2 Cell Injury Flashcards
1
Q
What happens when cells reach the limits of their adaptive response?
A
- Reversible cell injury
- Irreversible cell injury and death
2
Q
Identify 4 factors which affect the extent of cell damage
A
- Type of injury
- Duration of injury
- Severity of injury
- Type of tissue
3
Q
What is hypoxia and how does it cause cell injury?
A
- Hypoxia is oxygen deprivation
- if persistent causes cell adaptation, injury or death
4
Q
Identify 5 physical agents which can cause cell injury
A
- Direct trauma
- Extremes of temperature (burns and severe cold)
- Sudden changes in atmospheric pressure
- Electric currents
- Radiation
5
Q
Identify 5 chemical agents/drugs which can cause cell injury
A
- Oxygen in high concentrations
- Poisons
- Alcohol
- Illicit drugs
- Therapeutic drugs
6
Q
Provide a 10-point summary of reversible hypoxic cell injury.
A
- Cell is deprived of oxygen
- Mitochondria stops ATP production & membrane ionic pumps stop
- Na+ and H20 seep into the cell
- Cell swells and initiates a heat-shock response (stress)
- Glycolysis keeps cell alive but pH drops as lactic acid accumulates
- Calcium enters the cell & activates: phospholipases, proteases, ATPase and endonucleases
- ER and other organelles swell
- Enzymes leak out of lysosomes and attack cell contents
- Cell membrane is damaged (show blebbing(bulge in plasma membrane)
- Cell dies – burst of a bleb
7
Q
Describe the effect of the following enzymes in causing cell injury:
- Phospholipases
- Protease
- ATPases
- Endonucleases
A
- Phospholipases – cause cell membranes to lose phospholipids
- Proteases – damage cytoskeletal structures and attack membrane proteins
- ATPases – cause more loss of ATP
- Endonucleases – cause nuclear chromatin to clump
8
Q
What is Ischaemia-Reperfusion Injury?
A
Ischaemia-reperfusion injury:
Tissue = damaged not yet necrotic
Cell=damaged as a result of blood flow return
9
Q
What causes Ischamia-Reperfusion injury? (3)
A
- Reoxygenation- increase in free radicals
- Increased neutrophil number- increase inflammation
- Complement proteins delivered- activate inflammatory pathway
10
Q
What are free radicals and what do they do?
A
- Free radicals are reactive oxygen species
- have a single unpaired electron
- This is an _unstable configuratio_n- v reactive
11
Q
How do free radicals injure cells?
A
Oxidative imbalance- overwhelm anti-oxidant system
- Attack lipids in cell membranes and cause lipid peroxidation- generate more free radicals
- Damage (oxidise) proteins, carbohydrates and nucleic acids= mutagenic, carcinogenic
12
Q
Identify 3 free radicals of particular biological significance in cells
A
- OH• (hydroxyl)
- 02- (superoxide)
- H202 (hydrogen peroxide)
13
Q
What causes cell injury, in terms of free radicals?
A
- Imbalance between free radical production and free radical scavenging
- Free radicals accumulate- oxidative stress
14
Q
Identify and describe the components of the antioxidant system
A
- Superoxide dismutase catalyse the reaction production of H2O2 (less toxic) from O2-
- Catalases and peroxidases catalyse the production of H2O and O2 from H2O2
- Free radical scavengers neutralise free radicals (eg vitamins a,c, and e)
- Storage proteins (eg transferrin) that sequester transition metals in the extracellular matrix
15
Q
Identify some free radical scavengers
A
- Vitamin A
- Vitamin C
- Vitamin E
- Glutathione
16
Q
Identify two storage proteins involved in the antioxidant system
A
- Transferrin
- Ceruloplasmin
17
Q
What are heat shock proteins?
A
Heat shock proteins are proteins triggered by any form of cell injury to protect the body in the stress response
18
Q
Provide 3 examples of heat shock proteins
A
- Stress proteins
- Unfoldases
- Chaperonins
19
Q
How do cells respond to the heat shock response?
