Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

GSSE > Cell injury and death > Flashcards

Cell injury and death Flashcards

1
Q

What are the 3 responses to cell damange

A

Adaptation
Degenerate
Die

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is sublethal injury

A
  • Atrophy
  • Loss of volume (Na & H2O) control, swelling
  • Intracellular accumulation (e.g. fat, iron, etc…)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is lethal injury

A
  • necrosis > always pathological
  • apoptosis > mostly physiological, sometimes pathological, BUT NEVER (+) INFLAMMATORY RESPONSE
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are the 7 ways cells can be injured

A
  1. Hypoxia > ischaemia, anaemia, impaired lung function, CCF, CO poisoning
  2. physical > trauma, heat, cold, radiation, electric shock
  3. chemical > alcohol, paracetamol (acetaminophen), cyanide, CCL4, lead, paraquat
  4. infection > viruses, bacteria, rickettsiae, fungi, parasites
  5. genetic derangements > chromosomal alterations, gene mutations
  6. nutritional
  7. immunological
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What mechanisms are implicated in cell injury (7)

A
  1. ATP depletion
    - Failure of energy dependent functions (Leads to reversible injury then necrosis)
  2. Mitochondrial damage
    - Sequelae of above, mitochondrial proteins leak (cytochrome C which causes apoptosis)
  3. Increased permeability of cellular membranes
  4. Accumulation of damaged DNA and misfolded proteins
    - Triggers apoptosis
  5. Accumulation of ROS
  6. Influx of Ca
  7. Unfolded proteins and ER stress
    - Normally triggers repair but if repair capacity is exceeded they trigger apoptosis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What does loss of calcium homeostasis promote and how does it occur

A

Ischaemia and toxins release calcium from cells.

  • increase in Ca, increases the permeability of mitochondria.
  • (+) phopholipases > degrade membrane phospholipids
  • (+) proteases > break down membrane & cytoskeletal proteins
  • (+) ATPases > exacerbate ATP depletion
  • (+) Endonucleases > DNA fragmentation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Explain necrosis with respect to
- Cell size
- Cell target zone
- Injury
- Mechanism
- Degradation
- Reaction
- Cellular contents
- Nucleus

A

Enlarged (swelling)
Membrane
Membrane disruption
ATP, phospholipase etc
Autolytic (lysosomal)
Acute inflammation
Enzymatic digestion, may leak out of cell
Pykinosis, karyorrhexis, karyolysis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Explain apoptosis with respect to
- Cell size
- Cell target zone
- Injury
- Mechanism
- Nucleus
- Reaction
- Cellular contents
- Plasma membrane

A
  • Reduced (shrinkage)
  • Nucleus
  • DNA denaturation
  • Endonuclease (endogenous)
  • Fragmentation
  • Phagocytosis (receptors)
  • Intact; may be released by apoptotic bodies
  • Inatact; altered structure, especially orientation of lipids
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Ultra structural changes indicating REVERSIBLE cell injury (5)

A
  1. Plasma membrane alterations
    - Blebbing, blunting and loss of microvilli
  2. Mitochondrial changes, swelling and the appearance of amorphous densities
  3. Accumulation of myelin figures (phospholipids from damaged cellular membranes)
  4. Dilation of the ER with detachment of of polysomes
  5. Nuclear alterations, disaggregaion of granular and fibrillar elements
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Two features consistently seen in early stages of injury

A
  1. Generalised swelling (Hydropic change or vaculoar degeneration)
    - dis-regulated ATP dependent Na/K pump, blebbing of membrane, detachment of ribosomes, clumping of nuclear chromatin.
  2. Fatty change
    - Metabolic pathways disrupted, accumulation of triglyceride filled vacuoles
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is necrosis characterised by

A

Denaturation of cellular proteins, leakage of cellular contents through damaged membranes, enzymatic digestion of the lethally injured cell.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are the sequelae of hypoxia (5)

A
  1. impaired respiration and ATP formation
  2. imbibition of water
  3. impaired synthesis of protein in membrane
  4. change from aerobic to anaerobic glycosis
  5. karyolysis (faint, dissolved nucleus)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Describe (in detail) the events of reversible cell injury

A

Hypoxia > loss of oxidative phosphorylation > decrease ATP synthesis by mitochondria, which causes the following
1. Na/K ATPase slow down/stop > Na pump out of cell > increase intracellular Na! swelling of cell and organelle
2. change of metabolism > anaerobic glycolysis ( decrease glycogen store) > accumulation of lactic acid, decrease intracellular pH
3. detachment of ribosomes from rER > decreased protein synthesis > increase lipid deposition

