Cell and Tissue Damage

Chapter 1 Cell and Tissue Damage



Cellular Physiology and Pathology 2

Control of Cell Number 3

Apoptosis 4

Cell Damage 5

Necrosis 6–8

Necrosis – Autolysis 9

Cell Damage – Hydropic Swelling 10

Cell Damage – Fatty Change 11

Cell Damage – Free Radicals 12

Cell Damage – Radiation 13

Atrophy 14

Ageing 15

Heredity, Genes and Disease 16, 17

Mitosis and Meiosis 18

Genetic Abnormalities and Associated Disorders 19–21

Amyloid Deposition 22, 23

Amyloid Classification 24

Calcification 25

Endogenous Pigmentation 26–28

Exogenous Pigmentation – Degenerations 29


Cellular Physiology And Pathology


Understanding disease requires knowledge of cellular function and dysfunction.


Cellular physiology involves:


(a) Close relationships between cellular components and activities.

(b) Balancing control mechanisms to maintain constant conditions (homeostasis).

(c) Compensatory and repair mechanisms to minimise damage.


Plasma Membranes


Main functions.


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Membrane damage may lead to cellular dysfunction or death.


MITOCHONDRIA These are the main sites of ENERGY production.


Disorder of energy production affects all cellular functions.


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Nucleus


The nucleus controls all cellular activities through the action of at least 10 000 genes, each of which encodes a protein with structural, enzymatic or control functions.


Damage to DNA (e.g. by ionising radiation) is particularly likely in dividing cells. There are effective repair mechanisms but severe damage usually leads to cell death by apoptosis (see p.4).


Germ cell DNA damage (i.e. to spermatogonia or oocytes)


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Somatic Cell DNA Damage


This is acquired during life. Damage to stem cells is especially important.


The development of cancer (p.152) through activation of oncogenes or loss of tumour suppressor genes is the most important example.



Lysosomes









These membrane bound organelles contain hydrolytic enzymes and are responsible for digestion and disposal of complex substances. → Disorder may lead to escape of enzymes or to accumulation of digestion products (e.g. storage disorders).


Control of Cell Number


In adult life the CELL NUMBER is fairly constant. Complex control mechanisms evenly balance new cell production with cell loss.


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During SOMATIC GROWTH cell proliferation outweighs cell loss.


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In the ATROPHY of old age, cell loss outweighs cell proliferation.


In many diseases the balance is lost.




Cell Proliferation – the Cell Cycle


In adult life, cells can be classified into 3 groups according to their proliferation potential.




















  Proliferation potential Examples
1. LABILE CELLS rapid proliferation and cell turnover gut-lining epithelial cells
2. STABLE CELLS slow proliferation and cell turnover hepatocytes
3. PERMANENT CELLS NOT able to proliferate neurones

In preparation for division, a cell passes through 4 consecutive phases (G1, S, G2, M) ending in Mitosis (M).


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A variety of growth promotors, inhibitors and drugs influence the cycle at various stages.


Knowledge of the cycle underlies the understanding of mechanisms involved in HEALING and REPAIR and in CARCINOGENESIS.



Apoptosis


A variety of noxious agents can damage cells. These include:


1. Reduced oxygen supply – respiratory disease, cardiovascular disease, anaemia

2. Physical agents – mechanical trauma, excessive heat or cold, radiation

3. Chemical agents

4. Toxins – bacteria, plants, animals (e.g. snakes)

5. Viruses

6. Abnormal immunological reaction – hypersensitivity states, glomerulonephritis

7. Nutritional deficiencies – vitamin deficiency and malabsorption syndromes

8. Genetic abnormalities – Down’s syndrome.

The severity of the injury determines the outcome:


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Apoptosis (programmed cell death) (Greek: apoptosis = falling off, like leaves from a tree) is an important process in health and disease by which, unlike necrosis (p. 5), abnormal or unwanted cells are eliminated. It involves activation of a programmed series of events co-ordinated by a dedicated set of gene products. It is an active process. A few examples are:


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Apoptosis in Health


In embryogenesis and development


(i) Metamorphosis of tadpole to frog.

(ii) Loss of autoreactive response of ‘T’ cells in the thymus preventing auto-immune attack.

(iii) In atrophy and involution, often on withdrawal of hormones, e.g. menstrual breakdown of endometrium.


Apoptosis in Disease



(i) Irradiation,

(ii) Virus infection,

(iii) Action of cytotoxic ‘T’ cells, e.g. in rejection of transplanted organs.

