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Pathobiology > Cellular Alterations 1-5 > Flashcards

Cellular Alterations 1-5 Flashcards

1
Q

What are the four basic types of cellular adaptations and are they reversible?

A

Hyperplasia, hypertrophy, atrophy, metaplasia

-> all reversible

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2
Q

What is the definition of hyperplasia and its etiology?

A

Increased number of cells which can increase tissue volume (cells must be capable of division)

Etiology:
Hormones
Growth factors
Cytokines

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3
Q

Give two mechanisms of hyperplasia

A
  1. Increased transcription of growth factors + receptors

2. Rarely - recruitment of stem cells

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4
Q

What are the two types of physiologic hyperplasia and give examples of each?

A
  1. Hormonal induced
    - > proliferation of breast epithelium in puberty / pregnancy
    - > smooth muscle of uterus in pregnancy
  2. Compensatory
    - > regeneration of liver after hepatectomy
    - > enlargement of contralateral kidney after unilateral nephrectomy
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5
Q

What are some examples of pathologic hyperplasia?

A
  1. Endometrial hyperplasia from unopposed estrogen
  2. Connective tissue hyperplasia in wound healing / repair
  3. Epithelial hyperplasia due to HPV
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6
Q

What is the definition of hypertrophy?

A

Purposeful increase in cell size due to increased synthesis of cellular components, which can lead to increased tissue volume (cells do not need to be capable of division, i.e. myocytes)

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7
Q

Give the two types of physiologic hypertrophy?

A
  1. Hormonal-induced -> increased uterine smooth muscle size during pregnancy (also an example of hyperplasia)
  2. Increased workload -> increased skeletal muscle size in weightlifters
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8
Q

What causes cardiac hypertrophy and what are its basic mechanisms?

A

Increased workload due to valvular stenosis or hypertension

Mechanisms:
Mechanical / trophic signals lead to transcription of normal as well as re-expression of fetal / neonatal genes which are more efficient and increase cardiac capacity / reduce workload

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9
Q

What is the definition of atrophy?

A

Decreased cell size due to reduced cellular components and subsequent reduction in tissue volume

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10
Q

What typically causes atrophy?

A

A slow ischemia or malnutrition (rapid = necrosis / apoptosis), denervation, reduced workload, decreased hormonal stimulation, compression, aging, and cytokines like TNF

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11
Q

What are some physiologic examples of atrophy?

A
  1. Embryologic structures - i.e. destruction of notocord
  2. Postpartum uterus
  3. Postmenopausal endometrium - loss of hormone
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12
Q

What are some pathologic examples of atrophy?

A
  1. Limb muscle atrophy after spinal trauma - disuse and denervation
  2. Cerebral atrophy - from reduced blood flow / aging
  3. Skeletal muscle atrophy in starvation
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13
Q

How does atrophy occur to reuse cellular components?

A
  1. Ubiquitin pathway - degradation of proteins in the proteasome
  2. Autophagic vascuoles - digestion of larger organelles in autophagolysosomes with lipofuscin left behind
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14
Q

What is fatty infiltration?

A

Filling of tissues with fat deposits to compensate for loss of cellular size / number (in the event atrophy is accompanied by apoptosis / necrosis)

**This is DIFFERENT than fatty CHANGE

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15
Q

What is the definition of metaplasia?

A

Replacement of one mature cell type by another

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16
Q

What typically causes metaplasia?

A

Chronic tissue trauma / irritation which leads to signals by cytokines / growth factors to change transcription in stem cells (i.e. basal cells of epithelium) and differentiate to new cell type

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17
Q

Give two types of epithelial metaplasia?

A
  1. Columnar to squamous -> common in respiratory tract of smokers
  2. Squamous to columnar -> common in lower esophagus of GERD patients, columnar epithelium as in gastric / intestinal glands is better able to handle the acid
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18
Q

What is the example of connective tissue metaplasia?

A

Skeletal muscle -> bone after trauma, calsed myositis ossificans

Since they are both derived from mesoderm

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19
Q

What is heterophagy?

A

One of the normal functions of lysosomes, occurs in professional phagocytes like neutrophils and macrophages

-> endocytosis of extracellular material and fusion with lysosomes to break down the debris and possible present antigens

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20
Q

What is autophagy and when does it occur?