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Morphology indicating necrosis

A
  • Ruptured/breakdown membrane
  • Nuclear changes (shrinkage, fragmentation and dissolution)
  • Abundant myelin figures
  • Leakage/ enzymatic digestion of cellular contents
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Morphology indicating apotosis

A
  • Cell shrinkage
  • Chromatin condensation (MOST CHARACTERISTIC)
  • Formation of cystoplasmic bleb and apoptotic bodies
  • Phagocytpsos of apoptotic bodies by macrophages
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Nuclear changes consistent with necrosis

A
  • pyknosis (small, dense nucleus) > nuclear shrinkage and chromatin condensation
  • karyorrhexis (nucleus broken up into many clumps)
  • karyolysis (faint, dissolved nucleus)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What cellular events are typically associated with necrosis

A
  • Severe mitochondrial damage with depletion of ATP
  • Rupture of lysosomal and plasma membranes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Why is it currently accepted that cell membrane damage is a central factor in the pathogenesis of irreversible cell injury from many causes

A

Loss of regulation of cell volume and ionic gradients, plus cell membrane ultrastructural defects, occur in the earliest stages of irreversible injury

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What are free radicals

A

Chemical species with unpaired electron in outer orbit, highly unstable and able to attack, CHO, lipids, proteins.
Some of these reactions are autocatalytic - i.e molecules that react with free radicals and are themselves converted into free radicals.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What are ROS and how are they produced

A

Oxygen derived free radical.
They are produced normally in cells during energy generation.
However ROS scavengers remove them.
Also produced by activated leukocytes during active inflammation (particularly neutrophils and macrophages).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

List 6 ways free radicals are generated

A
  • Reduction-oxidation reaction during normal metabolism
  • Absorption of radiation
  • Inflammation
  • Metabolism of exogenous chemicals or drugs (paracetamol and carbon tetrachloride)
  • Transition metals
  • Nitric oxide
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

How do cells prevent injury by free radicals

A
  1. antioxidants, e.g. lipid soluble Vit E, A, vit C and glutathione in the cytosol
  2. binding to storage and transport proteins, e.g. transferrin, ferritin, lactoferrin and ceruloplasmin
  3. enzymes mopping them up, e.g. catalase, superoxide dismutases, glutathione peroxidase
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

List the enzymes/ binding proteins that protect cells from free radicals

A
  1. superoxide dismutase enzyme system
  2. catalase enzyme system
  3. interaction with glutathione peroxidase
  4. interaction with plasma proteins cerulaplasmin and transferrin ! copper and iron binding proteins
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

List 5 ROS examples

A
  • NO (Nitric oxide)
  • H2O2 (Hydrogen peroxide)
  • O2 (Superoxide anion)
  • ONOO (Hydroxyl radical)
  • OH (Hypochlorite)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

List 3 pathologic effects of free radicals

A
  • Lipid per-oxidation in membranes (i.e punches holes in membranes)
  • Oxidative modification of proteins (oxidation of protein backbone, disrupts proteins, unfolds proteins, damages enzymes)
  • Lesions in DNA (Causes single and double stranded breaks in DNA)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

List the 5 types of necrosis

A

Coagulative
Liquefactive
Fat
Caseous
Fibrinoid

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What is coagulative necrosis

A
  • Form of necrosis in which the architecture of dead tissue is preserved for a span of a few days.
  • Affected tissue has a firm structure.
  • Injury denatures proteins and enzymes and organelles
  • Given enzymes are blocked dead cells cant be digested. Infiltrating leucocytes eventually degrade dead cells.
  • Cell swelling
  • Localised area of coagulative necrosis = INFARCT
  • Commonly seen in myocardium, kidney, liver & other organs (NOT seen in CNS)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What is liquefactive necrosis

A
  • Characterised by digestion of dead cells = viscous liquid
  • Occurs when autolysis & heterolysis prevail over protein denaturation
  • Focal bacterial or occasionally fungal infections
  • Necrotic area is soft and filled with fluid > creamy yellow because of presence of dead white cells
  • CNS cells always die by liquefactive necrosis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

What is fat necrosis

A
  1. Necrosis of adipose tissue, induced by action of lipases (from pancreatic duct, small intestine or macrophages)
  2. These catalyse FFA release from triglycerides
  3. FFA then binds with Ca > Ca soap
  4. These generate chalky white areas > fat saponification
  5. Think pancreatitis, trauma
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

What is caseous necrosis

A
  • Characteristic of TB
  • Appears grossly as soft, friable, ‘cheesy’ material
  • Microscopically as amorphous eosinophilic material with cell debris
31
Q

What is fibrinoid necrosis and when is it seen

A

Special form of vascular damage, seen in immune reactions involving blood vessels.
Complexes of antigens and antibodies are deposited in walls of arteries.

