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Pathology : is the science that deal with the study of
disease & its effect on the body . It has many
branches include :
1- Histopathology & Cytology : which study the
structural changes of the tissue by necked eye
inspection ,light & even electron microscope .
2- Biochemistry : study the abnormalities of body
fluid especially the blood .
3- Hematology : study the abnormalities of blood
cells & clotting mechanism .
4- Microbiology : Study the Microorganism (m.o)
responsible for diseases such as bacteria , virus ,
fungus , & protozoa .
5- Immunology : study the abnormalities in the
immune mechanism which is responsible for
defense mechanism .
Biopsy:
is a piece of tissue taken from living body during live
. it is of many types ;
* Incisonal biopsy in which part of the lesion is
removed .
* Exisonal biopsy in which the whole lesion is
removed .
* Fine needle aspirate : in which few cells from the
lesion is removed .
Autopsy : A peice of tissue taken from a living body
after death .
Pathology include the gross & microscopic appearance
.
Pathogenesis : The sequence of event in the disease
development from the onset till termination including
any influencing agent .
Causes of diseases :
1-Genetically determine : due to abnormalities in the
base sequence of the DNA & this abnormalities is either
inherited from parent or occur by mutation .
2- Acquired : include :
a- nutrional abnormality : either due to deficiency as
in malabsorption , anaemia or due to excess diet as in
obesity .
b- Chemical agent as poison drugs & air pollution .
c- Physical agents : trauma , extreme of temperature
,radiation , & electric shock .
d- Infectious agent : virus ,bacteria , fungi ….
e- Immunological causes : Autoimmune diseases
f-Psychological : anxiety & stress can cause disease
but the mechanism is unknown .
g-Iatrogenic: due to medical or surgical intervention
it may be predictable or unpredictable
H- Idiopathic.
Cell injury
Normally the cell preserve their immediate
environment to maintain normal homeostasis .
If the cell encounter physiological stress or
pathological stimuli then it can undergo adaptation by
which the cell achieve a new steady state to preserve
the viability .
Adaptation include atrophy, hypertrophy,
hyperplasia and metaplasia.
1-hyperplasia:- increase in size of organ due to
increase in no. of cell usually associated with
hypertrophy.could be physiological or pathological.
Physiological  hormonal as in breast enlarge during
pregnancy
 compensatory: hyperplasia of the
cell when part of the tissue is removed e.g. when part
of the liver is resected.
pathological due to excess hormone or growth factor
stimulation
e.g. endometrial hyperplasia after menstrual cycle.
2-hypertrophy:- increase in size of organ due to
increase in size of cell.
* physiological :
due to functional demand or
due to hormone stimuli.
e.g. as enlargement of uterus during pregnancy and
enlargement of skeletal muscle in lifter.
* Pathological as in the wall of intestine proximal to
site of obstruction .
3-Atrophy:- which decrease in the size of cell lead to
diminish in the size of organ.
*physiological : atrophy of thymus after puberty
*nutritional – generalize atrophy at starvation
*disuse – paralyzed limb
*neuropathic: in nerve cutting
*pressure atrophy: in benign tumor
*endocrine: damage to pituitary gland cause
reduction in trophic hormone  atrophy of thyroid
or adrenal gland.
4-metaplasia:- reversible change in which one adult
type of tissue is replace by other adult type of
tissue , it could epithelial or mesenchymal.
Epithelial metaplasia in the bronchus in which the
columnar cell is replaced by squamous cell , usually
occur due to chronic irritation of bronchus by
smoking .
Although the viability of the cell is maintain but it
loss its specialized protective function & in long
standing  neoplasia
mesenchymal metaplasia is rare. e.g bone may form
at site of injury
If the adaptation capacity is exceeded or if the
cell cannot undergo adaptation the cell injury will
occur &up to certain limit these changes are
reversible and then cell can return to normal if the
causative agent is remove however if the stress is
severe or persistent this lead to irreversible cell
injury & cell death which is of tow type:
1-necrosis 2- apoptosis
Principles related to cell injury:
*-Cellular response to injurious stimuli depend on
type of injury , its duration & its severity .