A

Process occurring in most cells which allows for survival in nutrient deprivation

-> moving intracellular material into autophagic vacuoles and forming autophagolysosomes

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21
Q

Give an example of abnormal lysosome function.

A 
Enzymatic dysfunction (acquired or inherited) which leads to excess accumulation of lysosomal contents and cellular injury
-> Lysosomal storage disorders like Gaucher's disease
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22
Q

What can lead to upregulation of smooth ER in hepatocytes?

A

Alcohol and barbiturates (like phenobarbital) which are potent inducers of the CYP system -> lead to increased processing of any other CYP-modifying drugs

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23
Q

Under what conditions are the number of mitochondria quantitatively altered?

A
  1. Cellular hypertrophy -> increased number

2. Cellular atrophy -> decreased number (generate energy / save proteins)

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24
Q

Give an example of an inherited and acquired alteration of microtubules?

A
  1. Inherited -> primary ciliary dyskinesia

2. Acquired -> i.e. drug induction via colchicine

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25
Q

What happens to intermediate filaments in alcoholic hepatitis?

A

They form abnormal aggregates which disrupt cytoskeletal function

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26
Q

What are three ways in which things can accumulate within cells?

A
  1. Cellular reaction rate imbalances -> absorption / production exceeds elimination
  2. Defects in cellular reactions -> altered synthesis, metabolism, or transport
  3. Lack of metabolic / secretory pathways
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27
Q

Give three etiologies of triglyceride accumulation in liver?

A
  1. Starvation - increased fatty acid uptake from adipose
  2. Kwashiorkor - protein malnutrition leads to decreased apoprotein synthesis and decreased VLDL export
  3. Alcohol abuse, diabetes, obesity, hypoxia -> alteration of production or removal
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28
Q

What is steatosis? How does it appear grossly and under the microscope?

A

Fatty change - i.e. triglyceride buildup (NOT fatty infiltration)

Grossly - enlarged, greasy, and yellow liver

Microscopic - clear on H&E, with cytoplasmic vacuoles within the hepatocyte parenchyma. Can displace the nucleus to the periphery if vacuoles are large enough.

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29
Q

How does cholesterol appear grossly and under the microscope?

A

Grossly - yellow discoloration
Microscope:
1. Foam cells -> large round cells with clear “bubbly” cytoplasm
2. Extracellular crystalized cholesterol esters

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30
Q

Where can foam cells be seen? Give a few examples.

A
  1. Atherosclerotic plaques
  2. Xanthomas - usually subcutaneous masses often seen in hyperlipidemia (mentioned in genetics of familial hypercholesterolemia)
  3. Sites of necrosis with inflammation
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31
Q

What is cholesterolosis?

A

Accumulation of cholesterol in subepithelium of gallbladder, seen often with gallstones

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32
Q

How do protein aggregates appear on the microscope? When can they be seen?

A

Variably sized, pink eosinophilic inclusions in the cytoplasm.

  1. Can be seen in renal tubular epithelial cells in proteinuria (reabsorbed here)
  2. Plasma cells with Russell bodies -> normally stain basophilic, but may appear pink with high Ig production
  3. alpha-1 antitrypsin mutation in liver leads to accumulation
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33
Q

How does glycogen appear on H&E and how can it be definitively told apart from cholesterol / TAGs?

A

Small, clear, cytoplasmic vacuoles

-> can be told apart by periodic acid schiff stain for carbohydrates

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34
Q

Give two examples of what would cause glycogen accumulation?

A
  1. Diabetes mellitus -> counterintuitive

2. Glycogen storage disease -> i.e. Pompe’s

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35
Q

Give the two exogenous pigments which persist in phagolysosomes which cannot be degraded?

A
  1. Carbon

2. Tattooing pigments (dermal macrophages)

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36
Q

What is anthracosis?

A

Blackening of the lung due to inhalation of carbon dust, with black macrophages in lungs and hilar lymph nodes
-> common in coal miners

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37
Q

What is lipofuscin? Where is it seen in the microscope? Is it endogenous / exogenous?

A

Wear-and-tear pigment from subcellular membrane lipid peroxidation / protein remnants which cannot be digested in the autophagolysosome.

