Pathoma Ch. 1 (Cell Growth/ Injury/ Death)

Question 1

Hyperplasia can lead to —> dysplasia —> cancer. Give an example and an exception to this ‘rule.’

Answer 1

Example: endometrial hyperplasia—> endometrial CA

Exception: BPH does NOT increase prostate CA risk

Question 2

What is myositis ossificans and what is it an example of?

Answer 2

Myositis ossificans- mesenchymal/ connective tissue—> bone during healing post-trauma

Example of Metaplasia

Question 3

What’s primary vs secondary amyloidosis? (What type of amyloid protein is deposited, what protein it’s derived from, example of disease)

Answer 3

Primary amyloidosis- systemic deposition of AL amyloid, derived from Ig light chain, ex: Multiple Myeloma

Secondary amyloidosis- systemic deposition of AA amyloid, derived from serum-amyloid associated protein, ex: Familial Mediterranean Fever

Question 4

Explain liquefactive necrosis.

Answer 4

Enzymes act on dead tissue—> liquified

(ex: BRAIN infarction, abscess, pancreatitis)

Question 5

Hallmark of cell death?

Answer 5

Loss of nucleus

(1. Pyknosis*- nucleus shrinks, 2. *Karyorrhexis*- nucleus breaks up, 3. *Karyolysis- nucleus further breaks down into building blocks)

Question 6

Explain coagulative necrosis.

Answer 6

Dead tissue that stays firm/ keeps its shape (in any tissue but the brain)

pale infarct= cut blood supply, wedge-shaped

red infarct= blood re-enters (ex: testicular infarction…the twisting/ torsion prevents blood from being drained through the collapsible veins, but the thick-walled artery remains open so blood can keep coming into the testicle)

Question 7

What is keratomalacia and what is it an example of. Explain.

Answer 7

Karatomalacia- metaplasia of conjunctiva lining the eye

-you need vitamin A to maintain the specialized epithelium of the eye. Vit A deficiency—> metaplasia of these specialized cells lining the eye= karatomalacia

Question 8

What’s the difference between slow-developing vs. acute ischemia? Give an example for each. What happens to the cells in both cases?

Answer 8

Slow-developing (cells have time to adapt)—> atrophy (ex: renal artery atherosclerosis)

Acute (cells don’t have time to adapt)—> cellular injury (ex: renal artery embolus)

(*causes of cellular injury: inflammation, nutritional deficiency or excess, hypoxia (low O2), trauma, genetic mutations)

Question 9

Dystrophic vs metastatic calcification?

Answer 9

Dystrophic calcification- calcium binds up fat in the setting of normal serum calcium levels

Metastatic calcification- calcium binds up fat in the setting of high serum calcium levels

(ex: hyperparathyroidism…you have too much PTH—> too much calcium reabosorption into blood)

Question 10

Where are free radicals seen (in normal physiology and in pathology)?

Answer 10

• ETC in ox phos (cyt C oxidase/ complex 4 transfers electrons to O2)
• ionizing radiation
• inflammation (NADPH oxidase in oxidative burst to kill bacteria/ foreign objects/ dead cells)
• metals
• drugs (Tylenol is a big one), chemicals (P450 system, CCl4 used in the cleaning industry)

Question 11

What is re-perfusion injury?

Answer 11

When you re-perfuse (ex: open up a blood vessel with a stent so blood can flow through coronary arteries again following an MI), you are introducing blood flow= introducing oxygen back to the area.

Oxygen brings in free radicals. This combined with the surrounding area of necrosis/ inflammation (+ loss of antioxidants to deal with free rads) can cause further damage mediated by the free-radicals.

(Re-perfusion injury would present like this: patient had MI. You placed a stent or gave a fibrolytic drug, re-perfusing the site. Now patients cardiac troponin levels are rising, indicating more cell death/ necrosis after you re-perfused.)

Question 12

Hallmark of reversible cell injury?

Answer 12

Cellular swelling

(loss of membrane microvilli, membrane blebbing, decreased protein synthesis)

Question 13

What are the 3 pathways of apoptosis? Explain them all.