*- Consequences of an injurious depend on type ,
status & genetic make up of the cell.
*- Four intracellular systems are vulnerable to injury
include : ATP , Protein synthesis , integrity of genetic
apparatus & cell membrane.
*- Structural & biochemical component of the cell
are closely connected regardless of initial locus of
injury, multiple secondary effects occur later
* cellular function is lost before cell death &
morphological changes of cell injury i.e cellular
dysfunction occur before them.
causes of cell injury
1- hypoxia: is the main cause of the cell injury &
either due to ischemia that is say reduction of
blood supply or due to poor oxygenation of
blood as pneumonia or decrease in oxygen
carrying capacity of blood as in anemia.
2- Any chemical agent even if innocuous
substance as glucose can cause disease if it is
concentrated. Other chemical agent such as
(poison, air pollutant and drug)
3- Physical agent such as trauma, extreme of
temp radiation and electric shock.
4- Infectious agent such as virus, bacteria, fungi
and protozoa.
5- Immunology mechanism: it is a defense
mechanism in the body, it may harmful as in
auto immune disease.
6-Aging .
7-Genetic ,
Mechanism of cell injury
1- ATP depletion: ATP is necessary for all
process in the cell so decrease in it can lead to
rapid shut down of all homeostatic process.
2-O2 deprivation and generation of active O2 species
(free radical) can cause cell injury .free radical is
any chemical substance with single electron in the
outer orbit such as super oxide O2, H2O2 , OH , No ,
these substance are unstable so it react with any
organic or inorganic substances to be stable .
Free radicals generated within the cell by:
1-Reduction oxidation reaction occur during
respiration .
2-Nitric oxide can form in different cells.
3-Radiation ( x-ray & UV light ) can
hydrolyze water into hydroxyl group &
hydrogen free radical .
4- enzymatic metabolism of certain
exogenous substance e.g carbon
tetrachloride
Free radical cause cell injury by:
 DNA fragmentation which lead to cell death &
neoplasia
 Peroxidation of lipid membrane
 cross link of protein which enhance Loss of
enzyme activity or Cause fragmentation of protein.
The body can defense itself against free radical by
either:
*anti oxidant  enzyme-s aSOD(super oxide
dismutase)-catalase & glutathion peroxidase zymes
*scavenger (Vitamin A;C;E 7 B carotene) .
2- loss Calcium ion homeostasis
Injury (ischemia or toxin) stimulate the influx of
Ca+2 inside the cell which stimulate the release of
Ca+2 from intracellular store which cause increase in
cytosolic calcium which affect many enzyme as
mentioned in the figure above .
4-defect in plasma membrane : Plasma membrane
may be damaged directly by certain bacterial toxin
,viral protein , complement , ATP depletion & by
calcium activation of phospholipase .
Defect of plasma membrane barrier lead to break
down of the concentration gradient of metabolite
necessary for normal metabolic activity .
5-Mitochondria damage : Increase in cytosolic
calcium ,oxidative stress & lipid breakdown ,all
lead to the formation of high conductive channel
in the inner mitochondrial membrane ,this pore
allow the proton (H) ion to dissipate & prevent
ATP generation ,In addition cytochrome also leak
lead to apoptosis .
Reversible cell injury :
It is a common type of cell injury usually due to
ischemia which lead to hypoxia & reduction in
oxidation phosphorelation lead to reduction in ATP ,
this reduction cause :
1- Decrease in sodium pump ,so it will accumulate
inside the cell , this stimulate influx of water &
calcium lead to cellular swelling .
2- It stimulate anaerobic glycolysis lead to reduction
in glycogen with lactic acid accumulation causing
reduction in PH which cause chromatin clumping
.
3- Detachment of the ribosome & conversion of
polysome into monosome ,this cause reduction in
protein synthesis .
If hypoxia is stopped i.e re-oxygenation of tissue take
place the cell will return to normal but if hypoxia
continue then irreversible cell injury take place
ending into cell death .
Morphology of reversible cell injury:
It is of two types :
* Cellular swelling : It is the first manifestation seen
in all form of cell injury & it is happen when the cell
fail to maintain water & ion homeostasis . it is
difficult to be shown by light microscope & it is more
apparent when the whole organ is involved in that
case the organ become pale & increase in weight .
