cell injury Flashcards
causes of cell death/injury
hypoxia, physical agents e.g cold, radiation or trauma, chemical agents e.g alcohol, microorganisms, immune mechanisms, dietry insufficiency or excess (obese) or genetic abnormalities (e.g errors of metabolism)
what is hypoxia and what are the different types
area/ whole body not getting enough oxygen. hyperaemic hypoxia - low o2 levels due to something like altitude, anaemic hypoxia due to haemoglobin not being able to carry enough oxygen, ischaemic hypoxia- interruption to blood supply or histolytic hypoxia - inability to utilise oxygen e.g from cyanide poisoning
how does the immune system damage body cells
hypersensitivity- e.g hives from an overly vigorous immune reaction or autoimmune - e.g graves disease where immune system unable to distinguish self cells and attacks them
which components of the cell are susceptible to injury
cell membrane, nucleus, proteins and mitochondria
describe reversible hypoxic injury
due to lack of oxygen there is low oxidative phosphorylation and low oxygen. results in low ATP production meaning the Na pump stop working allowing Na to diffuse in, with water following causing the cell to swell. as well as this there is more anaerobic glycolysis meaning more lactate in the blood decreasing the pH. This causes ribosome to detach from the ER meaning less protein synthesis and lipid deposition
describe irreversible hypoxic injury
ca2+ pump fails meaning Ca2+ conc increases inside cell activating enzymes including; ATPase- reduces ATP, phospholipase- degrades membrane, protease- degrades membrane and cytoskeleton and endonuclease- causes nuclear chromatin damage.
how the cold/ heat causes cell damage
crystallises or dissolves cell membrane.
how cyanide toxicity damages cell membrane
inactivates enzymes involved in oxidative phosphorylation meaning no ATP produced
how free radicals damage cells
when there is an imbalance between mechanisms to control radicals and the number of radicals then it results in lipid peroxidation and damage to proteins, carbs and DNA which cause potentially carcinogenic mutations
what are heat shock proteins
look up
how injured cells look under microscope
lighter pink cytoplasm because of it being diluted by water moving in from failure of sodium pump. organelles are also swollen, chromatin clumps due to low pH and later on nucleus fragments. lysosomes rupture from swelling and enzymes are released digesting cell contents.
what is oncosis
cell death with swelling, prior to death
what is necrosis
morphological changes after cell death
what are the different types of necrosis and their definitions
coagulative- protein denaturation dominates and proteins clump together forming solid dead cells where architecture is preserved. liqeffective- mainly enzymes release leading to liquifying of contents, looks very viscous under microscope. caseous- looks like clotted cheese, associated with infections. fat necrosis- release of free fatty acids which react with calcium to form chalky deposits, this is due to deposition of adipose tissue
define gangrene
visible necrosis, the clinical word for necrosis
define infarction
a cause of necrosis which can result in gangrene caused by reduction of arterial flow (verb)
define an infarct
area of narcotic tissue which results in loss of arterial blood supply (noun)
define the differences between dry, wet and gaseous gangrene
dry = modified by exposure to air (coagulative necrosis) wet= modified by infection (liquefactive necrosis) gas= wet gangrene where anaerobic bacteria produce gas (liquefactive)
what are the most common causes of infarction
thrombosis - blood clot which obstructs the blood flow and embolism- detached solid, liquid or gaseous material which is carried to a site elsewhere in the body. however tissues can also become infarcted by twisting and compression of blood vessels which restrict the flow
types of ischaemic necrosis (infarct) due to thrombosis for example
coagulative (e.g myocardial infarct), liquefactive (e.g cerebral infarct) and can also be a red or white infarct
what is a white infract
blockage of end artery suppling (only artery supplying that organ) haemorrhage. shows white wedge shape where there is no blood supply. commonly occurs in the heart, kidney and spleen
what is a red infarct
due to bleeding. blood inside dead tissue. organ has dual blood supply meaning that if one end artery becomes blocked the other still supplies the tissue with blood but not enough to fully supply it. happens in lung because has dual blood supply and loose tissue
what does the consequence of infarction depend on
whether there is an alternate blood supply, the speed of the ischaemia, what tissue is involved (much more dangerous in brain than in muscle because adapted for anaerobic respiration) and the oxygen content of the blood
what is apoptosis
cell death, a non random, active process where enzymes break down DNA and cell proteins
when does apoptosis occur (physiological reasons)
during embryogenesis (sporting fingers), or during involution (the shrinkage of an organ in old age or when inactive, e.g. of the uterus after childbirth)
when apoptosis occur (pathological reasons)
when cells are damage e.g with DNA damage or during cytotoxic T cell killing of virus infected or neoplastic (skin graft) cells
explain the basic process of apoptosis
during initiation the cell and the nucleus shrink, during execution the nuclei fragments and the during degeneration cell breaks up into apoptic bodies which are later cleared by macrophages. no inflammation because no enzymes released externally
intrinsic triggers of apoptosis
something goes wrong inside cell e.g DNA damage. P53 protein is activated and mitochondria membrane becomes leaky. caspases are activated and clear target proteins/DNA
extrinsic triggers of apoptosis
dangerous cells e.g tumours or contain virus. TNTa binds to receptor resulting in the activation of caspases
difference between apoptosis and oncosis
apoptosis is controlled and there is no inflammation whereas oncosis is more pathological and results in the release of many enzymes meaning many surrounding cells are affected and lots of inflammation occurs
name some examples of molecules which are related from injured cells
potassium, enzymes and myoglobin
effect of potassium release
usually have small amounts in extracellular fluid. if this rises may cause heart to stop. any celll injury means the K+ is related and will result in cardiac arrhythmia (irregular heart beat)
effect of enzyme release
troponin is related by myocytes after injury. shows if someone has had a myocardial infarction.