All pigments made in the body are endogenous

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38
Q

Where is lipofuscin found?

A

Seen near the nucleus**, finely granular, yellow-brown, only in LONG-LIVED cells like cardiomyocytes and neurons, but NOT macrophages / neutrophils which have a rapid turnover.

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39
Q

Where is melanin found? What is it?

A

Brown-black pigment made by melanocytes, can be phagocytosed by keratinocytes or macrophages

-> can be found in liver in melanoma

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40
Q

How is bilirubin made?

A

Red pulp macrophages eat aged RBCs. Heme component has Fe portion recycled by transferrin, and porphyrin ring is converted to biliverdin (green pigment).

Biliverdin -> unconjugated bilirubin, relatively water insoluble, still in macrophage.

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41
Q

How is bilirubin transported?

A

Unconjugated bilirubin is bound to albumin and transported in plasma

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42
Q

How is bilirubin excreted?

A

Hepatocytes conjugate bilirubin via glucuronidation, and bilirubin is excreted through bile canaliculi and ultimately the common bile duct into the gall bladder.

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43
Q

What factors can increase serum unconjugated bilirubin?

A
  1. Increased RBC destruction i.e. hemolytic anemia
  2. Hepatocyte dysfunction decreasing conjugation - i.e. genetic errors of UGT activity, or acquired hepatocyte injury from virus / alcohol
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44
Q

What factors can increase serum conjugated bilirubin?

A
  1. Hepatocyte dysfunction decreasing secretion of bilirubin

2. Cholestasis - due to obstruction leading to decreased bilirubin secretion

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45
Q

What are some things that can cause intrahepatic / extrahepatic cholestasis?

A

Intrahepatic - metastases of the liver, destruction of bile ducts, cirrhosis, etc

Extrahepatic - Gall stones stuck in bile duct (choledocholithiasis), malignancies pushing on bile duct (i.e. pancreatic cancer), etc

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46
Q

What causes jaundice and scleral icterus?

A

Increased plasma levels of bilirubin, conjugated or unconjugated

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47
Q

How does bilirubin appear as a pigment under the microscope? How to distinguish from lipofuscin?

A

A green to golden-brown pigment. Although it can be brown and near the nucleus at times, typically it is found in the bile ducts / bile canaliculi, and is much more globular in appearance (lipofuscin is very granular)

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48
Q

What is hemosiderin and how is it made?

A

A pigment made from aggregation of ferritin micelles which are enveloped by lysosomes and degraded into low bioavailability substance

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49
Q

What is ferritin and how does it aggregate?

A

Ferritin is the storage form of iron used to protect the cells from ROS which iron can make. Aggregates when there is too much iron, which normally is moved from transferrin into the cell. Iron is acquired from breaking down RBCs.

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50
Q

How does iron excess happen and what are a few pathologic mechanisms?

A

The only iron we lose each day is from desquamation, so if we have a long period of iron excess we will have hemosiderin problems.

Mechanisms:

  1. Increased dietary absorption of iron
  2. Parenteral iron excess from blood transfusions
  3. Degradation of hemoglobin by macrophages in localized hemorrhage or hemolytic anemias
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51
Q

How does hemosiderin appear under the microscope, and how is it told apart from carbon?

A

Coarsely granular, rusty-orange to brown, cytoplasmic pigment

Prussian blue stain -> granules stain deep blue (carbon will not change)

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52
Q

What serum test is directly proportional to the body’s total iron stores?

A

Circulating serum ferritin (NOT transferrin)

53
Q

What is transferrin saturation? What is the normal amount?

A

Serum iron levels (variable) divided by iron binding capacity (level of transferrin)

Normally, about 1/3 of transferrin iron-binding sites are filled

54
Q

What is hyaline change?

A

A smooth, pink tissue appearance in H&E due to accumulation of protein depositions.

It is NOT a diagnosis, just a histological description of going on.

55
Q

What are the two types of hyaline change? Give examples of each.

A
  1. Intracellular - i.e. Alcoholic hyalin building up in hepatocytes due to intermediate filament breakdown. Or Russell bodies in plasma cells.
  2. Extracellular - i.e. collagen in areas of longstanding injury, amyloid deposits, and thickened basement membranes
56
Q

What is the most common causative mechanism of depletion of ATP in a cell? What factors can cause this?

