Lec #3 (wk 1): Cell Injury, Inflammation, & Tissue Healing

Question 1

What does pathology mean?

Answer 1

The study of disease.

Question 2

When studying pathology, we look at the morphological changes which are?

Answer 2

Gross/Macroscopic appearance (what can be seen with the naked eyes), and the microscopic appearance (histology).

Question 3

What is the general stain used in routine pathology?

Answer 3

Hematoxylin & Eosin (H&E) stain. Hematoxylin has a deep blue color which stains the nucleus, and eosin has a Pink color which stains Proteins.

Question 4

What are the potential causes of cell injury?

Answer 4

Infectious agents.
Genetic defects.
Nutritional imbalance.
Immunological reaction.
Hypoxia.
Thermal sources.
Physical agents.
Drugs.
Chemical agents.

Question 5

Cell injury involves two types of damage: reversible & irreversible. What changes occur in the cell if it was injured reversibly?

Answer 5

Reversible cell injury is of short duration like in hypoxia, and changes in cell include:
- Partial damage to the Na+ pump.
- Swelling of the cell & organelles.

Question 6

Cell injury involves two types of damage: reversible & irreversible. What changes occur in the cell if it was injured irreversibly?

Answer 6

Long duration, the effects are irreversible which leads to necrosis. Changes in the cell include:
- Cell membrane damage.
- Cytoplasmic leakage.
- Nuclear changes: pyknosis, karyorrhexis, & karyolysis.

Question 7

What are the nuclear patterns in necrosis?

Answer 7

1- Pyknosis –> where the nucleus shrinks in size & is condensed.
Karyorrhexis –> (-rhexis means tearing apart) and here the nucleus is broken down to small fragments.
Karyolysis –> where the nucleus looks fade, chromatins are lysed, and DNA is lost.

Question 8

What are the types of necrosis?

Answer 8

1- Coagulative necrosis
2- Liquifactive/Colliquative necrosis
3- Gangrenous necrosis
4- Caseous necrosis
5- Fat necrosis
6- Fibrinoid necrosis

Question 9

What is coagulative necrosis?

Answer 9

This is typically seen where we have a restriction in blood flow, so seen in a hypoxic environment like in ischemia or infarction. It happens in tissues like the kidney, heart, & adrenal glands. This can occur in all organs BUT the brain. So here, the cells are dead bs its structure is preserved.

Question 10

What would be seen histologically in coagulative necrosis?

Answer 10

eosinophilic (pink), anucleate cells.

Question 11

What would be the gross appearance of coagulative necrosis? Microscopic appearance?

Answer 11

ischemia & infarction appears as pale area. Microscopic appearance: cells are pale (histologically: eosinophilic (pink) & anucleate)

Question 12

What is liquifactive/colliquative necrosis?

Answer 12

This involves the digestion of dead cells resulting in the transformation of the tissue into a liquid viscous. This is associated with pus or abscess. Typically seen in bacterial infections but sometimes fungal infection.

Question 13

Liquefactive/colliquetive necrosis is typically seen when?

Answer 13

When there is a bacterial infection but sometimes also fungal infection.

Question 14

Hypoxic death of cells in which organ usually evokes liquefactive/colliquetive necrosis?

Answer 14

Within the CNS (so in OSPE if brought a pic of the brain w liquid cells, this is liquefactive necrosis).

Question 15

Which type of necrosis is associated with pus?

Answer 15

Liquefactive/colliquetive necrosis.

Question 16

What is gangrenous necrosis?

Answer 16

This is considered a type of coagulative necrosis where it also occurs in the case where we have insufficient oxygen/blood flow, but here the cells+tissues start to rot & appears black (whereas coagulative is also insufficient oxygen but organ look normal).

Question 17

Provide some examples of where we can see gangrenous necrosis?

Answer 17

Lower limbs of a diabetic patient, and the GI tracts.

