Pathology Flashcards
0
Q
What is hypertrophy and what are three examples?
A
An increase in the size of cells.
- Physiologic enlargement of uterus during pregnancy
- Chiseled physique of a weightlifter
- Cardiac enlargement occurring with hypertension or aortic valve disease
1
Q
What is the definition of hyperplasia and what are three examples?
A
An increase in the number of cells.
- Hormonal - proliferation of glandular epithelium of female breast at puberty and during pregnancy
- Compensatory - residual tissue grows after removal or loss of part of an organ (regeneration of liver)
- BPH
2
Q
What is atrophy and what are three examples?
A
Shrinkage in the size of cell by loss of cell substance.
- Immobilization of limb to permit healing of a fracture
- Loss of hormone stimulation in menopause
- Denervation
3
Q
What is metaplasia and what are three examples?
A
Reversible change in which one adult cell type is replaced by another.
- In smokers - normal ciliates columnar epithelial cells of lung replaced by stratified squamous
- In chronic gastric reflux - normal stratified squamous of lower esophagus replaced by gastric or intestinal type columnar epithelium
- In soft tissues - in foci of injury
4
Q
What are the different causes of cell injury?
A
Oxygen deprivation Chemical agents - can derange osmotic environment Infectious agents Immunologic reactions (autoimmune and allergic reactions) Genetic factors Nutritional imbalances Physical agents Aging
5
Q
What are the 3 nuclear change seen morphologically in necrosis?
A
- Karyolysis - basophilia of chromatin my fade (cell is redder)
- Pyknosis - nuclear shrinks into solid, shrunken mass, increased basophilia
- Karyorrhexis - pyknotic nucleus undergoes fragmentation
6
Q
How can you recognize coagulative necrosis and where does it happen?
A
Eosinophilic anucleate cells persist
Characteristic of infarcts in all solid organs except the brain.
7
Q
How can you recognize liquefactive necrosis and where does it occur?
A
Tissue becomes liquid viscous mass.
Seen in purulent infections.
Seen in focal bacteria or fungal infections.
8
Q
How can you recognize gangrenous necrosis and where does it occur?
A
Dry or wet gangrene
Seen in a limb, particularly lower leg.
9
Q
How can you recognize caseous necrosis and where is it found?
A
Frothy yellow-white appearance of the area. A collection of fragments or lysed cells with amorphous granular pink appearance on H&E.
characteristic in granulomas.
10
Q
How can you recognize fat necrosis and where is it found?
A
Grossly visible chalky white areas. Basophilic calcium deposits.
Seen typically with release of pancreatic lipases.
11
Q
How can you recognize fibrinoid necrosis and where is it found?
A
Bright pink amorphous appearance.
Seen in immunologically mediated diseases like polyarteritis nodosa.
12
Q
What are the four principal targets and biochemical mechanisms of cell injury?
A
- Mitochondria and their ability to generate ATP and ROS under pathological conditions
- Disturbance in calcium homeostasis
- Damage to cellular (plasma and lysosomal) membranes
- Damage to DNA and misfolding of proteins
13
Q
What are the functional consequences of ATP depletion during cell injury?
A
- tissues with greater glycolytic capacity (like liver) better able to survive
- activity of pm ATP dependent Na pumps is reduced –> intracellular accumulation of sodium and efflux of potassium –> cell swelling
- increase in anaerobic glycolysis –> intracellular glycogen stores rapidly depleted and lactic acid accumulates
- failure of ATP dependent calcium pumps –> influx of calcium
- prolonged leads to structural disruption of protein synthetic apparatus
14
Q
How do mitochondria respond to and mediate cell injury?
A
Failure of oxidative phosphorylation leads to less ATP and eventually necrosis, abnormal OP leads to formation of ROS
15
Q
What are the major consequences of elevated intracellular calcium levels during cell injury?
A
Activates phospholipases --> membrane damage Proteases --> breakdown proteins Endonucleases ATPases --> faster depletion Caspases
16
Q
What do cells use to limit effects of reactive oxygen species?
A
Superoxide dismutases
Glutathione peroxidases
Catalase
Endogenous or exogenous antioxidants
17
Q
What are the three mechanisms through which ROS cause cell damage?
