1 Growth Adaptions, Cell Injury & Death

Question 1

Hypertrophy

Answer 1

Increase in size of cells via gene activation & protein synthesis to increase amount of cystoskeleton + increased production of organelles

NOTE: Cardiomyocytes, skeletal muscle, nerve tissue use hypertrophy ONLY, no stem cells

Question 2

Hyperplasia

Answer 2

Increase in number of cells from stem cells
Pathologic hyperplasia to dysplasia to cancer

(Physiologic hyperplasia is okay)

Question 3

Atrophy

Answer 3

Decrease in size via ubiquitin-proteosome degradation of cytoskeleton + autophagy (vacuole with lysosome) of cell components

Decrease in number of cells via apoptosis

Question 4

Metaplasia

Answer 4

Squamous epithelium (Keratinizing, Non-keratinizing)
Columnar epithelium
Transitional epithelium/ Urothelium
Mesenchymal tissues

Metaplasia
-Via “reprogramming stem cells”
-Reversible! Remove the stressor
-Vitamin A deficiency (needed for specialized epithelium)

Metaplasia to dysplasia to cancer
(Except: Apocrine metaplasia of breast)

Question 5

Dysplasia

Answer 5

Disordered cell growth
Proliferation of precancerous cells
Longstanding pathologic hyperplasia or metaplasia

Reversible! Remove the stressor
Progress to carcinoma, which is irreversible

Question 6

Cell Injury

Answer 6

When cells cannot overcome the stress
-Inflammation
-Hypoxia
-Trauma
-Genetic mutations
-Nutritional deficiency/ excess

Question 7

Hypoxia

Answer 7

Ischemia
Hypoxemia
Reduced carrying capacity of o2 by Hb
- CO poisoning
- Methemoglobinemia

Hypoxia impairs oxidative phosphorylation, ATP production

ATP needed for Na+/K+ pump which maintains fluid balance & Ca++ pump which keeps Ca++ out of cell/ from activating enzymes

Question 8

Phases of Cell Injury

Answer 8

Reversible Injury Phase
=Cellular swelling (as Na+ builds up in cell)
-Loss of microvilli
-Membrane blebbing
-Swelling of RER, decreased protein synthesis

Irreversible Injury Phase
=Membrane damage (of three membranes)
-Cell contents spill out (Ex. Cardiac troponin)
-Increase intra-cellular Ca++
-Loss of electron transport chain
-Cytochrome C leaks out, +Apoptosis
-Lytic enzymes escape lysosome

Question 9

Cell Death

Answer 9

Loss of nucleus via
1. Pyknosis (nucleus shrinks)
2. Karyorrhexis (nucleus breaks up)
3. Karyolysis (pieces breaks up into building blocks)

Question 10

Necrosis

Answer 10

Death of large group of cells
Followed by acute inflammation
Pathologic process

Question 11

Coagulative Necrosis

Answer 11

Tissue remains firm
Coagulation of cell proteins
No nuclei

Seen in ischemic infarction (Except: Brain)
-Infarct is wedge-shaped & pale
-Red infarct if blood re-enters, if tissue loosely organized

Question 12

Liquefactive Necrosis

Answer 12

Dead tissue becomes liquefied
Enzymatic lysis of cells & proteins

Brain infarct - Microglial cells, hydrolytic enzymes
Abscess - Neutrophils, hydrolytic enzymes
Pancreatitis - Pancreatic enzymes

Question 13

Gangrenous Necrosis

Answer 13

Coagulative necrosis that resembles mummified tissue, dry gangrene

Seen in ischemia of lower limb in diabetic patients

Superimposed infection of dead tissue causes liquefactive necrosis, wet gangrene

Question 14

Caseous Necrosis

Answer 14

Liquefactive + coagulative

Soft, friable dead tissue with “cottage cheese” appearance

Seen in granulomatous inflammation in TB or fungal infection

Question 15

Fat Necrosis

Answer 15

Dead fatty tissue
1. Free fatty acids bind with Ca++
2. Saponification
3. Chalky-white appearance because Ca++ deposition

Due to trauma to fat, pancreatitis-related damage of peri-pancreatic fat

Question 16

Calcification

Answer 16

Dystrophic Calcification
-Saponification (fat necrosis)
-Psammoma bodies (tumor outgrow blood supply)

Metastatic Calcification
-Serum Ca++ or Phos is elevated, forces Ca++ into tissues, & Ca++ precipitates
-Does not mean CA!

