week 2 Flashcards
what factors are needed to mainatin a stable cell
preserve genetic integrity
normal cell enzyme activity
intact membrane and transmembrane proteins
adequate supply of oxygen and nutrients
what is the affect of stress on cells?
To a certain extent cells can deal with stress by celullar adaption. However if there is to much stress then the cells become injured. Can have either reversible or irrerversible injury to the cells
what does hyperplasia mean?
increase in number of cells
What is hypertrophy? Give a example
The enlargement of an organ or tissue from the increase in size of its cells.
muscle cells undergo hypertrophy –> cannot increase in cell number and therefore increase in cell size to increase activity
what is atrophy?
the reduction of cell size and number
what is metaplasia?
the change in the morphology of a cell
give a example of pathological hypertrophy?
The increase in size of left ventricle because of systematic hypertension
Give example of physiological hypertrophy?
increase in size of muscle in atheletes
pathological hyperplasia give a example?
angiogenesis occuring during wound repair
what factors can cause cell injury?
lack of o2 and nutrients physical trauma chemical agens infectious agens radation genetic disorder ageing lack of essential vitamins and minerals immunological
what is hypoxia?
the reduction of oxygen to a tissue
what is anoxia?
the absence of oxygen to a tissue
why can Reperfusion of tissue causea problem?
Can lead to free radicals which can potentially damage other cells
give example of chemical agents that can damage the cells
alcohol, tobacco, drugs, occupation, enviroment, drugs and poison
give example of endotoxin?
produced by a bacteria when they die –> negative charged bacteria –> produce the toxin
what causes pseudomembranous colitis ?
Clostridium difficile infection
why is Clostridium difficile infection problem in hosptials?
Broad antibiotics are given which disrupt normal bowel flora and allow organisms to overgrow –> exotoxin is produced
How does radation damage cells?
Causes the formation of free radicals that then attack macromolecules and form more free radicals
which organs have a high sensitivity to radation?
bone marrow, gonads and intestins -> have a high cell turn over rate
what happens to the level of ATP in ischemic injury in mitochondria?
oxidative phosporylation levels decrease and so does ATP
what is the consequence of reduction of Activity of plasma membrane ATP-driven “sodium pumpin because of ischemic injury
influx of both sodium and calcium into the cells and isosmotic gain of water and acute cellular swelling
what are the end effects of ischemic injury to mitochondria ?
cellular swelling, ER swelling, lipid deposition, loss of microvilli –> hypoxia is associated with cellular swelling
Reduction of ATP and protein synthesis
what affect does alcohol have on a cellular level?
Cause fatty deposition and cloud cell swelling
what is free radicals?
Highly reactive ions or molecules with single unpaired electron in outer orbital
what process occurs when free radicals damage proteins and nucleic acids?
What proccess occurs when free radicals damage molecules in membranes?
apoptosis occurs to proteins and nucleic acid
Chain reaction happens to molecules in membranes as more free radicals are formed
what enzyne and antioxidans helps to protect against free radicals
superoxide dismutase and antioxidans –> vit A,C,E
What cells use free radicals to kill bacteria?
neutrophils and macrophages and depends on the formation of superoxides
what can cause membrane defects?
bacterial toxins, viral proteins, complement, cytolytic lymphocytes, and various physical and chemical agents
what is the consequence of membrane defect?
Loss of membrane barriers leads to breakdown in metabolite gradients
why do cells die?
Occurs when cells are unable to achieve a new steady state following environmental insults
what are the two types of cell death?
necrosis and apoptosis
cause of necrosis?
caused by lethal cell injury?
is necorsis a energy dependent reaction?
no it occurs naturally unless the cells can stop it from happening
what is the most common type of necrosis?
coagulative occurs in most cells and causes tissue to be hard and dry –> infarction and ischaemia
what type of necrosis occurs during TB?
caseous –> looks like cream cheese –> loose all structure
what type of necrosis occurs in brain and what is the site of injury eventually marked by
colliquitive necrosis –> liquidation of the brain where the site of injury is eventually marked as a cyst
what are the two types of gangerene?
wet and dry
how can you test of coagulative necrosis?
test for the specific proteins that should be in the tissue in the blood. If present then leakage and damge of that tissue
what type of inflamation occurs in caseous?
granulomatous inflammation that surrounds the cellular detial that has been destroyed
is infection assoicated with wet or dry gangrene?
wet.
Is there a clear demarcation in wet or dry gangrene?
Dry –> clearly see the line of the infection
what type of disease can you see dry gangrene?
diabetes
what is apoptosis?
energy dependent cell programmed death
give example of physiological apoptosis?
Embryogenesis
Involution
Elimination of self-reacting
lymphocytes
give example of pathalogical apoptosis?
