Path Week 1: Cell Adaptation, Injury, And Cell Death

Front 1

Morphology

Back 1

The appearance of organs, tissues, and/or cells on a gross, microscopic, and ultrastructural level.

Front 2

Etiology

Back 2

The agent or agents that initiate a chain of events, ultimately causing disease. Intrinsic (genetics) or extrinsic (acquired).

Front 3

Pathogenesis

Back 3

Mechanisms (chain of events) connecting the etiology (cause of disease) and the disease itself.

Front 4

4 types of cellular adaptation

Back 4

Hyperplasia
Hypertrophy
Atrophy
Metaplasia

Front 5

Hyperplasia

Back 5

More cells than there should be. Often associated with hypertrophy but not same thing. Since involved cell division, only cells which undergo cell division can undergo hyperplasia (ergo not permanent cells).

Front 6

Different cell types according to replication

Back 6

Labile - Always in cell cycle making new cells.
Stable - Not constantly dividing but can make new cells.
Permanent - Incapable of cell division, uve got all ur gonna get.

Front 7

Types of physiological hyperplasia and examples

Back 7

Hormonal - Breast epithelium during puberty/pregnancy
Compensatory - Regrowing liver.

Front 8

Pathologic Hyperplasia and example.

Back 8

Usually due to excess hormonal stim or GF influence. Often associated with increased risk of neoplasia.
Ex. endometrial hyperplasia caused by imbalance of estrogen/progesterone.

Front 9

Hypertrophy

Back 9

Increase in cell size not due to swelling. Associated with increased risk of neoplasia

Front 10

Causes of phisiological hypertrophy and examples

Back 10

Hormonal stimulation - Estrogen effect on uterine smooth muscle in pregnancy.
Increased functional demand - skel muscle.

Front 11

Pathologic Hypertrophy example

Back 11

Myocardial hypertrophy - Changes in signal transduction lead to changes which are adaptive at first but become pathologic.

Front 12

Atrophy

Back 12

Decrease in cell size due to loss of cellular components other than water. Often associated with apoptosis.

Front 13

Physiologic atrophy examples

Back 13

Embryonic structures (notocord, thyroglossal duct)
Post partum myometrium
Endometrium in menopause

Front 14

Causes of pathologic atrophy

Back 14

1) Workload reduction
2) Loss of innervation
3) Loss of blood supply
4) Inadequate nutrition
5) Aging
6) Pressure (like a tumor pushing up against other cells).

Front 15

Atrophy Mechanisms

Back 15

Decrease in protein synthesis with an increase in protein degradation (via lysosomes and proteases)

Front 16

Metaplasia

Back 16

Reversible change where one cell type becomes another. It is named after the new cell type. Cells dont acutally morph; stem cells just start producing a new cell type due to change in signals (cytokines, GF, ECM components ect).

Front 17

What type of metaplasia is:
1) Smoking
2) Barretts esophagus
3) Duct obstruction
4) Vitamin A deficiency

Back 17

Smoking = Squamous metaplasia
Barrett = Columnar metaplasia
Duct obstruction = squamous metaplasia
Vit A deficiency = squamous metaplasia.

Front 18

Connective tissue metaplasia examples

Back 18

Myositis ossificans - soft tissue undergoes metaplasia into bone.

Front 19

Necrosis

Back 19

Cell death often due to hypoxia leading to:
1) Cell Swelling
2) Protein denaturation
3) Organelle breakdown
4) Random breakdown of nucleic acids

Front 20

Apoptosis

Back 20

Programmed cell death leading to:
1) Cell shrikage
2) Formation of apoptotic bodies
3) Ordered breakdown of nucleic acids

Front 21

Necrosis vs Apoptosis (Cell size, Nucleus, Plasma membraine, Cellular contents, Adjacent inflamation, physiologic or pathologic)

