Case 2- cell adaptions

Question 1

Dystrophic calcification

Answer 1

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

Question 2

Metastatic calcification

Answer 2

The deposition of calcium salts in other wise normal tissue

Question 3

What can cause ischaemia and infarction

Answer 3

Necrosis, apoptosis, pyknosis, free radical damage and hypoxic changes

Question 4

Hypoxia- ischaemia and infarction

Answer 4

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

Question 5

Free radicals- ischaemia and infarction

Answer 5

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.

Question 6

Physical agents- ischaemia and infarction

Answer 6

Heat denatures proteins, acids can be corrosive. Bacteria may release toxins which lead to cell death

Question 7

Ionising radiation- ischaemia and infarction

Answer 7

Water when ionised can form highly reactive radicals which can cause DNA damage. It may not be repaired or is mis-repaired

Question 8

Necrosis- ischaemia and infarction

Answer 8

Pathological cellular/ tissue death in a living organism, irrespective of cause. Leads to an inflammatory response

Question 9

Apoptosis- ischaemia and infarction

Answer 9

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.

Question 10

The three pathways of apoptosis

Answer 10

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

Question 11

Pyknosis

Answer 11

Shrinkage of nucleus in necrotic cells

Question 12

Karyorrhexis

Answer 12

Fragmentation of nuclear membrane

Question 13

What are the cellular changes in angina

Answer 13

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.

Question 14

Cellular changes in myocardial infarction

Answer 14

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.

Question 15

Two types of cell death

Answer 15

Apoptosis and necrosis

Question 16

Types of necrosis

Answer 16

Fibrinoid, gangrene, fat, caseous, liquefactive and coagulative

Question 17

Why does cell injury occur

Answer 17

When the stress exceeds the ability of the cell to adapt

Question 18

Fibrinoid necrosis

Answer 18

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.

Question 19

Gangrene necrosis

Answer 19

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.

Question 20

Fat necrosis

Answer 20

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.

Question 21

Caseous necrosis

Answer 21

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.

Question 22

Liquefactive necrosis

Answer 22

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.

Question 23

Coagulative necrosis

Answer 23

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.

Question 24

Atrophy

Answer 24

A decrease in both size and number of cells

Question 25

Hypertrophy

Answer 25

Increase in cell size, cell number is never affected

Question 26

Hyperplasia

Answer 26

Increase in the number of cells of an organ or tissue

Question 27

Metaplasia

Answer 27

A reversible change where one cell type is replaced by another. The cell may be better able to withstand the stress

Question 28

Mechanism which brings about atrophy

Answer 28

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)

Question 29

Hypertrophy mechanism

Answer 29

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.

Question 30

Hyperplasia mechanism

Answer 30

Due to either growth factor driven proliferation or from stem cells

Question 31

Physiological Hyperplasia mechanism

Answer 31

• 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.

Question 32

Pathological Hyperplasia mechanism

Answer 32

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

Question 33

Metaplasia mechanism

Answer 33

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