A
- Lipid peroxidation of membranes
- Cross linking and other changes in proteins
- DNA damage
18
Q
What are some examples of apoptosis under pathological conditions?
A
Accumulation of misfolded proteins leading to ER stress
Pathologic atrophy in parenchymal organs after duct obstruction
19
Q
What is the intrinsic pathway of apoptosis?
A
Sensors of Bcl2 family are activated and in turn activate Bax and Bak, dimerize and form pore in mitochondria, cytochrome c leaks out forms apoptosome with AFAP that activates caspase 9.
bcl2 and Bcl-Xl antagonize Bax and Bak and block apoptosis
20
Q
What is the extrinsic pathway of apoptosis?
A
Death rectors are members of TNF receptor family, fas molecules cross linked by fasL on activated T cells and bind adaptor proteins via death domain that activate caspase 8 (can then activate proapoptotic Bid)
21
Q
What are some examples of intrinsic apoptosis?
A
Growth factor deprivation
DNA damage
ER stress from misfolded protins
Apoptosis of self reactive lymphocytes
22
Q
What is an example of extrinsic apoptosis?
A
Apoptosis of self reactive lymphocytes
Cytotoxic T cell mediated apoptosis
23
Q
What are the circumstances and morphological appearance of fat accumulations in cells?
A
- abnormal accumulation of triglycerides in parenchymal cells
- seen most in liver but also in heart, skeletal muscle, kidney, and other organs
- cells have larger vacuoles
24
What are the circumstances and appearance of cholesterol accumulations in cells?
- phagocytic cells may become overloaded with lipid
| - atherosclerosis
25
What are the circumstances and morphological appearance of protein accumulations in cells?
- seen in kidney
- pink hyaline cytoplasmic droplets
- excess presented to cells or they synthesize too much
26
What are the circumstances and morphological appearance of glycogen accumulations in cells?
- seen in liver
- frothy appearance
- abnormalities in metabolism of glucose or glycogen
- diabetes leads to it in renal tubular epithelium, beta cells of islets, and cardiac myocytes
27
When and where does carbon pigment happen?
Blacken draining lymph nodes and pulmonary parenchyma
| Air pollutant of urban life
28
What and where does lipofuscin pigment happen?
Brownish yellow appearance
Accumulations in many tissues especially heart, liver, and brain
Function of age or atrophy
Not injurious but marker of past free radical injury
29
When and where does melanin pigment happen?
Brown black pigment synthesized by melanocytes in epidermis
Adjacent basal keratinocytes can also accumulate it
Protective against uv radiation
30
When and where does hemosiderin happen?
Hemoglobin derived golden yellow to brown
Accumulate in tissues with local or systemic excess of iron
Small amounts normal in mononuclear phagocytes of bone marrow, spleen, and liver
31
What is dystrophic calcification and what is an example?
Deposition of calcium in dead or dying necrotic tissues
Serum calcium levels normal
Seen in aorta, large arteries, and aortic valves
End product is formation of crystalline calcium phosphate
32
What is metastatic calcification?
Can occur in normal tissues with hyercalcemia
Serum calcium is increased
Caused by excess parathyroid hormone, destruction of bone, vitamin d related disorders, and renal failure
33
What are the three phases of wound healing?
Inflammation
Epithelialization and formulation of granulation tissue
Tissue remodeling (maturation and scar contraction)
34
What is malformation?
Intrinsically abnormal developmental process, usually multifactorial, risk for recurrence
35
What is a malformation syndrome?
Recurring pattern of malformation with single underlying cause
Ex: chromosomal abnormality or single genetic mutation
36
What is disruption?
Secondary destruction of an organ or body region that was previously normal from an extrinsic disturbance, happens later in gestation
Ex: amniotic bands, viral infections, vascular accidents, maternal diabetes
37
What is deformation?
Extrinsic disturbance of development
| Ex: compression of growing fetus
38
What is a sequence?
Multiple congenital anomalies that result from secondary effects of a single localized abnormality, sporadic or multifactorial inheritance
Ex: oligohydramnios where fetus doesn't produce enough urine and is compressed
39
What is symmetric growth restriction and what causes it?
