzyme so once this cytochrome C comes outside the
mitochondrial matrix it in turn is probiotic so it L sits at a scale of mechanisms
where we CL to these proteins are get activated so these proteins in turn
capable of activating and enzymes enzyme so far as these initiator caspases
they are the enzymes which are nothing but cysteine aspartic acid residues so
they in turn capable of activating one more enzyme tsoukalos executional
copies so these proper torque figures in there activate important enzymes so
far as in doughnut is so we just happy just like a spy just ate and caspases mind
they will activate the DNA into this they break down they practice the nucleus
into multiple fragments so the nucleus will be broken down into multiple
fragments these fragmented nucleus will be broken down into multiple a

pathetic bodies so which contains a fragment of an invidious mitochondria
peroxisomes nice atoms so these are condensed operatic bodies so these are
products operatic bodies which are recognized by phagocytic cells so operatic
bodies will be recognized by phagocytic cells and that will be removed from the
body by phagocytosis so this is the first puppet that is in the mitochondrial
cytochrome c activates the the cascades the other pathway is an extensive part
of it where you know the cell will express this variety of proteins so cut ice fast
proteins so fast ligands will be there that if we get activated and various other
proteins so various or after proteins are get activated so again it initially the
initiator caspases so finally you sure to Casper just again activate the
executioner pathways where internet lasers again get activated either a calcium
are Magnum dependent under necklaces they are the one which will break
down the nucleus into multiple fragments so in signaling so the transmembrane
signals will be carried to the cells where it suppresses the pre-existing that
programs and initiates the that cascade the most important receptor that is get
activated again is that Yuma's necrosis factor that is the one which is get
activated in signaling pathway in control and integration pathway there is direct
transmission of death signals by a specific adopter proteins so these are not
rare proteins will they will execute the execution of pathways and there will be
a regulation of this membrane mitochondrial membrane permeability by family
of proteins open SBC a family of proteins mitochondrial permeability of
transition so what we'll call it as mbts so that is the one which really operatic
trigger so throw each the cytochrome c will leak outside from the mitochondrial
matrix into the cytoplasm and this cytochrome c binds to the cytosolic proteins
and activates them treating the executional caspases so this execution caspases
as the one which will initially further cascade of events so bcl-2 suppressors
appetizers by preventing increasing mitochondrial permeability so there are so
called as pro-apoptotic family of proteins and there are suppressed antiapoptotic family of proteins so bcl-2 family as well as the attacked as an
antibiotic whereas BCL mine as well as backs and bad they are the ones which

are protein in their nature so in execution of pathways the protein will broke
down the DNA content will broke down because of the and finally no cellular
contents will leak outside so it's only the contents of the cell will be broken
down into multiple pockets these pockets are called as a photonic bodies so
these operatic bodies will express a very peculiar paper for enzymes so called as
phosphatidylserine passed serene is the one which makes the phagocytic cells
to recognize these opportunity bodies so this expression of phosphatidylserine
so by which the phagocytic cells mainly the macrophages will identify this
opportunity bodies and it will come and enter these operatic bodies so by this
way the upper tonic bodies are removed from the body so what is the clinical
significance of knowing this complex mechanism of pertussis remember
humors are nowadays cured not only by surgery prior to surgery are
postoperatively they will give chemotherapy and radiotherapy so the intention
of giving the chemotherapy and radiotherapy is to kill the tumor cells by a
pertussis so by that way you can reduce the burden of a tumor mass so huge
the tumor can be reduced to the small tumor mass which can be easily
accessible easily removed from the body so preoperative as well as sometimes
when post-operative they give chemotherapy and radiotherapy it is main
intention is to kill the tumor cells by inducing apoptosis the measurement of
these opportunities how many erotic bodies are seen per high-power field so
that index apoptotic index itself is a good indicator of the tumor proliferation
rate so that use indirectly the idea about the the tumor prognosis is it having
the good prognosis are the better prognosis apoptosis in tumors increases
following the irradiation as well as the immune responses and measurement of
operatic bodies in vivo as well as in vitro following a treatment it predicts the
effectiveness of the treatment that you have given so that is the importance of
the upper ptosis as per the medical significance is considered so with that I end
up the very complex topic that is up ptosis let us see the various intracellular
accumulations"
Summary Points

- Apoptosis is a programmed cell death, which eliminates unwanted cells in the body
through an internally programmed series of events affected by dedicated gene products
...

