MoD week 1 - cell injury

Question 1

what causes hypoxia?

Answer 1

reduced oxygen supply due to ischaemia (lack of blood supply)

Question 2

what are the 4 types of hypoxia?

Answer 2

anaemic hypoxia
hypoxic hypoxia
histiocytic hypoxia
ischaemic hypoxia

Question 3

what is hypoxaemic hypoxia?

Answer 3

low arterial oxygen content

e.g. altitude & lung disease

Question 4

what is anaemic hypoxia?

Answer 4

lack of RBC so reduced O2 carrying capacity

Question 5

what is ischaemic hypoxia?

Answer 5

obstruction / interruption in blood flow (PE, tumour)

lack of blood flow

Question 6

what is histiocytic hypoxia?

Answer 6

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)

Question 7

what are reversible changes in cellular injury?

Answer 7

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)

Question 8

what are irreversible changes in cell injury?

Answer 8

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)
cell death

Question 9

What is reperfusion?

Answer 9

return of blood flow to an ischaemic tissue

Question 10

What is reactive hyperaemia?

Answer 10

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

Question 11

What is ischaemic reperfusion injury?

Answer 11

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

Question 12

what are some of the body’s protection against antioxidants

Answer 12

enzymes: SOD (O2.- –> H2O2) & catalase (H2O2 –> H2O + O2)
vit ACE
glutathione & NADPH

Question 13

what is oncosis?

Answer 13

cell death with swelling, changes that occur prior death

Question 14

what is necrosis?

Answer 14

morphological changes that occur after death

Question 15

what is apoptosis?

Answer 15

energy dependent programmed cell death with shrinkage

physiological: sculpt digits of fingers and toes & uterus contraction
pathological: cell damage in tumours

Question 16

What are the light microscopic changes of a cell under apoptosis?

Answer 16

chromatin condenses, pyknosis, karryhexis, karrylysis

cell appears to be shrunken and intensely eosinophilic (basic stained pink)

Question 17

what are the electron microscopic changes of a cell under apoptosis?

Answer 17

cytoplasmic budding –> fragmentation –> membrane budding (apoptotic bodies) - (contains cytoplasm, organelles & nuclear fragments), removed by macrophage in phagocytosis

Question 18

what is the extrinsic pathway of apoptosis?

Answer 18

external ligands e.g. TRAIL & Fas

binds to ‘death-receptors’ –> caspase activation via cas 8 (independent of mitochondria)

Question 19

what is the intrinsic pathway of apoptosis?

Answer 19

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

Question 20

what is coagulative necrosis?

Answer 20

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)

Question 21

what is liquifactive necrosis?

Answer 21

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

Question 22

caseous necrosis

Answer 22

amorphous debris, cheesy appearance, no structure

associated with infections e.g. TB and granulomatous inflammation

Question 23

fat necrosis

Answer 23

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

Question 24

gangrene

Answer 24

visible necrosis

Question 25

dry gangrene

Answer 25

exposure to air (dry out) bacteria can't grow when environment dehydrated so no infection coagulation e.g. umbilical coagulative necrosis is underlying process

Question 26

wet gangrene

Answer 26

necrosis modified by infection overgrown with fungi and bacteria if get into blood - septicaemia

Question 27

gas gangrene

Answer 27

a type of wet gangrene infected with anaerobic bacteria produce visible bubbles of gas e.g. motorbike accident

Question 28

infarction

Answer 28

necrosis caused by ischaemia (thrombus, embolism, compression, vovulus)

Question 29

white infarct

Answer 29

solid organs / end artery | e.g. heart, spleen, kidney

Question 30

red infarct

Answer 30

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

Question 31

what do molecules released by injured, dying & dead cells cause?

Answer 31

molecules leaked out can cause local irritation & inflammation, can be toxic to body but can help aid diagnoses (when appear in blood - give site)

Question 32

what are molecules released by injured, dying & dead cells?

Answer 32

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

Question 33

what are the main groups of cellular accumulations?

Answer 33

``` water & electrolytes lipids proteins pigments cholesterol ```

Question 34

what do water and electrolytes accumulations cause?

Answer 34

oedema (osmotic distrubance) | if in brain, can't swell as skull, so blood vessels squeezed and blood supply reduced

Question 35

what do lipids accumulation cause?

Answer 35

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

Question 36

What does cholesterol accumulation cause?

Answer 36

``` 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 ```

Question 37

What does accumulation of proteins cause?

Answer 37

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)

Question 38

what does accumulation of pigments in the cells cause?

Answer 38

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

Question 39

what is dystrophic calcification?

Answer 39

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

Question 40

metastatic calcification

Answer 40

widespread calcium disturbance as opposed to localised | hydroxyapatite crystals

Question 41

alcohol fatty change

Answer 41

alcohol causes up regulation of lipogenesis causing steatosis (fatty liver) and hepatomegaly (enlargement from the fats)

Question 42

what is acute alcoholic hepatitis?

Answer 42

increased aldehyde causes focal hepatocyte necrosis forming mallory bodies (damage to proteins in hepatocytes) neutrophil infiltrate usually reversible symptoms: fever, tenderness & jaundice (protein haem damaged)

Question 43

what is cirrhosis?

Answer 43

results in hard, shrunken liver histological: micronodules of regenerating hepatocytes surrounded by bands of collagen irreversible