ELEMENTARY LESIONS TO CELLS, TISSUES, AND ORGANS
Plan
- GENERALITIES :
1-DEFINITION
2-INTEREST OF THE QUESTION
- REMINDERS
1-THE NORMAL CELL
2-THE EXTRA-CELLULAR MATRIX
3-FABRIC
4-ADHESION MOLECULES
4–1DEFINITION
4–2 MAIN FAMILIES
4–3HIGHLIGHTING OF ADHESION MOLECULES
- ELEMENTARY LESIONS OF CELLS/TISSUES/ORGANS
1-PATHOGENIC AGENTS
2-DAMAGE TO CELLULAR ORGANITES
2-1 ALTERATIONS OF THE NUCLEI
2-2NUCLEOLUS LESIONS
2-3RIBOSOMAL INJURIES
2-4ENDOPLASMIC RETICULUM LESIONS
2-5 PATHOLOGY OF LYSOSOMES
2-6 MITOCHONDRIA INJURIES
2-7CYTOSKELETAL INJURIES
2-8 PLASMA MEMBRANE LESIONS
VI. DEATH OF CELLS AND TISSUES: NECROSIS
1-APOPTOSIS
2-ALTERATION OF THE NUCLEUS
2-1REVERSIBLES
2-2IRREVERSIBLE
3-ALTERATION OF CYTOPLASM
*BY HYPER HYDRATION:
-BALLOONIZING DEGENERATION
-VACUOLAR DEGENERATION
*ALTERATION A TYPES OF HYPEREOSINOPHILIA
-EOSINOPHILIC CONDENSATION (ACIDOPHILIC NECROSIS)
*OTHERS
-TUMEFACTIONTROUBLE
-Ca2+ (CYTOSTEATONECROSIS)
4-TISSUE NECROSIS
4-1COAGULATION NECROSIS
4-2 LIQUEFACTION NECROSIS
4-3CASEOUS NECROSIS
4-4CYTOSTEATONECROSIS
4-5WET (GAS) GANGRENE
4-6 SUPURATED NECROSIS
V. ADAPTIVE CELLULAR AND TISSUE MODIFICATIONS :
1-ATROPHY
2-HYPERTROPHY
3-HYPERPLASIA
4-DYSTROPHY
5-METAPLASIA
6-CELLULAR METAMORPHOSIS
7-ANAPLASIA
VI. CONCLUSION
ELEMENTARY LESIONS TO CELLS, TISSUES, AND ORGANS
I. Introduction :
Cells are complex structures with regulatory mechanisms that ensure a balance between anabolism (construction) and catabolism (destruction).
The disruption of this balance under the action of numerous pathogenic factors leads to an alteration of the function and, to a greater degree, an alteration of the structure.
The lesion corresponds to a visible morphological modification of normal structures, during a pathological process, it affects one or more organelles at a time, cells, a tissue or an entire organ.
The elementary lesion corresponds to the lesion unit that can be isolated by the analysis of a set of lesions.
In front of the patient, many means are put in place in order to achieve this elementary lesion, we will cite respectively: the interrogation, the clinical examination, the various paraclinical examinations and possibly the histopathological examination.
Today, other means are used to reinforce this pre-therapeutic assessment, such as immunohistochemistry and molecular biology, in order to choose the best possible treatment.
II- Reminders:
2.1 The Normal cell:
The cell is the smallest unit of living matter that can exist and reproduce independently.
The eukaryotic cell is made up of:
- From a cytoplasm surrounded by a cytoplasmic membrane (this cytoplasm contains within it the different cellular organelles necessary for the functioning of the cell).
- From a nucleus surrounded by a nuclear membrane.
- When cells acquire a particular shape and internal organization characteristic of the type to which they belong, they are said to be differentiated.
(Nerve cells, epithelial cells).
2.2 Fabrics:
Tissues correspond to a set of differentiated cells which bathe in an extra-cellular matrix and which possess their own functional and biological characteristics.
There are 03 major groups of tissues:
- Epithelia
- Common and specialized connective tissue
- Nervous tissue.