Back 21

Necrosis = Swelling . Apoptosis = Shrinkage
Necrosis = Karyolysis/pyknosis/karyorrhexis . Apoptosis = Fragmentation into nucleosome sized fragments (pyknosis or karyorrhexis)
Necrosis = plasma membrane disrupted . Apoptosis = intact but altered structure
Necrosis = enzymatic digestion, may leak out of cell . Apoptosis = intact, may be released in apoptotic bodies.
Necrosis = adjacent inflammation frequent . Apoptosis = Not
Necrosis = always pathologic . Apoptosis physiologic or pathologic

Front 22

5 intracellular systems most vulnerable to to injury

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1) Aerobic respiration
2) Cell membrane integrity
3) Protein synth
4) Cytoskeleton
5) Genetic integrity

Front 23

Depletion of ATP consequences

Back 23

1) No Na+ pump > influx of Na+ and water (and efflux of K+) > cell swells (as do ER).
2) Increase in anarobic glycolysis > decrease in glycogen and increase in lactic acid > decrease in pH > clumping of chromatin
3) Detachment of ribosomes > decrease in protein synth and lipid deposition.
4) Calcium pumps fail > increase in intracellular calcium > activation of damaging enzymes
5) Proteins undergo misfolding leading to unfolded protein response.

Front 24

What can cause irreversible mitochondrial damage and what does it lead to?

Back 24

1) Increased intracellular calcium
2) Oxidative stress
3) Breakdown of phospholipids

Leads to expression of a mitochondrial permeability transition (MPT) causing leakage of protons and cytochrome C screwing up oxphos.

Front 25

What happens when calcium levels become elevated in a cell?

Back 25

Enzymes become activated:
-Phospholipases damage membranes
-Endonucleases damage DNA
-Proteases damage proteins
-ATPases decrease ATP stores resulting in more calcium influx enhancing the effect.

Front 26

What are free radicals and what are their effects

Back 26

Highly reactive, autocatalytic molecules with an unpaired electron. Cause:
1) Lipid peroxidation - leads to membrane damage
2) Oxidative protein dmg - causes degredation of critical enzymes
3) DNA damage - causes single stranded breaks possibly related to aging and cancer.

Front 27

How can one inactivate a radical

Back 27

1) Antioxidants (vit A, E, ascorbic acid, glutathione)
2) Binding reactive molecule (like a transition metal) to a transport protein to prevent redox reactions
3) Chemical modification via enzymes (catalase, superoxide dismutase, glutathione peroxidase).

Front 28

Causes of free radical formation

Back 28

1) Normal redox Rxs
2) Redox Rxs involving transition metals
3) NO can act as a free radical
4) Absorbtion of radiant energy
5) Enzyme mod. of endogenous chemicals

Front 29

3 main causes of membrane permeability defects

Back 29

Decreased ATP, activation of phospholipases, cytoskeleton damage via proteases.

Front 30

2 major types of reversible cell injury the characteristics of reversible cell injury

Back 30

Can be either swelling or fatty change.
Tissue has pallor, increased turgor, and increased weight.

Front 31

Characteristics of of irreversible cell injury

Back 31

Extensive plasma membrane damage, lysosomal swelling, mitochondrial vacuolization.

Front 32

Pkynosis, Karyolysis, Karyorrhexis

Back 32

Types of nuclei of necrotic cells:
Karyolysis - Blue nucleus fades to pink losing basophilia.
Pyknosis - Shrinkage and increase basophilia (blueness) of nucleus (also seen in apoptosis).
Karyorrhexis - Fragmentation of a pyknosis nucleus (also seen in apoptosis).

Front 33

Coagulative necrosis

Back 33

Most common kind in general and during ischemia.
Firm Texture
LM: -loss of cytologic detail
-retains basic cell outline
-retains tissue architecture.

Front 34

Liquefactive necrosis

Back 34

Typical necrosis of CNS and certain infections.
Viscous mass due to complete digestion of cells
LM: -loss of cytologic detail
-loss of basic cell outline
-loss of tissue architecture

Front 35

Caseous necrosis

Back 35

Typical of tuberculosis.
Cheese like.
LM: -loss of cytologic detail
-retention of basic cell outline
-loss of tissue architecture.