Question 18

Difference between wet and dry gangrenous necrosis?

Answer 18

Dry –> where you have blocked circulation, appears black BUT NOT INFECTED.
Wet –> in addition to the gangrenous necrosis, you also have an infection. Here the morphological appearance changes to liquefactive necrosis.

Question 19

What is the morphological appearance of wet necrosis?

Answer 19

Liquefactive necrosis.

Question 20

What is caseous(cheesy) necrosis?

Answer 20

This is considered a combination of coagulative & liquefactive necrosis. Dead cells are not completely digested, leaving granular particles. The necrotic tissue appears as white, clumped cheese. This is the type of necrosis seen in tuberculosis.

Question 21

What is the typical cause of caseous/cheesy necrosis?

Answer 21

Tuberculosis.

Question 22

What is the gross appearance of caseous necrosis?

Answer 22

cheese-like, so yellow-white appearance of the area of necrosis.

Question 23

What is the microscopic appearance of caseous necrosis?

Answer 23

Necrotic cells appear as giant cells, formed by the fusion of epithelioid cells (macrophages). Histologically, appear as a collection of fragmented/lysed cells with an amorphous (shapeless) granular pink appearance in H&E stained tissue sections. Unlike coagulative necrosis, the tissue architecture is completely obliterated and cellular outlines cannot be distinguished.

Question 24

What is fat necrosis?

Answer 24

This occurs in organs with adipose tissue like the pancreas and they appear as yellowish-whitened firm deposits. This type of necrosis occurs due to trauma or activated lipases.

Question 25

Describe what happens when the lipases are activated in fat necrosis.

Answer 25

The release of activated pancreatic lipases into the substance of the pancreas & the peritoneal cavity like in acute pancreatitis.
Triglyceride is converted to fat acids using lipases, and fat acid+ Ca2+ is converted to white chalky deposits (Soap).

Question 26

Which type of necrosis uses Ca2+?

Answer 26

Fat necrosis.

Question 27

Microscopical appearance of fat necrosis?

Answer 27

Cloudy appearance.

Question 28

What is fibrinoid necrosis?

Answer 28

Necrosis happening in smooth muscle cells allow fibrins (which is a plasma protein) to deposit in the area of necrosis. This type is detected only via histological examination.

Question 29

Where does fibrinoid necrosis happen?

Answer 29

Arterial wall like vasculitis.

Question 30

Describe the stages of apoptosis.

Answer 30

This is a programmed cell death.
1- cell shrinking and the chromatins condensing.
2- Membrane starts blebbing and organelles disintegrate.
3- Nucleus and organelles collapse while membrane continues to bleb.
4- Apoptotic bodies are formed.
5- Macrophages phagocyte these apoptotic bodies.
NO INFLAMMATION IS END RESULT.

Question 31

What is the difference between necrosis & apoptosis?

Answer 31

1- Necrosis is always because of pathological, whereas apoptosis could be pathological or physiological.
2- Necrosis causes inflammation whereas apoptosis doesn’t.
3- Plasma membrane is disrupted and cellular contents leak out in necrosis, but in apoptosis all of these are intact.
4- Cell size is swollen in necrosis but shrunk in apoptosis.
5- The nucleus in necrosis undergoes: pyknosis, karyorrhexis, and karyolysis. Whereas in apoptosis: fragmentation only.

Question 32

What is an inflammation?

Answer 32

Non-specific immune response to help the body fight infection. It is clinically denoted by the suffix (-itis).

Question 33

What are the 5 cardinal signs of an inflammation?

Answer 33

1- Rubor: redness.
2- Tumor: Swelling.
3- Calor: heat.
4- Dolor: pain.
5- Functio Laesa: loss of function.

Question 34

When we have a damaged cell, what does it release?

Answer 34

Prostaglandins are released from the damaged cell and they contribute to PAIN.

Question 35

What does the endothelium release when we have a damage to the cell?