A
- Decrease usual protein synthesis
- Increase synthesis of HSPs
20
Q
Identify 4 reversible changes involved in cell injury as seen in electron microscopy
A
- Swelling of cell & organelles
- Cytoplasmic blebs
- Clumped chromatin
- Ribosome separation from the rER
21
Q
Identify 5 irreversible changes involved in cell injury as seen in electron microscopy.
A
- Nuclear changes
- Swelling and rupture of lysosomes
- Membrane defects
- The appearance of myelin figures
- Lysis of the ER
22
Q
Identify and describe the three types of nuclear changes that can occur in cell injury.
A
23
Q
Define oncosis
A
Oncosis is cell death with swelling and the spectrum of changes that occur prior to death in injured cells
24
Q
Define necrosis
A
- Necrosis is the morphologic changes that occur after a cell has been dead some time e.g. 4-24 hours
- Not a type of cell death, i.e. it is an appearance and not a process
25
How is necrotic tissue removed?
- Necrotic tissue is removed by **enzymatic degradation** and **phagocytosis** by white cells
- If some remains it may **calcify** (dystrophic calcification)
26
What is caseous necrosis?
- Contains amorphous (structureless) **debris**
- Associated with **infections** *e.g. TB*
* (inbetween coagulative and liquefactive)*
27
What is fat necrosis?
- **Lipase** releases **fatty acids** from triglycerides
- Fatty acids complex with **calcium** to form **soaps**
- Soaps appear as **white chalky deposits**
- Associated with pancreas (pancreatitis), breast and the salivary glands
28
What is gangrene?
**Gangrene** =_clinical term_ used to describe _necrosis_ that is _visible to the naked eye_
29
Classify the different types of gangrene
- **Dry gangrene** – necrosis is modified by _exposure to air *(coagulative necrosis)*_
- **Wet gangrene** – necrosis is modified by _infection_ with a mixed bacterial culture *_(liquefactive necrosis)_*
30
Define apoptosis
* **Apoptosis** is cell death with shrinkage
* Induced by a _regulated intracellular program_
* --\>cell activates enzymes that degrade its own nuclear DNA and proteins
31
What is gas gangrene?
- **Gas gangrene:**
**--\>** _wet gangrene_ where the tissue has become _infected_ with _anaerobic bacteria_
*- It produces visible and palpable bubbles of gas within the tissues*
32
What is infarction?
**Infarction=** cause of _necrosis_, namely _ischaemia_ (reduced blood supply)
## Footnote
*(Infarct= area of necrotic tissue)*
33
Identify the 2 most common causes of infarction
- Thrombosis
- Embolism
(could be eg twisted bowel)
34
Explain how infarcts can be described by their colour and what this indicates?
- Infarcts can be **white / red**
- It indicates how much **haemorrhage** there is into the infarct
35
Where are white infarcts found?
A **white** (anaemic) **infarct** occurs in ‘solid’ organs after occlusion of an “end” artery
36
Where are red infarcts found?
A **red** (haemorrhagic) **infarct** occurs where there is extensive haemorrhage into dead tissue due to:
1. - Loose tissue
2. - A dual blood supply
3. - Numerous anastomoses
4. - Re-perfusion
37
Identify 3 consequences of infarction
- Local irritation
- Local inflammation
- General toxic effects on the body
38
Identify 3 types of molecules released from an infarction (high conc in blood).
- Potassium
- Enzymes *e.g. Creatine Kinase, AST, troponin*
- Myoglobin
39
Why does apoptosis not induce inflammation?
- Apoptotic bodies are removed by macrophage phagocytosis
- No leakage of cell contents occurs
40
What does apoptosis look like under a light microscope?
- Apoptotic cells are **shrunken** and appear **intensely eosinophilic**
- Pyknosis and karyorrhexis are seen
41
What does apoptosis look like under an electron microscope?
- Cells show **cytoplasmic budding** (not blebbing as is seen in oncosis)
- This progresses to fragmentation into membrane-bound **apoptotic bodies**
42
Why are apoptotic bodies phagocytosed?
