GENPATH Cellular Injury Flashcards

1
Q

5 Adaptive Cellular Responses

Increased cellular activity: Increase in size ([…]) or number of cells ([…]); results from increased functional demands or increased hormonal stimulation

Decreased cellular activity: Reduction in size ([…]) or number
of cells ([…]), results from reduced functional demands on tissue or from decreased hormonal stimulation

Alteration of cell morphology: Change in cell differentiation ([…]) or disordered growth or maturation ([…])

A

5 Adaptive Cellular Responses

Increased cellular activity: Increase in size (hypertrophy) or number of cells (hyperplasia); results from increased functional demands or increased hormonal stimulation

Decreased cellular activity: Reduction in size (atrophy) or number
of cells* (hypoplasia/involution),* results from reduced functional demands on tissue or from decreased hormonal stimulation

Alteration of cell morphology: Change in cell differentiation* (Metaplasia)* or disordered growth or maturation (Dysplasia)

Note that metaplasia is not synonymous with** dysplasia** and is not directly considered carcinogenic!!

Metaplasia: an initial change from normal cells to a different cell type (such as chronic irritation of cigarette smoke causing ciliated pseudostratified epithelium to be replaced by squamous epithelium more able to withstand the insult)

Dysplasia: an increasing degree of disordered growth or maturation of the tissue (often thought to precede neoplasia) such as cervical dysplasia as a result of human papillomavirus infection. Dysplasia is still a reversible process. However, once the transformation to neoplasia has been made, the process is not reversible.

Thus, there is a natural history from metaplasia to dysplasia to neoplasia. This is best evidenced in development of uterine cervix and respiratory tract neoplasms.

TLDR, dysplasia is closer to neoplasia and hence cancer but metaplasia can be an early predisposition to cancer as well (smoking induced lung carcinoma)

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

Apoptosis is programmed cell death, which can be physiological or pathological. Executed by […]

Physiological examples:
- Deletion of lymphocytes / other immune cells that react with the body’s own tissues. Failure to do so result in autoimmune disease eg. SLE, Graves disease, Hashimoto’s thyroiditis and Myasthenia Gravis.
- **Endometrial cells **in normal menstrual cycle.
- Crypt regeneration in gastrointestinal tract.
- Formation of digits from the limb buds.

Pathological examples:
- Hepatitis (liver inflammation). Hep. B and C viruses induce the hepatocytes to undergo apoptosis (cell drop out) with release of intracellular liver enzymes.
- HIV / AIDS. Virus cause CD4 helper T lymphocytes to undergo apoptosis which lead to decrease CD4 counts which in turn causes severe immune suppression.

A

Apoptosis is programmed cell death, which can be physiological or pathological. Executed by* caspases*

Physiological examples:
- Deletion of lymphocytes / other immune cells that react with the body’s own tissues. Failure to do so result in autoimmune disease eg. SLE, Graves disease, Hashimoto’s thyroiditis and Myasthenia Gravis.
- Endometrial cells in normal menstrual cycle.
- Crypt regeneration in gastrointestinal tract.
-
Formation of digits
from the limb buds.

Pathological examples:
- Hepatitis (liver inflammation). Hep. B and C viruses induce the hepatocytes to undergo apoptosis (cell drop out) with release of intracellular liver enzymes.
- HIV / AIDS. Virus cause CD4 helper T lymphocytes to undergo apoptosis which lead to decrease CD4 counts which in turn causes severe immune suppression.

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

Atrophy/Involution

Decrease in […]/[…]. Can be triggered by loss of stimulation, lack of sustenance, degradation of cellular proteins or autophagy.