A

Decreased oxygen availability.

  1. Ischemia (most common)
  2. Decreased oxygenation of blood from respiratory / heart failure
  3. Decreased oxygen carrying capacity of blood due to anemia or CO poisoning
57
Q

What is ischemia and its major direct consequences?

A

Decreased blood flow to a tissue or organ.

Consequences:

  1. Hypoxia
  2. Decreased supply of nutrients
  3. Decreased removal of waste products
58
Q

What are the deleterious cell reactions which can occur with a depletion of ATP?

A
  1. Increased H20 / Na in cell -> Decreased function of Na/K ATPase
  2. Drop in cellular pH leading to chromatin clumping -> glycolysis / fermentation
  3. Influx of Ca+2 -> failure of Ca+2 ATPase
  4. Abnormal protein synthesis -> loss of RER integrity
59
Q

What things can cause an increased cytosolic Ca+2?

A
  1. Decreased activity of Ca+2 ATPase due to ATP depletion

2. Increased membrane permeability of subcellular or plasma membranes (often MAC or complement deposition)

60
Q

Why is accumulation of cytosolic calcium bad?

A

It increases activity of numerous intracellular enzymes with a variety of activities.

  1. ATPases -> further deplete ATP
  2. Phospholipases -> further degrade membranes
  3. Proteases -> degrade structural proteins including cytoskeleton
  4. Endonucleases -> breakdown of DNA
61
Q

Other than depletion of ATP and increases in intracellular calcium, what is one additional mechanism of cellular injury / death?

A

Generation of Free Radicals

62
Q

What factors increase the number of ROS in or around a cell?

A
  1. Aerobic oxidative respiration
  2. Ionizing radiation - source of hydroxyl radical
  3. Drug / toxin metabolism
  4. Neutrophil activation
63
Q

What enzymes are responsible for detoxifying superoxide anion, hydrogen peroxide, and hydroxyl radical?

A

Superoxide anion: SOD - superoxide dismutase

Hydrogen peroxide: Catalase and glutathione peroxidase

Hydroxyl radical: glutathione peroxidase

64
Q

What are two other mechanisms by which the cell is protected from ROS?

A
  1. Antioxidants like vitamins A, C, and E (A & E in the membrane because they are lipid-soluble, C in the cytoplasm as it’s water-soluble)
  2. Iron and copper-binding proteins
65
Q

What structures due ROS typically damage?

A
  1. Lipids - via peroxidation of plasma + subcellular membranes
  2. Proteins - alteration + degradation
  3. DNA
66
Q

What organelle is really bad to injure and how does this happen?

A

Mitochondria - via activation of Ca+2 dependent intracellular enymes and free-radical mediated damage

67
Q

What can happen when mitochondria are damaged?

A
  1. Decreased production of ATP -> further damage
  2. Increased permeability of membrane -> loss of membrane potential
  3. Escape of cytochrome c into cytosol -> apoptosis
68
Q

What is thought to be the absolute breaking point of cellular damage where it becomes irreversible?

A

Lysosomal membrane injury -> release and activation of numerous lytic enzymes into cytoplasm

69
Q

What are some causes of ischemia?

A
  1. Arterial occlusion
  2. Venous obstruction
  3. Severe hypotension (reduces blood flow due to decreased blood pressure)
70
Q

What determines the extent of the ischemic injury for a cell? Is ischemia typically better or worse than just hypoxia?

A

Particular cell type’s vulnerability, as well as severity + duration of hypoxia.

Ischemia is worse than hypoxia because it also decreases availability of glycolytic substrates and stops waste removal.

71
Q

What is atrophy vs reversible cellular injury?

A

Atrophy -> decreased metabolic requirements of cell to balance the reduced oxygen supply

Reversible cellular injury -> more rapid than atrophy, leads to depletion of ATP and subsquent Na+ and H20 influx which leads to cellular swelling and decreased function. However, you can come back from this.

72
Q

What causes irreversible cellular injury?

A

Persistent or more severe hypoxia which leads to degradation of cellular membranes and DNA, mitochondrial and lysosomal damage

73
Q

What are myelin figures?

A

Ultrastructural membrane formations which are very characteristic of necrotic cell death

74
Q

What is reperfusion injury and its main mechanism?