Brain is reduced in size with other organs
| Causes are intrinsic to developing fetus - chromosomal abnormalities and fetal infections
40
What is asymmetric growth restriction and what causes it?
Brain retains normal size relative to other organs
| Cause - compromise of uteroplacental blood supply
41
What are the two ways an infection can reach the placenta or amniotic sac?
Ascending infections - more common, enter through vagina and cervix
Hematogenous infections - enter through maternal bloodstream transplacental
42
What is acute chorioamnionitis?
Ascending infection from vaginal flora or enteric bacteria
43
What are the two mechanisms that incite an acute inflammatory response?
1. Danger signals recognized by pattern recognition receptors on phagocytes, dendritic cells, and epithelial cells
2. Microbial products, dead cells, and urate crystals activated inflammasome which activates caspase 1 which cleaves IL-1 which recruits inflammatory cells
44
What are the five cardinal signs of acute inflammation?
```
Hot
Red
Swollen
Painful
Loss of function
```
45
Which three cardinal signs of acute inflammation do changes in blood vessels cause?
Redness
Heat
Swelling
46
Which two changes occur during the vascular response in acute inflammation?
1. Vasodilation - relaxation of smooth muscle walls and sphincter of precapillaries opens new capillary beds --> increased blood flow called hyperemia
2. Increased vascular permeability - protein rich plasma escapes into interstitial space, caused by contraction of endothelial cells from inflammatory mediators or direct injury
47
What are three roles of lymphatics in acute inflammation?
1. Remove fluid exudate, leukocytes, cell debris, plasma proteins and fibrin
2. Serve as conduit for dendritic cells delivering foreign antigen to lymph nodes
3. Carry inflammatory mediators away from inflammatory site
48
What are the mediators in the vascular response to acute inflammation?
```
Vasoactive amines (histamine and serotonin)
Plasma proteases
Arachidonic acid derivatives (prostaglandins and leukotrienes)
```
49
What does histamine do in the acute inflammatory response?
From mast cells, dilates blood vessels by relaxing smooth muscle wall and stimulates endothelial cells to contract
50
What 3 things cause the release of histamine?
1. Trauma or exposure to heat or other injurious stimuli
2. Binding of IgE to Fc receptors on mast cells in hypersensitivity reactions
3. C3a and C5a fragments induce mast cell degranulation
51
When is serotonin released and what does it do during acute inflammation?
Effects similar to histamine, released from platelets by PAF synthesized by activated endothelial cells
52
What three systems in plasma produce mediators that increase vascular permeability?
Kinin
Fibrinolytic
Complement
53
What triggers the kinin and fibrinolytic systems and what activates it?
Hageman factor 12 - activated when in touch with a negative surface (glass or collagen)
54
What does bradykinin do during acute inflammation?
```
Increase vascular permeability
Causes vasodilation
Induces pain
Causes bronchoconstriction
Stimulates arachidonic acid metabolism
```
55
What does plasmin do during acute inflammation?
Digests fibrin in clot to form split products that increase vascular permeability
Cleaves kininogens to form bradykinin
Activates complement system by cleaving C3
56
What four things is the complement system and important effector mechanism for?
1. Mediation of vascular response through histamine release
2. Chemotaxis of neutrophils
3. Opsonization
4. Directly causing damage
57
What are the different things C3a and C5a do?
3 - mucous secretion
| 5 - binds to phagocytes to increase adherence to endothelium, neutrophil chemotaxis and respiratory burst
58
Which two ways is arachidonic acid metabolized?
Cyclooxygenase pathway to prostaglandins
| 5-lipoxygenase pathway to leukotrienes
59
What do prostaglandins do in acute inflammations and which ones specifically do it?
PGD2 PGE2 and PGF2 produce vasodilation, increase vascular permeability and produce pain and fever
60
What does leukotriene B4 do?
Chemo tactic factor for neutrophils, macrophages, and other inflammatory cells
61
What are the cysteinyl leukotrienes and what do they do?
C4 D4 and E4 - increase vascular permeability and contract smooth muscle to cause bronchoconstriction, vasoconstriction, and stimulation of mucous secretion
62
What are three ways other than mediators that vascular permeability is affected during acute inflammation?
