regressive_lesions-2.pdf

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Fatty liver

Regressive lesions -2

- Steatosis (fatty degeneration, fatty change) it is a particular type of

intracellular degeneration which consists in extensive accumulation of

lipids in parenchymal cells of affected organ

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Fatty liver

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Haemochromatosis (liver)

21 -

Fibrinoid necrosis (rheumatoid nodule)

Fatty change of the liver. In most cells, the well-

preserved nucleus is squeezed into the displaced rim

of cytoplasm about the fat vacuole

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Caseous necrosis (tbc)

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Enzymatic necrosis of pancreatic fat tissue

(Balser type)

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Apoptosis (viral hepatitis)

- Adiposity (interstitial fatty infiltration) it is abnormal increase in

adipocytes in stroma of affected organ (hyperplasia of adipose tissue)

18 - Fatty liver

Fatty change is often seen in the liver because it is the major organ

involved in fat metabolism, but it also occurs in heart, muscle, and kidney

In normal circumstances no lipids are histologically demonstrable within

hepatocytes

18. NAFLD and NASH

In industrialized nations, by far the most

common cause of significant fatty change in

the liver (fatty liver) is alcohol abuse

Excessive accumulation of lipids in

hepatocytes may arise from:

• NAFLD (non-alcoholic fatty liver disease) first

described in 1980

• Liver disease developes in individuals who do not

drink alcohol

2 groups:

•

• Increase in mobilization of fatty acids from

adipose tissue

• Increase in intensity of hepatic lipogenesis

• Decrease in fatty acids utilization (oxidation)

• Reduction in secretion of lipoproteins

Steatosis (fatty liver)

•

NASH - non alcoholic steatohepatitis

Schematic diagram of the possible mechanisms leading to accumulation of triglycerides

in fatty liver. Defects in any of the steps of uptake, catabolism, or secretion can result in

lipid accumulation .

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Fatty liver (Steatosis hepatis)

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Fatty liver

MA: fatty change may be either asymptomatic or present with mild

enlargement and tenderness of the liver. In the case of severe chronic fatty

change liver is enlarged, with stretched out capsule, rounded edges, and

decreased concistency. In diffuse panlobular steatosis, cut surface is

uniformly yellowish with blurred lobular pattern

The causes of steatosis include:

drugs (e.g. corticosteroids, salicylates, tetracyclines)

toxins (e.g. mushroom- Amanita phalloides - toadstool)

protein malnutrition,

diabetes mellitus,

obesity,

Anoxia,

Fatty liver.

This liver is slightly enlarged and has a

pale yellow appearance, seen both on

the capsule and cut surface.).

Insulin resistance

Dyslipidemia (hypertriglicerinemia, low high density lipoprotein

cholesterol, high low density lipoprotein cholesterol)

18 - Fatty liver

MI: microscopically, hepatic fatty change can be subdivided into micro- and macrovesicular

ones . The former is observed for example in Reye’s syndrome. Macrovesicular we can see in

alcohol abuse, obesity, acute mushrooms poisoning. Macrovesicular (large droplet) steatosis

hepatocytes show large fat globule in central area of cytoplasm. They are frequently enlarged

with nucleus pushed towards stretched fat.

Because of presence of large, apparently empty round cells with peripheral nuclei, at first sight

fatty liver microscopically resembles adipose tissue. In fact lipids are absent on presented

slides, being dissolved out by routine tissue processing

Reye syndrome

•

Fatty change in the liver and encephalopathy

•

Affects children younger than 4 years of age

•

The pathogenesis: loss of mitochondrial function

•

Is associated with aspirin administration during viral

illnesses

•

MI: changes within hepatocytes and astrocytes

•

Sceletal muscle, kidneys and heart may reveal

mitochondrial alteration

•

The most severe forms are fatal

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Haemochromatosis (liver)

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Haemochromatosis (liver)

Hemochromatosis is a severe iron-storage disorder arising from abnormal

increase in intestinal iron absorption

Inborn or acquired damage to the barrier results in higher intestinal iron

absorption which surpasses the amount necessary for the synthesis of

heme.

