Cell Injury Flashcards
What is cyanosis ?
Bluish discolouration of skin & nails
Sign of hypoxia/increase in deoxygenated haemoglobin
What is is the difference between hypoxia & ischaemia ?
Which is worse ?
Hypoxia - reduced oxygen to tissue
Ischaemia - reduced blood supply to tissue
Ischaemia is worse
What is hypoxaemic hypoxia?
Low oxygen in arteries
What is anaemic hypoxia ?
Hypoxia causes by reduced functional haemoglobin
What is ischaemic hypoxia?
Hypoxia caused by disrupted blood supply to tissue
What is histiocytic hypoxia?
- Enough oxygen available to tissue but cells unable to use it
- due to inhibited oxidative phosphorylation enzymes (eg cytochrome oxidase)
What are 2 causes of hypoxaemic hypoxia?
- high altitude = reduced inspiration of o2
- lung disease = reduced o2 absorption
What are 2 causes of anaemic hypoxia?
- Anaemia
- CO poisoning
What are 2 causes of ischaemic hypoxia?
- local blockage of blood supply eg thrombus/embolus
- heart failure = low perfusion pressure = global ischaemia
What is a cause of histiocytic hypoxia ?
Cyanide poisoning - inhibits oxidative phosphorylation enzyme
Which cells would be disabled first without o2?
Neurones within few mins
How long can fibroblasts last without o2?
Few hours
What are urticaria? And what causes them ?
Hives
Hypersensitivity reaction
What is a hypersensitivity reaction?
Over active immune system injuring host tissue
What is an auto immune condition?
Failure of immune system to distinguish self from non self.
Which components of the cell are most susceptible to injury?
- membrane
- nucleus
- structural proteins - enzymes
- mitochondria (oxidative phosphorylation)
At a molecular level, how can Low ATP be detrimental to a cell?
1) inactive na+/k+ ATPase pump = na+, ca2+, h2o influx = swelling
2) increase in glycolysis = increase pyruvic acid = lower PH
3) detachment of ribosomes = reduced protein synthesis = reduced lipid transportation = lipid deposition.
How does increased ca2+ in the cytoplasm of a cell damage the cell?
Activates enzymes which will break up molecules/structures in the cell
What enzymes does increased cytosolic ca2+ active?
- Proteases
- Phospholipases
- ATPases
- Endonucleases
What do endonucleases do ?
Break down DNA
What are free radicals?
Molecules that have one or more unpaired electrons in their outer orbit
What is the most common type of free radicals in the body?
Reactive oxygen species
What are the 3 main reactive oxygen species in the cells?
Hydroxyl radical
Superoxide 02^-
Hydrogen peroxide h2o2
What is the most dangerous reactive oxygen species ?
Hydroxyl radical
How are free radicals produced ?
Slide 16 lecture
How are ROS produced in normal, daily biochemistry of cell?
- oxidative phosphorylation (as oxygen is reduced along electron transport chain)
- intermediates in enzyme reactions
What is Haemachromatosis?
Hereditary disorder in which iron salts are deposited in the tissues. Leads to
- liver damage
- diabetes
- bronze skin
Free radial damage occurs in this condition
What is Wilson’s disease?
Autosomal recessive
Copper deposits in tissues
= free radicals
How can free radicals be overproduced in cells?
- inflammation
- radiation
- iron deposits - Fenton reaction
- copper deposits
- drug and chemical metabolism in liver
- hypoxia
Which vitamins protect against free radicals?
A
C
E
Donate electrons to free radicals
What are antioxidants ?
Substances that remove damaging reactive oxygen species
What are 2 Functions of transferrin?
- transport iron in the serum
- thus controls amount of free radicals in body
What is Ceruloplasmin?
Copper carrying protein
Involved in iron metabolism
Which enzymes neutralise free radicals?
Superoxide dismutase
Catalase
Glutathione peroxidase
Which part of the cell do free radicals target the most?
Phospholipids in memebrane
What causes lipid peroxidation?
Free radicals
What is the name of the process in which free radicals attack cell membranes?
Lipid peroxidation
What are 3 ways in which free radicals attack a cell?
1) lipid peroxidation - target membranes
2) oxidise proteins, carbohydrates = alter shape/cross link them
3) mutagenic = oxidise DNA = carcinogenic
What are heat shock proteins?
Proteins that mend mis-folded/damaged proteins during cell injury
What are other names for heat shock proteins?
Unfoldases
Chaperonins
Give an example of a heat shock protein?
Ubiquitin
What is ubiquitin?
A heat shock protein/chaperone protein/unfoldases
What is pyknosis?
Condensation of chromatin in nucleus after cell death during necrosis & apoptosis
What is karyorrhexis?