  • Rheumatic fever
  • Malignant hypertension
  • The arthus phenomenon
  • x-ray damage of the skin
32
Q

What happens to necrotic cells that are not promptly destroyed or reabsorbed

A
  • They become a foci for calcium and other minerals to deposit and thus tend to become calcified.
  • Dystrophic calcfication
  • Happens in all tissue types of necrosis
33
Q

Is serum calcium normal or abnormal in dystrophic calcificaiton

A

Normal

34
Q

What is the histological morphology of dystrophic calcification and give examples

A
  • Basophilic amorphous granular
  • Asbestos bodies
  • atheroma, e.g. calcium in atherosclerosis, Monckeberg’s sclerosis
  • damaged heart valves, e.g. aortic valve calcification
  • TB, e.g. Ghon lesions
  • Cancer
    a. psammoma bodies in papillary thyoid cancer
    b. psammoma bodies in papillary ovarian cancer
    c. calcified comedo breast cancer
35
Q

What histological sign is diagnostic of necrosis

A

nuclear pyknosis

36
Q

How do chemicals directly injure cells

A

By binding to some critical component of a molecular pathway.

For example
- Mercury binds to cell membrane proteins. This increases membrane permeability and inhibits ATPase dependent transport.
- Mainly occurs in GI tract and kidneys

37
Q

How do chemicals indirectly injure cells

A

By converting them to toxic metabolites, normally by CP450 oxidases in the smooth ER of the liver and other organs

38
Q

How does Carbon tetrachloride indirectly injure cells

A

CCL4 (common dry cleaning chemical) is converted to CCL3 (highly reactive free radical) in sER of the liver.
- This initiates lipid peroxidation and autocatalytic reactions.
Results in
- Cell swelling and breakdown of ER, dissociation of ribosomes
- Reduced hepatic protein synthesis
- Reduced lipid export from liver cells because impaired production of apoprotein
- lipid accumulation and fatty change in liver
- progressive cellular swelling, plasma membrane damage
- Cell death

39
Q

How does acetaminophen indirectly injure cells

A

Acetaminophen (paracetamol) is metabolised in the liver and excreted in the urine (as sulfate of glucuronate), with a small amount being converted to a toxic metabolite (NAPQI) (through the activity of CYP).
NAPQI is normally mopped up by glutathione but when large doses of paracetamol are ingested hepatocellular injury occurs.
- Glutathione is depleted, ROS injury occurs.
- NAPQI binds to hepatic proteins which damages membranes and mitochondria.

40
Q

Is it good to still re-perfuse early and why

A

Despite reperfusion damage, the eventual volume of necrosis is significantly reduced by early re-perfusion > this is the rationale for streptokinase/tP A use early in the evolution of myocardial infarction

41
Q

What is ischaemia-reperfusion injury

A
  • Restoration of blood flow to ischaemic tissues can promote recovery of cells it they are reversibly injured, but can also paradoxically exacerbate cell injury and cause death.
  • Therefore, re-perfused tissues may sustain loss of viable cells in addition to those that are irreversibly damaged.
42
Q

How does ischaemia-reperfusion injury occur (4 mechanisms)

A
  1. Oxidative stress
    - Increased generation of ROS and and nitrogen species. Incomplete reduction of oxygen. Produced by parenchymal and endothelial cells) Damaged cells are sensitive to free radical damage (antioxidant mechanisms have been compromised)
  2. Intracellular calcium overload
    - Calcium influx exacerbated by ROS.
  3. Inflammation
    - Immune cells release cytokines which results in more neutrophils circulating the re-perfused tissue.
  4. Activation of the complement system
    - igM antibodies have propensity to deposit in ischaemic tissues. When blood is re-perfused these antibodies bind to complement proteins.
43
Q

