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Cell Injury Flashcards

0
Q

What is hypoxia?

A

Oxygen deprivation resulting in decreased aerobic oxidative respiration

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1
Q

How can cell injury occur?

A

Hypoxia
Physical agents eg trauma, extremes in temperature
Chemical agents
Drugs

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2
Q

What does hypoxaemic mean?

A

Arterial content of oxygen is low

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3
Q

What can cause someone to be hypoxaemic?

A

High altitude

Lung disease

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4
Q

Definition of anaemia?

A

Decreased ability of haemoglobin to carry oxygen

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5
Q

What is ischaemia?

A

Interruption to blood supply causing lack of oxygen and metabolic substrates to tissue

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6
Q

What is oncosis?

A

Cell death with swelling

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7
Q

What is necrosis?

A

The morphological changes that follow cell death in living tissue

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8
Q

What is apoptosis?

A

Cell induced death by a regulated intra-cellular programme where a cell activates enzymes that degrade its own DNA and proteins

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9
Q

What is liquefactive necrosis?

A

Release of active enzymes is the dominant feature and tissue tends to liquefy - common with neutrophils

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10
Q

When does liquefactive necrosis commonly occur?

A

Bacterial infection due to neutrophils releasing proteolytic enzymes.
In the brain

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11
Q

What is coagulative necrosis?

A

When coagulative denaturation is the dominant feature and proteins clump together leading to solidity of the dead cells and tissue

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12
Q

What is fat necrosis?

A

Destruction of adipose tissue. Fatty acids released which react with calcium to form calcium soaps

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13
Q

When does fat necrosis often occur?

A

Trauma to fatty tissue eg in the breast - irregular scar is left which can mimic a nodule of breast cancer
Acute pancreatitis

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14
Q

Causes of infarction?

A

Thrombosis
Embolism
External compression of a vessel
Twisting of vessels

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15
Q

When and where does a white infarct occur?

A

After occlusion of an end artery in a solid organ
Solid nature limits the amount of haemorrhage from adjacent capillaries
Tissue dies and appears white

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16
Q

Which organs is a white infarct common in?

A

Heart
Spleen
Kidneys

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17
Q

When does a red infarct occur

A

Occurs in organs with a dual blood supply
Organs with numerous anastomoses
In loose tissue where there is poor stromal support for capillaries

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18
Q

What reversible changes occur in hypoxic cell injury?

A

Na/K pump failure so cell swells. Due to a lack of oxygen and therefore ATP
Calcium enters and damages cell components
Accumulation of lactic acid which lowers pH, affecting enzymes and chromatin clumping
Ribosomes detach from the ER, disrupting protein synthesis
Intra cellular accumulations of fat and denatured proteins

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19
Q

Effects of high cystolic calcium ion concentration?

A

Activates ATPase
Activates phospholipase which damages membranes
Activates proteases which break down membranes and cytoskeletal proteins
Activates endonucleases which damage DNA

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20
Q

What is ischaemia-reperfusion injury?

A

When blood flow is returned to tissue which has been subject to ischaemia but isn’t yet necrotic. Can cause tissue injury to be worse

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21
Q

Why does ischaemia-reperfusion injury occur?

A

Increased production of oxygen free radicals with reoxygenation
Increased neutrophils ➡️ more inflammation and tissue injury
Delivery of complement proteins and activation of complement pathway

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22
Q

What damage do free radicals cause?

A

Attack lipids in cell membranes
Damage proteins and nucleic acids
Mutagenic

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23
Q

What cells produce free radicals to kill bacteria?