Hereditary hemochromatosis – 4 genetic variants

The most common – an autosomal recessive disease caused by mutation in HFE

gene.

2 most common mutations – C282Y – 80% of hemochromatosis patients are

homozygous for the C282Y.

10% of hereditary hemochromatosis patients are compound heterozygotes for the

C282Y/H63D or homozygotes for H36D mutation

The remainder comprise variants of hereditary hemochromatosis that do not involve

the HFE gene

Acquired forms are known as secondary iron overload: multiple transfusion,

ineffective erythropoiesis (sideroblastic anemia, beta-thalasemia) and increase iron

intake (Bantu siderosis).

•

Iron is collected in form of haemosiderin in parenchymal

cells of various organs (predominantly liver, pancreas,

endocrine glands, heart).

•

It leads to cell damage.

Clinically the disease is mainly characterized by:

•

hepatic cirrhosis

•

diabetes mellitus due to the damage of beta cells

•

gray to bronze pigmentation due to overproduction of

ACTH and MSH secondary to adrenal gland insufficiency

•

heart failure

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Haemochromatosis (liver)

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Fibrinoid necrosis

( synonimously: fibrinoid degeneration)

MI: cirrhotic or non cirrhotic liver with numerous hepatocytes loaded with

golden brown haemosiderin granules. This deposits we can also see in

fibrous tissues, Kupffer cells or bile duct epithelium

It consists in the deposition of a deeply acidophilic substance called

„fibrinoid” in connective tissue and in the media of the vascular wall.

These deposits contain fibrin, IgG, IgM, complement, acid

glycosaminoglycans and amino acids. This resulted in the term „fibrinoid”

(fibrin like-substance).

Some of fibrinoid components derive from serum, others from ground

substance of connective tissue.

The most frequent fibrinoid constitutes the local effect of the action of

immune complex. Sometimes (e.g in the wall of renal arterioles in malignant

hypertension) etiology of this lesion is unknown.

It is a morphologic feature in a group of diseases named „ dissaminated

diseases of connective tissue” (historically „collagenoses” ) – rheumatoid

arthritis, SLE, scleroderma, periarteritis nodosa

Hemosiderin granules in liver cells. A , H&E section showing golden-brown,

finely granular pigment. B , Prussian blue reaction, specific for iron.

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Fibrinoid necrosis

( synonimously: fibrinoid degeneration)

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Fibrinoid necrosis

( synonimously: fibrinoid degeneration)

MI: histologically they are composed of a core of deeply eosinophilic

fibrinoid necrosis encicled by a rim of macrophages and fibroblasts showing

palisade-like arrangement

Rheumatoid nodule

Skin rheumatoid nodules occur in approximately 30% of patients with

rheumatoid arthritis, most frequently in the vicinity of joints, on extensor

surfaces of extremities or other areas subdued to pressure.

Such nodules are also found in internal viscera, including lungs, pleura,

gastrointestinal tube

MA: skin rheumatoid nodules attain about 1cm in diameter, are painless,

firm and easily movable.

Subcutaneous rheumatoid nodule with an area of fibrinoid necrosis surrounded by

a palisade of macrophages and scattered chronic inflammatory cells.

22 - Caseous necrosis (tbc)

It constitutes a distinctive subtype of coagulative necrosis .

Adjective „caseous” refers to the gross appearance of necrosis. Changed areas are

namely fragile, whitish-yelowish, similar to white cheese (Lat. „caseus” – cheese)

C.n. appears in non- or poorly vascularized, cell-rich tissues which are

subdued to the effect of endogenous toxins.

These conditions are fulfilled only by pathologic tissues: tuberculous and

luetic granulomas and malignant neoplasms.