Front 36

Gangrenous necrosis

Back 36

Coagulative necrosis of a big chunk of tissue due to aschemia:
Dry gangrenous necrosis - coagulative necrosis of tissue that has lost its blood supply.
Wet gangrenous necrosis - Same as previous but has also been secondarily infected, converting it into liquefactive necrosis.

Front 37

Fat Necrosis

Back 37

Coagulative necrosis of fat cells that have developed calcium deposits.

Front 38

Fibrinoid necrosis

Back 38

Typical of vascular immune Rxs with complexes deposited in walls of arteries making them look like fibrin.

Front 39

Reverseible hypoxic injury

Back 39

Leads to decreased aerobic respiration causing reduced ATP and the following results:
1) Influx of Na and water
2) Stimulation of glycolysis decreasing pH, causing nuclear chromatin clumping
3) Detachment of ribosomes from rough RER decreasing protein synth
4) Dispersion of cytoskeleton causing reduction of microvilli and bleb formation
5) Membrane injury leading to myelin figures
6) Swelling of mitochondria and RER

Front 40

Irreversible hypoxic injury

Back 40

2 main features:
1) Permanent mitochondrial dysfunction and inability to turn oxphos back on.
2) Loss of cell membrane integrity disallowing separation of internal mileu and external environment.

Front 41

Reperfusion Injury

Back 41

In a setting of ischemia, is increased injury after bloodflow is restored. Caused by new free radicals, cytokines, and inflammatory cells entering the wounded region causing additional damage.

Front 42

Chemical injury mechs

Back 42

2 general mechanisms:
1) Direct action to a critical molecular component or organelle
-Mercury poisoning
-cyanide
-chemo drugs
2) Metabolism of drug to a toxic metabolite
-Acetaminophen OD
-carbon tetrachloride poisoning

Front 43

Physiologic Apoptosis examples

Back 43

1) Embryogenisis
2) Hormone dependent involution in adults (ex. ovaries post menopause, breasts post breastfeeding)
3) Cell deletion in a proliferating cell pop (crypt cells in intestine)
4) Neutrophil death in inflammation
5) Deletion of self reactive T cells
6) Death induced by cytotoxic T cells

Front 44

Pathologic Apoptosis examples

Back 44

1) Cell death from DNA damaging stimuli
2) Cell death in certain viral diseases
3) Cell death in organs with duct obstruction
4) Cell death in neoplasms
5) Cell death in other processes that may also induce necrosis (the process).

Front 45

Morphology of apoptosis

Back 45

1) Cell shrinkage
2) Chromatin condensation
3) Formation of surface blebs that pinch off into apoptotic bodies
4) Phagocytosis of apoptotic bodies
5) Maintenance of cell membrane integrity until late part of process
6) Absence of inflammatory response

Front 46

Biochemistry of apoptsis

Back 46

1) Protein cleavage by caspases
2) Ordered DNA breakdown
3) Expression of phosphotidyl serine on outer membrane signaling non-inflammatory phagocytosis

Front 47

Extrinsic Apoptosis Initiation

Back 47

Initiated via engagement of cell surface death receptors which have a cytoplasmic death domain (ex. fas and fas ligand).

Front 48

Intrinsic Apoptosis Initiation

Back 48

Initiated by a withdrawal of survival factors (GHs, hormones), or application of certain injurious stimuli.
Mitochondria expresses more pro-apoptotic genes and less anti-apoptotic genes. This increases mito. membrane permeability causing proteins like cytochrome c to activate caspases in cytoplasm.

Front 49

Decreased Apoptosis and disease

Back 49

Malignant neoplasms and autoimmune disorders (lack of t cell pruning)

Front 50

Increased Apoptosis and disease

Back 50

Neurodegenerative disorders, ischemic injury, death of virus infected cells.

