PATHOLOGY Flashcards
what vascular change can occur due to acute inflammation?
changes in flow and vessel calibre such as vasodilation
what can acute inflammation be caused by? (6)
infection injury trauma foreign bodies immune reaction necrosis of any cause
describe vasodilation as an inflammatory response (3)
first involves arterioles then capillary beds
mediated by histamine and nitric oxide
results in increased heat and redness
what does metaplasia commonly occur in response to?
a noxious stimulus
what can cause a change in signals to stem cells that will cause metaplasia?
cytokines
growth factors
other chemicals in the cells microenvironment
what does metaplasia represent?
a change in signals delivered to stem cells causing them to differentiate down a different line
what is metaplasia?
the reversible change from one mature cell type to another mature cell type due to stress on the cell
what are the precursor stages to neoplasia?
dysplasia
metaplasia
hyperplasia
what occurs in epithelial malignancy?
malignancy goes beyond the basement membrane
what does malignant mean?
neoplasm has metastatic potential which means it has the ability to spread to other sites
where can neoplasms be found?
anywhere in the body
what can a neoplasm be?
benign
premalignant
malignant
is neoplasia in response to a stimulus?
no
what does neoplasia mean?
new growth
what can a tumour be?
benign
malignant
inflammatory
foreign body
what is cancer?
uncontrolled cell proliferation and growth that can invade other tissues
what are two causes of cellular necrosis?
oxidative stress
accumulation of toxic metabolic by products
does apoptosis or necrosis cause a significant inflammatory response?
necrosis
what cell clears up debris after apoptosis?
macrophages
what happens to cells during apoptosis?
pyknosis
chromatin condenses and the nucleus breaks up
cytoplasm breaks up
what is caused by too much apoptosis?
neurodegenerative diseases
what is caused by too little apoptosis?
cancers
autoimmune diseases
what does p53 do if DNA cant be repaired?
stimulates caspases and induces apoptosis
name one protein that stimulates the caspase cascade that can be released from the mitochondria
cytochrome C
describe the intrinsic pathway in apoptosis
growth signals promote anti-apoptotic molecules in the mitochondrial membrane
when these are removed they are replaced by bak and bax
they increase the permeability of the mitochondria which leads to the release of proteins that stimulate the caspase cascade
what type of pathway is the intrinsic pathway?
mitochondrial
what do people with Fas mutations often get and why?
autoimmune diseases - Fas is involved in the recognition of self cells and can lead to apoptosis in lymphocytes
name two death receptors
tumour necrosis factor
Fas
describe the activation of the extrinsic pathway for apoptosis
FasL binds to Fas receptor
activates Fas activated death domain
activates caspase cascade
what is a death receptor?
a cell membrane receptor with a death domain
what initiates the extrinsic pathway?
death receptors
what are the two mechanisms for apoptosis?
extrinsic pathway
intrinsic pathway
what needs to be activated for apoptosis to occur?
the caspase cascade
what is pathological apoptosis in response to? (6)
injury radiation chemotherapy viral infections cancers graft versus host disease
when is apoptosis physiological? (3)
part of normal growth - fingers and toes
removes self reactive lymphocytes
hormonal dependant involution - removes cells produced by hormones when not needed anymore
does apoptosis require energy?
yes
what do you ask for if someone has TB?
culture
PCR
result of Ziehl Neelson stain
what is caseous necrosis associated with?
TB
what is caseous necrosis?
granulomatous inflammation with central necrosis
what is liquefactive necrosis often the result of?
localised bacterial and fungal infections
stroke in the brain
what happens during liquefactive necrosis?
no cell structure is left, it is all turned in to liquid
pus is often produced
where is coagulative necrosis often seen?
in cardiac muscle after an MI
why cant processes such as proteolysis occur during coagulative necrosis?
the microenvironment formed is too toxic
what are dead cells consumed by in coagulative necrosis?
various enzymatic processes and cells
what is the most common form of necrosis?
coagulative
what is preserved in coagulative necrosis?
the outline of the cell
what are the three types of necrosis?
coagulative
liquefactive
caseous
what is necrosis always?
pathological
does necrosis require energy?
no
what are the two types of cell death?
apoptosis and necrosis
what is resolution?
complete restoration of the tissue to normal after removal of inflammatory components
what is what happens after inflammation dependent on and why?
the site of imjury - different capacity for repair and different vascular supplies
the type of injutry - severity
duration of injury - can it be removed, is it being sustained
when are mediators of inflammation produced?
only as long as the stimulus persists
what can progress to fibrosis?
suppuration
chronic inflammation
what can occur after acute inflammation?
resolution suppuration repair fibrosis restitution chronic inflammation
what cell characterises acute inflammation?
neutrophil
what is dolor and what is it mediated by?