Microscopically : At the beginning the cytoplasm
show many vacuoles & this is called (vacuolar
changes) , if the vacuoles combine with each other
the cell appear as balloon & in that case the condition
is called (hydropic changes )
* Fatty changes : It is less universal & seen only
in cell participate in lipid metabolism It is
abnormal deposition of triglyceride in paranchymal
cells as liver ,kidney .Although fatty changes is an
indicator for reversible cell injury however it may
be seen adjacent to area of necrosis .
Causes :
1- toxin as alcohol .
2- hypoxia .
3- protein malnutrition .
4- diabetes mellitus .
5- obesity
Normally fatty acid derived to the liver from two
sources mainly ,the G.I.T the adipose tissue &
small amount is formed in the liver from acetate .
The majority of fatty acid by the action of
alpha glycerol phosphate is converted into
triglyceride & small amount of fatty acid is
converted into phospholipids & keton . Then
triglyceride join apoprotein forming lipoprotein
which diffuse outside the liver .
Pathogenesis ( mechanism of fatty changes ) :
1- increase the amount of fatty acid entering the
liver .
2- increase in the conversion of acetate to fatty
acid .
3- increase in alpha glycerol phosphate .
4- decrease in the conversion of fatty acid into
phospolipid & keton .
5- reduction in apoprotein .
6- block in the excretion of lipoprotein to the
circulation .
Grossly : the liver enlarge , soft & greasy .
Microscopically : small fat globules appear in the
cytoplasm , later they join form one big vacuole that
push the nucleus to one side of the cell form signet
ring appearance ,occasionally adjacent cells may
rupture form fatty cyst . by H&E stain fat vacuole
appear as empty space , however fat can be
demonstrated by special stain ( oil red ) which should
be used on frozen section & the fat appear as red or
orange .
Irreversible cell injury:
1.
2.
necrosis
apoptosis
Necrosis:- sequence of morphological change that
follow cell death in a living tissue.
The morphological changes in necrosis result from
two processes :1 : enzymatic digestion of the cell either by its own
enzyme (autolysis) or the cell digest by proteolytic
enzyme secreted from inflammatory cell infiltrate &
this is called (heterolysis)
2 : denaturation of protein.
The morphological change of necrosis usually
required (4-12)h to bee seen by light microscope ,
although ultra structural change can be demonstrate
within 20-40 m while the enzyme released from
damage cell can be detected within 2hrs in the serum
such as (CPK- creatinin phosphokinase ) which is
secreted in myocardial infarction .
Morphology ( microscopic feature of necrosis ) :
* changes in cytoplasm include :
1. increase eosinphilia: due to increase binding of
eosin to denature protein and decrease in basophilia
of ribosome.
2. It show more glassy appearance than viable cell .
3.
calcification may occur
* nuclear change (path gnomonic ) :
pyknosis: nuclear shrinkage & increase basophilic
appearance of nucleus
karyorrhexis: pyknotic cell fragment in 1-2 day & the
nucleus completely
disappear.
karyolysis: fading of basophilia of the chromatin .
types (gross appearance) of necrosis
It depend on the mechanism of necrosis , if
enzymatic digestion dominate liquifactive necrosis
occur, if denaturation of protein dominate coagulative
necrosis happen however other type of necrosis can
occur.
1- coagulation necrosis
2- liquifactive necrosis
3- fat necrosis
4- caseous necrosis
5- fibrinoid necrosis
6- gangrene
coagulative necrosis:
1. commonest 2. Occur Any where in the body
except C.N.S 3. usually due to hypoxia 4. the
Outline of tissue is preserved because denaturation of
protein involve the enzyme of the cell .e.g.
myocardial infraction ,the cardiac muscle become
pale, swollen, firm and microscopically the cell
become more eosinophilic , loss of striation, absence
of nucleus & the outline is preserved .
Liquifactive necrosis: The second most common type
of necrosis
usually occur in association with bacterial infection
and sometime with fungal infection and in CNS due
to hypoxia which may be due to high content of lipid
in CNS.