Question 17

Fibrinoid Necrosis

Answer 17

Dead blood vessel wall
Proteins leak from vessel into wall, see bright pink staining (hyaline)

Seen in malignant HTN or vasculitis or pre-eclampsia (fibrinoid necrosis of placental blood vessels)

Question 18

Apoptosis

Answer 18

Energy-dependent
Genetically programmed
Single cells or small groups of cells

Ex. Endometrial shedding during menstrual cycle
Ex. Embryogenesis
Ex. CD8+ killing of virally infected cells (via MHC-1)

Cell shrinks, turns pink because cytoplasm concentrates
Nucleus condenses, shrinks, fragments
Apoptotic bodies cleared by macrophages
No inflammation!

Apoptosis Mediated by Caspases
-Activate proteases for cytoskeleton
-Activate endonucleases for DNA

Question 19

Intrinsic Mitochondrial Pathway (of Apoptosis)

Answer 19

Activated by cell injury, DNA damage, decreased hormone stimulation that inactivates BCL2

Without BCL2, cytochrome C leaks out into cytoplasm & activates caspases

Question 20

Extrinsic Receptor-Ligand Pathway (of Apoptosis)

Answer 20

Something from outside world binds to cell receptor, initiating apoptosis

Ex. FAS ligand binds FAS death receptor (CD95) on T cell in negative selection (when T cell binds too strongly to self-Ag)

Ex. TNF binds TNF receptor

Question 21

Cytotoxic CD8+ T Cell Pathway (of Apoptosis)

Answer 21

CD8+ recognizes its Ag on MHC-1
-Releases perforins to create holes in target cells
-Releases granzyme to enter pores & activate caspases

Question 22

Free Radicals

Answer 22

Chemical species with unpaired electron
-Normally generated in electron transport chain
-Pathologically generated by ionizing radiation, inflammation, Cu & Fe, drugs

***Hydroxyl free radical is most damaging

Free radical damage via…
-Peroxidation of lipids, in membranes
-Oxidation of DNA & proteins

Question 23

Elimination of Free Radicals

Answer 23

Antioxidants, vit A/C/E

Metal carrier proteins for Cu & Fe

Enzymes
-Superoxide dismutase for o2-
-Catalase for h2o2
-Glutathione peroxidase for OH-

Question 24

Free Radical Injury

Answer 24

Carbon Tetrachloride (CCl4)
-Classically seen in dry-cleaning industry
-Gets into blood, converted to CCl3 by P450 system
-CCl3 free radical damages hepatocytes
-Reversible damage with cell swelling & loss of RER
-Decreased protein synthesis & apolipoproteins
-Fatty accumulation/ change in liver

Reperfusion Injury
-Reduced ability of dead tissue to deal with free radicals, causing even more injury in that area

Question 25

Amyloid

Answer 25

Misfolded proteins deposited in ECM, often around blood vessels
Causes cell injury, tissue damage

Beta-pleated sheet configuration
Congo red staining
Apple-green birefringence with polarized light

Localized or systemic

Question 26

Systemic Amyloidosis

Answer 26

Primary Type
-Deposition of AL amyloid (Ig light chain)
-Plasma cell dyscrasias/ abnormalities causing overproduction of Ig light chain

Secondary Type
-Deposition of AA amyloid (SAA, acute phase reactant)
-Chronic inflammatory states like malignancy or “Familial Mediterranean Fever” causing overproduction of SAA

Amyloid cannot be removed
Damaged organs must be transplanted

Question 27

Familial Mediterranean Fever

Answer 27

AR dysfunction of neutrophils
Fever, acute serous inflammation:
-Nephrotic syndrome
-Cardiomyopathy or arrhythmia
-Tongue enlargement
-Malabsorption
-HSM

Requires tissue biopsy to see amyloid (Use abd fat pad or rectum)

Question 28

Localized Amyloidosis

Answer 28

Senile Cardiac Amyloidosis
-Deposition of serum transthyretin
-Asymptomatic
-Seen in elderly commonly

Familial Amyloid Cardiomyopathy
-Deposition of mutated serum transthyretin
-Restrictive cardiomyopathy
-5% African Americans carry mutated gene

Non-Insulin Dependent DM2
-Deposition of amylin in pancreatic islets
-Derived from insulin

Alzheimer Disease
-Deposition of AB plaques in brain
-Derived from Beta-amyloid precursor protein
-Seen early in Down Syndrome

Dialysis-Associated
-Deposited Beta-2-microglobulin in joints
-Derived from MHC-1

Medullary Carcinoma of Thyroid
-Deposition of calcitonin in tumor
-Creates amyloid in association with this CA