pain
prostaglandins and bradykinin
what is tumor and what is it caused by?
swelling
vascular changes i.e. leakiness of vessels
tumours, cysts, inflammation
what is calor and what is it caused by?
heat
caused by increased perfusion, slow flow and increased vascular permeability
what is rubor and what is it caused by?
redness
increased perfusion, slow flow and increased permeability of vessels
what are the clinical features of inflammation?
rubor calor tumor dolor loss of function
what do phagocytes produce that are used to kill and degrade foreign material?
reactive oxygen species - NADPH oxidase
reactive nitrogen species - nitric oxide synthase
cytotoxic granules
what do phagocytes use to engulf foreign material?
extensions of the cytoplasm called pseudopods
what are pathogens coated in that make them stand out?
proteins called opsonins
- such as components of the complement cascade and imunoglobulin
what do phagocytes look for that is found on the surface of bacterial cells?
mannose
what are the three phases of phagocytosis?
recognition and attachment
engulfment
killing and degradation
what can make a chemical gradient for chemotaxis?
bacterial components
complement
leukotrienes
cytokines - interleukins
what is chemotaxis?
when white cells have moved out of the bloodstream and follow a chemical gradient and move along it
what is VEGF?
vascular endothelial growth factor
what mediates transcytosis?
VEGF
what causses endothelial contraction?
histamine
bradykinin
substance P
leukotrines
why do blood vessels become permeable?
endothelial contraction
direct injury
white cells causing harm to the inside of vessels
transcytosis
VEGF makes new vessels but also increases permeability
what does vascular permeability cause?
loss of proteins
change in osmotic pressure
water follows protein out the vessel = swelling
what do proteoglycans do?
increase the affinity of VCAM and ICAM for integrins
what do chemokines bind to?
proteoglycans on the surface of endothelial cells
what increases endothelial cell expression of VCAM and ICAM?
tumour necrosis factor (TNF)
interleukin 1
what increases selectin expression?
histamine and thrombin from inflammatory cells
what increases the affinity of the ligands binding white cells to the luminal surface of blood vessels?
chemokines
what proteins are expressed in blood vessels and on white cells that slow flow during an inflammatory response
selectins (on endothelial cells and white cells)
integrins (bind to ICAM)
vascular cell adhesion molecule
intercellular adhesion molecule
what do vessels express during inflammation?
various proteins on the luminal surface that have a matching protein on the surface of the white cells
what is white cell margination?
larger white blood cells moving peripherally in blood vessels due to vascular dilation
what happens in normal blood flow?
blood flows centrally within a blood vessel
what cellular changes occur in acute inflammation? (5)
stasis white cell margination rolling adhesions migration
what are the different causes of disease?
vascular infectious/inflammatory neoplasia drugs and toxins iatrogenic congenital autoimmune trauma endocrine/metabolic psychological
what is vascular disease?
disease in blood vessels including inflammation, clots and blockages
what does neoplasia mean?
new growth
what is iatrogenic disease?
caused by a doctor, medical complications
what is a congenital disease?
conditions someone is born with, not necessarily genetic
who is more likely to have a congenital disease?
young people
when does resolution occur? (4)
minimal cell death
tissue has the capacity to repair
good vascular supply
injurious agent easily removed
what is suppuration?
the production of pus
what does pus contain?
living, dead and dying cells
what is an empyema?
a space filled with pus that has been walled off
why wont an abscess go away by itself and why cant they be treated with antibiotics?
they have no vascular supply
what is needed to heal and repair any injury?
a good vascular system to deliver white cells and to remove injurious agents
what is organisation/restitution?
scarring
when does restitution occur?
when an injury produces lots of necrosis or fibrin
poor blood supply
tissue cant regenerate
what type of healing is favoured when the damage goes beyond the basement membrane of the epithelium?
restitution, because you need a basic structure to remain for resolution to occur
how does restitution occur?
defect infiltrated by capillaries and myofibroblasts
deposit collagen and smooth muscle cells for things to be built upon
what can scarring and fibrosis cause?
loss of function and contraction
what is fibrosis in the liver called?
cirrhosis
what does cirrhosis result in?
liver failure, liver cant remove toxins or make proteins, disturbs large volume of blood that needs to flow through the liver
what does chronic inflammation not tell you anything about?
duration or severity of injury
what cell characterises chronic inflammation?
the lymphocyte (macrophages also present)
when is chronic inflammation favoured?
there is suppuration or scarring persistent foreign injury persistent infectious agent autoimmune disease transplant rejection
what is a granuloma?
aggregate of epithelioid histiocytes caused by an inflammatory response
what are granulomas caused by?
foreign bodies
endogenous substances
exogenous substances
infections such as parasites, worms, mycobacterium