Physiological Examples:
- Thymus involution (hypoplasia)
- Thyroglossal duct atrophy during fetal development

Pathological Examples:
- Muscular atrophy
- Kidney atrophy due to renal artery stenosis –> systemic arterial hypertension
- Brown atrophy of heart (accumulation of lipofuscin granules w haemosiderin)
- Marrow hypoplasia –> agranulocytosis –> anemia, susceptibility to infections, bleeding diathesis (hypocoagulability)

A

Atrophy/Involution

Decrease in size/number of cells. Can be triggered by loss of stimulation, lack of sustenance, degradation of cellular proteins or autophagy.

**Physiological **Examples:
- Thymus involution (hypoplasia)
- Thyroglossal duct atrophy during fetal development

**Pathological **Examples:
- Muscular atrophy
- Kidney atrophy due to renal artery stenosis –> systemic arterial hypertension
- Brown atrophy of heart (accumulation of lipofuscin granules w haemosiderin)
- Marrow hypoplasia –> agranulocytosis –> anemia, susceptibility to infections, bleeding diathesis (hypocoagulability)

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

**Caseous Necrosis **
- Secondary to […] infection. Just rmb caseous necrosis = TB.
- “Cheese-like” with cavities and friable yellow white lining of the cavities
- Granulomatous inflammation

A

Caseous Necrosis
- Secondary to Mycobacteria Tuberculosis infection. Just rmb **caseous necrosis = TB. **
- “Cheese-like” with cavities and friable yellow white lining of the cavities
- Granulomatous inflammation

For understanding:
- Histiocytes are macrophages that came out into the tissue. In the brain, they are called glial cells.
- MGCs form due to chronic inflammation, where single macrophages are not sufficient. Hence T cells signals macrophages to combine (power ranger) and form this “GIGANTIC KILLING MACHINE” (Derrick Lian, 2020)

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

Cell injury and death depends on
1. […] of injury –> Ischaemic, toxic, chemical
2. Exposure […] –> longer = higher likelihood of cell death
3. […] of Injury –> partial vs complete ischaemia, volume of poison

A

Cell injury and death depends on
1.* Type* of injury –> Ischaemic, toxic, chemical
2. Exposure time –> longer = higher likelihood of cell death
3.** Severity **of Injury –> partial vs complete ischaemia, volume of poison

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Cells maintain their intracellular milieu within a narrow range of physiologic parameters. A successful cell needs Energy (mitochondria), Comparmentalization of Organelles (lipid bilayer + intracellular organelles) + ** Control Mechanism** (nucleus signalling pathways)

When cells are faced with:
- Physiologic stress / mild pathologic stimulus –> […]
- Pathologic injurious stimulus / inability to adapt –> […]
- Irreversible injury –> […]

A

Cells maintain their intracellular milieu within a narrow range of physiologic parameters. A successful cell needs Energy (mitochondria), **Comparmentalization of Organelles **(lipid bilayer + intracellular organelles) + Control Mechanism (nucleus signalling pathways)

When cells are faced with:
- Physiologic stress / mild pathologic stimulus –> adaptation
- Pathologic injurious stimulus / inability to adapt –> cell injury
- Irreversible injury –>* cell death – apoptosis / necrosis*

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Coagulative Necrosis **
- Secondary to […] or ischemia/infarction (loss of blood supply)
- Component cells are dead while external architecture is temporarily preserved such that the affected tissue retains […] texture
-
Ghost outlines w loss of nuclei**
- Hypoxic death in all tissue except brain

A

Coagulative Necrosis **
- Secondary to hypoxia or ischemia/infarction (loss of blood supply)
- Component cells are dead while external architecture is temporarily preserved such that the affected tissue retains
* firm* texture
-
Ghost outlines w loss of nuclei**
- Hypoxic death in all tissue except brain

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

Fatty Change in Liver (Steatosis)

Gross Description:
- Liver, diffused lesion
- Diffusely […] with […], […] appearance
- […] appearance

Microscopic Features
- intracytoplasmic lipid vacuoles in hepatocytes, causing expansion in size but cytoplasm and nucleus pushed to the periphery
- stained red with […]!

