Lecture 2 Flashcards
1
Q
4 Mechanisms of Cell Injury
A
- Abnormal metabolism
- Defect in protein folding transport
- Lack of enzyme
- Ingestion of indigestable materials
2
Q
Reversible Changes
A
Non-lethal damage which can be corrected by removal of the stimulus.
3
Q
Irreversible Changes
A
There is lethal damage leading to death of cell.
4
Q
Non-lethal outcomes of cell injury
A
- Temporary alteration in cell function
- Decreases or ceases specialised functions
- Functions to survive - Effective adaptive mechanisms triggered
- Ion channels open or close
- Harmful chemicals detoxified or removed
- Metabolic stores mobilised - Structural damage with permanent impairment of function
- DNA mutation
5
Q
What influences injury outcome?
A
- Type of injury
- Duration of injury
- Severity of injury
- Current status of tissue
- Adaptability of tissue
6
Q
Type of cell/tissue being injured?
A
Labile cells:
- Constantly divide to replenish the dead/lost cells.
- Skin, mucous membranes, bone marrow
- Low cellular turnover
- High mitotic rate
Stable cells:
- Have ability to divide but will only do so occasionally
- Liver, kidney,glands
- Low cellular turnover
- Low mitotic rate
Permanent cells:
- Have lost ability to divide
- Neurones, cardiac muscle, skeletal muscle
- Cells lost progressively and not replaced
- No mitotic activity
7
Q
What cellular structures & processes are most vulnerable to injury?
A
- Proteins, membranes, DNA and other structures
- Mitochondrial damage (cause ATP depletion)
8
Q
Events after injury?
A
Changes at molecular level
- Can be detected using molecular technique PCR
Morphological changes
- Electron or light microscope or gross appearance
9
Q
Processes that may occur following injury:
A
- Oncosis
- Decreases in ATP synthesis - Depletion of cytoplasmic glycogen
- Swelling of endoplasmic reticulum
- Decrease in protein synthesis
- Aggregation of particles within the plasma membrane
- Fatty changes or steatosis may occur
- Cellular adaptions
10
Q
Irreversible Cell Injury
A
- Vacuoles appear in the cytoplasm
- Severe mitochondrial damage
- Rupture of lysosomes
- Massive influx calcium and efflux of enzymes and proteins into the circulation
- Changes occur in the cell nucleus
- Pyknosis
- Karyorrhexis
- Karyolysis - Lysis of the endo[lasmic reticulum
- Cell membrane defects worsen
- Irreversible cell injury results in cell death “necrosis”
11
Q
Ischaemia
A
- Inadequate blood flow to tissues
- Due to narrowing 1 or more arteries, tissues do not recieve oxygen.
- Causes Hypoxia
12
Q
Hypoxia
A
- Decrease in tissue oxygenation
13
Q
Anoxia
A
- Absence of tissue oxygenation and may be due to ischaemia or a number of other causes
14
Q
Cells may accumulate abnormal amounts of various substances that:
A
- Either transiently or permanently
- May be harmless or may cause varying degrees of additional injury
- A result of stressors, or simply due to normal but inefficient cell function.
15
Q
Sources of Substrates
A
- Outside the body (carbon particles from polluted)
- Inside the body from a normal substance (water, glycogen, fat, protein)
- Inside the body but abnormally created (Abnormal metabolism or synthesis)
16
Q
Mechanisms of Substrate Accumulation
A
17
Q
Examples of substances which may be accumulated:
A
- Water = Oncosis
- Fat = Steatosis
- Glycogen = Glycogen storage diseases
- Carbohydrates and lipids. = Lysosomal storage disease
- Proteins = neurofibrillary tangles of Alzheimers disease
18
Q
Pigments and Other Substrates Accumulation: Melanin
A
Pigmented moles, melanomas.
19
Q
Pigments and Other Substrates Accumulation: Bilirubin
A
A yellow-green pigment from red blood cell breakdown, cause jaundice
20
Q
Pigments and Other Substrates Accumulation: Calcium
A
Dystrophic (Accumulation in dead or injured cells) and Metastatic (In normal cells as result of hypercalcemia)
21
Q
Pigments and Other Substrates Accumulation: Urate
A
Accumulation due to either an increase in production of uric acid.
22
Q
Pigments and Other Substrates Accumulation: Inorganic
A
Coal dusts, silica dust, asbestos may accumulate in the lungs and it lymph nodes
23
Q
Cell death types
A
- Apoptosis (type I)
- Autophagic (type II)
- Necrosis (type III)
24
Q
Pigments and Other Substrates Accumulation: Haemosiderin
A
A yellow-brown pigment derived from haemoglobin. May accumulate where there is an excess of iron in the body, or in areas of bruising.