A

Exacerbation of ischemia cell damage after blood flow is restored to the area, primarily due to production of oxygen free radicals (ETCs were saturated with electrons before oxygen rapidly came in)

75
Q

What is an example of direct cellular toxicity by a chemical?

A

Cyanide inhibits oxidative phosphorylation by binding cytochrome c oxidase

76
Q

What is the mechanism of carbon tetrachloride toxicity (CCl4)?

A

CCl4 is metabolized by CYP450s in the liver to make CCl3 radical, which starts the lipid peroxidation of membranes in the cell.

  • > decreases RER protein synthesis in liver, leading to apoprotein deficiency and fatty change of liver
  • > also damages mitochondria / cellular membranes leading to cellular death longterm
77
Q

What is the cellular swelling of reversible cellular injury called? Is this always apparent?

A

Hydropic change or vacuolar degeneration

-> not always apparent morphologically, when injurious agent is mild / short lived

78
Q

How does hydropic change appear grossly, microscopically, and on EM?

A

Grossly - organ will be pale & heavy

Microscopically - cells enlarged with pale / clear cytoplasm (like lipid / glycogen inclusions -> distinguish with PAS)

Electron microscopy - cell surface blebs, distended mitochondria / ER

79
Q

What is a reversible cellular injury morphology which is common in heart and liver? What causes it?

A

Fatty change

  • > due to ER injury, decreases protein synthesis (i.e. apoprotein)
  • > intracellular accumulation of fat
80
Q

How does fatty change appear microscopically?

A

As cytoplasmic lipid vacuoles

81
Q

What is the first thing to go away during cellular injury?

A

Cell function (followed by biochemical alteration)

82
Q

Does physiological necrosis occur?

A

No - it is always pathologic

83
Q

How does the appearance of the cytoplasm change in necrosis and why?

A
  1. Increased eosinophilia
    - > RNAase degradation from lyosomes
    - > Decreased pH due to lactic acidosis
    - > denatured proteins accumulate
  2. Dense, clumped, irregular appearance
    - > decreased glycogen which normally gives cell a granular appearance
    - > disrupted cytoskeleton from enzymatic activation
84
Q

What are the three types of nuclear change which occur in necrosis?

A
  1. Karyolysis - fading of nuclear chromatin
  2. Karyorrhexis - nuclear fragmentation
  3. Pyknosis - nuclear condensation and shrinkage
85
Q

What causes the nuclear changes in necrosis?

A

Decreased pH -> clumping of chromatin

Activated lysosomal enzymes -> DNAses

86
Q

What frequently surrounds areas of necrosis?

A

Host inflammatory response, including PMNs and MACs

87
Q

What are the ultrastructural changes in necrosis?

A

Myelin figures, membrane disruptions, and amoprhous intracellular debris

88
Q

Does necrosis persist indefinitely?

A

No, ultimately areas of necrosis will undergo enzymatic degradation and phagocytosis by immune system

89
Q

What is the type of necrosis present in most tissues? What is its cause?

A

Coagulation necrosis = infarcation

  • > cause is hypoxia / ischemia in ALL tissues
  • > hypoxia / ischemia will NOT cause coagulative necrosis in the CNS, however
90
Q

What is the microscopic morphology of coagulative necrosis?

A

Initial preservation of tissue architecture, with eosinophilic ghost cellular remnants / structural outlines intact

91
Q

What are the causes of liquefactive necrosis? What is the exception?

A
  1. Pyogenic bacterial infections with acute inflammatory infiltrate, and release of WBC lysosomal enzymes which enzymatically digest tissue.
  2. Exception - caused by hypoxia / ischemia in CNS due to high lipid content and a small amount of PMNs
92
Q

What is the microscopic morphology of liquefactive necrosis? Example?

A

Focal loss of tissue architecture -> replacement by cellular debris and inflammatory cells (i.e. neutrophils)

Example: Abscess

93
Q

What is wet vs dry gangrene?

A

Dry - peripheral ischemia of extremities
-> coagulative necrosis

Wet - progression from dry, in which ischemic tissue becomes infected
-> liquefactive necrosis

94
Q

What is caseous necrosis?

