Flashcards in MoD week 1 - cell injury Deck (43):
what causes hypoxia?
reduced oxygen supply due to ischaemia (lack of blood supply)
what are the 4 types of hypoxia?
what is hypoxaemic hypoxia?
low arterial oxygen content
e.g. altitude & lung disease
what is anaemic hypoxia?
lack of RBC so reduced O2 carrying capacity
what is ischaemic hypoxia?
obstruction / interruption in blood flow (PE, tumour)
lack of blood flow
what is histiocytic hypoxia?
poison - no ox/phos
cynaide, disabled ox/phos (from binding to complex 4 - higher affinity than oxygen so e-, H+ and O2 can't bind)
what are reversible changes in cellular injury?
no oxygen, so ox/phos so no ATP production (decrease Na+/K+/ATPase),
no Na+/K+/ATPase leading to cell swelling from Na+ withint cell,
no oxygen leading to increase anaerobic glycolysis (increased production of lactic acid) = pH acidic
ribosomes detach due to lack of ATP (reversible)
chromatin clumping (no ribosomes to produce proteins)
autophagy (protein degradation for survival)
what are irreversible changes in cell injury?
oncosis (cell death by swelling) leading to necrosis
membrane disturbance (from swelling) - affects Ca2+ channels (activating), increase [Ca2+] activating ATPase, phospholipases, proteases, endonucleases (DNA)
intracellular substances leak into circulation (detectable)
ER organelles swell causing blebbing (necrosis & oncosis)
nucleus: pyknosis (shrinkage) / karryohexis (fragmentation) / karryolysis (dissolution)
What is reperfusion?
return of blood flow to an ischaemic tissue
What is reactive hyperaemia?
during ischaemia, metabolites are released e.g. K+/H+/Pi/ADP etc. to cause vasodilation, but when you reperfuse the tissues, the metabolites will be washed away causing vasoconstriction which increases cell injury
What is ischaemic reperfusion injury?
when the metabolites spread around the body cuasing widespread vasodilation and distributive shock
there is also a large production of ROS and neutrophils that the body isn't ready to defend itself agains, leading to increased inflammation
Ca2+ influx can damage cells
what are some of the body's protection against antioxidants
enzymes: SOD (O2.- --> H2O2) & catalase (H2O2 --> H2O + O2)
glutathione & NADPH
what is oncosis?
cell death with swelling, changes that occur prior death
what is necrosis?
morphological changes that occur after death
what is apoptosis?
energy dependent programmed cell death with shrinkage
physiological: sculpt digits of fingers and toes & uterus contraction
pathological: cell damage in tumours
What are the light microscopic changes of a cell under apoptosis?
chromatin condenses, pyknosis, karryhexis, karrylysis
cell appears to be shrunken and intensely eosinophilic (basic stained pink)
what are the electron microscopic changes of a cell under apoptosis?
cytoplasmic budding --> fragmentation --> membrane budding (apoptotic bodies) - (contains cytoplasm, organelles & nuclear fragments), removed by macrophage in phagocytosis
what is the extrinsic pathway of apoptosis?
external ligands e.g. TRAIL & Fas
binds to 'death-receptors' --> caspase activation via cas 8 (independent of mitochondria)
what is the intrinsic pathway of apoptosis?
triggered by DNA damage / withdrawal of growth factors / hormones
protein p53 is the 'guardian genome' activates apoptosis during DNA damage
trigger leads to increased mitochondrial permeability --> release of cytochrome C (from mito)
cytochrome interacts with APAF1 + cas 9 to form apoptosome (which activates a downstream cascade)
all activation happens within mitochondria
what is coagulative necrosis?
protein denaturisation & coagulate, solid and white, ghost outline (cell architecture preserved), normally in solid organs e.g. MI, pancreas
mostly ischaemic (lack of blood), incites acute inflammation (phagocytosis)
what is liquifactive necrosis?
