SCBM341 - Cell InjuryHand-out/L01-Cell Injury and... · SCBM341 - Cell Injury 1 ... Common Causes...

SCBM341 - Cell Injury

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Associate Professor Dr. Wannee Jiraungkoorskul

Department of Pathobiology, Faculty of Science, Mahidol University

Tel: 02-201-5563, E-mail: [email protected]

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• 1. Discuss reversible and irreversible cellular injury in terms

of different etiology, type, pathogenesis and morphology.

• 2. Discuss cause of cell injury (ischemia, hypoxia)

• 3. Compare type of necrosis (coagulation, liquefactive,

caseous, fat and gangrenous) in terms of etiology, common

tissues involved, pathogenesis, and morphology.

Objectives

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• Injury : Any physical or chemical stimulus that

perturbs cellular homeostasis.

– Lethal injury : is followed by the death of cell.

– Sublethal injury : is not followed by cell death and

the cell is able to adjust by reaching some altered

steady states (-----> Cell Adaptation).

Basic Concept and Definition

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Vulnerable intracellular systems

1.ATP generation - Mitochondrial

aerobic respiration

2. Cell membrane integrity - Ionic and

osmotic homeostasis

3. Protein synthesis - Cell structure and

function

4. Integrity of the genetic

apparatus - Interactions with DNA

Injured Cells: Mechanisms

1 3

2

4

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Immunology

Cellular

Injury

Microbiology

GeneticPhysical

Chemical

Ischemic/

hypoxicNutrition

Common Causes of Cell Injury Malnutrition, Vitamin deficiency,Obesity

Autoimmune disease,Hypersensitivity

Virus, bacteria, fungi, parasite

Organic and inorganic agents

Temperature, Radiation

Free radical

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• Oxygen deprivation:

– Ischemia is a decrease or loss of blood supply, a

consequence of which is hypoxia, and also loss of

nutrients such as glucose.

– Hypoxia or decreased O2 in the blood, interrupts

aerobic respiration in cells e.g.,

• carbon monoxide (CO) poisoning (hemoglobin

can’t carry O2)

Common Causes of Cell Injury

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• 1. Cellular (Hydropic) swelling

• Reduced activity of sodium pump

• Increase in cell size secondary to water influx

• Acute and reversible, Pale cytoplasm

Morphology of Reversible Cell Injury

11http://clinicalscienceblogyaseen.files.wordpress.com/2013/02/hydropic-swelling2.jpg

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Mitochondria swelling

http://classconnection.s3.amazonaws.com/770/flashcards/998770/jpg/picture41326418189241.jpg

Cellular Swelling• Cellular swelling (synonyms: hydropic change, vacuolar degeneration,

cellular edema) is an acute reversible change resulting as a response to

nonlethal injuries. It is an intracytoplasmic accumulation of water due to

incapacity of the cells to maintain the ionic and fluid homeostasis. It is

easy to be observed in parenchymal organs : liver (hepatitis, hypoxia),

kidney (shock), myocardium (hypoxia). It may be local or diffuse,

affecting the whole organ.

• Gross examination, the affected organ is enlarged, pale and soft.

• Microscopically, the cells are enlarged, with a clear cytoplasm (due to the

presence of small clear or pale vacuoles, with indistinct shape and limits)

and a normal nucleus in central position; blood capillaries are compressed,

explaining the organ's pallor. 13

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2. Fatty Accumulation

Normal Liver Morphology of

Reversible Cell Injury

15http://clinicalscienceblogyaseen.files.wordpress.com/2013/02/fatty-change-liver_steatosis.jpg

Fatty Change

• Fatty change or Steatosis represents the intracytoplasmic accumulation

of triglyceride (neutral fats) of parenchimal organs, such as: liver,

myocardium and kidney.