A

The necrosis in the center of a granuloma, which is formed by Th1 cells and macrophages
-> i.e. TB and histoplasmosis

95
Q

What is the microscopic morphology of caseous necrosis? How is it distinguished from coagulative?

A

Focal loss of cellular architecture, replacement with eosinophilic amorphous debris. Area will be surrounded (but not infiltrated) by macrophages and lymphocytes

From coagulative -> will have a ring of cells around it and the cells’ normal “ghost” outline will not be there

96
Q

What is fat necrosis and where does it typically occur?

A

Necrosis from inappropriate release and activation of pancreatic lipases, leading to breakdown of membranes / intracellular TAGs to free fatty acids + MAGs.
-> leads to saponification (soap formation) of calcium bound to free fatty acids

-> typically occurs in pancreas (acute pancreatitis)

97
Q

What is the gross and microscopic appearance of fat necrosis?

A

Gross - white, chalky patches of fatty on pancreas usually

Microscopic - hazy, basophilic outlines of adipocytes with acute inflammation associated.
-> looks like coagulative necrosis + basophilic hue from the calcium

98
Q

What is fibrinoid necrosis?

A

Deposition of abundant fibrin due to vascular injury from disorders such as immune-mediated vasculitis or malignant hypertension

99
Q

Where does fibrinoid necrosis normally appear, and what does it look like under the microscope?

A

Normally appears around blood vessels (small arteries, arterioles, or capillaries)

Has a smudged, hyper-eosinophilic appearance to necrotic areas

100
Q

What do elevated tropinins mean?

A

There is an increase in permeability of membranes of cardiomyocytes
-> sensitive detection of myocardial injury / coagulative necrosis for 1-2 weeks

101
Q

Which liver enzyme is elevation is most specific for liver injury and why?

A

Alanine aminotransferase - ALT

Aspartate aminotransferase is present in other tissues as well

102
Q

What marker, when elevated, means there is necrosis of tissue SOMEWHERE?

A

Elevated lactate dehydrogenase (LD)

103
Q

What enzymes tend to e elevated in acute pancreatitis?

A

Amylase and lipase

104
Q

What are the two primary differences between apoptosis and necrosis?

A
  1. Apoptosis is not associated with inflammation, whereas necrosis always is
  2. Apoptosis can be physiologic or pathologic, whereas necrosis is always pathologic
105
Q

What are some physiologic uses for apoptosis?

A

Deletion of lymphocytes that recognize self

Loss of hormonal / growth factor stimulation (i.e. regression of lactating breast, along with atrophy)

embryologic structures

106
Q

What are some pathologic mechanisms / causes of apoptosis? What is ER stress?

A

Viral infections -> kill virus-infected cell (normal thing, but occurs in pathology)

Irreparable DNA damage following radiation / chemo “genotoxic stress”

Accumulation of misfolded proteins which cell cannot refold in time “ER stress”

107
Q

What is the mechanism by which cytotoxic T cells induce apoptosis?

A

If they detect foreign antigen on MHC Class 1:

Use perforins to open up the cell, which mediates entry of granzymes.

Granzymes activate caspases and also Bid protein, which stimulates cytochrome C release from mitochondria

108
Q

What are the two general pathways of apoptosis? Are they interconnected? Which caspases mediate them?

A
  1. Intrinsic - mitochondrial-initiated pathway - mediated by caspase-9
  2. Extrinsic - death receptor-initiated pathway - mediated by caspase-8

They are both interconnected. I.e. death receptor pathway can induce activation of intrinsic pathway.

109
Q

What are the first steps in induction of the intrinsic pathway?

A

Sensor proteins are activated due to stressors like DNA damage or excessive misfolded proteins.

Pro-apoptotic proteins like BAX and BAK replace anti-apoptosis protein BCL-2 in mitochondrial membrane
-> increasing mitochondrial membrane permeability

110
Q

What occurs once mitochondrial membrane permeability has been increased in the intrinsic apoptosis pathway?

A
  1. Cytochrome c is release into the cytosol
  2. Cytochrome c forms a complex into the “apoptosome”
  3. Apoptosome activates caspase 9, which neutralizes other inhibitors of apoptosis
  4. Caspase 9 activates cascade of additional caspases into execution phase
111
Q

What is the main mechanism of the extrinsic apoptosis pathway?