2.3 The extracellular matrix:
The extracellular matrix includes the basement membrane (which supports polarized cells) and the interstitial tissue, it is made up of collagen type IV (basement membrane), type I and II (interstitial tissue), glycoproteins (laminin, fibronectin) and proteoglycans.
2.4 Adhesion molecules:
2.4.1 Definitions:
These are proteins expressed on the surface of the cell membrane, capable of ensuring selective or even specific adhesion between cells and the extracellular matrix.
The selectivity of an adhesion molecule is based on the ability to interact with a limited number of molecules called ligands.
They have 02 roles in the body: structural (ensuring the cohesion of a tissue) and functional (allowing the cell to ensure a specific, transient biological role).
2.4.2 Main:
1- Cadherins:
E-cadherin (all epithelia), N-cadherin (nervous and muscular tissue) and P-cadherin (mesothelia and epidermis).
Monomeric membrane glycoproteins.
Provide intercellular adhesion.
2- Immunoglobulins:
N – CAM (neutral cell adhesion molecule), intervenes in embryogenesis, expressed by nervous tissue in adults.
- ACE
- ICAM1 (intercellular adhesion molecule 1), ICAM (ia m2) and VCAM (vascular cell adhesion molecules).
- CD2: molecular adhesion proteins.
- Intervene in immunity (HLA, complement, etc.).
3- Integrins:
B1 and B3: adhesion of cells to the extracellular matrix.
B2 characteristics of leukocytes, intervenes in their functional interaction with the endothelium.
4- Selectines:
E-selectin and P-selectin, expressed by endothelial cells.
L selectin specific to a subpopulation of lymphocytes.
Monomeric transmembrane glycoproteins.
Involved in the adhesion of circulating leukocytes to endothelial cells.
CD44:
Surface glycoproteins.
Involved in the adhesion of cells to each other and to the extracellular matrix.
They would be involved in metastatic and inflammatory processes.
2.4.3 Highlighting adhesion molecules:
Example: during acute inflammation, the extravasation of circulating leukocytes involves different families of adhesion molecules.
1st stage: early and transitional:
Endothelial cells express P-selectin and E-selectin on their surface.
- This induction takes place in less than 2 hours and lasts for 10 to 20 hours.
- It is induced by certain cytokines.
- is responsible for slowing down circulating leukocytes (rolling).
- The leukocytes then express the ligands of these 02 molecules on their surface.
ELEMENTARY LESIONS TO CELLS, TISSUES, AND ORGANS
2nd stage : late and lasting:
- ICAM1 expression on endothelial cell, induced by interferon g, tumor necrosis factor and interleukin 1.
- VCAM expression on endothelial cell induced by tumor necrosis factor, lipopolysaccharides and interleukin-1.
- The expression of VCAM and ICAM allows the adhesion of leukocytes to endothelial cells thanks to the ligands present on their surface; leukocyte B2 integrins and integrin a 4B1.
Leukocytes thus migrate specifically to the inflammatory site, because only activated vessels can express the molecules responsible for slowing down the leukocytes, which is the necessary step for inducing the process.
III Basic lesions of cells/tissues/organs :
3.1 Pathogens:
A pathogen is any factor capable of causing a lesion or triggering a morbid process.
It can be exogenous, physical (trauma, etc.), chemical (caustic, etc.) or biological (virus, bacteria, etc.).
It can be endogenous, metabolic (calcium, cholesterol, etc.), immunological (deposition of C3 during SLE, autoimmune diseases, etc.), trophic (infarction, etc.).
The pathogen can act directly (e.g. HPV virus and koilocytes), or indirectly (helicobacter pylons and chronocellular gastritis, malti lymphoma). The same pathogen can induce different lesions depending on the mechanism involved; example: hepatitis B virus which can induce serious hepatitis.
Benign, depending on the immune mechanisms involved.
The same lesion can be caused by several different agents such as alcohol, medications, viruses responsible for chronic hepatitis.
3.2 Damage to cellular organelles:
3.1.2 Alterations of the nuclei:
(seat of genetic information and cell division):
Size anomalies:
Increase in size, regular in non-tumor pathology, irregular in tumor pathology.
Number anomalies:
Binucleation: reflects damage to the hepatocyte during viral hepatitis.