Answer 13

1. Intrinsic/ mitochondrial pathway- cell injury—> knocks out Bcl2 (a regulator of apoptosis)—> cyt C leaks out of mitochondria—> cyt C activates caspases
2. Extrinsic receptor-ligand pathway- FAS (or TNF) binds to FAS death receptor aka CD95 (or TNF receptor)—> the binding activates caspases (ex: this type of apoptosis happens in negative selection of tymocytes the thymus)
3. Cytotoxic CD8+ T-cell pathway- CD8+ T-cels poke holes in the membrane of the target cell—> granzymes leak out—> activates caspases

*For all pathways:caspases= enzymes that mediate apoptosis. They do this by activation ofproteasesto break down the cytoskeleton of the cell andendonucleases to break down its DNA—> dying cell shrinks, becomes more pink/ eosinophilic, nucleus condenses, macrophages remove debris.

Question 14

What is amyloid? What sheets is it made of? What is it’s staining?

Answer 14

Misfolded protein

made of beta-pleated sheets

congo-red staining

Question 15

What is dialysis-associated amyloidosis?

Answer 15

Dialysis—> beta-2 microglobulin not filtered well—> this misfolded protein deposits in joints

Question 16

Explain caseous necrosis.

Answer 16

Dead tissue that looks like cottage cheese

it is coagulation + liquefactive necrosis

(ex: TB or fungal infection)

Question 17

Explain fat necrosis.

Answer 17

Dead tissue that is chalky-white (due to calcium deposition)

fat dies—> FAs released—> fat can bind to calcium (saponification)

(ex: trauma to breasts (fat tissue) and pancreatitis damaging surrounding fat)

Question 18

Decreased blood= decreased O2= decreased ATP. What channels/ biochemical processes does this disrupt? What electrolyte changes will occur in a cell that lacks ATP?

Answer 18

Disrupts Na+/K+ pump and Ca2+ pump—> Na+/ water/ Ca2+ build up in the cell—> cell swells (—> loss of microvilli, membrane blebbing, dec protein synthesis—the cell is injured)

Also disrupts oxidative phosphorylation (since you have low O2 and O2 is needed to run this aerobic process)—> switch to anaerobic glycolysis—> you get less ATP + lactic acid build up—> decreased pH (denatures proteins, precipitates DNA)

Question 19

What amyloid deposits are seen in T2DM? Alzheimer’s disease?

Answer 19

T2DM—> amyloid deposits in pancreatic islet cells

Alzheimers—> A-beta amyloid deposits in the brain

Question 20

Talk about Barrett esophagus. How is this an example of metaplasia? What specific type of cancer can it lead to and how?

Answer 20

Esophageal cells switch from squamous—> columnar to handle the increased stress (the acid refluxing up from GERD)

Can progress to esophageal cancer: metaplasia (Barrett esophagus)—> dysplasia—> CA (adenocarcinoma affecting the lower 1/3rd of the esophagus)

Question 21

Are the PaO2 and SaO2 levels high, low, or normal in anemia? CO poisoning?

Answer 21

(PaO2= oxygen that gets into blood, SaO2= oxygen that saturates/ binds to Hb)

Anemia- PaO2 is normal, SaO2 is normal

(plenty of oxygen in the blood, plenty of oxygen bound to Hb—problem is there’s decreased Hb)

CO poisoning- PaO2 is normal, SaO2 is low

(plenty of oxygen in the blood, decreased oxygen bound to Hb bc CO is stealing it away)

Question 22

Give the definitions for: hypertrophy, hyperplasia, atrophy, metaplasia, dysplasia, aplasia, and hypoplasia.

Answer 22

Hypertrophy= increase size of cells

Hyperplasia= increase number of cells

Atrophy= decrease size and number of cells

Metaplasia= change in stress—> change in cell type

Dysplasia= disordered cell growth (pre-cancer)

Aplasia= no growth (—> no organ)

Hypoplasia= decreased growth (—> underdeveloped organ)

Question 23

Hyperplasia and hypertrophy often occur together. What’s an example of this?

Answer 23

The uterus in pregnancy

Question 24

How does medullary carcinoma of the thyroid relate to amyloidosis?

Answer 24

Malignancy of C-cells in the thyroid—> increased calcitonin, amyloid is in the background on histo

Question 25

Necrosis vs. apoptosis? Definition, small or large groups of cells involved?, inflammation?

Answer 25

**Necrosis**- “cell murder,” large groups of cells involved, followed by inflammation **Apoptosis**- “cell suicide,” small groups of cells involved, NOT followed by inflammation

Question 26

Explain how CCl4 (carbon tetrachloride—found in the cleaning industry) can lead to fatty change of the liver.

