Cell Injury or Death Flashcards
what is hypoxia
oxygen depravation
what are some environmental causes of cell injury
direct trauma
extremes of temperature
changes in pressure
electric currents
radiation
microorganisms
immune mechanisms
nutritional
what is hypoxaemic hypoxia
arterial content of oxygen is low
- reduced inspired p02 at altitude
- reduced absorption secondary to lung disease, pneumonia
anaemic hypoxia
decreased ability of haemoglobin to carry oxygen
- anaemia
- carbon monoxide poisoning
ischaemic hypoxia
interruption to blood supply
- blockage of vessel
- heart failure
histiotoxic hypoxia
inability to utilise oxygen in cells due to disabled oxidative phosphorylation enzymes
-cyanide poisoning
how does the immune system damage the body’s cells?
hypersensitivity reactions- host tissue is injured secondary to an overly vigorous immune reaction - hives
autoimmune reactions- immune system fails to distinguish self from non self
what cell components are the most susceptible to injury
cell membranes
nucleus- DNA
proteins
mitochondria
what are the reversible consequences of reduced intracellular ATP during cell injury
there is no oxygen so thers no oxidative phosphorylation in the mitochondria so no ATP is being produced.
Na pump cant work as it is ATP dependant, so there is an influx of Ca, water and Na to the cell which causes swelling, loss of microvilli and blebs, ER swelling
decrease in glycolysis which leads to a drop in pH and in glycogen which causes chromatin tO clump
decrease in protein synthesis as ribosomes detach
what are the irreversible consequences to an influx of calcium
calcium moves in to mitochondria and ER and water follows so it bursts
increased cytosolic calcium concentration affects the action of important enzymes in the cell
- ATPase
- Phospholipase C
- Protease
- Endonuclease
what are free radicals
single unpaired electron in an outer orbit- an unstable configuration hence react with other molecules often producing further free radicals
what are the biologically significant free radicals and which is the most dangerous?
- OH DOT - hydroxyl- the most dangerous
- O2 - superoxide
- H2O2 Hydrogen peroxide
what causes the formation of free radicals
oxidative phosphorylation radiation transition metals drugs and chemicals normal part of inflammatory response
how do free radicals affect lipids
cell and organelle membranes damaged
lipid peroxidation
extensive damage
how do free radicals affect proteins
oxidation of amino acid side chains
protein-protein cross linkages
results in protein fragmentation
how do free radicals affect nucleic acids
reaction with thymine
single strand breaks in DNA
mutagenic and therefore carcinogenic
what causes oxidative stress
an imbalance between free radical generation and radical scavenging systems
how does the body control free radicals
decay spontaneosly
free radical scavengers- anti-oxidants
enzymes that neutralise free radicals
- superoxide dismutase- 02 minus converted into hydrogen peroxide
- catalase- hydrogen peroxide into oxygen and water
- glutathione peroxidase
how does the body control free radical damage IN PROTEINS
heat shock proteins that mend mis-folded proteins and maintain cell viability
-protein chaparones and ubiquitin
free radicals cause proteins to cross link and fragment
what is pyknosis
shrinkage of chromatin
what is karyorrhexis
fragmentation of nucleus
karyolysis
dissolution of nucleus
what do you see under an electron microscope when cells are injured or dying
reversible blebs swelling clumping of chromatin ER swelling mitochondrial swelling
irreversible rupture of lysosomes and autolysis pyknosis karyolysis karyorrhexis lysis of ER
what is oncosis
cell death with swelling, the spectrum of changes that occur in injured cells prior to death
what is necrosis
in a living organism the morphological changes that occur after a cell has been dead some time seen after 12-24 Hours
- coagulative
- liquefactive (colliquitive)
- caseous
- fat necrosis
- fibrinoid necoris
what is apoptosis
programmed cell death
- cell death and shrinkage
- regulated intracellular program where a cell activated enzymes that degrade its own nuclear DNA and proteins
- characteristic DNA breakdown
condensation of chromatin, fragmentation and apoptic bodies
coagulative necrosis
protein dentauration- they coagulate when they denature
- ischaemia of solid organs
- ghost outline
- features of cell death
liquefactive necrosis
neutrophils secrete proteases that breakdown the cells
enzyme degradation is substantially greater than denaturation
caseous necrosis
contains amorphous debris
particularly associated with infections especially tb
what is pathological apoptosis
cytotoxic T cell killing of virus-infected or neoplastic cells
-when cells are damaged, particularly with damaged DNA
what are the stages of apoptosis
initiation
execution
degradation & phagocytosis
what is the intrinsic pathway of apoptosis
initiating signal comes from within the cell
Triggers:
- most commonly irreparable DNA
- Withdrawal of growth factors or hormones
p53 protein is activated and this results in outer mitochondrial membrane becoming leaky
