Unit I: Cellular Accumulations

Question 1

Cell accumulation mechanisms (x5)

Answer 1

1. cell injury/aging–MOST COMMON
2. Defect in packaging/transporting mechanism (fatty change)
3. genetic defects in protein folding, packaging, transport, secretion (alpha-1 antitrypsin)
4. genetic enzyme deficiency (lysosomal storage diseases)
5. abnormal exogenous material accumulation (ex: carbon/silica)

Question 2

Types of cell accumulations (x7)

Answer 2

1. proteins
2. cytoskeletal elements
3. lipids
4. cholesterols
5. glycogen
6. pigments
7. calcium salts

Question 3

• lipofuscin-define
  
  1. ​what does it cause?
  2. where is it?
  3. is it bad?

Answer 3

• lipofuscin- primary lipid waste product–undigested remnants of lipid peroxidation–occurs with cellular aging
  
  1. causes discoloration when deposition occurs during atrophy= brown atrophy
  2. collects near nucleus, especially in heart and liver
  3. NON toxic

Question 4

• Autophagy
  
  • process
  • purpose

Answer 4

• Autophagy- digestion of intracellular material
  
  • ribosome free area of ER makes autophagic vacuole that fuses with lysosome or golgi==> autophagolysosome
  • removes damaged organelles

Question 5

• Heterophagy-
  
  • definition
  • process
  • cell types

Answer 5

• Heterophagy- digestion of extracellular material
  
  • Endocytosis, phagocytosis, or pinocytosis
  • phagolysosome fusion
  • Usually in phagocytic cells

Question 6

• Steatosis- define,
  
  • what tissues does this occur in?
  • possible Etiology?
    
    • most common causes?
  • Gross changes
  • microscopic changes

Answer 6

• Steatosis= Fatty change- abnormal accumulation of triglycerides in cytoplasmic vacuoles
  
  • Tissues: usually liver, but can also occur in heart, muscle kidney
  • Etiology: toxins (EtOH), protein malnutrition, diabtetes, obesity, anorexia, CCl4 poisoning, Reye’s syndrome
    
    • USUALLY: alcohol abuse and diabetes
  • Gross changes: yellow, enlarged (liver)
  • Microscopic changes: intracytoplasmic vacuoles, non staining

Question 7

Non-alcoholic fatty liver pathophysiology?

Answer 7

• overproduction of fatty acids from glucose and glycogen
• Big part of early stage Type II Diabetes

Question 8

Alcoholic fatty liver progression

Answer 8

1. fatty deposits start as microvesicles
2. cytoplasm is replaced by one large macrovesicle of lipid==> liver expansion= enlarged greasy and yellow

Question 9

Clear vacuoles mean….?

Answer 9

Clear vacuoles can contain:

1. water
2. lipid - Oil Red O and Sudan black can detect lipid in frozen sections
3. glycogen- PAS or periodic shiff stains

Question 10

Atherosclerosis

Answer 10

Phagocytic cells become overloaded with lipids (triglycerides, cholesterol and choleesteryl esters).

Question 11

Hyaline change- define, describe (histo), 5 examples

Answer 11

• Non-specific depositions of protein intracellulary OR extracellularly.
• It is pink (eosinophilic) and glassy/granular/fibrillar (depending on protein type)
• Examples:
  
  • Hyaline membrane (lung)
  • Mallory bodies (liver)
  • alpha-1 antitrypsi deficiency
  • Russel bodies
  • nephrotic syndrome

Question 12

Hyaline Membranes

1. what are they
2. location
3. pathophysiology?

Answer 12

Hyaline Membranes

1. extracellular collection of fibrin and other plasma proteins
2. line alveolar space
3. damaged alveolar capillaries allows them to leak out

Question 13

Mallory bodies

Answer 13

Mallory bodies= intermediate keratin filament deposition (hyaline) in alcoholic liver disease

Question 14

Glycogen accumulation

1. associated with:
2. Microscopic appearance
3. Where does it accumulate?

