CELL INJURY AND CELLULAR ADAPTATIONS I.

(necrosis, atrophy, intracellular accumulations, pigments) (Encephalomalacia, haemorrhagic lung infarction, anemic kidney infarction,

focal necrosis– myocardial infarction, diffuse liver necrosis, muscular

atrophy, hydropic change kidney, vacuolar change, liver steatosis,

lipomatosis of pancreas, amyloidosis of kidney and tongue)

General medicine

MUDr. Zuzana Čierna

MUDr. Svetoslav Štvrtina

MUDr. Michal Palkovič, PhD. Lucia Donárová

Department of Pathology, Faculty of Medicine UK & UH

Branch : Staré mesto

Sasinkova 4, Bratislava

Prof. MUDr. Ľudovít Danihel, CSc.

vital tissue

Pathological agent: (Hypoxia a ischaemia.

Physical agents.

Chemical agents and drugs.

Microbial agents.

Immunologic agents.

Nutritional derangements.

Ageing.

Psychogenic diseases.

Iatrogenic factors.

Idiopathic diseases.)

CELLULAR

ADAPTATIONS

(atrophy,

hypertrophy,

hyperplasia,

metaplasia,

dysplasia)

REVERSIBLE

CELL INJURY

(intracellular

accumulations)

IRREVERSIBLE

CELL INJURY

(cell death –

necrosis,

autolysis,

apoptosis)

Necrosis • irreversible injury

• intravital cell death

• types:

- coagulative necrosis

- liquefaction (colliquative) necrosis

- caseous necrosis

- fat necrosis

- fibrinoid necrosis

• outcome of necrosis:

– resorption

– reparation

– pathologic calcification

– gangrene (large ischemic coagulative necrosis – extremities, appendix,...); wet gangrene = infected necrosis caused by anaerobic microorganism

• distinguish from apoptosis!!!

Encephalomalacia (91)

• Liquefaction necrosis of the brain tissue

• With or without bleeding

• Etiology - focal necrosis of the brain tissue (thrombosis, embolia, atherosclerosis, hypotension...)

• Characteristic finding: debris-laden macrophages (eliminatory reaction)

• Result – postnecrotic (postmalatic) pseudocyst

Encephalomalacia

Oedematous brain tissue Debris-ladden macrophages

Detail - Debris-ladden macrophages

Hemorrhagic lung infarction (6)

• Coagulative necrosis of the lung tissue

• Cause – ischemia through lung embolism

(mostly deep vein thrombus)

• Develops only if there isn’t lung circulation

failure – patient survives

• At the same time there must be lung

hypertension and/or lung venostasis

• Triangular shape of lung infarction has its base

under the pleura, peak points towards lung hilus

Hemorrhagic

lung

infarction

Base is under the pleura

Peak points towards lung hilus

Numerous erythrocytes in the alveoli, shadow of alveolar septa.

Anemic kidney infarction (5)

• Coagulative necrosis of the kidney tissue

• Cause – local ischemia of the kidney tissue

• Demarcation edge is composed of leukocytes and

erythrocytes (hyperemia)

• Result - scar

Anemic infarction Hyperemic edge

Scars after infarction

Kidney

Infarction

Kidney

Anemic kidney infarction

Infarction - necrosis Demarcation reaction –

leukocytes, hyperemia

Necrosis – tissue shadowing

Scar after kidney infarction

Focal necrosis – myocardial infarction (93)

• Local ischemia of the tissue – coagulative necrosis

• Causes - thrombosis, embolism, atherosclerosis or spasmus of

coronarny artery, change in the amount and composition of

blood, arteritis (syphilis, LCA – large cell arteritis), increased

energy output

• Located predominantly in the left ventricle of the heart

• Transmural (STEMI) / non-transmural (N-STEMI)

• Complications – arrhythmia, blood pressure and volume

changes, heart failure, wall aneurysm (thromboembolism),

myocard rupture (cardiac tamponade), pericarditis

• Result - myocardial scar or death

Typical

appearance

of myocardial

infarction

myocardial infarction

myocardial infarction - detail

Scar after myocardial infarction

Diffuse liver necrosis (111)

• Etiology - toxic damage or inflammation

• Hepatocytes are preserved only in islands of

living tissue, perifocally with lymphocytic

inflammatory cells

Cellular adaptations

• Physiologic adaptation – to the physiologic needs

• Pathologic adaptation – to non-lethal pathologic injury

• Adaptations:

• 1. atrophy – reduction of the number and size of cells

• 2. hypertrophy – increase in the size of cells

• 3. hyperplasia – increase in the number of cells

• 4. metaplasia – reversible change of one type of mature cells to another type of mature cells

• 5. dysplasia – disordered cellular development

Atrophy (cellular adaptation)