Answer 26

CCl4 free radical damage—\> cell swelling—\> ribosome los (ribosomes, the protein-making factories, pop off)—\> decreased protein synthesis—\> this includes decreased apolipoprotein synthesis—\> fat stays (can’t get re-packaged/ sent out of the liver)—\> fatty change of the liver

Question 27

Example of hypoplasia?

Answer 27

Streak ovary in Turner syndrome (hypoplasia= decreased growth—\> underdeveloped organ)

Question 28

Caspases are the enzymes that drive apoptosis...but how? (They use 2 things). What changes do we see in a cell dying by apoptosis?

Answer 28

Caspases mediate apoptosis by: 1. Activation of proteases to break down the cytoskeleton of the cell 2. Activation of endonucleases to break down its DNA The dying cell shrinks—\> becomes more pink/ eosinophilic—\> nucleus condenses—\> macrophages remove debris

Question 29

Name all the causes of hypoxia and hypoxemia.

Answer 29

**_Hypoxia (dec oxygen to tissues)_**- 1. Hypoxemia 2. Decreased cardiac output (or ischemia: atherosclerosis, Budd-Chiari syndrome, shock) 3. Anemia 4. CO or CN poisoning **_Hypoxemia (dec oxygen in blood) w/ normal A-a gradient_**- 1. High altitude 2. Hypoventilation **_Hypoxemia (dec oxygen in blood) w/ high A-a gradient (diffusion issue)_**- 1. V/Q mismatch 2. R—\> L shunt (bypasses lungs for oxygenation)

Question 30

What has to happen for hypertrophy to take place? What has to happen for hyperplasia to take place?

Answer 30

_Hypertrophy (inc size of cells)_- 1. Gene activation, 2. Protein synthesis, 3. Cell has to make more organelles _Hyperplasia (inc number of cells)_- stem cells make new cells

Question 31

What’s the difference between: FiO2, PAO2, PaO2, and SaO2?

Answer 31

**FiO2**- oxygen you breathe in **PAO2**- oxygen that gets to alveoli **PaO2**- oxygen that gets to blood **SaO2**- oxygen that saturates Hb (percent of Hb bound to O2)

Question 32

What deposits are seen in senile cardiac amyloidosis? Familial amyloid cardiomyopathy? How do these 2 conditions differ?

Answer 32

**Senile cardiac amyloidosis**—\> serum transthyretin deposits (asymptomatic) **Familial amyloid cardiomyopathy**—\> misfolded serum transthyretin deposits (leads to restrictive cardiomyopathy- *the heart is restricted from filling properly due to these infiltrates*)

Question 33

What are the 3 permanent cells? Do they do hypertrophy, hyperplasia, or both?

Answer 33

1. **Cardiac** cells (ex: myocytes in response to HTN) 2. **Skeletal** cells 3. **Nerves** (neurons) They do HYPERTROPHY (inc size of cells) only! (Cannot inc number of these cells)

Question 34

What’s an exception to the ‘rule’ that metaplasia—\> dysplasia—\> cancer?

Answer 34

Metaplasia of the breast (fibrocystic change) does NOT increase risk for breast cancer

Question 35

Explain fibrinoid necrosis.

Answer 35

Dead blood vessel wall—\> leakage of proteins (fibrin) into vessel wall (in vasculitis, etc.)

Question 36

Hallmark of irreversible cell injury?

Answer 36

Membrane damage (leads to cell death) (leakage of enzymes like Troponin in cardiac cells, increased calcium in cell, loss of ETC, cyt C leaks out of damaged mitochondrial membranes—\> apoptosis)

Question 37

Explain gangrenous necrosis.

Answer 37

Dead tissue that looks like a mummy Dry gangrene- type of coagulative necrosis Wet gangrene- type of liquefactive necrosis (get it if there’s an infection of dead tissue) (this type of necrosis happens in the lower limbs + GI tract)

Question 38

In atrophy, what is responsible for decrease in size? What is responsible for decrease in number of cells?

Answer 38

Dec size—\> ubiquitin-proteosome degradation (degrades cytoskeleton. Other parts of the cell are degraded by autophagy, where vacuoles fuse w/ lysosomes) Dec number—\> apoptosis