A

Fatty Change in Liver (Steatosis)

Gross Description:
- Liver, diffused lesion
- Diffusely enlarged with pale, yellowish appearance
- Greasy appearance

Microscopic Features
- intracytoplasmic lipid vacuoles in hepatocytes, causing expansion in size but cytoplasm and nucleus pushed to the periphery
- stained red with Oil Red O!

Very basic patho card. Need to know.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Hyperplasia

Increase in […]. Same trigger as hypertrophy (increased fn demand, stimulus) but only in cells capable of […]. Can occur concurrently with hypertrophy.

**Physiological **Examples:
- Liver cell proliferation after partial hepatectomy
- Granular proliferation in breast at puberty

**Pathological **Examples:
- Thyroid hyperplasia in goiter
- […] (BPH) due to aging
- Endometrial hyperplasia due to increase in oestrogen

A

Hyperplasia

Increase in* number of cells. Same trigger as hypertrophy (increased fn demand, stimulus) but only in cells capable of *replication. Can occur concurrently with hypertrophy.

**Physiological **Examples:
- Liver cell proliferation after partial hepatectomy
- Granular proliferation in breast at puberty

Pathological Examples:
- Thyroid hyperplasia in goiter
-
* Benign prostatic hyperplasia
* (BPH) due to aging
- Endometrial hyperplasia due to increase in oestrogen

Patients with BPH usually presents with obstructive uropathy (block of flow = infection) and urinary retention. Note back pressure effects and hence** bladder hypertrophy, hydroureter** and** hydronephrosis.** Treatment is with androgen blockers or** TURP **(TransUrethral Resection of Prostate)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Hypertrophy

Increase in […] due to increased production of cellular proteins. Can be triggered by functional demand (mechanical trggers) or hormones/growth factors (trophic triggers)

**Physiological **Examples:
- Skeletal muscle
- Uterine smooth muscle in pregnancy

**Pathological **Examples:
- Cardiac muscle hypertrophy due hypertension/pressure overload –> […]
- Arterial smooth muscle hypertrophy in response to hypertension
- Bowel smooth muscle hypertrophy in response to colon obstruction

A

Hypertrophy

Increase in* size* due to increased production of cellular proteins. Can be triggered by functional demand (mechanical trggers) or hormones/growth factors (trophic triggers)

**Physiological **Examples:
- Skeletal muscle
- Uterine smooth muscle in pregnancy

**Pathological **Examples:
- Cardiac muscle hypertrophy due hypertension/pressure overload –> Myocardial Infarction
- Arterial smooth muscle hypertrophy in response to hypertension
- Bowel smooth muscle hypertrophy in response to colon obstruction

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Intracellular accumulations due to sublethal damage can be caused by
- Excessive […] of a normal substance beyond levels that cell can handle
- Defective […] pathways that leads to the substance being trapped in the cell
- Defective […] leading to accumulation (storage diseases)
- Ingestion of […] that the cell is unable to properly metabolize or expel

Appropriate examples:

  1. Triglyceride accumulation: Fatty Change (steatosis)
    - Commonly due to alcoholism/diabetes and other […]
    - Grossly presented as […], […] liver with […] consistency
    - Microscopically, fat lobules in cytoplasm displaces nucleus to […], stained red with […] stain
  2. Cholesterol accumulation: Atherosclerosis
    - Macrophages engulf […], resulting in foamy appearance
    - Corresponding […] activation leads to formation of platelet plug on top of original plague –> further narrows artery
A

Intracellular accumulations due to sublethal damage can be caused by
- Excessive ingestion / production of a normal substance beyond levels that cell can handle
- Defective export pathways that leads to the substance being trapped in the cell
- Defective metabolic pathways leading to accumulation (storage diseases)
- Ingestion of abnormal substances that the cell is unable to properly metabolize or expel

Appropriate examples:

