3. Cell injury and cell death Flashcards
1
Q
What is atrophy
A
decrease in size or number of cells due to loss of cell substance
-resulting in a decrease in the size of the organ
2
Q
Physiologic or pathologic atrophy
A
- decreased workload (atrophy of disuse)
- loss of innervation
- diminished blood supply
- inadequate nutrition (cachexia)
- loss of endocrine stimulation
- aging
- fetal development (atrophy of thyroglossal duct)
3
Q
What is hypertrophy
A
increase in the size of cells
- resulting in an increase in the size of the organ
- cells do not divide, number of cells stay the same, just the cells become larger
4
Q
Physiologic hypertrophy
A
skeletal muscle with exercise
5
Q
Pathologic hypertrophy
A
left ventricle hypertrophy in hypertension
6
Q
What is hyperplasia
A
increase in number of cells and usually the size of the organ
- occurs in organs capable of cellular division
- often associated with hypertrophy
7
Q
Physiologic hyperplasia
A
- hormonal (breast/uterus during pregnancy)
- compensatory (partial hepatetectomy)
8
Q
Pathologic hyperplasia
A
excessive hormonal/growth factor
- thyroid
- endometrial hyperplasia
9
Q
What is metaplasia
A
reversible change in which one adult cell type is replaced by another adult cell type
- genetic reprogramming of stem cells
- e.g:
a) cigarette smoking - respiratory pseudostratified columnar epithelium -> stratified squamous
b) Barrett’s oesophagus - stratified squamous -> simple columnar
10
Q
Causes of cell injury
A
- oxygen deprivation
- hypoxia - low oxygen delivery to tissue
- ishcaemia - decrease in blood flow (decrease oxygen and nutrients)
- shock - decrease in perfusion - physical agents
- trauma, thermal injury, radiation - chemical agents
- poison, environmental pollutant, drugs - infectious agents
- immunologic reactions
- genetic defects
- nutritional deficiency or excess
11
Q
Mechanism of cellular injury
A
- inhibition of aerobic respiration -> ATP depletion
- generatin of oxygen free radicals
- defects in membrane permeability
- disruption of calcium homeostasis (calcium influx)
- damage to DNA and proteins
12
Q
How does decreased oxidative phosphorylation within mitochondria cause cellular injury
A
- reversible injury
- reduced ATP
- increased anaerobic glycolysis -> accumulation of lactic acid
- reduced activity of sodium pump -> accumulation of sodium and water
- reduced activity of calcium pump -> increase cytosolic free calcium -> activates enzyme:
a) ATPase - decreased ATP
b) phospholipase - decreased phospholipids
c) endonuclease - nuclear chromatin damage
d) protease - disruption of membrane and cytoskeletal proteins - irreversible injury
- mitochondrial changes
- extensive plasma membrane damage
- injury to lysosomal membranes:
a) activation of enz -> degrades the damaged cell
b) release of enz -> damage the surrounding cell
13
Q
What is free radicals
A
extremely unstable, highly reactive chemical species with a single umpaired electron in outer orbit
14
Q
Where does activated oxgen species come from
A
- physiologic generation during oxidative phosphorylation
- radiation
- inflammation
- oxygen toxicity
- chemicals and drugs (paracetamol)
- metals (copper and iron)
- reperfusion injury
15
Q
Example of free radicles
A
- superoxide
- hydrogen peroxide
- hydroxyl ion
16
Q
Why is there free radical degeneration
A
- unstable with spontaneous decay
- inactivation by enzymes
- antioxidants (Vit E,C)
17
Q
How does free radicals cause cell injury
A
- lipid peroxidation of membranes
- free radicals and membrane lipids react to produce highly reactive lipid peroxide - oxidative modification of proteins
- cross linking of proteins -> damage to celllular enzyme - react with DNA and cause mutation
18
Q
Morphologic changes associated with reversible injury
A
decrease sodium-potassium pump -> increased cellular H2O
- cellular swelling
- hydropic change, vacuolar degeneration - ultra structural changes
- plasma membrane alteration - blebbing
- loss of microvilli
- mitochondrial swelling
- dilation of endoplasmic reticulum with detachments of ribosomes
- nuclear alterations
19
Q
Morphologic changes associated with irreversible injury
A
membrane damage
- plasma membrane -> enzyme released (e.g. troponin, amylase)
- mitochondrial membrane
- lysosome
20
Q
Morphologic changes associated with necrosis
A
- death of large group of cells
- due to pathological process
- enzymatic digestion of cell:
a) autolysis- digest themselves
b) heterolysis - digest neighbouring cells - inflammation of surrounding tissue
- cytoplasmic eosinophilia - become more pink than usual, protein damage so they take up the colour
- nuclear changes:
a) pyknosis - condensation of nucleus and clumping of chromatin (shrinking of nuclei)