Answer 35

Nitric oxide, & cytokines.

Question 36

What do mast cells release?

Answer 36

Histamine which is a vasodilator and also causes gaps to appear between the endothelial cells (vascular permeability).

Question 37

What is the difference between transudate & exudate?

Answer 37

1- Exudate is the one associated with inflammation, it refers to the plasma, plasma proteins, and other cells leaking out of the blood vessel & into the extravascular tissue. Whereas transudate refers to plasma only leaking out (trans = transparent), and is NOT associated with inflammation.

2- Appearance of transudate is clear/transparent, whereas exudate is cloudy as it contains plasma proteins and cells too.

3- The specific gravity (lab test which shows the concentration of all the chemical particles in urine) is <1.01 in transudate, and >1.02 in exudate.

Question 38

What is the pathogenesis of inflammation?

Answer 38

Has 3 stages:

1- Vascular changes
- Vasoconstriction for a few seconds.
- Vasodilation
- Increased vascular permeability

2- Cellular events
Emigration of leukocytes from the intravascular to extravascular space.

3- Mediators
- Cellular derived inflammatory mediators.
- Plasma derived inflammatory mediators.

Question 39

What are the stages of leukocyte extravasation?

Answer 39

1- Margination
2- Rolling
3- Adhesion
4- Diapedesis

Question 40

What are the systemic effects of inflammation?

Answer 40

1- Fever (>37.8 or >100F)
This fever causes increased pulse and blood pressure + causes anorexia (loss of apetite).

2- Leukocytosis; increased WBC count.

3- Increased ESR (Erythrocyte Sedimentation Rate); this means in 1 hour what is the height of RBC aggregate formed in mm. For e.g in a normal person maybe its 10mm but in inflammation ESR is higher so could be 40mm.

4- Increased C-reactive proteins; during inflammation, the liver starts producing more C-reactive proteins.

Question 41

What does neutrophilia indicate?

Answer 41

Bacterial infection.

Question 42

What does Lymphocytosis indicate?

Answer 42

Viral infection.

Question 43

What does eosinophilia indicate?

Answer 43

Parasitic infection or allergy.

Question 44

What is the cause of acute inflammation?

Answer 44

Rapid onset with short duration. Causes:
Trauma, foreign body, infection, physical or chemical agents.

Question 45

What is the cause of chronic inflammation?

Answer 45

Slow onset with long duration.
Causes:
- Persistant infection like Tb.
- Persistant exposure to toxic agents like silicosis.
- Autoimmunity.

Question 46

What WBC is predominant at the site of ACUTE inflammation?

Answer 46

Neutrophils.

Question 47

What WBC is predominant at the site of CHRONIC inflammation?

Answer 47

Lymphocytes.
Macrophages.

Question 48

How do the cardinal signs of inflammation develop?

Answer 48

As soon as the damage happens, vasoconstriction happens in a split second but then the histamine produced by the mast cells cause vasodilation as well as increases vascular permeability. Vasodilation leads to the 2 cardinal signs: heat & redness. The prostaglandins and cytokines causes the information to be sent via the nerves to the brain that you are in pain. then the WBCs do margination where they stand at the margins of the BV and leave the circulation in a process called ‘extravasation’. Also, the plasma & proteins leaving to the ECF causes swelling in a process called exudate.

Question 49

What are the morphological patterns of acute inflammation, in terms of the exudate?

Answer 49

Serous exudate –> watery (less cellular amount). It is yellow in color.

Serosanguineous exudate –> Pale, pink, and watery consistency. It contains erythrocytes.

Suppurative/purulent exudate –> Thick, yellowish-green & foul smell (basically pus).

Question 50

What would be the gross appearance of acute inflammation?

Answer 50

Blister
Suppurative exudate (pus)

Question 51

What would be the histological appearance of acute inflammation?

Answer 51

1- Fluid accumulation separating the epidermis from the dermis. This could be serous or serosanguineous exudate.
2- Many neutrophils occupying the site.