Here enzyme digestion & autolysis is predominate so
the area become
soft  cystic
Microscopically : complete loss of tissue architecture
, the cyst contain necrotic debris & macrophage,
while the wall show capillary, inflammatory cell +
proliferating glial cell(brain) or fibroblast (any where
in the body).
caseous necrosis: it is a special form of necrosis
usually see n in tuberculosis grossly : it has white
cheesy appearance
Microscopically : the necrotic area has structurless
granular and amorphous material surround by
multiple granulommata ,which consist of collection
of epitheloid cells which is large flat cells with
eosinophilic cytoplasm & ill define cell membrane &
langhan,s giant cell in which the nucleus arrange at
the periphery of the cell or it has horse shoe
appearance .the granuloma surround by collar of
lymphocyte & fibrosis ,
Fat necrosis:
1- enzymatic fat necrosis: which usually follow
acute pancreatitis due to release of pancreatic enzyme
 necrosis of pancreatic tissue & release of free fatty
acid, the later combine with calcium form fat
saponification
2- traumatic fat necrosis: occur in the breast after
trauma which caused release of fatty acid from cell
this stimulate macrophage infiltration which engulf
fat  foamy macrophages (lipid laden macrophage)
and giant cell infiltrate with massive fibrosis so the
lesion grossly become hard mimic carcinoma
fibrinoid necrosis: characterized by deposition of
fibrin like material in the tissue as in :
* immune complex vasculatis (auto immune disease)
&-arthus reaction
* wall of peptic ulcer
* hypertensive change of arteriole
Microscopically bright eosinophilic material seen in
the wall of b.vessel or in the luminal surface of
peptic ulcer.
Gangrene
It is a form of necrosis of a tissue with superadded
putrefaction , the type of necrosis is usually
coagulative due to ischemia . There are 3 types of
gangrene dry , wet & gas gangrene .
Dry gangrene :
It occur in the distal part of the limb due to arterial
occlusion as in old patient due to arteriosclerosis ,
other causes are Rayanaud,s disease , thromboangitis
obliterans , trauma & ergot poisoning .
The gangrene spread slowly upward until it reaches a
point where the blood supply is adequate so a line of
separation is formed between the viable &
gangrenous tissue .
X : the affected part is dry , shrunken with black
discoloration due to the formation of iron sulfide .
RBC--------- Hb + H2S( produced by bacteria)-------- Iron sulfide .
Wet gangrene :
It occur in moist tissue such as mouth , bowel , lung ,
diabetic foot is other cause of wet gangrene due to
high sugar content .
Wet gangrene is usually occur due to venous block &
less commonly due to arterial block (due to
thrombosis or embolism) as in strangulated hernia &
volvolus . The absorbed toxic product cause features
of septicemia .
X : the affected part is soft moist swollen & dark
with lack of line of demarcation .
Gas gangrene :
Caused by gas forming bacteria (Clostridia) which is
gram positive anaerobic bacteria which enter the
tissue through an open contaminated wound or as a
complication of operations on the colon which
normally contain clostridia .
Clostridia produce various toxin which produce local
necrosis & oedema in-addition to the features of
septicemia .
X : the affected part is swollen , oedematous, painful
with crepitation due to accumulation of gas bubbles
within the tissue , subsequently the affected tissue
become dark black with foul smelling .
fate necrosis:
1- it cause acute inflammation with acute
inflammatory cell infiltrate in the surrounding
tissue follow by macrophage infiltration which
tried to removed the dead tissue then healing can
occur which is either by the same type of cell
(regeneration) or by fibrosis (organization).
2- Calcification :deposition of calcium seen in
necrotic tissue as in caseous necrosis or in fat
necrosis.
3- Gangrene
Effect of necrosis: it is variable depending on the
type of the cell involve, extent of necrosis (small,
large), the involve organ and the proliferation
capacity of the cell involved .
Extensive necrosis in spleen which lead to
autospleenctomy as in sickle cell anemia is capable
for normal life.
While ischemic necrosis involved few cells in the
brain can lead to the paralysis.
Apoptosis: it is another type of cell death in
which the cell shed after it reach the end of its life
span and this is called programmed cell death.
