Pathology Workshop 1-Part 1

8/3/2019 Pathology Workshop 1-Part 1

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First workshop: part I

Hypertrophy: increase in volume of tissue secondary to

increase in volume of cells. Its the only adaptation

possible for permanent tissue.

This is cardiomegaly with enlargement of left ventricle.

Secondary to hypertension.

Hypertrophic cells: enlarged cells

Increase in volume of cytoplasm: nucleomegaly.

Enlargement with increase of synthesis of structural

proteins.

Hyperplasia. (prostatic)

Abundant cells. Normal volume but abundant.

They dont fit in the lumen of the gland and they crowd

(speudopapillary projections) as they dont fit

Endometrial hyperplasia: glands covered by columnar cells

with areas of stratification.

Some tissues have hypertrophy and hyperplasia. In

pregnancy, they increase number and increase the

individual volumes of the cells by increasing the synthesis

of structural proteins.


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Atrophy: decrease in volume of tissue secondary to loss of

cells. This is secondary to lack of endocrine stimulus,

growth factors deficiency or ischemia (chronic decrease in

blood supply)

Loss of brain parynchyma

Atrophy secondary to lack of hormonal stimulus that

affects the endometrium after menaupasue and theres

physiologic and pathologic atrophy.

Ssecond image is a physiologic atrophy

Metaplasia is the change of a normal mature tissue for

another normal mature tissue but abnormal in

topography.

This corresponds to endocervical epithelium or bronchial

epithelium affected by squamous metaplasia.

Common causes of squamous epithelium of bronchus is

smoking, avitaminosis A.

Endocervix: columnar epithelium of endocervix have clear

large cytoplasma. Cells secrete mucin (transparent) which

is secreted mostly in the middle of the ovarian cycle (

around ovulation period) . with round unifirm nuclei at the

base of the cells. At the basal pole of the cels.

There are also reserve cells which are tissue specific stem

cells. Have the capacity to reproduce and differentiate.

They reproduce and have a squamous rather than a

columnar differentiation and in later stages, they replace

the single columnar one.

If cause of metaplasia is an intrauterine devide,

chlamydiasis, then metaplasia is an adaptation.

If the cause of the adaptation is an infection (HPV

infection), this is a a pathologic metaplasia


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Barretts esophagus as a type of metaplasia. Normaly

esophageal mucosa is squamous, the abnormal region is

the velvet hyperemic mucosa. That area (redish)

corresponds to glandular pattern.

Glandular metaplasia (Barretts esophagus)

Adenocarcinoma secondary to barretts esophagus. Not all

barretts esophagus becomes the adenocarcinoma , but

the reverse is true.

Dysplasia is an adaptation. We classify it as mild, moderate

and severe from left to right

clinical example of dysplasia: in prostate, breast lesion in

proliferative diseases of the breast (fibrocystic disease of

the breast)

Best known : cervical dysplasia as a consequence of HPV

infection. B nucleated cells. And clear perinuclear hallows.

Coliocytosis

Cell damage: ultrastructural changes with reversible or

irreversible damage.

Reversible is secondary to swelling. Cytosol swelling,

mitochondrial swelling. Here the mitochonia has early

signs of swelling, enlargement of organelles and area of

clear mitochondrial matrix.


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Here this is normal RER of liver

Example of swelling of mitochondria thats very evident.

Remanent of RER.

Cytosol occupied by detached ribosomes from the RER.

First sign of irreversible damage: calcifications. Dark spots

in the mitochondria.

Microscopic evidence of irreversible damage: cytoplasma

show shrinking wit hypereosinophilia: particularly in early

stages.

Nucleus show destruction of membrane, karyolysis

(removal of nuclear material).

Theres also Edema present.

This is the CNS.

In the capillary vessel, we see a dilated space thats

occupied by Edema. This space may be widened in acute

brain edema and is occupied by a transudate. May be

occupied by inflammatory cells : viral encephalitis. Wehre

theres natural killer cells ,t lymphocytes and microbial

cells.

Patterns of necrosis:

After irreversible damage, theres death and necrosis or

apoptosis.

Extreme coagulation necrosis to cascious necrosis

(spectrum)

Coagulation necrosis

Myocardial infarct as classical example of coagulation

necrosis

In coagulation necrosis we see hypereosinophilic plasma,

karyolysis and karyopignosis. (nuclear destruction)

Profile of cells is more or less preserved. We can tell the

celluar borders.


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Acute tubular necrosis:

Casued by ischemia (shock state) hypovolumic shock state.

Or toxocity (myoglobin and drugs toxic). Aminoglucoside

(nephrotoxins)

Coagulation necrosis is the most common outcome after

an ischemic damage.

Brain is the single important exception. After ischemic

damage theres liqiufaction necrosis.

Most common cause of liquifaction necrosis (aside from

brain) is infections (particularly bacterial or protozoal

infections: ambeobic ulcers)

In liquifaction necrosis (of this brain infarct), we can still

see some dying cells with hypereosinophilic cells. Theres

the fibrillary frame. Normal meshwork.At the right of the image, we dont see the normal mesh.