• reduction of the number and size of cells

of normal developed organs / tissues

• Simple atrophy – shrinking of cells, tissues and

organs

• Numeric atrophy – reduction in the number of

cells

• Hypoplasia – developmentally small size

• Aplasia – failure of development

Atrophy - simple

Atrophy - numeric

Physiologic – normal process of ageing

(lymphoid tissue in thymus, gonads after

menopause)

Pathologic: 1. Starvation atrophy

2. Ischemic atrophy

3. Atrophy of inactivity

4. Neuropathic atrophy

5. Endocrine atrophy

6. Pressure atrophy

7. Idiopathic atrophy

Atrophy (cellular adaptation)

Muscular atrophy (302)

• Etiology – vascular, neurogenous,

metabolic, endocrine, functional

• Next image – striated muscle, left: partially

preserved hypertrophic muscle fibers,

right: atrophic muscle fibers.

Intracellular accumulations

(„dystrophy“)

Intracellular accumulations

(„dystrophy“) • Accumulation of constituents of normal cell

metabolism produced in excess (lipids,

proteins, carbohydrates, amyloid, urate)

• Accumulation of abnormal substances due to

lack of some enzymes (storage diseases,

inborn errors of metabolism)

• Accumulation of pigments; endogenous,

exogenous

Morphology of reversible cell

injury

1. Hydropic change (cloudy swelling,

vacuolar degeneration)

- intracelul.accumulation of sodium →

flow of water into the cell → mitochondrial

swelling and cellular swelling

e.g. hydropic change kidney

Hydropic change kidney (1)

(„parenchymatous dystrophy“)

• Toxic, ischemic, higher drainage

• Epithelial cells of proximal ducts are

enlarged with narrowing of the lumen,

nucleus is preserved, eosinophilic

granulated cytoplasm, electronogram

shows mitochondrial swelling

Vacuolar change (201)

(„vacuolar dystrophy“) • Electrolyte balance disorder (infusion of

hyperosmotic glucose, saccharose, changes in excretion of aldosterone), toxic impact, lack of oxygen

• Kidney – proximal ducts, enlargement of ductal epithelial cells, clear cytoplasm, nucleus preserved

• Histochemically there is a need to distinguish between glycogen, fat, mucus

Morphology of reversible cell

injury 2. Fatty change:

a) steatosis – intracellular accumulation of neutral

fat within parenchymal cells

- mostly in hepatocytes

b) lipomatosis – deposition of mature adipose cells

in the stromal connective tissue

Similar finding in storage disease

c) lipidosis (lysosomal, non- lysosomal)

Steatosis of liver

• Intracelullar accumulation of fat substances

• Etiology:

1.Conditions with excess fat (obesity, DM, congenital

hyperlipidaemia)

2.Liver cell damage (alcohol, starvation, hypoxia, chronic

illnesses, hepatotoxins, drugs)

- Microvesicular

- Macrovesicular

Oil red

Lipomatosis of pancreas (78)

• Etiology – metabolic, functional

• Increase of fat cell number

• Replacement of the pancreatic cells for

preservation of size and shape

Morphology of reversible cell

injury 3. Hyaline change:

-Intracellular hyaline (hyaline droplets, hyaline degeneration,

Mallory`s hyaline, hyaline inclusions, Russell`s bodies)

-Extracellular hyaline (hyaline arteriolosclerosis in ren. vessels

in hypertension, hyalinised glomeruli in chronic GN, corpora amylacea,

hyalinised scar of fibrocollagenous tissues)

4. Mucoid change:

-Epithelial mucin

-Connective tissue mucin

Intracellular accumulations

(„dystrophy“) • Metabolic glycid (sacharide) disorders

– Diabetes mellitus

• Type 1. (old name - insulin dependent)

• Type 2. (old name - insulin non-dependent)

• Impaired glucose tolerance (Impaired Fasting Glucose)

• Gestational Diabetes mellitus

– Glycogenosis (I. – VIII. Type) storage diseases

• I. Gierke disease

• II. Pompe disease

• III. Forbes disease

• IV. Andersen disease

• V. McArdle-Schmidt-Pearson disease

• VI. Hers disease

• VII. Type of colagenosis

• VIII. Type of colagenosis

Amyloidosis („amyloid dystrophy“)

• Pathologic, nondecomposable protein of a

β-structure with fibrillary aggregation

• fibril proteins (95%) and non-fibrillar

components (5%)

• Systemic (generalised) and Localised

• Primary and Secondary

Amyloidosis of kidney (tongue) (2)

• Outcome of chronic process

(inflammation, tumors)

• Presence of homogenous eosinophilic

material (amyloid) in the wall of glomerular

capillaries

Staining with - Congo Red

Staining with Congo Red - Fluorescence

Tongue – hematoxiline-eosine dye, amyloid

Staining with - Congo Red - Fluorescence

Tongue - amyloid