b) Karyorrhexis - fragmentation and breakdown of nucleus
c) karyolysis - pallor and dissolution
21
Q
What is pyknosis
A
condensation of nucleus and clumping of chromatin (shrinking of nuclei)
22
Q
What is karyorrhexis
A
fragmentation and breakdown of nucleus
23
Q
What is karyolysis
A
pallor and dissolution
24
Q
Type of necrosis
A
- coagulative necrosis
- liquefactive necrosis
- caseous necrosis
- fat necrosis
- fibrinoid necrosis
- gangrenous necrosis
25
What is Coagulative necrosis
specific morphologic pattern of necrosis with preservation of the structural outlines
- characteristic of hypoxic cell death except in the brain
- cell shape and organ structure is preserved
- nuclei disappear
26
What is Liquefactive necrosis
transformation of solid tissue into a liquid mass
- complete digestion of cells
- tissue structure destroyed
- enzymatic lysis of cells
- characteristic of bacterial and some fungal infection (abscess) and hypoxic cell death in the CNS
27
What is Caseous necrosis
distinctive form of necrosis, characteristic of tuberculous infection
- chessy, crumbly, white gross appearance
- granular debris surrounded by a ring of granulomatoud inflammation
28
What is Fat necrosis
necrosis of fat induced by lipases (pancreas or macrophage)
- fatty acids complex with Ca2+ to create calcium soap
- chalky white area (fat saponification)
29
What is Fibrinoid necrosis
necrotic damage to blood vessel wall
| -associated with malignant hypertension and vasculitis
30
What is Gangrenous necrosis
not a distinctive pattern of cell death
- coagulative necrosis (mummified tissue - dry gangrene)
- liquefactive necrosis (ischaemia with secondary bacterial infection - wet gangrene)
- characteristic of ischaemia of the lower limb
- gas gangrene - clostridium infection
31
What is apoptosis
programmed cell death
- involves single cell or small clusters
- energy dependent
32
Physiological cause of apoptosis
- embryogenesis
- hormone (involution of hormone dependent tissue: regression of lactating breast, endometrial shedding)
- death of inflammatory cells after inflammation
- cell deletion in proliferating population - intestinal epithelium
- deletion of autoreactive T cells in thymus (failure might result in autoimmunity)
33
Pathological cause of apoptosis
- virus infected cells
- cells with DNA damage
- tumour cells
34
Characteristic of apoptosis
- plama membrane remain intact
- activation of self-degrading enzyme
- shrinkage of cell
- eosinophilia of cytoplasm
- condensation of chromatin
- fragmentation of DNA
- formation of apoptotic bodies
- apoptotic bodies and cells are phagocytosed without inducing an inflammatory response
35
What is apoptosis triggered by
1. internal signals
- mitochondrial damage
- DNA damage
- decreased hormonal stimulation
2. external signals
- surface suicide receptor (FAS receptor) is stimulated
- TNF/TNFR (tumour necrosis factor)
36
Process of apoptosis
1. activation of caspase (family of cysteine proteases) -> protein cleavage
2. activation of endonuclease -> stepwise fragmentation of DNA
3. phagocytosis of apoptotic cells
37
Disorders associated with increased apoptosis
1. AIDS
| 2. neurodegenerative disease
38
Disorders associated with increased cell survival
1. neoplasia
| 2. autoimmune disease
39
Intracellular accumulations
1. endogenous
- normal substance produced at normal or increased rate
- rate of metabolism inadequate for removal (fatty layer, lipofuscin)
- normal or abnormal substance cannot be metabolised (storage diseases)
2. exogenous
- cell cannot degrade substance (carbon, tattoos)
40
What is lipofuscin
pigment like waste product, rich in lipid, accumulates in old age
41
What is pathologic calcification
abnormal deposition of calcium salts with smaller amounts of iron, magnesium and other mineral salts
- 2 types:
a) dystrophic calcification
b) metastatic calcification
42
What is dystrophic calcification
deposition of calcium in a necrotic tissue
| -normal serum calcium
43
What is metastatic calcification
deposition of calcium in a normal tissue
a) occurs with hypercalcaemia
- hyperparathyroidism
- destruction of bone occurring with tumours involving bone
- vitamin D intoxication
- sarcoidosis - abnormal collections of inflammatory cells that form lumps known as granulomas
- renal failure
b) occurs in normal tissue
c) primarily affects vessels, kidneys, lungs, and gastric mucosa
44
Two theories of cellular aging
1. wear and tear
- accumulation of metabolic and genetic damage over a long period of time
- free radical damage throughout life
2. intrinsic cellular ageing
- replicative senescence
- predetermined genetic programming
- telomere shortening (incomplete replication of chromosome ends -> cell arrest)