Rupture of the nucleus during apoptosis and necrosis
What is karyolysis?
Nucleus dissolves after cell death
Using a light microscope what structures will be visible during cell death?
Cell membrane and nucleus
What can happen to the nucleus during cell death?
- pyknosis : enlarges
- karyorrhexis : breaks up
- Karyolysis : dissolves
What can be seen under an electron microscope during reversible cell injury and how can it be reversed if hypoxia was the cause?
- blebs : disruption to cytoskeleton by proteases activated by ca2+
- swelling of cell
- swelling of organelles
Reversed by o2 if hypoxia is the cause
What can be seen in a irreversibly injured cell?
- lysis of organelles
- autolysis of cell from lysosome enzymes
- holes in membrane
- myelin figures : fat deposits in and around cell
- nucleus changes: pyknosis, karyorrhexis, karyolysis
What is oncosis and necrosis ?
Oncosis: changes that occur to cell before cell death (cell swelling)
Necrosis: changes that occur to cell after cell death
What are 4 types of necrosis?
Main
- Coagulative
- Liquefactive
Special type
- Caseous
- Fat necrosis
Describe coagulative necrosis
- involves solid tissues/organs eg heart, kidney
- denatured proteins
- cell architecture preserved
- can lead to dry necrosis
- white infect
Describe liquefactive necrosis
Involves liquid areas/areas with less connective tissue eg brain
- enzymatic digestion of tissue
- cell architecture lost
- can lead to wet necrosis
- red infarct
Which infection is caseous necrosis associated with?
Tuberculosis
Describe caseous necrosis
Amorphous debris
Associated with infections
Cottage cheese appearance around lung in TB
What does fat necrosis look like?
Candle wax
Describe fat necrosis and in a condition that it can be seen
- Fatty acids produced from breakdown of triglycerides by enzymes
- Fatty acids react with ca2+ to form calcium soaps = candle wax appearance
Seen in pancreatitis
What is Gangrene?
Visible necrosis
What is an infarction?
Necrosis of a tissue caused by ischaemia
What is an infarct?
Area of ischaemic necrosis on a tissue
In which type of necrosis would you see dry gangrene?
Coagulative necrosis
In which type of necrosis would you see wet gangrene?
Liquefactive necrosis
What is dry gangrene?
Visible necrosis modified by air
What is wet gangrene ?
Visible necrosis modified by infection
Involves anaerobic bacteria that produce gas
What causes an infarction ?
Thrombosis
Embolism
What’s the difference between thrombosis and an embolism ?
Thrombosis - formation of clot inside intact blood vessel
Embolus - travelling clot
What results in white infarct?
Solid tissue
Occlusion of end artery
No haemorrhage
Coagulation infarction
What causes red infarcts?
Loose tissue Dual blood supply to tissue Numerous anastomoses Raised venous pressure (congestion of blood in venous end) Liquefactive infarction
What is it called when oxygen is returned to a damaged (not yet necrotic) tissue resulting in even more damaged tissue?
Ischaemia - reperfusion injury
What are the causes of ischaemia-reperfusion injury ?
- increased reactive oxygen species
- increased inflammation from cells in blood
- activation of complement pathway
How is cell death caused in necrosis ?
Cell swelling
During necrosis what things can leak out from the dead cell?
- k+ : stops heart beating
- proteins : CK, troponin
- myoglobin : skeletal muscle break down, brown urine
What can lead to myoglobin in urine?
Brown urine
- Caused by breakdown of skeletal muscle
- Extreme exercise without enough water
How does apoptosis cause cell death?
- Regulated and controlled Shrinkage of cell
- non random degradation of DNA and proteins
Does apoptosis require energy?
Yes
Is membrane integrity maintained in apoptosis?
Yes
Are lysosomes involved in apoptosis?
No
Is apoptosis pathological or physiological ?
Can be both
When does apoptosis occur physiologically?
Metamorphosis of limbs during embryonic development
When does apoptosis occur pathologically?
- via cytotoxic T cells
- DNA mutated cells
- grafts/transplants
Name the 2 mechanisms that can initiate apoptosis
Intrinsic pathway
Extrinsic pathway
Which enzymes are activated in apoptosis and what do they do?
Caspases
Cleave proteins and DNA
What is formed at the end of apoptosis?
Apoptic bodies
What can trigger intrinsic apoptosis of a cell ?
- DNA damage
- withdrawal of growth factors/hormones
What is P53?
Tumour suppressor protein
In which pathway for apoptosis is p53 activated?
Intrinsic
What does the activation of p53 in a cell do during intrinsic apoptosis ?
Makes outer mitochondrial membrane more Permeable so that cytochrome C can be released.
