Exam 1 Flashcards

1
Q

What does necrotic tissue look like under the microscope?

A
  • eosinophilia (cells stain bright pink)
  • pyknosis (nuclear shrinking + basophilia)
  • karyorrhesis (fragmentation of pyknotic nucleus)
  • karyolysis (loss of some DNA)
  • nuclei are lost
  • cell fragmentation
  • high neutrophil recruitment
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2
Q

Coagulation necrosis

A
  • associated w/ severe ischemia - best appreciated in solid organs - ghost-like remnants of intact cells w/o nuclei
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3
Q

Liquefactive necrosis

A
  • associated w/ bacterial infections and BRAIN ISCHEMIA - bacteria release enzymes which cause abscess (collections of pus)
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4
Q

Caseous necrosis

A

Associated w/ granuloma (dead cells in center of granulomatous cell reaction [multi-nucleated, giant “angry” macrophages])

Necrotic tissue is white/ friable, resembling cheese curds

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5
Q

Enzymatic fat necrosis

A
  • associated w/ focal death in pancreas/ adjacent fat cells (acute pancreatitis) - enzymes from damaged cells digest adipose cells - fatty acids combine w/ Ca2+ forming yellow/white insolable soaps
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6
Q

Gangrene

A
  • coagulative necrosis of the bowel, gall bladder or an extremity - wet = w/ infection (+liquefactive); dry = w/out infection
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7
Q

What type of cells dominate in acute inflammation? In chronic inflammation?

A
  • neutrophils - macrophages
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8
Q

Chemotaxis

A
  • unidirectional movement of leukocytes along a chemical gradient, towards an injury site - key for transmigration
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9
Q

Local clinical manifestations of inflammation

A

Rubor, Calor, Dolor and Tumor

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10
Q

Key interleukin of acute inflammation

A

IL-8; produced by innate immune cells; stimulates bone marrow to increase maturation, proliferation and release of PMNs.

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11
Q

Myeloperoxidase

A

Major enzyme in a granule that is used as a killing mechanism by leukocytes use at injury site.

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12
Q

Scale of severity for acute inflammation

A

SEROUS- least severe [aka transudate] –> pressure w/o endothelial opening (fluid leak only) FIBRONOUS- intermediate SUPPURATIVE/ABSCESS- most severe [aka exudate] –> hydrostatic pressure + endothelial opening (fluid + protein leakage) ULCERATIVE- special category

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13
Q

Left shift

A

When neutrophil populations shift to more immature precursors because the body is trying to quickly pump out neutrophils (as opposed to giving them time to mature). Indicates infection/inflammation.

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14
Q

NETS

A

PMN chromatin laden w/ granules, used to trap bacteria and fungi

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15
Q

Characteristics of chronic inflammation

A
  1. predominance of M1s, lymphocytes and plasma cells 2. collateral tissue damage 3. repair processes occurring in parallel w/ persistent inflammation
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16
Q

Chronic high levels of inflammatory cytokines cause…

A

(1) Increased rates of hepatic production of defense proteins (2) Increased hepcidin production (which thereby decreases Fe2+ in blood leading to anemia) (3) Increased growth factor for platelets and monocytes

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17
Q

Granulomatous Inflammation

A

Distinct form of chronic inflammation associated with persistent T-cell activation. Seen with TB, macrophage ingestion of foreign bodies and sarcoidosis/IBD.

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18
Q

Acute phase reactants

A

Biochemical changes which are the reflection of hepatic protein adjustments to inflammation (ex. decreased albumin as liver increases formation of defense proteins)

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19
Q

C-reactive protein

A

Liver produced factor closely linked to IL-6 levels which can be used to indirectly assess intensity of inflammation. Obesity can give a false positive.

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20
Q

Cell classifications

A

(1) LABILE- continuously divide [skin epithelium, gut, hematopoietic] (2) STABLE- divide when stimulated [ex. liver] (3) PERMANENT- non-dividing [cardiac, neural, skeletal]

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21
Q

Granulation tissue

A

IMMATURE PRE-SCAR Specialized tissue that fills defects in organs when non-regenerative cells or connective tissue framework is destroyed. Proliferative fibroblasts lay immature connective tissue elements.

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22
Q

Organization

A

MATURE SCAR The process of transforming granulation tissue into dense scar

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23
Q

Important cells of skin lac healing

A
  1. macrophages- remove debris
  2. fibroblasts- produce matrix
  3. myofibroblasts- contract wound
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24
Q

Hyperemia vs Congestion

A

HYPEREMIA: Active process of arteriolar dilatation and increased blood flow. Tissue appears redder. CONGESTION: Passive process of impaired outflow of venous blood from a tissue. Tissue appears “red-blue” color.