Multinucleation in macrophage reactions and in tumor cells.
Irreversible damage following cell death:
Pyknosis: condensation of chromatin into a dense, homogeneous, retracted block.
Karyolysis: the nucleus disappears, the chromatin is no longer colored.
Karyorhexis: fragmentation of the nucleus into small blocks dispersed throughout the cell.
Nuclear inclusions:
Nuclear vacuoles: by invagination of the cytoplasm into the nucleus.
Nuclear inclusions: of viral origin, the most frequent.
Metabolic: lead and bismuth poisoning.
Cell division abnormality:
Stopping the mitotic process
DNA duplication abnormalities.
3.2.2 Nucleolus lesions:
Number anomalies :
- Increased number of nucleoli in tumor cells.
- Nucleolar segregation: separation of its different constituents with reduction in protein synthesis (toxic substances, irradiation).
3.2.3 Ribosome damage:
(Protein synthesis agents)
Number anomalies:
Rarefaction: normal during cell maturation
Disaggregation of ribosomes which leads to cell death, results in a loss of normal basophilia of cells and is seen during chromatolysis of neurons, cellular anoxia or necrosis.
Agglomeration: in the form of grains or filaments, during lead poisoning.
3.2.1 RE lesions:
(intercommunicating gaps, support for many enzymatic activities, detoxification, triglyceride synthesis)
– Distension of the lacunae:
By accumulation of non-excreted substances, for example: hepatocyte steatosis.
Mott cells: accumulation of plasma cells in the dilated cisterns which become visible in the BM in the form of eosinophilic balls, example: chronic inflammation, Mott cell myeloma.
Due to α-1 antitrypsin deficiency.
REL hypertrophy:
By alcoholic barbiturate intoxication, results in the MO by an eosinophilic, abundant, finely granular cytoplasm.
3.2.5 Lysosome pathologies:
Lysosome overload:
- By congenital enzymatic deficiency: the consequence of which is the distension of the lycopods which become visible to the MO in the form of inclusions in a hypertrophied cell
Example :
- Dyslipoidosis: accumulation of complex fats.
- Mucopolysaccharidoses.
- Glycogenosis.
3.2.6 Mitochondrial damage:
(Cellular metabolism: phosphorylation, oxidation, Krebs cycle).
Size anomaly (reversible or irreversible):
- The low amplitude swelling is reversible, by widening of the inter-membrane space, the transfer of water takes place between the two compartments of high amplitude: concerns the internal compartment, irreversible.
Number anomaly:
- Results in the oncocytic aspect.
- Seen in the liver, thyroid, …… adaptive reaction? Membrane abnormality:
- By excess of calcium, sodium ….
Size anomaly :
- Increased size during alcohol intoxication, excess iron, insufficient oxidation of fatty acids.
3.2.7 Cytoskeletal damage:
(Microtubules and microfilaments responsible for the movements of cellular organelles, chromosomes, cilia, etc.).
Eyelash abnormalities:
Recurrent bronchopulmonary infections, sterility due to lack of sperm motility.
Microtubule abnormalities:
Mitosis block at anaphase.
Chediak-higashi syndrome
Micro filament anomalies:
Lazy leukocyte syndrome.
3.2.8 Plasma membrane damage:
- Receptive or exchange or contact surface.
- Shape abnormalities, sickle cell anemia.
- Abnormalities of membrane receptors, example: ID diabetes.
- Lysis of cell membranes EXP: by action of anesthetics: lymphocyte. Complement, bacterial toxins.
IV Death of cells and bacteria:
- Apoptosis:
- Physiological cell death programmed at a precise stage of the terminal maturation of the cell.
- At the embryonic stage, cells already carry the information of their own destruction at a specific moment in their existence.
- Cells do not die after an external aggression but by an active mechanism requiring energy and transcription.
Role of apoptosis:
- Regulation of various cell types in the body.
- Tissue homeostasis and maintenance of the growth/involution ratio)
- Elimination of unwanted cells: damaged, precancerous.
Circumstances of occurrence:
Physiological:
- Embryogenesis
- Hormonal regulation of homeostasis.