1. Neutrophils secrete toxins that damage endothelial lining
2. VEGF forms channels through endothelial cells by fusion of intracellular vesicles
3. New vessels formed are immature and lack tight junctions so they are leaky
63
How do neutrophils roll?
P and E selectins on endothelial cells and L selectin on neutrophils upregulated, weak binding between sialylated oligosaccharides and mucin-like glycoproteins on cell surfaces allows blood flow to dislodge neutrophil and make it roll
64
How does adhesion of neutrophils happen?
Activation by chemokines causes integrins on leukocytes to cluster and change to high affinity form, bind ICAM1 and VCAM on endothelial cells (upregulated by IL1 and TNF
65
What do neutrophils do to get through the basement membrane during diapedesis?
Digest it by secreting proteases
66
What are some important chemo tactic factors for neutrophils?
Leukotriene B4
Chemokines
C5a
Bacterial products
67
What is the timing of neutrophils and monocytes in acute inflammation?
Neutrophils dominate in first 6-24 hours
| Monocytes most abundant 24-48 hours
68
What are the most common causes of leukocyte dysfunction?
Patients with bone marrow suppression
Neutrophils in pAtients with chronic renal failure have low integrin levels
Diabetics neutrophils function poorly
69
What are four rare inherited diseases caused by neutrophil dysfunction?
1. Leukocyte adhesion deficiency type 1 (LAD1) - defective synthesis of integrin subunit
2. Leukocyte adhesion deficiency type 2 (LAD2) - defect in fucose metabolism leads to absence of oligosaccharide on leukocytes that binds to selectins
3. Defects in microbial activity- in chronic granulomatous disease there is defect in ROS generation
4. Defects in phagolysosome formation
70
What are important mediators in the cellular response of acute inflammation?
Cytokines (IL1 and TNF alpha) and chemokines
ROS
nitric oxide
Lysosomal enzymes
71
What are three important functions of nitric oxide in the inflammatory response?
1. Cytotoxic agent in activate macrophages
2. Produces vasodilation at inflammatory site
3. Inhibits platelet activation and limits recruitment of leukocytes
72
What do lysosomal enzymes do to the lung?
Chronic low grade inflammation results in destruction of elastin and loss of normal elastic recoil of pulmonary parenchyma to produce emphysema
73
What are three outcomes of acute inflammation?
1. Complete resolution
2. Progression to chronic inflammation - leads to resolution or scarring
3. Scarring or fibrosis - fibrin itself can promote fibrosis
74
What are the features of serous inflammation?
Fluid containing low levels of proteins (transudate)
| Seen in body cavities or blisters
75
What are the features of fibrinous inflammation?
Fibrinogen escapes into tissue or onto serosal surfaces, polymerizes to form fibrin, layer of protein rich exudate can form adhesions between parietal and visceral layers, can form thickened white scars over serosal surfaces
76
What are the features of suppurative inflammation?
Exudate with large numbers of neutrophils, typically produces necrosis and abscess ensues, mononuclear cells and fibroblasts produce fibrous capsule, after exudate removed capsule contracts and a fibrous scar remains
77
What is the definition of an ulcer?
When inflammation occurs near an epithelial surface and destroys epithelium, underneath infiltrated by neutrophils and surface covered with fibrinopurulent exudate
78
What cell types are present during chronic inflammation?
```
Macrophages
Lymphocytes
Angioblasts
Fibrosis
(Plasma cells)
```
79
What are two key differences in the features of chronic inflammation as opposed to acute?
May not be painful
| No prominent vascular component
80
What are four things that can cause chronic inflammation and what are examples of each?
1. Infectious agents - tb or fungi like histoplasmosis
2. Foreign bodies - silicone, inhaled particles, splinters, hair, sutures and talc
3. Products of metabolism - cholesterol excess can lead to formation of xanthomas, urate crystals in hyperuricemia form nodule called a tophus
4. Immune reactions - production of autoantibodies is in RA
81
What is the definition of granulomatous?
Adjective describing chronic inflammation with activated or epithelioid macrophage or giant cells, may not contain granulomas
82
What is the definition of a granuloma?
Granulomatous inflammation organized into a circle, surrounded by fibroblasts and collagen
83
What is granulation tissue?