A

FasL on T-cells binds Fas receptor on cell to die.

  1. Binding of FasL
  2. Fas receptors cross-link
  3. Binding of Fas-associated death domain (FADD) adaptor protein
  4. Activation of Caspase 8 and executioner caspases
112
Q

What do caspases do in the execution phase?

A

They are proteases which rapidly, sequentially activative other caspases

  1. Degradation of cytoskeleton and matrix
  2. Endonuclease activation - specific internucleosome DNA cleavage sites (can be seen as a ladder on gel electrophoresis)
113
Q

How are cell membranes modified in apoptosis and what is the purpose of this?

A

Phosphatidylserine becomes expressed on the outside rather than interior of cells

  • > enhanced macrophage recruitment and phagocytosis
  • > efficient removal of apoptotic cell without inflammation
114
Q

How can apoptosis be seen on morphology?

A

Cells are often hard to find and coexist with necrosis

  • > rounded, condensed, hypereosinophilic cell which is reduced in size, with peripherally compacted nuclear chromatin
  • > will form dense, membrane-bound apoptotic bodies
115
Q

What type of death pathway does TNF binding usually trigger?

A

Caspase-8-mediated death receptor-dependent cell death (extrinsic pathway)

116
Q

What is necroptosis? Can it be physiologic?

A

Programmed cell death with features of apoptosis and ultimately necrosis

Yes, it is a mechanism which can be active physiologically

117
Q

Why does the necroptosis pathway exist?

A

If the caspase-8 pathway is inhibited (i.e. by a pathogen evasion mechanism or a tumor mutation), apoptosis will still occur via necrosis

-> necrosome causes metabolic alterations and necrotic cell death via decreased ATP and increased ROS

118
Q

What is pyroptosis? What cell types does it usually occur in?

A

A form of programmed cell death in which one cell sacrifices for the good of all, leading to massive cytokine release and immune recruitment

Usually in macrophages and dendritic cells

119
Q

How does pyroptosis work and what cytokines are involved?

A

Microbial infections / certain tissue damage results in activation of inflammosome, leading to release of IL-1 and IL-18 via Caspase-1 mediated pathway.

120
Q

What is the relative activity of telomerase in somatic, stem, and germ cells?

A

Germ cells - total activity

Stem cells - partial activity

Somatic cells - no activity - senescence after a finite number of divisions (Limited proliferative capability)

121
Q

What is cumulative nonlethal cellular energy? What factors contribute?

A

A determinant of aging

  • > repetitive damage by oxygen derived free radicals from Ox-Phos
  • > Repeated damage and decreased repair of DNA
  • > Decreased normal folding of proteins / accumulation of misfolded proteins
122
Q

What are the two major types of pathologic calcification and which is most common? Which one is associated with abnormal serum calcium levels? Which will produce tissue dysfunction?

A
  1. Dystrophic - most common, associated with tissue damage / necrosis. Much more likely to cause tissue dysfunction
  2. Metastatic - associated with abnormally high serum calcium
123
Q

What is the pathogenesis of dystrophic calcification?

A

In cell injury / necrosis, there is increased membrane permeability. Extracellular vesicles form which bind calcium, and calcium pours into the cell.

  • > phosphate binds intracellular and extracellular calcium
  • > development of calcium phosphate crystals in and around necrotic tissue (i.e. bicuspid aortic valve)
124
Q

What is the pathogenesis of metastatic calcification? Causes?

A 
Increased serum calcium levels leads to systemic deposition of calcium salts
Causes include:
-> excess PTH leading to bone resoprtion
-> lytic skeletal disorders
-> increased vitamin D activity
125
Q

What tissues are more susceptible to metastatic calcification?

A

Normal organs with alkaline interstitium (calcium precipitates in basic conditions)

  • > places which secrete acids
  • > stomach, kidneys, lungs
126
Q

How do calcifications appear grossly?

A

Hard, white foci

127
Q

How do calcifications appear under the microscope?

A

Basophilic particulate material

128
Q

What are two unique variants of dystrophic calcification?

A
  1. Psammoma bodies - circular, onion-like concretions with concentric layering
  2. Ectopic bone - i.e. myositis ossificans

Pathobiology (20 decks)

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