Answer 14

1. abnormal glucose/glycogen metabolism= diabetes, glycogen storage disorders
2. non staining cytoplasmic vacuoles–can be stained with PAS/Periodic Shiff
3. renal tubulear epithelium, cardiac mycotes (pompe disease), beta cells of islets of langerhans

Question 15

Russel Bodies

Answer 15

• Plasma cell RER accumulates newly synthesized immunoglobulins
• round, eosinophic

Question 16

• Normal protein filtration in kidney?
• Nephrotic syndrome (with regards to protein accumulation)

Answer 16

• Normal: albumin filtered in glomerulus and pinocytosed in PCT
• Nephrotic Syndrome: protein leakage across glomerulus==> higher rate of reabsorption in PCT==>protein accumulation in vesicles
  
  • pink hyaline cytoplasmic droplets

Question 17

Anthracosis

Answer 17

• carbon (most common exogenous pigment) aggregates in and blackens draining lymph nodes and pulmonary parenchyma
• carbon is phagocytsed by alveolar macrophages and transported through lymph to tracheobronchial nodes
• Not carcinogenic

Question 18

Hemosiderin-define

1. characteristics
2. etiology
3. examples

Answer 18

Hemosiderin- breakdown product of hemoglobin by macrophages

1. Characteristics: granular gold-brown pigment from excess iron deposition
2. etiology: excess bleeding, phagocytosis of red cells, hereditary increased deposition of iron (ie hemochromatosis)
3. Examples: bruising (localized hemosiderosis); hemochromatosis,

Question 19

Hemosiderosis

Answer 19

aggregation of hemosiderin (Fe granules from Hb breakdown by macrophages)

Question 20

Bilirubin accumlation

1. what is it
2. normal method of excretion
3. deposits where?
4. called ____ when accumulates in tissues, ___ in eyes

Answer 20

Bilirubin

1. non-iron part of hb
2. normally excreted in bile
3. extracellular or intracellular
4. jaundice, icterus

Question 21

What causes excess bilirubin deposition ?

Answer 21

• excess RBC hemolysis
• liver disease
• causes yellow discoloration of sclera (icterus) or skin (jaundice)

Question 22

Calcification

1. Where does it occur
2. what are the two types?

Answer 22

1. extracellular or intracellularly
2. dystrophic or metastatic

Question 23

Hemachromatosis

1. what is it
2. what does it cause?

Answer 23

1. Excess iron causes damage (over decades) due to ROS (fenton rx).
2. causes diabetes (pancreatitis, bronzing of skin, myocardial scarring and arrhythmias, and liver cirrhosis (which can progress to cancer)

Question 24

Dystrophic calcification

1. what is it?
2. Where is it deposited?
3. Features?
4. Serum calcium levels?

Answer 24

1. calcium complexes with lipid from cellular debris. the calcium is attracted to membrane phospholipids
2. LOCALIZED in necrotic tissue
3. amorphic basophilic deposits
4. normal serum calcium

Question 25

Two steps of dystrophic calcification

Answer 25

1. initiation 2. propogation

Question 26

**Metatstatic calcification** 1. serum calcium levels 2. distribution 3. examples

Answer 26

1. HYPERCALCEMIA 2. systemic distribution, especially in vessles, kidney and lung 3. hyperparathyroidism, VitD toxicosis, tumors (associated with increased bon metabolism, renal failure (secondary to hyperparathyroidism, multiple myeloma

Question 27

Aortic stenosis in old people is commonly caused by?

Answer 27

Dystrophic calcification

Question 28

**Dystrophic calcification**- where do initiation and propogation occur extracellularly and intracellularly

Answer 28

1. Initiation * **Extracellular**: membrane bound vesicles derived from degenerating cells * **Intracellular:** mitochondria of dead or dying cells 2. Propagation: in both extra and intracellular dystrophic calcification, propagation occurs at place of initiation and depnds on concentrations of calcium, phosphate, mineral inhibitors and degree of collagenization.

Question 29

matrix vesicles

Answer 29

physiologic place of dystrophic calcification in bones and cartilage?

Question 30

Senescence

Answer 30

pre-programmed limits to proliferation. ie telomeres

Question 31

Neoplasms reporoduce indefinitely due to....

Answer 31

expression of telomerase that lengthens telomeres with cell division

Question 32

Mechanisms involved in cellular aging

Answer 32

1. DNA damage 2. telomeres (Werner's syndrome have shorter telomeres) 3. defective protein homeostasis (chaperones less active, less translation, more turnover) 4. exposure to elements that cause cellular aging 5. activation of tumor suppressor genes 6. nutrient sensing

Question 33

tumor suppressor genes

Answer 33

* usually inhibit progression from G1--\> S * defect can increase changes of cancer

Question 34

Telomerase activity in different cell types?

Answer 34

germ cells\>stem cells\> somatic cells

Question 35

nutrients and cell aging?

Answer 35

Caloric restriction ==\> decreased IGF-1 and insulin==\> enhanced repair