Cytochrome C activates caspases which cleaves proteins and DNA
What is cytochrome C?
Protein found in mitochondria involved in oxidative phosphorylation and apoptosis
How is Cytochrome C involved in intrinsic apoptosis ?
Activates caspases which cleave DNA and protein
What proteins are involved in intrinsic apoptosis ?
P53
Cytochrome C
Caspases
What are some triggers of the extrinsic pathway ?
- tumour cells
- virus infected cells
What is TNFalpha ?
Tumour necrosis factor alpha
Cell signalling protein (cytokines)
Involved in extrinsic pathway of apoptosis
Where does TNFalpha come from ?
Secreted by T killer cells
How is TNF alpha involved in extrinsic apoptosis ?
Secreted by T killer cells
Binds to cell membrane receptor
Activates caspases which cleave DNA and proteins
In Apoptosis what happens to the apoptotic bodies produced?
Phagocytosed
Give 7 ways in which necrosis and apoptosis differ?
See table in lecture
What are the 5 main groups of intracellular accumulation ?
Water & electrolytes Lipids Proteins Fats Pigment
How does hypoxia result in cerebral oedema ?
Low o2 = low ATP = inactive na+/k+ ATPase pump.
Na+ & h20 rush into cells
Brain becomes compressed against skull
What is Steatosis and where is it seen the most?
Accumulation of triglycerides
Liver
What is the major organ of fat metabolism?
Liver
What are the causes of steatosis ?
Alcohol
Diabetes mellitus
Obesity
Toxins
Can cholesterol be broken down? And is it insoluble or soluble
Cannot be broken down
Insoluble
Which is the only organ that can eliminate cholesterol ?
Liver
What happens to excess cholesterol in the liver?
Stored in cell vesicles
What are foam cells?
Macrophages in atherosclerotic plaques
What are xanthomas?
Fatty deposits under skin/tendons
Seen in hyperlipidaemias
What are Mallorys hyaline?
damaged keratin filaments within the hepatocytes.
Seen in alcoholic liver disease
Where is alpha 1 antitrypsin protein made?
Liver
What is alpha 1 anti trypsin deficiency?
Liver producing incorrectly folded alpha 1 anti trypsin
Build up within ER
What is alpha 1 anti trypsin protein?
Protease inhibitor
What secondary disease can alpha 1 anti-trypsin deficiency lead to do ?
Emphysema in lungs
When do pigments accumulate in cells ?
- pollution
Tattoo
Which cells do pigment accumulate in?
Macrophages
What is Haemosiderin?
Iron storage molecule in cells formed when there is excess iron.
What is haemosiderosis ?
Accumulate of iron storage molecule haemosiderin
Leading to excess of iron
Give an example when haemosiderins are seen ?
Excess iron
So bruising
What is cirrhosis ?
Scarring of the liver
What is hereditary haemochromatosis?
Excess iron in a number of organs
Skin looks bronze
What is the treatment of hereditary haemochromatosis?
Repeated bleeding
What colour is bilirubin ?
Yellow
What substance accumulates in jaundice?
Bilirubin
What is bilirubin
Breakdown product of heme
Where is bilirubin formed ?
All cells
Where is bilirubin removed ?
In liver via bile
How does bilirubin get from tissue to liver?
Via albumin
What is jaundice ?
Build up of bilirubin in blood due to disruption of bile flow
What is dystrophic calcification?
Local deposit of calcium salts within tissue
Is dystrophic calcification caused by abnormal calcium metabolism/abnormal phosphate/abnormal serum calcium concentrations
No
What is dystrophic calcification?
Local deposits of calcium salts in tissue
Give 2 examples of dystrophic calcification
- atherosclerosis
- calcified heart valves
How is dystrophic calcification formed
Nucleation of hydroxyapatite crystals
What is metastatic calcification?
Hydroxyapatite crystals deposited in tissue throughout the whole body
What type of crystals are deposited in calcification of tissues ?
Hydroxyapatite crystals
How does metastatic calcification occur?
Secondary to disturbances in calcium metabolism/ as a result of hypercalcaemia
What does the parathyroid hormone do?
Increases calcium in the blood
What are two causes of hypercalcaemia ?
- increased secretion of parathyroid hormone (parathyroid tumour, renal failure)
- destruction of bone tissue (cancer, Paget’s disease)
What is pagets disease?
Excessive breakdown and formation of bone followed by disorganised bone remodelling
When does an ageing somatic cell stop dividing?
When telomeres reach a critical length
Which type of cells contain the enzyme telomerase ? What does telomerase do?
Germ cells, stem cells, some cancer cells
Maintains original length of telomeres