The apoptotic bodies express **proteins** on their surface which are recognised by phagocytes or neighbouring cells
43
Compare and contrast the structural changes in oncosis/necrosis and apoptosis in terms of:
- Pattern
- Cell size
- Nucleus
- Plasma membrane
- Cellular contents
- Adjacent inflammation
- Physiological/pathological role
44
What are the five main groups of intracellular accumulations?
- Carbohydrates
- Water and electrolytes
- Lipids (triglycerides and cholesterol)
- Proteins
- Pigments (exogenous and endogenous)
45
Hydropic swelling is a type of abnormal cellular accumulation.
What occurs?
Fluid accumulating in cells- due to hypoxia- indicates severe cellular distress. Na+ and water flood into cell
46
When and where does hydropic swelling occur?
- Occurs when **energy supplies** are cut off *e.g. hypoxia*
- Particularly occurs in the **brain**
47
What is steatosis?
- **Steatosis** is the accumulation of triglycerides
- If mild, it is asymptomatic
48
What is the most common site of steatosis?
Liver (major organ of fat metabolism)
49
Identify 4 causes of steatosis
- Alcohol
- Diabetes mellitus
- Obesity
- Toxins
50
What might cause choletserol to accumulate in cells?
- Cannot be broken down and is **insoluble**
- Can only be eliminated through the **liver**
- Excess stored in cell in **vesicles**
51
How are foam cells formed?
**Foam cells** formed from:
_cholesterol_ accumulating in the _smooth muscle cells_ + _macrophages_ of _atherosclerotic plaques_
52
Where are xanthomas found?
**Xanthomas:**
* present in macrophages in skin and tendons
* -people with hereditary hyperlipidaemias
53
How do protein accumulations appear in tissues?
- Look like eosinophilic **droplets**
- Look like **aggregations** in the cytoplasm
54
How would an α1-antitrypsin deficiencyn cause abnormal protein accumulation in cells?
- **Liver** produces **incorrectly folded** α1-antitrypsin protein
- Protein **cannot be packaged** by **ER**, accumulates and is **not secreted**
- **Systemic deficiency**
_--\>(emphysema)_ (proteases in lungs act unchecked)
55
When might endogenous pigments accumulate in cells?
* **Tatoos:**
* - Phagocytosed by macrophages in **dermis** and remains there
* - Some pigment will reach draining **lymph nodes**
* **Haemosiderosis:**
* ****-deposition haemosiderin in many organs (caused by blood transfusions/haemolytic anaemias
* HAEMOSIDERIN=iron storage molecule- derived from haemoglobin. If in excess=bruise
56
Explain how coal, dust or soot (endogenous pigments) accumulate in the body.
- _Pigment inhaled_ and _phagocytosed_ by **_alveolar macrophages_**
- _Anthracosis_ and _blackened peribronchial lymph nodes_
- *Harmless unless in large amounts (fibrosis/emphysema)*
57
What is pathological calcification?
**Pathological calcification** is the abnormal deposition of calcium salts within tissues
58
What are the 2 types of pathological calcification?
- Dystrophic calcification (local – more common)
- Metastatic calcification (general)
59
What is dystrophic calcification?
- **Dystrophic calcification** is when a local change or disturbance in the tissue favours the nucleation of *_hydroxyapatite crystals_*
***-** No abnormality in calcium metabolism*
60
Identify 4 locations where dystrophic calcification occurs
- An area of dying tissue
- Atherosclerotic plaques
- Aging or damaged heart valves
- Tuberculous lymph nodes
61
What is metastatic calcification?
**Metastatic calcification** :
* hydroxyapatite crystals are deposited in normal tissues throughout the body
* due to hypercalcaemia _secondary to disturbances in calcium metabolism_
(can regress if cause corrected)
62
Distinguish between the acute and chronic liver disease
- **Acute liver disease** is when damage to the liver develops over a few months
- **Chronic liver disease** is when damage to the liver occurs over a number of years
63
Identify 2 effects of chronic excessive alcohol intake on the liver
- **Oxidative stress** – liver tries to break down alcohol and the resulting chemical reaction damages its cells, leading to inflammation and scarring
**- Toxins** – alcohol damages our intestine which releases toxins from gut bacteria into the liver, leading to inflammation and scarring
64
What causes jaundice?