DNA/protein damage
Viral infections
Cell killing by cytotoxic T-cells
what two proteins are sequestered in mitochondria but released when ischemia injury occurs and what do they activate?
cytochrome C and Apoptosis initiating factor and they active capses which are effector molecules of apoptosis
What does P53 do?
very important in recognising DNA damage and inducing apoptosis
Why is mutation in p53 key for tumor growth?
allowing cells to accumulate genetic abnormalities and become malignant
what does BCL-2 do?
sequesters cytochrome C and thus inhibits apoptosis
what does mutation in BCL-2 do?
over activation and allows tumors to grow as apoptosis is further inhibited
what is intrisic pathway?
where apoptosis is triggered from within the cell
what is extrinisic pathway?
when apoptosis is triggered outside the cell due to a protein binding to a cell receptor on the surface of the cell
what are the number of cells invovled in necrosis and apoptosis ?
multiple in necorsis and single in apoptosis
what is the cell size after necoriss and apoptosis?
necrosis –> swelling –> enarlages before it dies
apoptosis the cell reduce in size
what happens to the nucles during necrosis?
Pyknosis → karyorrhexis → karyolysis
What is Pyknosis ?
is the irreversible condensation of chromatin in the nucleus of a cell undergoing necrosis or apoptosis
what is karyorrhexis ?
is the destructive fragmentation of the nucleus of a dying cell whereby its chromatin is distributed irregularly throughout the cytoplasm
what is karyolysis?
dissolution of a cell nucleus, especially during mitosis.
what is a chromatin ?
the material of which the chromosomes of organisms other than bacteria are composed, consisting of protein, RNA, and DNA
what happens to the nucleus of a apoptic cell?
Fragmentation → apoptotic bodies
what happens to cellular content during necrosis and apoptosis?
necrosis –> Enzymatic digestion; may leak out of cell
apoptosis –> Intact; may be released in apoptotic bodies
is there adjecent inflamation during necrosis?
frequently?
is there adjecent inflamation during apoptosis?
no
what are the different causes of tissue death?
Ischaemia, Trauma, Toxins
Chemical insults , Thermal injury. Radiation
what is the most common type of infenction for accute inflammation?
‘pyogenic’ bacterial formation
what does pyogenic mean?
formation of pus
what are the two ways in which healing can occur after accute inflammation?
regeneration and growth of cells
healing is done by the cells being repaired
what are the purposes of acute inflammatory response ?
clear away dead tissue
allow access of immune system components
localise the infection
what are the 4 cardinal signs of inflammation?
calor --> heat tumor --> swelling rubor -->redness dolor --> pain also functio laesa --> disturbance of function
what are the different types of acute inflammation?
serous –> the outpouring of serous fluid
fibrinous –> precipitation
purulent
Pseudomembranous
in order give the components of the acute inflammatorty response
vascular reaction –> dilation (rubor) and also change in blood flow
Exudative reaction - formation of inflammatory exudant –> leaky
Cellular reaction - migration of inflammatory cells out of vessels into the tissues
what is pyrexia?
increased body temperature
what are acute phase reactions and give a example
roteins produced by the liver and c reactive proteins
what are the non mediated causes of vascular reaction?
direct damage to endothelium –> trauma and physical agent
what are the mediated causes of vascular reaction?
Histamine Bradykinin NO Leukotriene B4 Complement components
in normal blood vessel is the hydrostatic pressure or oncotic pressure of macromolceulces greater at the artery end?
hydrostatic pressure –> macrolecules move out
in normal blood vessel is the hydrostatic pressure or oncotic pressure of macromolceulces greater at the venous end?
oncotic pressure –> causes the moleceules to move back into the blood vessel
in the exudative reaction of acute inflammation what is in the protein rich substance produced?:
fribinogen and immunoglobins
what are the outcome of turn over during exudative reaction?
Dilution of noxious agents Transport to lymph nodes Supply of nutrients, O2 metabolic requirement of inflammatory response Spread of inflammatory mediators Spread of antibodies Spread of drugs important at BBB
what WBC is involved in the cellular reaction of acute inflammatory response?
Accumulation of neutrophils in extracellular space
In severe cases, accumulation of neutrophils, cellular debris and bacteria forms pus
Where is neutrophil produced and how common is it?
What is there life span
Produced in bone marrow
Commonest white cell in blood
Short life span –> few hours in tissue
what enzyme is invovled in the 02 dependent reaction of phagocytosis of a neutrophil and what is produced?
Myeloperoxidase
H2O2, Cl-, O2-, OH- –> free radicals that damage the substance being engulfed
what is pavementing?
the movement of neutrophils next to the endothelium lining and eventually adhering to it
What is the normal flow of neutrophils and how does margination change this?
Normal flow of neutrophils is axial stream .
Margination causes the movement of macromolecules away from the axial flow and to the periphery
what factors in plasma mediate acute inflammation?