Front 51

Steatosis

Back 51

When TGs and cholesterol accumulate in heart, liver, kidney, muscle due to toxins, protein malnutrition, diabetes mellitus, obesity, or anorexia.

Front 52

What causes steatosis in liver and heart

Back 52

Liver:
-Alcohol
-Carbon tetra chloride
-protein malnutrition
-Starvation
Heart:
-Hypoxia

Front 53

Pathologic accumulation of cholesterol examples

Back 53

-Athrosclerosis
-Xanthomas
-Foamy macs in necrosis
-Cholesterosis
-Type C Niemann-Pick disease.

Front 54

2 methods of protein accumulation and examples

Back 54

1) Exceeding catabolic activity of the cell. (ex Reabsorbtion droplets in proximal tubule, russell bodies in chronic inflamation).
2) Defect in protein folding (trypsin deficiency, amyloidosis).

Front 55

Unfolded protein response

Back 55

Initially leads to increased chaperone production and decreased protein translation.
If unfolded proteins continue to accumulate, leads to apoptosis via caspase activation.

Front 56

Endogenous pigment examples

Back 56

1) Lipofuscin
2) Melanin
3) Hemosiderin
4) Bilirubin

Front 57

Lipofuscin

Back 57

Endogenous pigment. Looks brown, granular. Telltale of free radical injury and lipid peroxidation. Also known as the wear and tear or aging pigment. Seen in liver and heart of elderly as well as malnourished people or people with cancer cachexia.

Front 58

Melanin

Back 58

Endogenous pigment. Brown-black pigment.

Front 59

Hemosiderin

Back 59

Endogenous pigment. Golden yellow to brown, granular or crystalline. Formed in the breakdown of hemaglobbin and is the major storage form of iron. Lots of it is seen in hemachromatosis and hemosiderosis

Front 60

Bilirubin

Back 60

Endogenous pigment. Yellow green. Hemoglobbin derrived, non iron containing, found in bile. Leads to color of jaundice.

Front 61

Morphology of calcification

Back 61

Fine white granuals, hard.
Microscopically appears basophilic granuals, sometimes clumped.

Front 62

Dystrophic Calcification

Back 62

Occurs in dying tissue despite normal calcium levels/metabolism. Is initiated by the calcium buildup in the mitochondria of dying cells.

Front 63

Metastatic calcification

Back 63

Occurs in living tissue and is due to hypercalcemia usually due to problem with calcium metabolism. Can be caused by:
^PTH secretion
-destruction of bone (bone tumors or paget disease)
-Vitamin D disorders
-Renal failure

Front 64

Hyaline Change

Back 64

Is a Morphologic Descriptor implying homogenous, glassy, eosinophilic microscopic appearance. Can be intracellular or extracellular. Examples include:
-Reabsorbtion dropletts and Russell bodies.
-old scars
-amyloidosis
-Arterial walls in HTN/DM

Front 65

3 enzymes which inactivate radicals

Back 65

1) Catalase
2) Superoxide Dismutase (SOD)
3) Glutathione Peroxidase

Front 66

What would cause a strawberry appearance in a gall bladder?

Back 66

Lipid deposition

Front 67

Russel Body

Back 67

Expanded eosinophilic ER of a plasma cell caused by Ig synthesis in chronic inflammation. Is a mech of protein accumulation in a cell.

Front 68

Reabsorbtion Droplet

Back 68

Caused by increased protein in the epithelial cells of the proximal tubules during excessive protein catabolic activity. Look granular and eosinophilic. Is a mech of protein accumulation in a cell.

Front 69

Diseases with misfolded protein problems

Back 69

A1 antitrypsin deficiency
CF
Familial hypercholestermeia
Parkinsons/huntingtons
Amyloidosis

Front 70

Types of diseases which cause glycogen accumulation

Back 70

diabetes and storage diseases.