Tissue under a scab, loose connective issue and new blood vessels growing into fibrin over the wound
84
What are the roles of macrophages activated by the classical and alternative pathways?
Classical - macrophages adept at killing organisms through secretion of lysosomal enzymes ROS and NO
Alternate - important in healing response as they secrete growth factors for angiogenesis and fibroplasia
85
What are acute phase proteins and what are six examples?
Any protein whose plasma concentration increases or decreases by at least 25 percent during an inflammatory episode
Positive (increase) - fibrinogen, serum amyloid A, C-reactive protein)
Negative (decrease) - albumin, transferrin, insulin growth factor 1
86
How are acute phase proteins synthesized?
By liver in response to elevated TNF, IL1, and IL6 produced at inflammatory site
87
What are some functions of acute phase proteins?
C reactive aids in elimination of infecting organisms, down regulate inflammatory response
88
How does elevated serum fibrinogen increase erythrocytes sedimentation rate?
Excess fibrinogen binds to erythrocytes resulting in their aggregation and leading to more rapid sedimentation
89
How does fever contribute to the healing inflammatory response?
Increasing mobility of leukocytes
Enhancing phagocytosis
Increasing proliferation of T cells
Compromising survival of temp sensitive pathogens
90
What is leukocytosis and a leukomoid response?
Elevated WBC count
Release of immature neutrophils causes a left shift and extreme elevation (from 4,000-10,000 to 40,000-100,000) resembles leukemia = leukomoid response
91
What key processes happen during the inflammation stage of wound healing?
Blood clot releases inflammatory mediators
PDGF activates and attracts macrophages and fibroblasts
Neutrophils infiltrate
Monocytes infiltrate in response to TGF beta
M2 macrophages transform into reparative - express colony stimulating factor 1, TNF alpha, and PDGF
92
What happens during epithelialization of wound healing?
Epidermal cells migrate into tissue separating superficial scab from underlying viable tissue - route dictated by integrins on surface - secrete collagenase to clear pathway rough fibrin clot
93
What cell types are active during formulation of granulation tissue?
Macrophages - secrete growth factors for the other two
Fibroblasts - parallel to wound, forms collagen and elastin
Angioblasts - forms capillaries perpendicular to wound
94
When does granulation tissue reach its peak?
5 days after injury
95
How does tissue remodeling happen during wound repair?
Fibroblasts assume myofibroblast type
| In time fibroblasts and capillaries apoptose and leave white collagenous scar
96
What controls degradation of collagen during scar formation?
Matrix mellanoproteinases
97
What is the difference between healing by first intention and by second intention?
First - resolution or repair of uninfected wound whose edges apposed with sutures or surgical glue
Second - occurs in gaping wound like ulcer of burn, myofibroblasts important here to contract scar
98
In what situations is wound healing compromised?
```
Wound is septic
Vitamin c deficiency - collagen synthesis impaired
Steroids
Mechanical stress
Foreign bodies
Diabetes
Vascular disease
Exuberant granulation tissue can block epidermal cells migrating into wound
```
99
What is a keloid?
Dramatic raised scars
| Contain atypical fibroblasts that deposit excessive amounts of collagen, fibronectin, elastin, and proteoglycans
100
What are labile cells?
Divide constantly throughout life to replace lost cells, spend little time in G0
101
What are stable cells? And what are three examples?
Remain in G0 for extended periods but can enter mitotic cycle if stimulated
Fibroblasts, endothelial cells, and smooth muscle cells
102
What are permanent cells? What are two examples?
No known capacity to divide
| Neurons and cardiac myocytes
103
What is the ECM and what is its role in wound repair?
Matrix between cells and basement membrane
Glycosaminoglycans link to proteins to form proteoglycans and fibrous proteins that include collagen, elastin, fibronectin, and laminin
Hyluronan and other proteoglycans allow diffusion of nutrients and signaling molecules - prolong and localize mediators
104
What are mutations in fibrillin 1's roles in Marfans?
Fibrillin 1 is ECM glycoprotein critical for formation of elastin fibers, also binds to TGF beta and sequesters it in ECM - increased levels in elastin rich tissues which leads to low grade inflammation
105
What medicine is used in Marfans and how?
Losartan - blocks angiotensin II receptor and lowers TGF beta levels