- Erythropoiesis
- Regulation of immunity
- Removal of growth factors
- Cell renewal in organs and during senescence
- Factors that induce apoptosis are virtually the same effectors that induce necrosis but at a lower concentration.
ELEMENTARY LESIONS TO CELLS, TISSUES, AND ORGANS
Morphology:
- Condensation of the cytoplasm and preservation of the morphology of mitochondria and ribosomes.
- Loss of contact areas with neighboring cells and isolation of the apoptotic cell.
- Disintegration of the nucleolus, decrease in the size of the nucleus.
- Chromatin condensation and marginalization
- Invagination of the nuclear membrane.
- Invagination of the cytoplasmic membrane.
- Constitution of round and smooth fragments, surrounded by a membrane and excluding trypan blue: apoptotic bodies.
- Phagocytosis of apoptotic bodies
Genetic controls of apoptosis:
The bcl-2 family, bcl-x, bax, bad and bak repress apoptosis.
Fas/APO-1 protein, ICE family encode proteins that induce apoptosis.
Biochemical characteristics of apoptosis:
Are not fully elucidated:
- Pre-commitment: reversible, marked by increased Ca2+, IP3 and/or cAMP.
- Commitment: irreversible, degradation of DNA from its hydrolysis.
Different types of apoptosis:
- Type I: caused by corticosteroids and radiation
- Type II: caused by TNF
- Type III: Caused by cytotoxic T lymphocytes.
Methods for identifying apoptosis:
- DNA electrophoresis
- Flow cytometry
- Immunohistochemistry
Initiation of apoptosis:
External agents: physical, chemical, viral, etc.
Internal agents: hormones, cytokines, killer cells….
Classic cell death is due to exogenous or endogenous aggression
It is linked to multiple main causes:
- Anoxia: cessation of oxygen supply
- Ischemia: decreased or stopped blood supply
- Toxins: bacteria, fungi, mercury, etc.
- Immunological lysis, complement, cytotoxic lymphocytes ……….
Whatever the aggressor, the ultimate lesion corresponds to an alteration of the plasma membrane with massive influx of calcium and an irreversible alteration of the mitochondrial membrane, with stopping of the oxidative chain.
4.2 Core alterations:
4.2.1 Reversible:
Condensation of chromatin into dense blocks (reversible then irreversible).
4.2.2 Irreversible:
- Pycnosis
- Karyolysis
- Karyorrhexis
4.3 Alterations of the cytoplasm:
By hyperhydration: entry of water and Na + .
Ballooning degeneration: the cell is swollen, clear and homogeneous cytoplasm, the organelles are not altered.
Vacuolar degeneration: the cell is swollen with small clear intracytoplasmic vacuoles (dilation of mitochondria and ER).
Hypereosinophil type alteration:
¨eosinophilic condensation, acidophilic necrosis.
Others :
Irreversible swelling, degradation of structural proteins, observed in the state (fresh in the cell).
Ca2 + (cytosteatonecrosis)
4.4 Tissue necrosis:
Necrosis: sudden and immediate death in response to a pathological stimulus or severe aggression, it corresponds to a rapid loss of control of ionic flow.
Leading to water penetration, swelling of the cell and organelles until they burst.
4.4.1 Coagulation necrosis:
Example: visceral white infarction (heart, kidney, adrenal).
Macroscopy: affected area, white-grayish in color with firm consistency.
Microscopy : the cells transform into an opaque eosinophilic mass with loss of nuclei and preservation of the cellular silhouette allowing the tissue architecture to be recognized.
This aspect of necrosis probably results from the denaturation of proteins which are made insoluble, thus delaying their proteolysis.
Dead cells are then liquefied and resorbed by fragmentation and phagocytosis by NPs and histiocytes.
1.1.2 liquefaction necrosis:
Example: brain softening:
Macroscopy: results in a gray tissue area, soft then quickly liquid when the lesion is recent, after a few days the ischemic focus becomes clearer, friable, and creamy on a fresh piece, later the focus is replaced by a retracted, gray, yellowish or buff tissue which depresses the cortex on the surface.
Microscopy: disintegration of structures, the tissue is no longer recognizable, cytolysis and cerebral edema are found, swelling of the cytoplasm, pyknosis and disappearance of Niss1 bodies are noted.
The axons fragment, the glial cells are the site of severe degenerative lesions.
Blood capillaries show endothelial turgor, congestion, and RBC extravasation.
Later, influx of polymorphonuclear cells and macrophages.
Liquefaction necrosis results from the powerful accumulation of hydrolytic enzymes of lysosomal origin.
4.4.3 Gas necrosis (homogenization necrosis):
Characteristic of tuberculosis:
- Macroscopy: the caseum appears opaque white-grayish homogeneous soft, pasty, reminiscent of cheese or more crumbly and calcified.
- Microscopy : areas of eosinophilic tints, finely grained and containing cellular remains and fragments of nuclei or homogeneous, cellular, it can liquefy, fibrose, calcify.
ELEMENTARY LESIONS TO CELLS, TISSUES, AND ORGANS
4.4.4 Cytocteatonecrosis:
Observed in acute pancreatitis and reflects autolysis of the gland.
Adipose tissue lesions in which the action of lipases releases fatty acids and glycerol.
Macroscopy: opaque, whitish focus, of chalky consistency contrasting with the yellow fatty background, in candle stain.
Microscopy: whitish nodules, surrounded by an inflammatory reaction, rich in PN.
Presence of necrotic, granular, irregularly acidophilic material.
Fatty acid crystals are almost always present.
A lipophagic granuloma surrounds the area of cytosteatonecrosis.
The evolution is towards encircling sclerosis.
4.4.5 Wet (gas) gangrene:
Example: lower limb ischemia.
Originally, gangrene referred to a massive necrosis of a part especially of the foot with putrefaction which resulted from the increase of saprophytic microorganisms.
Currently, it is characterized by the combination of ischemic necrosis and infection with anaerobic germs of the clostridium group (necrosis + putrefaction).
Wet gangrene is a combination of coagulation and liquefaction necrosis , dry gangrene applies to uninfected foci of dried and mummified coagulation necrosis.
Its very low water content allows resistance to putrefactive bacteria.
It is located on the extremities: feet, hand, tip of the nose, earlobe), it is a bluish plaque, which becomes firm then turns brown and black, there is no odor or formation of gas.
4.4.6 Suppurative necrosis:
Example: abscess, phlegmon.
Macroscopy : unctuous or granular pus, greenish yellow.
Microscopy : tissue lysis with accumulation of altered PN (pyocytes).
5. Cellular and tissue adaptive modifications:
5.1 Cellular or tissue atrophy:
Corresponds to the overall reduction acquired in the size of a cell, a tissue, an organ by reducing the size of the cells or the number of cells.
It can be physiological:
Involution of the thymus in adolescents, gonadal atrophy in the elderly.
It can be pathological:
- Due to nutritional deficiency (vitamin A, proteins)
- Hormonal in origin: testicular castration
- Circulatory disorders: myocardial atrophy in chronic coronary arteries .
- Innervation disorders: section of a motor nerve causes muscle atrophy.
- By compression: by a mass (tumor), abnormal distension of the natural cavities (renal parenchyma)
- Atrophy of an organ is not systematically followed by a reduction in its size since the atrophied cells can be replaced by fibrosis.
5.2 Hypertrophy:
Increase in the overall volume of the cell by increasing its organelles and/or the number of cells.
This cellular hypertrophy determines when it involves a large number of cells.
Physiological:
Athlete muscle, pregnancy uterus
Pathological:
- Alcoholic hepatitis (regeneration nodules), myocardial hypertrophy (aortic insufficiency).
- Obesity and overeating thyroid hypertrophy (iodine deficiency), cell hypertrophy, accumulation in interstitial tissue (fibrosis, amyloidosis).
5.3 Hyperplasia:
Increase in the number of cells without increasing their own volume.
5.4 Dystrophy:
Example: fibrocystic dystrophy of the breast.
Acquired tissue or cellular alteration, linked to a nutritional disorder (vascular, nervous, hormonal, metabolic).
Phenomenon of cellular adaptation.
ELEMENTARY LESIONS TO CELLS, TISSUES, AND ORGANS
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