effect of myoglobin release
related by any dead/damaged muscle. rhabdmyololysis shows large amounts of myoglobin related due to trauma
discuss water and electrolyte accumulation in cells
when cell is damaged cells become enlarged because water enters the cell. this is very dangerous in brain because the pressure can damage the brain or spinal cord by pressing on important structures and by restricting blood flow into the brain.
discuss lipid accumulation in cells
steatosis (accumulation of TAG) is often seen in the liver of diabetics, obese and alcoholics. cholesterol can’t be broken down it can only be removed (via the liver) therefore when there is an excess of things needing to be broken down fat is stored in vesicles which can lead to the formation of foam cells and atherosclerotic plaque
discuss protein accumulation in cells
Mallory’s hyaline- damaged keratinocytes build up in hepatocytes. This happens in alcoholic liver disease
alpha 1 antitrypsin deficiency- when unable to correctly fold alpha 1 trypsin meaning it can’t be packaged and accumulates in the ER. if unchecked can cause emphysema
exogenous pigment accumulation
air pollution e.g carbon is phagocytosed by macrophages causing blackened lymph nodes.harmless unless in large amounts- can cause fibrosis and emphysema = coal worker pneumoconiosis or anthracosis(milder).Y
This is due to build up of carbon in lungs. also accumulate during tattoo. sometimes pigment also reaches lymph node.
exogenous pigment accumulation
air pollution e.g carbon is phagocytosed by macrophages causing blackened lymph nodes.harmless unless in large amounts- can cause fibrosis and emphysema = coal worker pneumoconiosis or anthracosis(milder).Y
This is due to build up of carbon in lungs. also accumulate during tattoo. sometimes pigment also reaches lymph node.
endogenous pigment accumulation
haemosiderosis- forms when overload of iron is deposited in haemosiderms (iron storage molecule) from bruise.
hameochromatosis- overload of haemosidersms in many organs. happens because too much is absorbed from diet and its damaging because can’t get rid of it. when builds up in pancreas causes diabetes and in liver causes chirrosis. treatment is to remove blood and give blood with reduced iron.
jaundice- accumulation of bilirubin when can’t leave via bile duct due to obstructed flow. bilirubin becomes deposited in tissues= yellow skin
endogenous pigment accumulation
haemosiderosis- forms when overload of iron is deposited in haemosiderms (iron storage molecule) in many organs. happens because too much is absorbed from diet and its damaging because can’t get rid of it. when builds up in pancreas causes diabetes and in liver causes chirrosis. treatment is to remove blood and give blood with reduced iron.
jaundice- accumulation of bilirubin when can’t leave via bile duct due to obstructed flow. bilirubin becomes deposited in tissues= yellow skin
why can germ cells keep replicating forever and other cells can’t
have mechanism to maintain telomere length due to enzyme telomerase. other cells can’t do this which is why they enter replicative senesce which is a point where telomere length to short to replicate. unfortunately cancer cells also have ability to replicate forever
what is metastatic calcification
further away from site of dying tissue due to hypercalcaemia from calcium homeostasis disruption. hydroxyapatite crystals deposited throughout tissues in body. increased PTH means more bone resorption, can happen during renal failure or tumour. destruction of bone tissue is down to disease, imoblisition and tumours especially myeloma.
what are the effects o chronic excessive alcohol intake on the liver
fatty change (retention of lipids in liver), acute alcoholic hepatitis(inflammation of liver) and finally cirrhosis ( liver does not function properly due to long-term damage. This damage is characterized by the replacement of normal liver tissue by scar tissue). progressive order of disease.