Usually involve single cell however it may
involve group of cell, is either due to physiological
causes as in shedding of gastro-intestinal epithelium
or due to hormone dependant involution of the tissue
which occur in the endometrial during menstrual
cycle. Or pathological as in the malignant tumor,
radiation , steroid and cytotoxic therapy.
Apoptosis is usually active process that is to say need
energy or ATP and not associated with acute
inflammation.
Microscopically: apoptosis appear in
hematoxylen eosin stain section as around or oval
mass with intense eosinophilic cytoplasm and
condense chromatin. The chromatin is broken into
regular fashion by endnuclease enzyme and at the
same time transglutaminase convert the cell into rigid
shrinkage shell show intense eosinophilic staining
then the dead cell break down into many fragment
some of them are shaded from free surface of the cell
or taking by adjacent cell or by macrophage.
Mechanism of apoptosis: Include 4 steps:
1. Signaling: apoptosis will be initiated by
different signal some of them are intrinsic as (
embryogenesis signal), or extrinsic as( injury
,radiation, toxin and free radical) or due to
withdrawal of growth factor or also due to
receptor legend interaction such as (TNF) and
TNF receptor or by cytotoxic T cell due to
release granzyme enzyme secreted from T cell .
2.
Control and interaction: which is caused by
certain type of protein that carry the signal
death to the execution capses, this signal is
carried either directly to the execution capses
by specific adaptor protein or indirectly due to
the interaction with mitochondria which release
the cytochrome c this substance combine with
protein and activate it and then carry the
information to the execution capses.
3.
the execution capses: characterized by
formation /or activation of a no. of catabolic
enzyme which is responsible for morphological
changes of apoptosis This include
endonuclease which cause fragmentation of
DNA and transglutaminaze which convert the
cytosolic protein into condense shell .
4.
removable of death cell: the apoptotic body
has cell marker on their surface facilitate their
uptake by the adjacent cell or macrophage.
Intra cellular accumulation :
Excess storage of substances inside the cells ,can
be seen in many conditions include :
1- Upset of normal metabolism by toxin or some
drugs result in accumulation of normal substance
e.g fatty changes .
2- Genetic defect in the enzyme lead to
accumulation of its substrate ( abnormal) as in
storage disease .
3- Some materials are incapable for digestion or
transport to other place so it will accumulate as a
pigment which is either exogenous or
endogenous .
Fatty changes :
.
Pigmentation :
There are two types : exogenous & endogenous
Exogenous pigmentation :
 Carbon ( as coal dust ) is a common air
pollutant in an urban area which when reach
the alveoli it is taken by the macrophage to the
regional lymph node which when contain
excess amount of coal it appear black & this
condition is called anthracosis . however if
there is excess deposition of carbon in the lung
it may lead to emphysema & it may cause
extensive fibrosis & the condition is called
pneumoconiosis .
 Tattooing : harmless , taken by injection .
Endogenous pigmentation : include :
1- Lipofuscin : yellow brown pigment seen inside
the cell of the liver , heart & brain ,seen in old
ages & it is a marker of damage by free radical
.
2- Melanin : Intracellular brown pigment seen in
the melanocyte inside the epidermis ,produce
from tyrosin by the action of tyrosinase , it is
a screen mechanism against the harmful effect
of ultra violet radiation .
* Generalized hyperpigmentation :
As in addison disease ( generalize
hyperpigmentation especially in exposed part
&
buccal
mucosa
)
&
chloasma
(hyperpigmentation of face , nipple & genitalia
during pregnancy ) .
* Focal hyperpigmentation :
As in Café-au –lait spot , melanosis coli (
pigmentation of the colon ) & melanocytic
tumors as pigmented naevi & Peutz-Jegher
syndrome( focal oral pigmentation).
* generalized hypopigmentation as in albinism
* Localize hypopigmentation: as in
leucoderma ( partial albinism ) & vitiligo .
3- Hemosidrin : a golden yellow to brown
pigment
occur
any
where
I
in the body which has excess iron store .
in side the cell iron combines with apoferritin
to form
ferretin which if accumulate
in excess amount it will form hemosidrin which
can be demonstrated by Prussian blue reaction .