25
Necrosis
- Sum of cellular changes after local death and the process of cellular self-digestion, known as autodigestion or autolysis
26
Pigments and Other Substrates Accumulation: Lipochrome
Yellow-brown pigment that generally builds up over time as a result of wear and tear.
27
Pigments and Other Substrates Accumulation: Organic dusts
Mouldy hay, bird droppings
28
Name 6 factors which can influence the impact of stressors on cells and tissues.
1. Type of injury
2. Type of cell/tissue
3. Duration of injury
4. Severity of injury
5. Current status of tissue
6. Adaptability of tissue
29
Name the cell structures and processes which are most vulnerable to injury.
- Mitochondria
- Mambrane
- DNA
- Formation of free radicals
- Increasing calcium influx
30
What are the characterisitc of reversible injury?!!
1. Oncosis
2. Depletion of cytoplasmic glycogen
3. Swelling of ER
4. Decrease in protein synthesis
5. Aggregation of particles in cell membrane
6. Fatty changes or steatosis
7. Abnormal accumulations within cells
8. Adaptations
31
What are characteristics of irreversible injury?!!
1. Vacuoles appear in cytoplasm
2. Severe mitochondrial damage
3. Rupture of lysosomes
4. Influx of calcium and efflux of enzymes and proteins into circulation
5. Changes in cell nucleus
6. Lysis in ER
7. Cell membrane defects worsen
8. Necrosis
32
Non-lethal injury which can be corrected by removal of the stimulus is known as reversible/irreversible injury.
Reversible
33
Cells which have an ability to divide, but only do so when required are called labile/stable/permanent cells
Stable
34
Abnormal accumulation of fat within cells is called oncosis/steatosis
Once cell death is inevitable, there is degeneration and condensation of nuclear chromatin. This is known as pyknosis/ karyorrhexis / karyolysis. Fragmentation of the nucleus is called pyknosis/ karyorrhexis / karyolysis.
1. Steatosis
2. Pyknosis
3. Karryorrhexis
35
Cell adaptations are generally reversible/ generally irreversible/ either reversible or irreversible
Either reversible or irreversible
36
Reactive oxygen species (ROS) are chemically reactive/ unreactive and are formed during normal nuclear/ mitochondrial activity.
1. Reactive
2. Mitochondrial
37
Cell damage may occur as a result of an increase in ROS / free radicals / increase in ROS as well as free radicals.
Increase in ROS as well as free radicals.
38
True or False:
Ischaemia can cause hypoxia or anoxia
True
39
True or False:
Hypoxia generally results in hypoxaemia
False
40
True or False:
Ischaemia and hypoxaemia need to both occur in order to cause tissue hypoxia
False
41
True or False:
Ischaemia can cause infarction
True
42
True or False:
Necrotic tissue which occurs as a consequence of ischaemia is called an infarct.
True
43
True or False:
Accumulation of abnormal amounts of a substance within a cell is usually irreversible
False
44
True or False:
Substances that may accumulate within cells generally come from outside the body.
False
45
True or False:
Substances that may accumulate within cells may occur due to inefficient cell functioning, as well as via the action of stressors.
True
46
Name the substance(s) which is accumulating in each of the following:
a. Jaundice
b. Gout
c. Steatosis
d. Oncosis
e. Neurofibrillary tangles in Alzheimer’s disease
f. Lysosomal storage disease
g. Glycogen storage disease
h. Bruises
i. In dead or dying cells
j. Anthracosis
a. Bilirubin
b. Urate
c. Fat
d. Water
e. Proteins
f. Carbohydrates & lipids
g. Glycogen
h. Haemosiderin
i. Calcium
j. Inorganic dusts (Carbon)
47
Explain the difference between:
Biochemical and histological necrosis
Biochemical:
- Early changes during "point of no return" before changes can be seen in the tissue
Histological:
- State in necrotic cell that can be seen microscopically such as pyknosis.
48
Explain the dofference between:
Autolysis and coagulation of cellular contents
Autolysis:
- Tissue is digested by hydrolytic enzymes
Coagulation:
- Tissue structure is preserved but protein is denatured.
49
The most common type of necrosis in the body. Occurs in solid organs e.g. heart, kidney, spleen, liver. Results in an area of coagulated tissue
Coagulative
50
Occurs in the brain due to autolysis, progressing almost to completion with little coagulation.
Liquefactive/Colliquative
51
Occurs in tuberculosis (infection with Mycobacterium tuberculosis ) due to a Type 4 hypersensitivity reaction and the nature of the bacterium
Caseous
52
Infection of necrotic tissue with anaerobic bacteria, especially Clostridium species
Gangrenous
53
Occurs in suppuration due to neutrophils lysing bacteria and tissue, i.e. heterolysis. It may occur in any tissue infected with pyogenic bacteria.