Examples of diseases caused by mis-folding proteins

A
  • CF (CFTR)
  • Familial hypercholesterolemia (LDL receptor)
  • Tay-Sachs disease (Hexosaminidase B subunit)
  • Creutzfeldt-Jacob disease (Prions)
  • Alzheimer disease (AB peptide)
44
Q

Rationale for reperfusion in MI

A

Despite reperfusion damage, the eventual volume of necrosis is significantly reduced by early reperfusion ! this is the rationale for streptokinase/tP A use early in the evolution of myocardial infarction

45
Q

What is apoptosis, what is it designed for and is it pathological or physiological

A
  • Type of cell death, when cells destined to die activate intrinsic enzymes to degrade DNA.
  • Can occur as part of normal physiological processes and as part of pathophysiologic mechanisms.
  • Serves to eliminate cells no longer needed (that has obtained damage) and to control cell numbers
46
Q

List the physiological scenarios in which apoptosis occurs (5)

A
  1. Removal of supernumerary cells (i.e excess cells during development)
  2. Involution of hormone dependent tissues on hormone withdrawal
    - e.g endometrial breakdown during menses, regression of lactating breast after weaning, ovarian follicular atresia in menopause
  3. Cell turnover in proliferating cell populations
    - Immature lymphocytes in bone marrow, thymus
  4. Elimination of potentially harmful self-reactive lymphocytes
  5. Death of cells that have served their purpose e.g neutrophils in an inflammatory response and lymphocytes in an immune response
47
Q

In what pathological circumstances does apoptosis occur

A
  • DNA damage (by things like radiation, anti-cancer drugs)
  • Accumulation of misfolded protein
  • Induced during certain infections (Adenovirus, HIV, GVHD, cytotoxic T lymphocytes)
  • Exocrine duct obstruction (pancreas, parotid, kidney)
48
Q

What enzymes are activated in apoptosis

A

Caspases

49
Q

What are the 2 major pathways that initiate apoptosis

A
  1. Mitochondrial (intrinsic)
  2. Death receptor (extrinsic)
50
Q

Outline how apoptosis occurs via the intrinsic pathway

A
  • Triggered by DNA damage, protein misfolding, growth factor wtithdrawl
  • Results from increased permeability of the mitochondrial outer membrane which releases death inducing molecules. e.g Cytochrome C when released into cytoplasm initiates the suicide program of apoptosis.
  • Normally proteins like BCL2 keep the membrane impermeable and prevent cytochrome C from leaking.
  • Death inducing molecules include BAX/ BAK (BH3) are upregulated by the stimuli above. They make the membrane more permeable, allowing cytochrome C to leak. They may also bind to BLC2 and block its function.
  • Once Cytochrome C is released it binds to APAF-1 forming a complex called Apoptosome. This complex binds to capase 9 and initiates the caspase pathway.
51
Q

What is the execution phase of apoptosis

A

The intrinsic and extrinsic pathways converge on the caspase pathway.
- Intrinsic activates 9 extrinsic activates 8 and 10.
- Both activate the execution pathway (e.g 3 and 6)

both activate DNAse allowing DNA degradation to commence, promoting fragmentation of nuclei
(e.g endonuclease which is calcium depdendent)

52
Q

How is the extrinsic pathway initiated

A

Initiated by engagement of plasma membrane death receptors
Mechanism of killing by cytotoxic T lymphocytes.
TNF1
FASL

53
Q

How are dead cells removed in apoptosis.

A

Formation of apoptotic bodies ie bite sized fragments for phagocytes.
They express proteins or part of the complement system that serve as signals to promote apoptosis.

54
Q

What is adaptation

A

Reversible changes in size, number, phenotype, metabolic activity or function of cells in response to changes in their environment
- Hypertrophy
- Hyperplasia
- Metaplasia
- Atrophy

55
Q

What is metaplasia

A

Change in phenotype of differentiated cells, often in response to chronic irritation, makes cells better able to withstand stress. May result in reduced functions or increased propensity for malignant transformation
REVERSIBLE once stimulus goes away

56
Q

What is the most common epithelial metaplasia and give examples of where this occurs

A

Columnar to squamous
Vitamin A deficiency - squamous metaplasia in the resp tract and in the cornea
Stones in excretory ducts of salivary glands, pancreas, bile ducts

57
Q

Give two other examples of metaplasia

A

Squamous to columnar - Barretts oesophagus
Connective tissue metaplasia - Formation of bone, adipose tissue or cartilage in tissues that do not contain these elements e.g bone in muscle (myositis ossificans can occur after intramuscular haemorrage) (this type of metaplasia is not associated with increased cancer risk.