  1. Triglyceride accumulation: Fatty Change (steatosis)
    - Commonly due to alcoholism/diabetes and other metabolic derangements
    - Grossly presented as **enlarged, yellowish **liver with **greasy **consistency
    - Microscopically, fat lobules in cytoplasm displaces nucleus to periphery, stained red with **Oil Red O **stain
  2. Cholesterol accumulation: Atherosclerosis
    - Macrophages engulf lipoproteins (oxLDL), resulting in foamy appearance
    - Corresponding **endothelial **activation leads to formation of platelet plug on top of original plague –> further narrows artery
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Late changes following cell injury (irreversible)

  • Pyknosis = nuclear […]
  • Karyolysis = nuclear […]
  • Karyorrhexis = nuclear […]
  • Densities in mitochondrial matrix
  • Cell membrane disruption
  • Lysosome rupture

**Death of cell **follows development of late morphological changes!!

A

Late changes following cell injury (irreversible)

  • Pyknosis = nuclear* shrinkage*
  • Karyolysis = nuclear dissolution
  • Karyorrhexis = nuclear **fragmentation **
  • Densities in mitochondrial matrix
  • Cell membrane disruption
  • Lysosome rupture

Death of cell follows development of late morphological changes!!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

**Liquefactive Necrosis **
- Complete digestion of the cell, leaving a liquid mass
- Characteristic of […] infarts where there is no strong external architecture

A

Liquefactive Necrosis **
- Complete digestion of the cell, leaving a liquid mass
- Characteristic of **
cerebral **
infarts where there is no strong external architecture

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

Metaplasia

Reversible change from one […] cell type to another type more suitable to survive, due to chronic irritation (cytokines, growth factors, ECM components).
- It is NOT a phenotypical change of differentiated cells but rather due to reprogramming of stem cells to differentiate along a new pathway!
- Predisposition to malignancy and dysplasia
- **Loss of original functions may compromise usual protective mechanisms **(eg. mucus secretion lost)

**Physiological **Examples:
- Squamous metaplasia of cervix

Pathological Examples:
- Columnar to squamous –> smoking
- Squamous to columnar –> Barrett’s oesophagus
- Connective tissue metaplasia –> Intestinal metaplasia of stomach due to Helicobacter pylori infection, Bile reflux or gastric acidity (increased gastrin, dietary factors)

A

Metaplasia

Reversible change from one matured/differentiated cell type to another type more suitable to survive, due to** chronic irritation** (cytokines, growth factors, ECM components).
- It is NOT a phenotypical change of differentiated cells but rather due to reprogramming of stem cells to differentiate along a new pathway!
- Predisposition to malignancy and dysplasia
- Loss of original functions may compromise usual protective mechanisms (eg. mucus secretion lost)

Physiological Examples:
- Squamous metaplasia of cervix

**Pathological **Examples:
- Columnar to squamous –> smoking
- Squamous to columnar –> Barrett’s oesophagus
- Connective tissue metaplasia –> Intestinal metaplasia of stomach due to Helicobacter pylori infection, Bile reflux or gastric acidity (increased gastrin, dietary factors)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

**Necrosis **is defined as the death of cells in living tissues characterised by breakdown of cell membrane.
- Always pathological
- Occur because of digestion and denaturation of cellular proteins by release of hydrolytic enzymes from damaged lysosomes.
- Results in cessation of function, release of intracelluar enzymes and initiation of […]

“subtypes” of necrosis
1. C[…]
2. C[…]
3. L[…]
4. H[…]
5. S[…]
6. Gangrenous
7. Fat
8. Fibrinoid

A

Necrosis is defined as the death of cells in living tissues characterised by breakdown of cell membrane.
- Always pathological
- Occur because of digestion and denaturation of cellular proteins by release of hydrolytic enzymes from damaged lysosomes.
- Results in cessation of function, release of intracelluar enzymes and initiation of inflammatory response

“subtypes” of necrosis
1. Coagulative
2. Caseous
3. Liquefactive
4. Haemorrhagic
5. Suppurative
6. Gangrenous
7. Fat
8. Fibrinoid

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Necrosis vs Apoptosis (6 differences) (IMPT)

[…]

A

Necrosis vs Apoptosis (6 differences) (IMPT)

FYI:
Pyknosis, or karyopyknosis, is the irreversible condensation of chromatin in the nucleus of a cell undergoing necrosis or apoptosis.