Liquefactive/Colliquative
54
Occurs in connective tissue within blood vessel walls. Seen especially in hypertension and in autoimmune diseases. Collagen becomes denatured, fibrinogen from blood enters necrotic tissue and becomes fibrin
Fibrinoid/hyline
55
Occurs when adipose tissue in any site is injured by trauma e.g. a blow to the breast
Fat (traumatic type)
56
What type of necrosis occurs only around the pancreas; associated with adipose tissue injury and release of pancreatic lipases (e.g. in alcoholics)
Fat (enzymatic type)
57
The term which refers to ‘programmed’ cell death which is a highly organised process is called
Apoptosis
58
The term which refers to activities such as cell remodelling and removal of damaged organelles, often creating a phagolysosome is called
Autogaphy
59
List 3 differences between Autophagy vs. Necrosis
1. Mechanism:
Autophagy: Controlled process where cells recycle damaged parts for survival.
Necrosis: Uncontrolled cell death caused by damage, leading to membrane rupture.
2. Outcome
Autophagy: Often promotes survival, but excessive autophagy can lead to death.
Necrosis: Leads to cell death and tissue damage.
3. Inflammation
Autophagy: Typically doesn’t cause inflammation.
Necrosis: Triggers inflammation due to cell membrane rupture.
60
Types of Necrosis
1. Coagulative
2. Colliquative/Liquefactive
3. Gangrenous
4. Caseous
5. Fat (enzymatic & traumatic)
6. Fibrinoid
61
Coagulative Necrosis
- Tissue architecture and cellular outlines are preserved due to protein denaturation, often caused by ischemia or infarction
- Typically seen in organs like the kidney, heart, and adrenal glands
- Most common type
62
Colliquative/Liquefactive Necrosis
- Dead tissue transforms into a viscous, liquid mass, often associated with infections or internal chemical burns.
- Seen in abscess, tissue has been destroyed & replaced by thick white-yellow fluid "pus"
63
Gangrenous Necrosis
- A serious condition where body tissue dies due to a lack of blood supply, leading to discolored or black tissue, often accompanied by foul-smelling gas.
64
Caseous Necrosis
- A type of cell death that causes tissue to appear cheese-like
- Often in foci of tubercolosis
- White gross appearance of central necrotic area
65
Fat Necrosis
- Focal areas of fat destruction
Enzymatic type:
- Occurs due to the release of pancreatic enzymes into surrounding fatty tissue after pancreatic injury, leading to fat destruction, and the formation of chalky, white areas .
Traumatic Type:
- Occurs when subcutaneous fat dies due to injury or trauma, leading to inflammation, fibrosis, and potentially a palpable mass
66
Fibrinoid Necrosis
- Where blood vessel walls degenerate and become filled with fibrin-like material, often due to damage from conditions like autoimmune diseases or severe hypertension, leading to cell death
- Collagen becomes denatured, fibrinogen from blood enters necrotic tissue & converted into fibrin
67
List 3 differences between autogaphy and apoptosis
1. Process Type:
Autophagy: A survival mechanism where cells degrade and recycle damaged components to maintain homeostasis.
Apoptosis: A programmed, controlled process of cell death, eliminating unwanted or damaged cells in a regulated manner.
2. Cell Outcome:
Autophagy: Often helps the cell survive stress by removing damaged organelles or proteins.
Apoptosis: Leads to cell death without causing inflammation, as the cell breaks down in an orderly way.
3. Role in Health
Autophagy: Protects cells from damage and helps maintain cellular health.
Apoptosis: Removes damaged, dangerous, or unneeded cells, playing a key role in development and disease prevention.
68
List 3 differences between apoptosis and necrosis
1. Cell Death Process:
Apoptosis: A controlled, programmed cell death process, involving a series of regulated steps.
Necrosis: An uncontrolled, accidental cell death due to severe damage or trauma, often resulting from injury or lack of oxygen.
2. Cellular Outcome
Apoptosis: The cell undergoes a tidy breakdown, with no inflammation, as it’s engulfed by neighboring cells.
Necrosis: The cell bursts open, releasing its contents, which causes inflammation in the surrounding tissue.
3. Impact on surrounding tissue
Apoptosis: Does not trigger an inflammatory response because the process is clean and contained.
Necrosis: Causes inflammation and damage to surrounding tissues due to the release of cellular debris and harmful substances.
69
Pyknosis
Degeneration and condensation of nuclear chromatin
70
Karyorrhexis
Fragmentation of the nucleus
71
Karyolysis
Dissolution of the nucleus