Question 52

What are the outcomes of acute inflammation?

Answer 52

1- Complete resolution.
2- Abscess.
3- Fibrosis.
4- If we frequently get many acute inflammations, this can cause chronic inflammation.

Question 53

What is the microscopical appearance of a chronic inflammation?

Answer 53

Central necrosis with giant cells.

But acute it was many neutrophils to the site AND fluid accumulation that separates the dermis from the epidermis (could be serous or serosanguinous)

Question 54

What could be the causes of chronic inflammation?

Answer 54

1- Bacterial
- Syphilis
- Tuberculosis
- Cat scratch disease
- Granuloma inguinale
- Leprosy
- Actinomycosis

2- Fungal
- Blastomycosis

3- Parasitic
- Schistosomiasis

4- Inorganic metals & dusts
- Silicosis
- Asbestosis

5- Miscellanous
- Sarcoidosis
- Crohn’s disease

Question 55

What are the outcomes of chronic inflammation?

Answer 55

1- Cirrhosis
2- Organ failure

Question 56

What are the 2 distinct processes of healing?

Answer 56

Regeneration; necrotic cells replaced by new cells.
Repair; proliferation of connective tissue which causes fibrosis & scarring.

Question 57

How do the following heal;
Mild injury?
Severe injury?

Answer 57

Mild injury which involves damage to the epithelium only can be resolved by regeneration.

Severe injury involving the connective tissue are resolved by scar formation.

If the damage is so severe that it is incapable of returning to normal; fibrosis happens, although fibrous scar isn’t normal, it provides enough structural stability for the normal function.

Question 58

What happens within 24 hours of healing?
24-48 hours?
3 days?
5 days?
2 weeks?

Answer 58

Within 24 hours:
- Hemostasis
- Clot formation
- Migration of neutrophils
- Increased mitotic activity of the basal cells.

Within 24-48 hours:
- Epithelial cells proliferate from both edges & meet in the midline.

3 days:
- We now have macrophages instead of neutrophils.
- The incision space is invaded by granulation.
- Collagen starts to appear.
- Epithelial cells continue to proliferate.

5 days:
- Neovascularization
- Collagen bridges the incision.
- Epidermis is recovered.

2 weeks:
- Collagen accumulates and fibroblasts proliferate.
- Leukocyte infiltration & edema is diminished.

Question 59

What are the types of healing?

Answer 59

1- first intention healing (primary healing)
- Clean and uninfected
- Not much loss of cells and tissues.
- Edges of the wound are approximated by surgical sutures & can be surgically incised.

2- Second intention healing (Secondary healing)
- Open & may be infected.
- Extensive loss of cells & tissues.
- Wounds aren’t approximated by surgical sutures thus are left open.

3- Tertiary healing
Where the surgeon combines primary & secondary healing. The contaminated wound is given time to granulate & 5-7 days healing for the aim of observing & cleaning. Once the risk of infection appears minimal, wound is sutured.

Question 60

What are the factors which could influence wound healing?

Answer 60

Local factors: infection, poor blood supply, less movement, size & location of injury.

Systemic factors: age, nutrition, history of glucocorticoids, uncontrolled diabetes, & hematological abnormalities.

Question 61

What are some of the complications associated with wound healing?

Answer 61

1- Pigmentation
2- Infection to the wound
3- Inadequate scar formation due to inadequate granulation tissue.
4- Keloid (overgrowth of dense fibrous tissue).
5- Dupuytren’s contracture; fibrous tissue over-proliferates in the tendon of the 4th+5th digit.

Question 62

What is dupuytren’s contracture?

Answer 62

Fibrous tissue over-proliferating in the tendon of the 4th & 5th digit. This could be a complication of wound healing.

Question 63

What is keloid?

Answer 63

Overgrowth of dense fibrous tissue, could be a complication of wound healing.