Accumulation of bilirubin
65
What is bilirubin?
**Bilirubin** is a breakdown product of heme, formed in all cells of body and excreted in bile
66
How does jaundice arise?
* - Bile flow is obstructed or overwhelmed
* - Bilirubin in blood rises and is deposited in tissues extracellularly or in macrophages
67
What is chronic hepatitis?
**Chronic hepatitis** is defined as over 6 months history with histology of inflammation and necrosis in the liver
68
Identify 5 laboratory features of hepatitis
- Raised serum ALT, AST and LDH
- Raised bilirubin
- Decreased albumin
- Raised PT (prothrombin)
- Raised ammonia
69
Identify 3 laboratory features of alcoholic liver disease
- Raised bilirubin
- Raised alkaline phosphatase
- Raised gamma GT (glutamyl transpeptidase)
70
What are the clinical and laboratory features of acute pancreatitis?
- Raised serum amylase in first 24 hours
- Raised serum lipase from 72-96 hours
- Glycosuria (10%)
- Hypocalcaemia possible
71
How do we take measurements to identify myocardial infarctions?
Measure blood levels:
- intracellular macromolecules that leak out of injured myocardial cells
72
Identify 5 substances which indicate the occurrence of a myocardial infarction
- Troponin T (TnT)
- Troponin I (TnI)
- Creatine kinase (CK)
- Lactate dehydrogenase (LDH)
- Myoglobin
73
What are the 4 different types of hypoxia and how are they caused?
1. **Hypoxaemic hypoxia**: O2 arterial content=low eg high altitude
2. **Anaemic hypoxia**: Oxygen carrying capacity of blood=reduced eg CO poisoning
3. **Ischaemic hypoxia**: blood supply interuption
4. **Histiocytic hypoxia**: disabled oxidative phosphorylation, inability to use oxygen eg cyanide poisoning
74
When and what causes free radicals to be produced? (5)
1. Normal metabolic rxns eg oxidative phosphorylation
2. Radiation
3. Inflammation: oxidative burst of neutrophils
4. Contact with unbound metals in body eg iron
5. Drugs and chemicals
75
What are the types of necrosis? (4)
1. **Coagulative** -most cases
2. Liquefactive (colliquitive) -brain
3. Caseous
4. Fat necrosis
76
Differentiate between the 2 main types of necrosis.
77
What are the consequences of potassium levels in the blood getting to high?
Arythmia, ventricular fibrillation, tachycardia
78
How does apoptosis occur?
1. Equal and opposite force to mitosis
2. Enzymes activated
3. Membrane integrity maintained
4. NOT using lysosomal enzymes
5. Quick- few hours
79
What causes abnormal cellular accumulations?
* Metabolism of cell=deranged.
* Sublethal/chronic injury
80
What is a xanthoma?
Abnormal accumulation of cholestrol/ lipid in skin
81
What accumulation in the liver cells might we see with alchoholic liver disease?
Mallory's hyaline
82
What is hereditary haematochromatosis?
1. Increased intestinal absorption-dietary iron
2. Iron= deposited in skin, liver, pancreas etc
3. (Associated w./ liver and pancreas cirrhosis)
4. Causes:
1. Liver damage
2. Heart dysfunction
5. =bronze diabetes
Treatment= repeated bleeding to expel iron
83
Whar are the 2 main causes of hypercalcaemia?
1) Increase secretion- **PTH** (stimulates osteoclast activity)
2) **Destruction of bone tissue**
84
What are the 3 different causes of increased PTH secretion?
1. Primary-tumour/parathyroid hyperplasia
2. Secondary- renal failure&retention of phosphate
3. Ectopic- malignant tumours
85
What may cause destruction of bone tissue?
1. Primary tumours of bone marrow eg leukaemia
2. Paget's disease of bone (acclerated bone turnover)
3. Immobilisation
86
Why can't cells live forever?
Cells age, accumulate damage
Telomeres shorten- eventually length=critical
87
What is the function of telomerase?
Maintain original length to telomere- present in germ cells
(many cancer cells have telomerase)