Kinin system
Clotting pathway
Thrombolytic pathway
Complement pathway
what factors in cells mediate acute inflammation?
stored in the cell –> histamine
synthesised in cells –> Prostaglandins, Leukotrienes
PAF ,Cytokines (IL1,8; TNFa), NO, Chemokines
what is one mechanism in ensuring that acute inflammation does not occur for too long?
all substance that mediate acute inflammation have a short half life and are brocken down or scavenging occurs of them
what does TNF do?
neutrophil adhesion
Prefix of “ana” indicates what?
Absence–> anemia
Prefix of “dys” indicates what?
Disorder–> dysplasia
Prefix of “meta” indicates what?
Change from one state to another –> metaplasia
Suffix of “itis” indicates what?
Inflammation
Suffix of “oma” indicates what?
Tumour –> carcinoma
Suffix of “penia” indicates what?
A lack of something –> Thrombocytopenia
Suffix of “cytosis” Indicates what?
Increased number of cells –> leukocytosis
Suffix of “ectasis” indicates what?
Dilation –> bronchiectasis
Suffix of “plasia” indicates what?
Disorder of growth –> hyperplasia
What type of change occurs in barrets oesophagus?
Metaplasia
From squamous epithelium to glandular columnar epithelium
Due to gastric reflux
what are the Targerts of cell injury?
Cytoskeleton Membrane integrity and function Genetic apparatus Mitochondria Protein synthesis and function
Loss of membrane protection leeds to a break down of membrane gradient. What is the consequence of this?
The increaes levels of calcium which causes activation of various enzymes as calcium is coenzyme
What enzymes are activated by increase levels of ca2+due to membrane break down?
ATPases (thereby hastening ATP depletion),
Phospholipases (which cause membrane damage),
Proteases (break down membrane and cytoskeletal proteins)
Endonucleases (responsible for DNA fragmentation)
What are the features of Coagulative necrosis?
Denaturation of intracytoplasmic proteins
Dead tissue are firm and slightly swollen
Tissue retains microscopic architecture
Cytoplasmic proteins can seep into blood
Common in ischeamia but not in the brain
What occurs in fat necrosis?
Fat is traumatised and you get break down of lipid chains and see free fatty acid chains
The level of calcium increase
What occurs in fibrinoid necrosis?
Occuris in arterial walls and it is assoicated with malignant hypertrophy
what happens in vascular dilation?
Microvascular dilation
Increase in initial blood flow then a decrease
Due to the increase permeability
When will the level of neutrophil increase and how do you test for it?
Increase in blood when there is acute inflammation
Can test neutrophil to see how bad the acute inflammation
Do a blood count
To see if the treatment is working/how the infection is developing
How to neutrophils move?
They are mobile, amoeboid and move through tissue
They move along the concentration gradient
Directional chemotaxis
Bradykinin acts as what mediator of acute inflammation?
Increase permeability
Histamine and NO act as what mediators in acute inflammation?
Vascular dilation and increase permeability
What mediators are invovled in neutrophil adhesion
IL-8 and IL-1
TNF
What mediators are invoveld in neutrophil chemotaxis
IL-8
Chemokines
What is the 3 laboratory assesment of inflammation?
Acute phase reaction
Full blood count
Erythrocyte sedimentation rate
What are the 4 outcomes of acute inflammation?
Resolution
Fibrosis
Suppuration –> abscess
Chronic inflammation
What is the result of “resolution” after acute inflammation?
There is no tissue damage and the organ/tissue goes back to working normally
What is the result of “fibrosis” after acute inflammation?
There is so tissue damage and the tissue is not replaced by normal tissue but by collagen so therefore have scar tissue. If this occurs on a organ it will potentially not work as well
What is the result of “suppuration” after acute inflammation?
There is absecess and a marked neutrophil reaction.
Tissue is damaged
How does chronic inflammation occur?
The noxious agent causing the acute inflammation persists and is not dealt with leading to chronic inflammation
What are the two ways in which neutrophils engulf bacteria?
Engulph them by phagocytosis to form a phagolyzosome Oxygen dependent - Enzyme myeloperoxidase makes free radicals which damage the macromolecules from which the bacteria are formed thus killing them
Oxygen independent - Involves specific enzymes such as lysozyme which break down bacteria cell walls
Explain the process in which neutrophils go from the blood vessels and out to the tissues?
Normal flow in the blood vessel is an axial stream so neutrophils dont come into contact with the endothelium When vessels dilate and exudate moves out of the vessles the flow is slowed and neutrophils are no longer adhered to an axial stream, they come into contact with the endothelium and various ligand-receptor reactions take place Have: 1) Margination 2) Rolling - adhesion (pavementing when the neutrophils line up on the endothelium) 3) Migration into the tissues (facilitated by the increased permeability of the vessels)