(iv) In tumours, apoptosis and proliferation rates together control the rate of tumour growth.

Apoptosis is a rapid process usually affecting SINGLE CELLS scattered in a population of healthy cells. It is considered in 2 stages:



Cell Damage


Stage 1: Cell death


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Stage 2: Cell elimination


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1. The surrounding cells move together to fill the vacant space, leaving virtually no evidence of the process.

2. The plasma membranes around the apoptotic bodies remain intact.

3. There is no inflammation.

4. Apoptosis is tightly regulated by many genes including ced and bcl-2. These co-ordinate cell death through the control and integration stage and final execution phase.


Necrosis


This term describes death of a cell or group of cells, typically following severe hypoxia, physical or chemical injury. Death of the cell is associated with rapid depletion of intracellular energy systems. Initially there are no morphological changes, but within a few hours the cell membrane and intracellular organelles are disrupted. Electron microscopy demonstrates these changes earlier than light microscopy.


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What we recognise as necrosis is due to denaturation and coagulation of protein and/or digestion of the cell by released enzymes. There are several naked eye appearances depending on which of these predominates.



Necrosis



Coagulative Necrosis


This type of necrosis is frequently caused by lack of blood supply, e.g. infarcts of the heart, spleen and kidney.


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The following changes are seen using the light microscope:


1. The nucleus shows one of three changes: (a) Karyolysis, (b) Karyorrhexis or (c) Pyknosis.

2. The cytoplasm becomes opaque and strongly eosinophilic (affinity for the red dye, eosin).
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At electron microscope (E.M.) level, in addition to the above nuclear changes, disorganisation and disintegration of the cytoplasmic organelles and severe damage to the plasma membrane are seen with the formation of surface blebs.



Colliquative Necrosis (Liquefactive Necrosis)


Death of cells in the brain result in liquefactive necrosis in which the dead cells are broken down to form a liquid mass. There is complete loss of structure (see p. 535).


An abscess (see p.39, 40) is another example of colliquative necrosis.



Gangrene


This is a complication of necrosis, which occurs when tissues are invaded by bacteria which release proteolytic enzymes. These enzymes degrade the necrotic tissue releasing foul-smelling gases. The tissue becomes green or black due to breakdown of haemoglobin. Obstruction of the blood supply to the bowel, for example, is almost inevitably followed by gangrene:


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A special type of gangrene follows infection with clostridial organisms (gas gangrene; see p.70).



Caseous Necrosis


This is commonly seen in tuberculosis (p. 72). The necrotic tissue has a cream-cheesy appearance.


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Fat Necrosis


This is a descriptive term for a form of fat destruction seen, for example, in trauma and pancreatitis. The appearances are due to the action of lipases on triglycerides as follows:


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Fibrinoid Necrosis


This is a descriptive term in which connective tissues and especially arterial walls are infiltrated by a strongly eosinophilic hyaline material which shows some of the characteristics of fibrin.



Necrosis – Autolysis



Sequels of Necrosis



1. When small numbers of cells are involved, the cellular debris is removed by phagocytosis (see p. 36).

2. With larger numbers of dead cells, there is an inflammatory response with organisation and fibrous repair (see p.40).

3. When the necrotic tissue cannot be completely removed or organised, deposition of calcium may be an additional feature, for example in tuberculous caseous necrosis. This feature is important in radiological diagnosis. It is known as ‘dystrophic calcification’ (p.25).


Autolysis


The process of ‘self-digestion’ begins after the death of the cell (as described above) and proceeds at a rate dependent on the local enzyme content. The term is hence more commonly applied to the changes which take place in tissues removed from the body and in the whole body after death.



Cell Damage – Hydropic Swelling


The various agents which can cause cell necrosis may also cause lesser cell damage which is reversible when the injurious agent is removed.


The appearances and effects are considered under these headings: 1. hydropic swelling, 2. fatty change, 3. radiation and 4. atrophy.



Hydropic Swelling


Under the light microscope: Electron microscopic (EM) appearances indicate the mechanisms:


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Naked eye: The damaged organs become swollen and are pale.



Cell Damage – Fatty Change



Fatty Change


This is accumulation of fat in non-fatty tissues, e.g. skeletal muscles and the heart.


These tissues cannot metabolise the amount of lipid presented to them, resulting in its accumulation within the cells. Examples include:


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Anoxia due to anaemia, cardiac failure, respiratory disease.
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Related posts:

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  3. Liver, Gall Bladder and Pancreas
  4. Neoplasia

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Jul 23, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Cell and Tissue Damage

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