In that region, there are no normal cells : foamy

macropahges present in that region.

Dilated branch of portal vein.

Liver cells and isnucoids.

In the center, we see cadavers of leukocytes ( this is a liver

abscess)

Another example of liquifaction necrosis

Caseous necrosis:

Material has a cheesy consistency

Dry gangrenous necrosis: caused by ischemia or physical

damage:

Gangrenous necrosis

(other gangrene is wet : liquifaction and associated withinfection)

Enzymatic fat necrosis : of fat tissue (affecting mostly

breast)


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Adenocytes ingested by pancreatic lipases and amylasess.

Serum pancreatic amylases and lipases are signs of acute

pancreatitis

Perfusion damage:

Delay in enzymatic treatment after myocardial infarct and

delay in clot destruction leads to a reperfusion causing

widening of the previously infarcted area with further

damage caused by oxygen radicals. Morphologic clue:

tranferse irregular contraction bands.

Definition: Pathway of cell deathregulated by a suicide

program

Types: - Physiologic- Pathologic

Causes (of each type)

Apoptosis: pathway of cell death regulated by a suicide

program.

Intrinsic pathway: mediated by mitochondrialphenomenon: cytochrome C leak.

Extrinsic : regualted by dead receptors.

Vax genes are regulators of apoptosis

Physiologic apoptosis: embryogenesis.

Disidua detachment is physiologic apoptosis

Example of pathologic apoptosis.SC carcinoma: accelerated cellular turnover and some have

the capacity to kill themselves :mechanism to develop the

development of neoplasia.

In carcinomas (malignant neoplasia of epithelium origin)

Fatty liver:

Vacules are due to a dialted golgi apparatus.

Due to dietary defects: there could be fatty liver. If diet is

carbohydrate based and theres no milk or meat or

proteins consumed, liver cells wont have resources to

build up apoproteins. Those triglycerides from the diet will

accumulate in golgi apparatus.

Mallory hyaline .


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Unconjugated billiruin attachment

Wilsons disease: copper pigment accumulation.

Pigment accumulates in liver

Central nervous system and cornea accumulation of

cornea: classical clinical Kaiser Fleisher ring

Inflammation:

In acute inflammation the first cellular events are the

margination of leukocytes, addition to endothelial surface.

Rolling of them and migration.

Some leukocytes may migrate through capillary wall.

Defects in adhesion:

Glucocortisteroids represent a defect in addition

Diabetis mellitus is a complex disease with perfusion

defects in the vessels: disease of microcirculation

characterized by lazy leukocytes, defect in addition and

repair and collagen synthesis

Alcohol intoxication:

IATROGENIC

D.M.

ALCOHOL INTOXICATION

LEUCOCYTES DEFECTS:

- AR

- Chronic bacterial infections

chronic and systemic granulomatose disease is an example

of leukocyte dysfunction.

Example: young kid with light skin, hair and iris. He

presents a medical history of infection (pyogenic infection

)

Peripheral blood analysis show a band form of neutrophil

with gigantic granules. The granules are the lysosomes.

Theyre a hallmark of granulocytes. Theyre large because

they cannot degranulate.

The cells have the capacity to phagocyte but cannot

degranulate.


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Contraction of cytoplasma leading to inter endothelial cells

gaps increasing the vascular permeability leading to

transudate and exudate.

Histamine and serotonin are stored in mast cells and

endothelial cells. (preformed)

mediators synthesized denovo: require injury to

synthesize.

Wet gangrene is a phenomenon of necrosis mostly

associated with infection because tehre are many bacteria

that synthesize phospholipase. They use phospholipases as

weapons to invade tissues.

Clostridium P.

PAF and arachidonic acid

In response to bacterial infection

Arachidonic acid pathways:

Three major families of chemical mediators: leukotriens,

prostaglandines and lipoxines.

Leukocytes products accumulate in lysosomes. Lysosomes

are filled with enzymes .

Neutrophils and macropahges have neoperoxidases,elastasis.


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Pneomonia with lysosomal enzymes. Many cells present is

an early onset of acute inflammation (within first three

days)

Macrophages predominant in this slide: this is a later stage

of acute inflammation. Mediated by lysosomal enzymes.

Cytokines are mediators synthesized denovo by

macrophages and CD4 positive T cells. There are many

forms of cytokines . TNF and interferons are families (TNF

alpha)

TNF alpha and interleukin 1 are among the most important

one (with interferon gamma), they mediate addition

molecules, further synthesis of other cytokines, provoke

eicosanoid production (arachidonic acid metabolites) and

chemokiens and they activate oxygen radicals.

Also lead to aggregation and priming.

Elevation of acute phase reactants also mediated by TNF

and IL.

Chronic syntehsis of IL and TNF causes cachexia in cancers

and terminal inflammatory infections.

Hypotension (shosk state) by TNF.

Cachexia: TNF alpha and IL1 lead to this.

All the chemical meidator of inflammation have a

protective goal, but all can become causes of death.

Oxygen and free radicals mediate tissue damage as well as

nitrogen oxide

Pathology Workshop 1-Part 1

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Transcript of Pathology Workshop 1-Part 1