active enzymes released causing autolysis (proteins dissolution by own enzymes)
dead tissues liquefy - large number of neutrophils
rich in proteolytic enzymes e.g. proteases
in organs with no robust collagenous matrix support - becomes a viscous mass
in bacterial infection / ischaemic necrosis of brain
can have pus if acute inflammation arise
amorphous debris, cheesy appearance, no structure
associated with infections e.g. TB and granulomatous inflammation
destruction of adipose tissues,
pancreatitis due to lipase release
lipase act on fatty tissue of pancreas for release of fatty acids
fatty A can react with Ca2+ --> calcium soaps (chalky deposits)
e.g. after direct trauma to fatty tissue e.g. breast
exposure to air (dry out) bacteria can't grow when environment dehydrated so no infection
coagulative necrosis is underlying process
necrosis modified by infection
overgrown with fungi and bacteria
if get into blood - septicaemia
a type of wet gangrene
infected with anaerobic bacteria
produce visible bubbles of gas
e.g. motorbike accident
necrosis caused by ischaemia (thrombus, embolism, compression, vovulus)
solid organs / end artery
e.g. heart, spleen, kidney
extensive haemorrhage into dead tissue due to dual blood supply
numerous anastomoses or secondary arterial supply
normally loose tissue with poor stromal support
e.g. lung & brain anastamosis
what do molecules released by injured, dying & dead cells cause?
molecules leaked out can cause local irritation & inflammation, can be toxic to body but can help aid diagnoses (when appear in blood - give site)
what are molecules released by injured, dying & dead cells?
1. K+ e.g. from severe burns / tourniquet shock, can cause MI or massive necrosis if reach heart, tumour lysis syndrome (chemotherapy releases K+)
2. enzymes: shows organ involved and timing
3. myoglobin: from dead myocardium & straited muscles
what are the main groups of cellular accumulations?
water & electrolytes
what do water and electrolytes accumulations cause?
oedema (osmotic distrubance)
if in brain, can't swell as skull, so blood vessels squeezed and blood supply reduced
what do lipids accumulation cause?
steatosis (fatty change - accumulation of TAGs)
normally in liver (metabolise fat - alcoholic liver disease)
can be reversible within 10 days of alcohol withdrawal, liver becomes golden yellow and not red
What does cholesterol accumulation cause?
cholesterol can't be broken down in body, insoluble, eliminated through liver
atherosclerotic plaque (fatty streaks - accumulate in smooth muscle & macrophages - foam cells)
santhoma, xanthelasma, corneal arcus
What does accumulation of proteins cause?
mallorys hyaline: proteins in hepatocytes damaged due to altered keratin (alcoholic liver)
a1-antitrypsin deficiency: incorrectly folded, therefore not packaged by ER and never secreted by liver, deficiency means proteases acts unchecked and cause emphysema (from breaking down proteins in lungs)
what does accumulation of pigments in the cells cause?
normal cellular pigments - melanin
endogenous pigments: coal/carbon/soot (when inhaled cause blackened lung tissue, macrophage migrated from lungs to lymph nodes
if high dose becomes fibrotic lung / emphysematous (damaged alveoli)
lipofuscin: age pigment
haemosiderin (from Fe2+ buildup) e.g. haemorrhage into tissue from bruise
bilirubin in jaundice (bile pigment) heme from haemoglobin
what is dystrophic calcification?
in areas of dying tissue, in atherosclerotic plaques (buildup of fatty deposits)
local changse favour hydroxyapatite crystals
metastatic due to calcium abnormalties e.g. PTHrP, or leukaemia destroying bones
widespread calcium disturbance as opposed to localised
alcohol fatty change
alcohol causes up regulation of lipogenesis causing steatosis (fatty liver) and hepatomegaly (enlargement from the fats)
what is acute alcoholic hepatitis?
increased aldehyde causes focal hepatocyte necrosis forming mallory bodies (damage to proteins in hepatocytes)
symptoms: fever, tenderness & jaundice (protein haem damaged)