- Apoptosis can be both physiological and pathological, and examples of physiological
apoptosis include cell deletion in a proliferating population, such as in the skin and GI tract,
or the elimination of harmful self-reactive T lymphocytes in the thymus gland
...

- Morphologically, apoptotic bodies are shrunken, with condensed chromatin,
fragmented nucleus, and intensely used Netflix structures, and can be identified using HN
staining
...

Summary Points
- The immune system has two main components: innate and adaptive immunity
...

- Adaptive immunity is specific to a particular pathogen and involves lymphocytes (B and
T cells) and their products (antibodies and cytokines)
...

- A balance between the immune system's abilities is important, as both immune
suppression and exaggerated immune responses can be harmful
...
why can appear like as if he is appearing like a 70 a word person so
other syndromes like ataxia telangiectasia are due to ATM gene
mutation xeroderma pigmentosum again very peculiar skin disorder pay
there's a defect with the nucleotide excision repair so DNA damage
whatever if it happens it will not be repaired so these patients are very
much prone for skin Marik nursing's like squamous cell carcinomas
melanomas this is all customers very tough malignancies can occur at
very Engage say at an age of around 18 years or 20s they can come with
the multiple cutaneous malignancies so this again one of the important
syndrome xeroderma pigmentosum patients very commonly they suffer

from skin disorders and Fanconi anemia again this again due to the
defective the DNA cross-linked repair mechanism so there are plenty of
other syndromes and disorders genetic disorders all will manifest with
the early aging process what are the morphological changes that seen in
various organs as they age advances so skin will loses its elasticity there
will be enough ptosis hair loss will be there a trophy of our skin will
takes place easy brewing will takes place then joints will show Sinai
osteoarthritis very common manifestation in elderly immunosuppression
will take place as the age advances the heart will show very peculiar a
trophy so Pat has premiere pro of the heart arsenal a trophy of the heart
will takes place the unavoidable atherosclerosis and arterial sclerosis will
take place which can in turn lead to the model instruction day one
stroke the neoplasms will DARAB as the age advances so increasing is
itself is a very important risk factor for development of the American
seas and even CNS will undergo the seneye atrophy of the brain will take
place so cerebral degeneration and memory loss or all contributory
factor for due to the aging process so in conclusion cellular aging
process is influenced by mainly by Delta factors around 60% and
remaining 40% is by environmental factors the way you view the way
you spend your time there were personal habits they were in take a foot
or the dietary intake all those factors will contribute for the aging
process so daily intake of antioxidants is said to be very much well
protective of phenomena to prevent the aging process and delaying
aging also can be due to the restriction of the calorie intake so eat less
no more that should the attitude or operation of good health habits like
increased intake of antioxidants avoiding the excess use of the DNA
repairing inhibitors like unnecessarily using of these antibiotics so use of
antibiotics which can hamper the DNA's so that can should be avoided

to avoid the aging process so that's about aging say astray espero is the
history tomorrow is the mystery right today is the gift so that's why we
have to live in today so that's percent"
Summary Points
- Aging is a progressive loss of structural and functional capacity of cells leading to cell
death
...

- Environmental factors include accidents, traumatic factors, disorders like syndromes,
diabetes, atherosclerosis, calorie intake, nutrition, obesity, psychological and social health
factors
...

- Morphological changes in cells include irregularly folded and optically folded nuclear
ropes, pleomorphic mitochondria, decreased endoplasmic reticulum, accumulation of
lipofuscin pigment and advanced glycation end-products (AGEs), accumulation of abnormally
folded proteins, and defective chaperones
...


- Types of adaptations include hypertrophy (increase in cell size), atrophy (decrease in
cell size), hyperplasia (increase in cell number), metaplasia (change in cell type), and
dysplasia (disordered arrangement of cells)
...

- Hypertrophy occurs due to increased functional demand or specific endocrine
stimulations and can reach a limit beyond which degenerative changes start taking place
...
g
...

Metaplasia is a reversible stage where one adult cell type is replaced by another, but if left
untreated, it can become a premalignant condition

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