58
Q

What is hyperplasia

A
  • Increased cell numbers in response to hormones and other growth factors.
  • Occurs in tissues whose cells are able to divide or contain abundant stem cells.
  • Characteristic response to viral infections (e.g warts with papillomaviruses)
  • Although hyperplasia is distinct from cancer - cancerous proliferations may arise from it (provides an ideal substrate)
59
Q

Is hyperplasia pathological or physiological

A

Can be either
Physiologic - In response to increased need (e.d. breast acini during lactation.
Pathologic- In response to inappropriate secretion of hormone (e.g endometrial hyperplasia in response to excessive estrogen stimulation.

60
Q

What is hypertrophy

A
  • Increase in the size of cells ie no new cells just larger cells
  • Cells capable of division may undergo hypertrophy and hyperplasia, non-dividing cells undergo hypertrophy only (e.g myocardial cells)
61
Q

Is hypertrophy pathological or physiological

A

Can be either
Pathological: Striated muscles in heart and skeletal muscle. They hypertrophy in response to
Physiological: Uterus in response to estrogen in pregnancy

62
Q

Describe the mechanism of hypertrophy

A
  • Mechanical sensors detect increased load
  • Activate a complex of downstream signalling pathways (PI3K/ AKT pathway or GPCR) which stimulate growth factors (IGF-1, endothelin 1, angiotensin II
63
Q

What is atrophy

A

Decreased cell and organ size, as a result of decreased nutrient supply or disuse; associated with decreased synthesis of cellular building blocks and increased breakdown o cellular organelles by increased autophagy.

64
Q

Is atrophy pathological or physiological

A

Can be both
- Physiological - e.g thyroglossal duct, decrease in size of uterus
- Pathological - Disuse atrophy and denervation atrophy

65
Q

What are the causes of fatty liver (7)

A
  1. alcohol abuse
  2. protein malnutrition
  3. Hep C (but not B)
  4. DM
  5. obesity
  6. hepatotoxins and drugs, e.g paracetamol
  7. acute fatty liver of pregnancy and Reye’s syndrome are rare but sometimes fatal > ?defect in mitochrondrial oxidation
66
Q

How does steatosis occur (6)

A
  1. excessive entry of FFA into liver (e.g. starvation, corticosteroid therapy)
  2. enhanced FA synthesis
  3. decreased FA oxidation
  4. increased esterification of FAs to TAG as a result of an increase in a-glycerophosphate (alcohol)
  5. decreased apoprotein synthesis (carbon tetrachloride poisoning)
  6. impaired lipoprotein secretion from the liver (alcohol, orotic acid administration)
67
Q

Does steatotis commonly cause derranged LFTs

A

NO

68
Q

Is steatosis associated with hepatitis

A

though common with active hep C, is not part of hep B infection

69
Q

Is steatosis reversible

A

yes

70
Q

What are the 4 causes of metasatic calcification

A
  • increased secretion of PTH, e.g. hyperparathyroidism, from parathyroid tumours, ectopic secretions
  • destruction of bone tissue, e.g. multiple myeloma, diffuse skeletal metastasis (e.g. breast cancer)
  • vitamin D-related causes ! including vit D intoxication & systemic sarcoidosis
  • renal failure ! causes secondary hyperparathyroidism
71
Q

Where does metastatic calcification occur

A

can occur anywhere, but mainly affects interstitial tissues of gastric mucosa, kidneys, lungs, systemic arteries, & pulmonary veins

72
Q

Give examples of metastatic calcification (5)

A
  • nephrocalcinosis
  • renal calcification complicating disseminated breast cancer
  • alveolar wall calcification complicating acute leukemia
  • calcium encrustation of internal elastic lamina of arteries
  • calcification of multiple myeloma
73
Q

What is a hamartoma associated with

A

Hamartomata is a/w
* Cystic hygroma
* Small intestinal polyp (Peut-Jehger type)
* Intradermal naevi

74
Q

What is a harmatoma

A
  1. this is a disorganized overgrowth of well differentiated mature cells at an appropriate site
  2. a lung hamartoma is relatively common, benign, nodular neoplasms that may contain
    * cartilage
    * respiratory
    * mixtures of tissues, e.g. fat, blood vessels, fibrous tissue

GSSE (16 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions