Case 2- cell adaptions Flashcards
Dystrophic calcification
The calcification which occurs in degenerated or necrotic tissue, a type of soft tissue calcification. It may progress to ossification, in which case a cortical and trabecular bone pattern is visible
Metastatic calcification
The deposition of calcium salts in other wise normal tissue
What can cause ischaemia and infarction
Necrosis, apoptosis, pyknosis, free radical damage and hypoxic changes
Hypoxia- ischaemia and infarction
Reduced oxyge delivery to the tissue. Can be due to ischaemia which is inadequate blood supply or hypoxaemia which is the reduced partial pressure pf oxygen in the blood. Reduced oxygen means less ATP is produced, there will be a shift to anaerobic respiration which leads to metabolic acidosis which denatures proteins
Free radicals- ischaemia and infarction
Chemical radicals with a single unpaired electron in the outer shell, this makes them highly reactive. They readily form chemical bonds and tend to initiate or participate in chain reactions, ie drugs. Can cause damage to cell membrane and DNA.
Physical agents- ischaemia and infarction
Heat denatures proteins, acids can be corrosive. Bacteria may release toxins which lead to cell death
Ionising radiation- ischaemia and infarction
Water when ionised can form highly reactive radicals which can cause DNA damage. It may not be repaired or is mis-repaired
Necrosis- ischaemia and infarction
Pathological cellular/ tissue death in a living organism, irrespective of cause. Leads to an inflammatory response
Apoptosis- ischaemia and infarction
Normal or pathological individual cell death which is programmed. It is characterised by activation of endogenous proteases and endonucleases. There is no inflammatory response and it is energy dependent.
The three pathways of apoptosis
1) The intrinsic mitochondrial through cytochrome C
2) The extrinsic receptor ligand which is the fast ligand and TNF.
3) The cytotoxic T cell pathway using perforins.
In all of them the nucleus condenses and fragments, the apoptotic bodies are phagocytosed. No inflammatory response because the cell membrane is intact
Pyknosis
Shrinkage of nucleus in necrotic cells
Karyorrhexis
Fragmentation of nuclear membrane
What are the cellular changes in angina
Cellular swelling (oncosis), this causes blebbing of the membrane (membrane bulges outwards), loss of microvilli and swelling of the rough ER. There are also fatty changes (steatosis) fats accumulate in cells. This is related to disturbances in ribosomal function and commonly occurs in the liver.
Cellular changes in myocardial infarction
Caused by damage to the plasma membrane. As well as the mitochondrial membrane- the cytochrome C within the membrane leaked out activating apoptosis. The lysosome membrane is also damaged, this can release lytic enzymes.
Two types of cell death
Apoptosis and necrosis
Types of necrosis
Fibrinoid, gangrene, fat, caseous, liquefactive and coagulative
Why does cell injury occur
When the stress exceeds the ability of the cell to adapt
Fibrinoid necrosis
Only in small blood vessels. Causes include malignant HTN, vasculitis. The blood vessels are under such pressure that there is necrosis of the smooth muscle wall. This causes seepage of plasma into the damaged vessel walls with the disposition of fibrin. They stain bright pink/red.
Gangrene necrosis
Necrosis with putrefaction (decay) of the tissues. This can be caused by a disruption of blood supply and is sometimes associated with the action of bacteria. The affected tissues appear black due to the deposition of iron sulphide from degraded haemoglobin. You can get dry gangrene which is reduced blood supply due to vascular problems. You can also get wet gangrene which is due to infection, the swelling from the infection occludes blood vessels causing superimposed liquefactive necrosis. The final type is gas gangrene, muscle necrosis causes sepsis and gas production, commonly caused by the bacteria clostridium perfringens.
Fat necrosis
Involves fat cells, it can occur in pancreatitis, the release of lipases causes enzymatic lysis (breaks down membranes) around the pancreas. The Hydrolysis of triglycerides releases fatty acids which can combine with calcium deposits, in a process called saponification, forming white chalk like areas of necrosis.
Caseous necrosis
Associated with TB and some fungi. It is a variant of coagulative necrosis. It is formed by the release of lipids from the cell walls of Mycobacterium tuberculosis after destruction by macrophages.
Liquefactive necrosis
Commonly occurs in the brain because of lack of substantial supporting stroma. The inflammation response from surrounding cells (glial response) can cause cyst formation. If associated with infection it can form an abscess, as the contents are liquified by enzymes from neutrophils.
Coagulative necrosis
Most common form of necrosis, occurs in ischaemia in any organ except the brain. The cells retain their outline as the proteins coagulate. If you look through a microscope you initially see no change then progressive loss of nuclear staining accompanied by loss of cytoplasmic detail. Initially normal/firm texture then softens as the tissue is digested by Macrophages. Can be catastrophic in myocardial infraction.
Atrophy
A decrease in both size and number of cells
Hypertrophy
Increase in cell size, cell number is never affected
Hyperplasia
Increase in the number of cells of an organ or tissue
Metaplasia
A reversible change where one cell type is replaced by another. The cell may be better able to withstand the stress
Mechanism which brings about atrophy
The ubiquitin-proteasome pathways. In this pathways targeted tissue proteins are conjugated with ubiquitin, a small regulatory protein. Attachment of ubiquitin, known as ubiquitination, allows proteasomes to attach to the targeted cell and degradation occurs via proteolysis. Can either be physiological (normal) or pathological (abnormal)
Hypertrophy mechanism
A cellular adaption to an external stressor. The trigger could be mechanical, for example, can be via a receptor which then stimulates local growth factors. Can be hormonal stimulation through endocrines. Once the signal has been received a target cell will initiate protein synthesis ad start increasing its cellular components and organelles. Physiological hypertrophy could be muscle growth, pathological hypertrophy can be cardiac hypertrophy.
Hyperplasia mechanism
Due to either growth factor driven proliferation or from stem cells
Physiological Hyperplasia mechanism
- Hormonal hyperplasia- under the influence of hormones the functional capacity of a tissue is increased through cell growth, for example, increasing the number of breast cells in a girl in puberty.
- Compensatory- it increases the tissue mass after damage or partial resection. For example, when someone donates half the liver the cells in the remaining liver proliferate so it grows back to its original size.
Pathological Hyperplasia mechanism
Caused by an excess of hormones or growth factors acting on a target cell. The hyperplasia can regress if the stimulus is removed. Can be caused by a viral infection
Metaplasia mechanism
Due to reprogramming stem cells in normal tissue, or reprogramming the undifferentiated mesenchymal cells present in connective tissue. This differentiation is triggered by signals generated by cytokines, growth factors and extracellular matrix components in the cells environment. This promotes the expression of genes which drive the cells towards a specific pathway of differentiation. Some other external factors cause metaplasia by altering the activity of transcription factors that regulate differentiation. It is a reversible change