A

Leukocytes

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24
Which enzymes are involved in defence systems against ROS?
- SOD catalyses O2- to H2O2 | - catalases and peroxidases convert H2O2 to oxygen and water
25
What are the free radical scavengers?
ACE vitamins | Glutathione
26
What do heat shock proteins do?
Ensure proteins are refolded correctly | Maintains protein viability and maximises cell survival
27
What are the main causes of cell injury and death?
``` Hypoxia Chemical agents Physical agents Microorganisms Immune mechanisms - hypersensitivity and autoimmune Dietary deficiency Genetic abnormalities ```
28
When are free radicals often produced?
Chemical and radiation injury Cellular ageing Ischaemia-reperfusion injury High oxygen concentrations
29
Name the three important free radicals
Superoxide Hydroxyl Hydrogen peroxide
30
When are heat shock proteins important?
When the folding step in protein synthesis goes wrong | When proteins become denatured during cell injury
31
What nuclear changes occur during cell injury?
Chromatin clumping Pyknosis Karryohexis Karryolysis
32
What does pyknosis mean?
When the nucleus shrinks and chromatin clumps
33
What is karryohexis?
Fragmentation of the nucleus
34
What is karryolysis?
Dissolution of the nucleus
35
What cytoplasmic changes occur under the light microscope during cell injury?
1. Reduced pink staining due to increase in water in cytoplasm 2. Increased pink staining due to increase in denatured proteins and detachment of ribosomes from the ER
36
When does coagulative necrosis commonly occur?
In most solid organs, where the cause of death is ischaemia
37
How does caseous necrosis appear?
Amorphous debris
38
What is caseous necrosis often seen with?
Granulatomous inflammation
39
What is gangrene?
A clinical term used to describe necrosis which is visible to the naked eye.
40
What type of necrosis is it if the gangrene is dry?
Coagulative necrosis
41
What can wet gangrene lead to?
Septicaemia
42
What is wet gangrene often due to?
Infection
43
Is an MI normally liquefactive or coagulative?
Coagulative
44
Is a cerebral infarction normally coagulative or liquefactive?
Liquefactive
45
What does the outcome of ischaemia depend on?
If there is an alternate blood supply How quickly ischaemia has occurred - may be time for other perfusion pathways to develop How vulnerable a tissue is to hypoxia Oxygen content of the blood - in anaemic patients may be more serious
46
Examples of when physiological apoptosis might occur
Embryogenesis Body needs to remove cells to maintain a steady state Cells infected by a virus Cancerous cells
47
During apoptosis, what changes occur which can be seen under the light microscope?
``` Shrunken Appear very pink (intensely eosinophilic) Chromatin condensation Pyknosis Fragmentation of nucleus ```
48
What changes occur that can be seen under the electron microscope during apoptosis?
Cytoplasmic blebbing which progresses to fragmentation into membrane-bound apoptotic bodies - contain cytoplasm, organelles and often nuclear fragments Apoptotic bodies are removed by macrophages in phagocytosis
49
Why does apoptosis not induce inflammation?
No leakage of cell contents
50
What are the three phases of apoptosis?
Initiation Execution Degradation
51
What are caspases?
Proteases that mediate the cellular effects of apoptosis
52
How do caspases work?
Cleave proteins to break up the cytoskeleton | Initiate the degradation of DNA
53
Why is the intrinsic pathway called intrinsic?
All of the apoptotic machinery is inside the cell
54
What are some triggers for intrinsic apoptosis?
DNA damage | Withdrawal of growth factors or hormones
55
Which protein is important in triggering intrinsic apoptosis?
p53
56
After being triggered, what happens in intrinsic apoptosis?
Membrane permeability of mitochondria increases Release of cytochrome C from mitochondria Interacts with APAF1 and caspase 9 to form an apoptosome that activates various downstream caspases
57
What are triggers of extrinsic apoptosis?
External ligands such as TRAIL and Fas | They bind to 'death receptors' which activate caspases
58
What does p53 do?
'Guardian of the genome' | Mediates apoptosis in response to DNA damage
59
Which three proteins make up the apoptosome?
Cytochrome C APAF 1 Caspase 9
60
What does bcl-2 do?
Inhibits apoptosis by preventing cytochrome c from being released from mitochondria
61
Name a death ligand and a death receptor
TRAIL | TRAIL-R
62
What is pathological calcification
The abnormal deposition of calcium salts within tissues
63
What is steatosis?
Accumulation of triglycerides in cells
64
What are common causes of liver steatosis?
Alcohol abuse Diabetes mellitus Obesity Toxins
65
What type of cells can cholesterol accumulate in? What are these cells known as?
Smooth muscle cells and macrophages in atherosclerotic plaques Foam cells
66
What is it called when cholesterol is deposited in the skin of people with hyperlipidaemia?
Xanthomas
67
What is Mallory's hyaline seen in?
Alcoholic liver disease
68
What is Mallory's hyaline caused by?
Accumulation of altered keratin filaments
69
What is the pathology of α1-antitrypsin deficiency