Excess iron accumulate either :
* Locally : which is seen in hemorrhage as in
bruses , here the extravasated red blood cell
hemolysed & the released hemoglobin is
digested into hemosidrin .
* Systemic iron over load : which could be :
a-Primary as in idiopathic hemochromatosis
which is an autosomal dominant disease
characterized by excess absorption of iron
from the gut . here the deposition hemosidrin
usually in the parenchyma cells as in the liver
cause ( fibrosis & cirrhosis ) , in the heart
cause (heart failure & arrhythmia ) in the
pancreas cause ( diabetes mellitus ) & in the
skin form bronze pigmentation so it is
sometime called bronze diabetes .
b-Secondary :as in
1- Increase absorption of dietary iron .
2- Ineffective erythropoiesis (thalassemia).
d-parental iron overload :as in repeated blood
transfusion as in aplastic anemia .
3- Excessive intake of dietary iron ( Bantu,s
disease) .
4- Chronic liver diseases as alcoholism .
4-Bilirubin pigment : Yellow brown pigment .
it is usually less than 1 mg / 100 ml in the
serum . If the level of bilirubin exceed
this level it will lead to a clinical condition
called jaundice which characterized by yellow
discoloration of skin & mucous membrane. .
Types( causes ) of jaundice :
a- Pre hepatic jaundice : due to increase in red
blood hemolysis .
b- Hepatic jaundice : due to failure in bilirubin
conjugation as in liver disease .
c- Post hepatic jaundice : due to obstruction in
the excretion of bilirubin & the site of
obstruction is either intra hepatic or post
hepatic .
Tests used for the diagnosis of jaundice :
1- Total serum bilirubin . If the direct fraction
increase mainly then it is due to obstruction
. If the indirect fraction increase mainly
then it is due to failure of conjugation .
2- SGPT ( serum glutamate pyruvate
transaminase) increase due to failure of
conjugation .
3- Serum alkaline phosphates : increase in case
of obstruction .
Heterotrophic ( pathological) calcification :
Abnormal deposition of calcium any where in the
body except in the bone & the teeth , & it is of two
types :
1- Dystrophic calcification : Deposition of
calcium occur in dead or degenerated tissue
such as caseous necrosis ,fat necrosis , chronic
abscess , thrombi , infarction ,dead parasite &
atherosclerosis . The condition is usually
associated with normal calcium metabolism &
normal calcium level .
Pathogenesis : is not well known , it could be
due to one of the followings :
 Increase in the PH of the tissue i.e become
alkaline .
 Release of alkaline phosphates which
stimulate the deposition of calcium .
 The presence of cellular product which act as a
nucleus that stimulate the deposition of
calcium around it .
2- Metastatic calcification : Abnormal deposition
of calcium in a normal tissue associated with
abnormal calcium metabolism & high calcium
level .
Causes :
 excess absorption of calcium from intestine as
in patient taken excess milk which is used
previously in the treatment of peptic ulcer .
 excess mobilization of calcium from the bone
as in hyperparathyroidism , prolong
immobilization ,& destructive disease of the
bone such as multiple myeloma & secondary
deposit in the bone
Here the calcium is usually deposit in the kidney
either in the renal tubules cause
nephrocalcinosis or in the renal pelvis form stone
.
Calcium may also deposit in the lung , blood
vessel & the cornea .
Amyloidosis:
It is clinical syndrome characterized by abnormal
deposition of protein called amyloid usually between
cells and adjacent to cell mucus membrane . or in the
wall of small blood vessels .
Physical nature of Amyloidosis :
95% of Amyloidosis is formed from non branching
fibril it is about 7.5-10 nm in diameter and it has Bpleated configuration that is to say the polypeptide is
arrange in sheets at right angle to the axis of
filament , remaining 5% include non fibril pentagonal
glycoprotein which is also called p- protein .
Chemical nature of amyloidosis :
It has about 15 subtype ,the most common 3 types are
:
1- AL amyloid (amyloid light chain protein ) :
compose of the whole light chain of immunoglobulin
or the NH2 terminal fragment of the light chain . It is
usually form from plasma cell & deposition is seen in
B cell monoclonal proliferation .