It is followed by karyorrhexis, or fragmentation of the nucleus.

karyolysis is the dissolution of a cell nucleus, especially during mitosis.

17
Q

Other lower yield types of necrosis

Haemorrhagic Necrosis
- In organs w […] (lung = pulmonary artery + bronchial artery, Liver = hepatic artery + portal vein)
- Also for necrosis secondary to chronic […] congestion, such as vovulus of intestine (kinking, blood cannot leave intestinal vein)
- In liver, it is normally around central veins. Btw hepatic vein occlusion is called** Budd-Chiari syndrome!**
- Right heart failure also can

Fat Necrosis
- Leakage of […] into peritoneal cavity (acute pancreatitis)
- Fat saponification produces visible white chalky areas (released FA combine w calcium)

Suppurative Necrosis
- describe abscess formation (large collection of neutrophils)

Gangrenous Necrosis
- Basically loss of blood supply (coagulative necrosis) + bacterial infection
- Can happen in diabetes due to microvascular pathology
- Frequently mentioned in bacteria lectures (“nasty stuff” - Tim)

Fibrinoid Necrosis
- Alteration of injured blood vessels
- Eosinophilic plasma proteins accumulate in vessel wall
- Usually follows damage to blood vessel due to malignant hypertension or vasculitis

A

Other lower yield types of necrosis

Haemorrhagic Necrosis
- In organs w* dual blood supply (lung = pulmonary artery + bronchial artery, Liver = hepatic artery + portal vein)
- Also for necrosis secondary to chronic **
venous
* congestion, such as vovulus of intestine (kinking, blood cannot leave intestinal vein)
- In liver, it is normally around central veins. Btw hepatic vein occlusion is called
Budd-Chiari syndrome!**
- Right heart failure also can

Fat Necrosis
- Leakage of activated lipases into peritoneal cavity (acute pancreatitis)
- Fat saponification produces visible white chalky areas (released FA combine w calcium)

Suppurative Necrosis
- describe abscess formation (large collection of neutrophils)

Gangrenous Necrosis
- Basically loss of blood supply (coagulative necrosis) + bacterial infection
- Can happen in diabetes due to microvascular pathology
- Frequently mentioned in bacteria lectures (“nasty stuff” - Tim)

Fibrinoid Necrosis
- Alteration of injured blood vessels
- Eosinophilic plasma proteins accumulate in vessel wall
- Usually follows damage to blood vessel due to malignant hypertension or vasculitis

18
Q

Reactions to cell injury

Increased expression of protective (cellstress/heatshock) proteins
- Molecular […] –> protect protein from further damage
- […] –> cofactor in proteolysis, removes damaged proteins

HOWEVER may lead to protein aggregates presenting as inclusion bodies
- eg. […] bodies in alcoholic liver damage
- eg. […] bodies (in neurons) in Parkinson’s disease

A

Reactions to cell injury

Increased expression of protective (cellstress/heatshock) proteins
- Molecular* chaperones* –> protect protein from further damage
- Uniquitin –> cofactor in proteolysis, removes damaged proteins

HOWEVER may lead to protein aggregates presenting as inclusion bodies
- eg. Mallory-Denk bodies in alcoholic liver damage
- eg.* Lewy* bodies (in neurons) in Parkinson’s disease

19
Q

Renal artery stenosis can lead to renal […]

A

Renal artery stenosis can lead to renal **atrophy **
which can lead to systemic arterial hypertension due to activation of RAAS