MA: necrotic masses resemble white-yellowish cheese, are matt and brittle

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Caseous necrosis (tbc)

MI: focus of caseous necrosis appears as amorphous, granular debris (without even

any shadow of underlying structure of organ) enclosed within a distinctive

inflammatory border known as granulomatous reaction

Characteristic tubercle at low magnification ( A ) and in detail ( B ) illustrates central

caseation surrounded by: epithelioid and multinucleated giant cells (Langhans cells

- derive from numerous fused macrophages –their nuclei form peripheral circle or

horse-shoe) and lymphocytes.

A tuberculous lung with a large area of caseous necrosis . The

caseous debris is yellow-white and cheesy.

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Enzymatic necrosis of pancreatic fat tissue

(Balser type) – Balser’s fat necrosis

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Enzymatic necrosis of pancreatic fat tissue

(Balser type) – Balser’s fat necrosis

Balser’s fat necrosis is a hallmark of severe form of acute pancreatitis

which is characterized by acinar cell necrosis and foci of haemorrhage.

MACROSCOPICALLY:

The resulted foci (of insoluble soaps) are chalky white, well discrete on

yellow background of unchanged adipose tissue

Acute necrotizing/haemorrhagic pancreatitis is most commonly associated with:

• alcohol abuse and cholelithiasis . Less common factors include:

• trauma, abdominal surgery, metabolic abnormalities.

Û Damage of acinar cells leads to activation of pancreatic enzymes, especially

lipase, tripsin, chymotrypsin.

Û Action of lipase leads to injury of adipose tissue located in and around affected

pancreas.

Û The enzyme hydrolyses triglycerides (from fat tissue) with release of fatty acids

and glycerol . The latter is absorbed into bloodstream but fatty acids bind calcium

and magnesium ions to form insoluble soaps (fat saponification) . Active lipase

circulating with blood may cause extrapancreatic and extraabdominal fat necrosis

as well.

Foci of fat necrosis (Balser’s fat

necrosis) with saponification in the

mesentery. The areas of white chalky

deposits represent calcium soap

formation at sites of lipid breakdown.

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Enzymatic necrosis of pancreatic fat tissue

(Balser type) – Balser’s fat necrosis

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Apoptosis (viral hepatitis)

Apoptosis means genetically programmed, spontaneous death of cells

(suicide of cells)

The term „apoptosis” derives from a Greek word which means the falling

down of leaves. They become detached one after another, never all

simultanously. The same is true for apoptosis and it is a difference with

necrosis which usually involves the majority of cells of a given area.

Apoptosis fails to secrete any mediators – there is no inflammatory

reaction (on the contrary to necrosis) . Necrosis almost always induced

the inflammation which leads to phagocytosis of necrotic mass.

Apooptosis is physiological but also results from pathogen for example

viruses

Microscopical examination of adipose tissue affected with Balser’s

necrosis reveals „ghosty” adipocytes with blurred cell membranes and

bluish, granular cytoplasm. Additionaly amorphous basophilic extracellular

depositions of calcium can be observed

Acute pancreatitis .

The microscopic field shows a region of

fat necrosis on the right and focal

pancreatic parenchymal necrosis

( center ).

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Apoptosis (viral hepatitis)

Apoptotic hepatocytes are typically for viral hepatitis. They are called

acidophilic bodies ( Councillman’s bodies )

Morphologically apoptosis is represented by a sign of necrosis in the

single cells.

In single hepatocytes we can find the signs of necrosis:

-pyknosis (condensation of chromatin)

-kariorexis – fragmentation of nuclei with margination of chromatin

followed by its encapsulation and formation apoptptic bodies

-in the end cells disappears

Apoptotic hepatocytes are deeply pink and their nuclei are

condensated

Apoptosis of epidermal cells in an immune-mediated reaction. The apoptotic

cells are visible in the epidermis with intensely eosinophilic cytoplasm and

small, dense nuclei. H&E stain

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