2- AA amyloid( Amyloid associated protein ) : It is
non immunoglobulin protein compose of 76 amino
acid residue , form in the liver from precursor called
SAA (serum associated amyloid ) & deposition occur
in chronic inflammatory state .
3-AB amyloid : less common seen in Alzheimer
disease .
Classification of amyloidosis : depend on clinicochemical state :
1- Localized amyloidosis : here the amyloid is
deposited in local area of tissue form a mass seen in
the larynx , skin , tongue ,eye , lung & urinary
bladder .sometime it is also seen in malignant
condition as in basal cell carcinoma of skin &
medullary carcinoma of the thyroid .
2- Systemic amyloidosis : includes :
a- primary amyloidosis ( AL amyloidosis ) : usually
seen in elderly patient of unknown causes , however
it may associated with multiple myeloma or with
monoclonal gammopathy in which malignant B
lymphocyte synthesize abnormal amount of single
immunoglobulin producing M band in serum protein
electrophoresis , plasma cells may also form kappa or
lambda light chain that secrete in urine as Bence
jones protein . The disease affect the heart , GIT ,
nerve , tongue ,skin & sometime affect solid
abdominal organs.
clinically the patient may have diarrhea ,
malabsorption syndrome or purpra . death usually
occur due to heart failure or renal failure .
B- secondary amyloidosis :usually associated with
chronic inflammatory state which is either due to:
1- ch inflammation of unknown cause as in
rheumatoid arthritis.
2-chron suppurative disease with pus forming as in
tuberculosis and chronic osteomylitis .
3- It may occur with certain malignant condition
such as Hodgkin's disease & renal cell carcinoma
.
4- Chronic non suppurativ disease such as leprosy &
syphilis .
It usually affect solid abdominal viscera such as liver
,pancreas , spleen , kidney , adrenal & thyroid
gland. .
3- Hereditary ( familial ) Amyloidosis :
Seen in certain familial condition such as familial
Mediterranean fever which is a rare disease
Occur in limited area , transmitted as autosomal
recessive & it is of AA type .characterized by
fever of unknown origin with inflammation of
serosal surfaces.
Pathogenesis of Amyloidosis :
Primary type : Usually of unknown cause , or due to
certain carcinogen , this stimulate B- lymphocyte
monoclonal proliferation which is differentiated
into plasma cell that form light chain
immunoglobulin --
Unknown cause,carcinogen
B- lymphocyte proliferation
& differentiation
Plasma cell
Light chain
Deffect in proteolysis
AL protein
Secondary type :
Chronic inflammation cause macrophage activation
which secrete interleukin 1&6 , they stimulate
liver cell to form amyloid precurssor (SAA) ,
normaly this substance is degraded by certain
proteolytic enzyme ,diffecency of this enzyme
lead to deposition of amyloid A protein .
Chronic inflammation
Macrophage activation
secretion of Interleukin 1&6
liver cell
SAA
defect in proteolytic enzyme
AA protein
Effect ( clinical correlation ) of Amyloidosis :
It is variable depend on the site & extension of
deposition :
 it is either remain silent ( undetected ) .
 or it may cause serious effect in the form of renal
involvement (as nephritic syndrome which may
lead to chronic renal failure) ,
 hepatosplenomegaly.
 Cardiac involvement in the form of arrhythmia
or cardiomyopathy which lead to heart failure .
Microscopic features :
In H&E stain section Amyloid appear as
eosinophilic refractile extra cellular material
which should differentiate from hyaline changes by
special stains include :
1- Lugols iodine : used for gross specimen only ,
tissue contain Amyloid stain deep brown while
normal tissue stain light brown .
2- Congo –red : Amyloid appear red under light
microscope & yellow green under polarized
microscope .
3- Electron microscope : it appear as amorphous
thin fibril .
4- Immunohistochemical stain : used to
differentiate the subtype of Amyloid .
Diagnosis of Amyloidosis :
1- Clinical signs & symptoms .
2- Biopsy ( rectal gingival or renal .
3- Serum & urine protein electrophoresis .