Liver produces a version of α1-antitrypsin that is incorrectly folded. Cannot be packaged by the ER so accumulates within it. Therefore not secreted by the liver.
70
How does α1-antitrypsin defence affect the lungs?
Proteases within the lung can act unchecked and patients develop emphysema as lung tissue is broken down.
71
What happens of someone has a high exposure to urban pollutants such as coal/coal dust?
Lungs can become fibrotic or emphysematous.
72
What happens to coal dust when it is inhaled?
Phagocytosed by macrophages within lung tissue and is seen as blackened tissue or blackened peribronchial lymph nodes.
73
Give some examples of endogenous pigments
Bilirubin Lipofusin Haemosiderin
74
How is lipofusin produced?
Sign of previous damage by free radicals and lipid peroxidation. Seen in ageing cells Brown pigment
75
When does haemosiderin form?
When there is localised or systemic excess of iron. | Eg bruises
76
What is haemosiderin derived from?
Haemoglobin
77
What colour is haemosiderin
Yellow/brown
78
What is haemosiderosis and what damage can it cause?
When haemosiderin is deposited in many organs. | Can damage the liver, pancreas and heart.
79
What conditions is haemosiderosis seen in?
Hereditary haemochromatosis Haemolytic anaemias Blood transfusions
80
What does dystrophic calcification occur in?
``` Dying tissues Atherosclerotic plaques Ageing Damaged heart valves Tuberculus lymph nodes ```
81
When does metastatic calcification occur?
As a consequence of hypercalcaemia secondary to disturbances in calcium metabolism.
82
Four main causes of hypercalcaemia?
Increased PTH secretion due to parathyroid tumours or ectopic secretion of PTH-related protein by malignant tumours Vitamin D related disorders Destruction of bone secondary to primary tumours of bone Renal failure
83
List some things that accumulate in cells as they age
Damage to DNA Abnormally folded proteins Lipofuscin
84
What is telomerase and which cells have it?
An enzyme which prevents the shortening of telomeres so cells can divide many times Stem and germ cells
85
What is ethanol broken down into and by which enzymes?
Ethanol ➡️ acetaldehyde dehydrogenase Alcohol dehydrogenase a cytochrome P450 enzyme - CYP2E1 catalase
86
What happens to acetaldehyde?
Acetaldehyde ➡️ acetic acid | Acetaldehyde dehydrogenase
87
Which enzyme involved in alcohol metabolism do women have a lower concentration of than men
Alcohol dehydrogenase
88
Which enzyme do about half of oriental people have reduced activity of? What does this result in?
Aldehyde dehydrogenase Build up of acetaldehyde Facial flushing
89
Toxicity of alcohol affects the liver by causing a fatty change. What is this?
Steatosis which can cause hepatomegaly. | It is reversible and generally asymptomatic.
90
What happens in acute alcoholic hepatitis?
Focal hepatocytes necrosis Mallory body formation Neutrophilic infiltrate
91
Symptoms of acute alcoholic hepatitis?
Fever | Liver tenderness and jaundice
92
What changes occur to the liver in cirrhosis?
Hard and shrunken liver | Micronodules of regenerating hepatocytes form surrounded by bands of collagen.
93
How is paracetamol detoxified?
Glucaronidation and sulphonation
94
Which enzyme in metabolism of paracetamol leads to the production of the toxic metabolite? What is it called?
When cytochrome P450 is used | NAPQI
95
How is NAPQI detoxified?
Interaction with glutathione
96
What does NAPQI do?
Binds sulphydryl groups on hepatocytes membranes, causing necrosis and liver failure
97
What can cause people to have lower reserves of glutathione?
``` If they drank alcohol with the paracetamol overdose If they are alcohol dependent If they are malnourished On enzyme inducing drugs HIV positive/AIDS ```
98
What is the antidote to paracetamol overdose?
N-acetylcysteine
99
What is measured to decide whether or not to give NAC
Serum conc of paracetamol | 4 hours after over dose
100
What is used to assess liver damage by paracetamol overdose?
The pro-thrombin time 24hrs after overdose
101
What does aspirin do?
Acetylates platelet cyclooxygenase | Blocks platelet ability to form thromboxane A2, a substance which activates platelet aggregation
102
What are the consequences of an aspirin overdose?
Stimulates respiratory centre ➡️ respiratory alkalosis Causes metabolic acidosis to compensate Interferes with carbohydrate, fat and protein metabolism and oxidative phosphorylation ➡️ production of lactate, pyruvate and ketone bodies ➡️ acidosis Deceased platelet aggregation Acute erosive gastritis and GI bleeding
103
What damage can free radicals cause?
Cross link proteins | Oxidise membrane lipids
104
Describe what is seen in fatty change of the liver after alcohol
Steatosis from toxicity of alcohol Hepatomegaly Acute, reversible and asymptomatic
105
Explain what is seen in acute alcoholic hepatitis
``` Alcohol and acetaldehyde are directly toxic Acute hepatitis Focal hepatic necrosis Mallory body formation Neutrophils infiltrate Fever, liver tenderness and jaundice ```
106
Explain changes seen in cirrhosis
Shrunken, hard liver Micro nodules of regenerating hepatocytes surrounded by bands of collagen Irreversible, serious, sometimes fatal

Mechanisms Of Disease (11 decks)

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