• Mechanisms : increase of free fatty acids (starvation, diabetes and

chronic ethylism/alcoholism), reduction of free fatty acids oxidation

(hypoxia, toxins, chronic ethylism/alcoholism), increase of esterification

of free fatty acids into triglycerides (due to increased free fatty acids or

reduction of their oxidation, chronic ethylism/alcoholism) and reduced

export of triglycerides due to deficiency of lipid binding apoprotein

(starvation/malnutrition, toxins). Initially, fatty change does not impair

the cells function, being reversible.19

2020

1. excess entry of free

fatty acid into the liver

2. Enhanced fatty acid

synthesis

3. Decreased fatty acid

oxidation

4. Increased esterification

of free fatty acid to

triglycerides

5. Decreased apoprotein

synthesis

6. Impaired secretion

from the liver

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Necrosis

• A sequence of morphological changes that follow

cell death in a tissue

• There are 2 major processes

• 1. Enzymatic digestion of the cell

– From dead cells (autolysis)

– From invading inflammatory cells (heterolysis)

• 2. Denaturation of proteins

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Types of Necrosis

Enzymatic necrosis vs. protein denaturation

Liquefactive necrosis Coagulation necrosis

Other patterns:

Gangrenous necrosis

Caseous necrosis

Fat necrosis

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Coagulation Necrosis

• Most common

• Preserves the structural outline of tissues for days

• Acids denature structural proteins and enzymes

• Characteristic of hypoxic death of cells in all

tissues except brain

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• Myocardial infarct

• Histology – 12-18 hours

– Eosinophilic, anuclear

fibers

– White blood cell infiltrate

• Gross – days 4-5

– Pale infarct

– Hyperemic border

Normal cardiac muscle


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http://library.med.utah.edu/WebPath/jpeg4/ENDO051.jpg

The contrast between normal adrenal cortex and the small pale infarct

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Liquefactive Necrosis

• Characteristic of focal

bacterial or fungal infections

• Attraction of inflammatory

cells generate the enzymatic

digestion pus

• Process obliterates structure

of the tissue

• Characteristic of necrosis in

CNS

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Kidney:

• Focal fungal infection

• Site is filled with

white blood cells and

debris

• The abscess destroys

structural detail

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Caseous Necrosis

Combination of coagulation and

liquefaction necrosis found

principally in the center of

infections caused by

Mycobacterium tuberculosis

Gross- soft, friable whitish-gray

debris resembling cheesy

(caseous) material

• Glass -the cells are not totally

liquefied nor their outline

preserved creating a destructive

amorphous granular debris

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In Granuloma (Tubercle) of Tuberculosis

Multinucleated Giant Cell (Langhan)

Caseous Necrosis

Johann Ferdinand Friedrich

Theodor Langhans

(1839-1915)

German pathologist

33https://secure.health.utas.edu.au/intranet/cds/pathprac/Files/Cases/Respiratory/Case36/Pictures36/G2.jpg

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Fat Necrosis

Specific morphological pattern of cell death

encountered, when lipases escape into fatty depot

e.g., acute pancreatic necrosis

lipase

Fat (triglyceride) Glycerol + Fatty acid + cations

saponification

cation soaps (Ca++, Na+, K+ etc.)

(Amorphous granular basophilic deposits)

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• Focal areas of fat necrosis in peritoneal cavity

– Caused by release of pancreatic enzymes

• Lipases

– Liquefy fat

– Hydrolyze triglyceride esters to release fatty acid

• Fatty acids combine with cations, e.g. calcium

– Fat saponification / chalky white areas

Fat Necrosis

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Fat necrosis, acute pancreatitis - Inflammation necrosis causes the

release of lipases from the pancreatic acini. Acute pancreatitis is a

result of alcoholism or gall stones.

http://www.cuhk.edu.hk/med/paf/slides/necrosis/images/I3.jpg

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Gangrenous Necrosis

* Not a distinctive pattern

* Usually refers to a limb which has lost its blood supply and has

subsequently been infected by bacteria

* When coagulative pattern is dominant the process may be termed

“dry gangrene” and when the liquefactive action is more

pronounced it may be designated as “wet gangrene”

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How do You Tell a

Cell is Dead?

• Cytoplasm becomes

hypereosinophilic,

• Nuclear pyknosis,

karyorrhexis, and

karyolysis are the easiest

ways to tell that cells are

dead.

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karyolysis

References

Kumar V, Abbas AK, Aster JC. Robbins Basic Pathology. 10th ed. Elsevier 2017.

Vinay Kumar

Stanley RobbinsAmerican Pathologist (1915–2003)1st ed Textbook of Pathology 1957

Abul K. Abbas

Jon C. Aster

The Internet Pathology Laboratory for Medical Education,

Mercer University School of Medicine

http://library.med.utah.edu/WebPath/

SCBM341 - Cell InjuryHand-out/L01-Cell Injury and... · SCBM341 - Cell Injury 1 ... Common Causes...

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