cytochrome C is released from the mitochondria and this causes activation of caspases
extrinsic pathway of apoptosis
initiated by extracellular signals
Triggers
-cells that are a danger- tumour cells
signals - TNF-alpha
- secreted by T killer cells
- binds to cell membrane receptor (death receptor)
- results in activation of caspases
degradation and phagocytosis
both intrinsic and extrinsic pathways cause the cells to shrink and break into apoptotic bodies
the apoptotic bodies express proteins on their surface
they can now be recognised by phagocytes or neighbouring cells
finally degradation takes place within the phagocyte/ neighbour
what is the difference between apoptosis and necrosis
apoptosis leads to shrinkage and chromatin condensation, budding and apoptotic bodies phagocytosed with no inflammation in single cells. Fragmentation into nucleosome size fragments ; form clumps beneath nuclear membrane, intact plasma membrane
necrosis occurs in contiguous groups of cells and has swelling, blebbing with disruption of cell membrane and the release of proteolytic enzymes with important inflammatory reaction as well as adjacent inflammation
pyknosis, karryorrhexis, karyolysis, disrupted plasma membrane, degradation of cellular contents
what is gangrene
necrosis visible to the naked eye
-an appearance of necrosis
what is infarction
necrosis caused by a reduction of arterial blood flow
- a cause of necrosis
- can result in gangrene
what is an infarct
an area of necrotic tissue which is the result of loss of arterial blood supply
-an area ischaemic necrosis
what does coagulative necrosis lead to
dry gangrene
- necrosis
- gangrene
what does liquefactive necrosis lead to
wet gangrene
- necrosis
- infection
what causes infarction
atherosclerosis
occlusion by thrombus or thromboembolism
twisting
compression
white infarct
‘solid organs’
occlusion of an end artery
often wedge-shaped
microscopically you see coagulative necrosis
red infarct
haemorrhagic infarct
- loose tissue
- dual blood supply
- numerous anastomoses
- prior congestion
- raised venous pressure
- re-perfusion
what is ischaemic-reperfusion injury
paradoxically, if blood flow is returned to a damaged but not yet necrotic tissue, damage sustained can be worse than if blood flow hadn’t been returned
what causes ischaemic-reperfusion injury
increased production of oxygen free radicals with reoxygenation
increased number of neutrophils resulting in more inflammation and increased tissue injury
delivery of complement proteins and activation of the complement pathway
what abnormal cellular accumulations occur after cell injury
normal cell components build up
abnormal components build up
pigment
mechanisms of intracellular accumulations
abnormal metabolism- fat
alterations in protein folding and transport
deficiency of critical enzymes
inability to degrade phagocytosed particles
what is steatosis
accumulation of triglycerides
commonly seen in liver
what causes steatosis
chronic alcohol misuse
obesity
diabetes mellitus
what complications can steatosis lead to
liver and metabolic dysfunction
liver function
liver cirrhosis
sudden death
atherosclerosis
cholesterol builds up in smooth muscle cells and macrophages/ histocytes (foam cells) = atherosclerotic plaque
xanthoma
cholesterol in macrophages within skin/ tendons, associated with hereditary hyperlipidaemias
diseases associated with accumulation of proteins
alcoholic liver disease- mallroys hyaline
alpha1 antitrypsin deficiency
pathological accumulation of calcium
localised in dying tissues- dystrophic
most common
generalised (metastatic)
deposition in otherwise normal tissue
due to hypercalcaemia due to dysfunction in calcium disturbance
what is metastatic calcification
hypercalcaemia secondary to disturbances in calcium metabolism
hydroxypatite crystals are deposited in normal tissues throughout the body
usually asymptomatic but can be lethal
what causes metastatic calcification
increased secretion of PTH resulting in bone resorption- primary hyperparathyroidism, secondary and teritary hyperthyroidism
destruction of bone tissue
- primary tumours of bone marrow
- diffuse skeletal metastases
- Paget’s disease of bone- when accelerated bone turnover occurs
- immobilism
effects of hypercalcaemia
bone disease renal stones confusion, drowsiness, coma, psychosis thirst and polyuria anorexia, nausea, vomiting and abdominal pain
what is present in the blood after a myocardial infarction and why
- Troponin T
- Troponin I
An area of cardiac muscle has undergone oncosis/necrosis due to lack
of blood supply/infarction (1 mark). In oncosis/necrosis cell
membranes become leaky and intracellular proteins leak out of the
cells and can be measured in the blood
name two other conditions in which fatty liver is commonly seen
excessive alcohol intake Diabetes mellitus Obesity Drugs (including alcohol), Carbon tetrachloride toxicity Toxins and infections.
In addition to fat, what else can accumulate within hepatocytes in
patients who drink alcohol to excess?
mallorys hyaline
How does
cirrhosis appear histologically?
Bands of fibrosis surrounding nodules of regenerating
hepatocytes