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25
Hemostasis
A series of regulated processes that maintain blood in a liquid state and prevents uncontrolled bleeding.
26
Virchow's Triad in Thrombosis
27
Types of Embolism
1. Fragments of thrombi 2. Amniotic fluid (enters placental membranes) 3. Air (gas) 4. Fat/marrow (soft tissue crush injury/ long bone injury)
28
What does protein C deficiency do?
Deficiency in protein C causes a hypercoagulative state because protein C is a zymogen whose active form works to counter different coagulative factors.
29
The 2 basic components of all neoplasias (benign and malignant)
1. **PARENCHYMA**- the actual neoplastic cells 2. **​STROMA-** supporting cells (connective tissue, blood vessels, immune cells, etc.)
30
Teratoma
Rare tumors which contain cells from multiple germ layer origins
31
Mixed tumors
Cells which come from one germ layer but can diverge to multiple cell types (ex. salivary gland capable of epithelial and myoepitheial differentiation)
32
Key cell morphology of benign neoplasms
Cells can range from well differentiated to dysplastic. Never penetrate the basement membrane.
33
Dysplasia
Disorderly architecture of a neoplasm. Altered cell cytology. No penetration of the basement membrane. Often occurs in metaplastic epithelium. Reversible. Full thickness dysplasia → Carcinoma In-situ
34
Cell morphology of malignant neoplasms
1. Vary from differentiated to anaplastic 2. Pleimorphic 3. Abnormal nuclear morphology (high N/C ratio; hyperchromatic; prominent nuclei)
35
Anaplasia
Cells that have changed so they don't look like they did originally. Loss of differentiation.
36
Pleimorphism
Variation in size and shape of cells or their nuclei
37
Lymphatic spread is typical of what type malignant neoplasms?
Carcinomas
38
Hematogenous spread is typical of what type of malignant neoplasm?
Sarcomas
39
p53
* Key cell regulator that puts a stop to cyclins (the workhorses driving the cell cycle) when there is an issue in the replication or DNA of a cell. * **​Most commonly mutated gene in cancers**
40
RAS
* Most common proto-oncogene in human tumors * Normal active RAS stimulates downstream regulators of proliferation * Mutant RAS loses ability to be turned off so it is constantly sending signals to cyclins, pushing through the cell cycle.
41
Li-Fraumemi Syndrome
Pts inherit one defective p53 so it only takes knocking out one more to cause cancer. 25x risk of cancer by age 5.
42
What does Rb normally do?
It normally guards the transition from G1 to S via E2F
43
Key anti-apoptotic genes
BCL-2; BCL-XL
44
Key pro-apoptotic genes
BAX, BAK (Intrinsic); Fas death receptor (extrinsic)
45
E-cadherins
Mediate adhesion of epithelial cells. Functional loss facilitates detachment of cells from primary tumor and use of collaganse to break through basement membrane, allowing for metastasis.
46
Key inhibitors and inducers of angiogenesis
**​INDUCER:** ​VEGF **INHIBITOR:** TSP-1
47
Two main types of carcinogens and examples
1. **Direct acting** require no metabolic conversion; carcinogenic by themselves (ex. alkylating agents) 2. **Indirect acting** ​require metabolic conversion; partially genetics based (ex. cigarette smoke)
48
Principles of radiation carcinogenesis
* long latent period * radiation initiation is irreversible * continue exposure is additive
49
HTLV-1
Virus which infects T-cells, causing polyclonal proliferation and neutralizing growth inhibitory signals. Can lead to T-cell leukemia/lymphoma.
50
Methods used by neoplasms to avoid immune surveillence
1. Failing to express HLA class I and escaping CTL attack 2. Eliminating strongly immunogenic subloclones 3. Suppressing host immune response (ex. expressing FasL, thereby inducing immune cell apoptosis) 4. Producing a thicker coat of glycocalyx molecules, thereby blocking access to immune cells.
51
Cancer cachexia
Loss of body fat, lean body mass, weakness, anorexia and anemia. Mediated by neoplasia produced cytokines.
52
Paraneoplastic syndrome
Symptom complexes notreadily explained by local or distant spread of neoplasms. (ex. ACTH secretion by small cell lung carcinoma)
53
Important tumor associated markers
AFP→ liver carcinomas, gonadal tissues CEA → Colon, pancreas, lung, stomach, breast carcinomas _Both used for surveillance, not primary diagnosis_
54
Grading of Cancer
Based on cytologic differentiation of tumor. **Estimates agressiveness** based on degree of differentiation, pleomorphism, loss of normal architecture and mitotic index. Well differentiated= low grade; poorly differentiated= high grade Most clinically useful for prostate cancer and chondrosarcoma
55
Staging of Cancer
**The most clinical valuable way to assess cancer progression** (except for with prostate cancer and chondrosarcomas). Based on size (T1-4) , spread to LN's (N0-3), and metastasis (M0 or 1). TNM system stages 0-IV
56
What is the relationship between hypoxia, sodium and cell damage? Hypoxia and calcium?
Hypoxia means that there will be no O2​ to be used to accept electrons so you will lack ATP. ATP is needed to fuel the Na+/K+ pump. W/o this pump, Na+ will build up within the cell and water will follow, causing swelling and cell damage. THe calcium pump is fueled by the same ATP mechanism causing calcium build-up and causing calcium to activate enzymes which it normally wouldn't, causing cell damage.
57
Key hallmark of reversible cell injury?
**Cellular swelling** (loss of microvilli, membrane blebbing, swollen RER, etc.)
58
Key hallmark of irreversible cell injury?
Membrane damage
59
The 3 components found in granulation tissue
1. Capillaries (brings nutrients) 2. Fibroblasts (secretes collagen-- type III collagen is intially secreted and later is converted to type I when mature scar is formed) 3. Myofibroblasts (contracts wound)
60
What is the cofactor collagenase uses when removing type III collagen and replacing it with type I during scarring?
Zinc
61
Dehissance
When a closed wound reopens
62
What type of collagen characterizes a keloid?
Type III collagen
63
Lactate and Cell Injury
A loss of ATP during hypoxic cell injury causes the cells to switch to anaerobic cell respiration (due to the lack of ATP needed for aerobic). Anaerobic cell respiration leads to a build-up of lactate and a state of metabollic acidosis as a result.
64
Reperfusion and free radicals
The rush of blood to site of ischemia during reperfusion can lead to the production of oxygen derived free radicals. This, paradoxically, can lead to further cell injury.
65
Acidophilic bodies are often a sign of what type of cell?
Apoptotic
66
Inflammasome
* Formed from DAMPS/PAMPS * Multi-protein complex defined by activation of _caspase 1_ * _​_​Cleavage of IL-1 to active form sets the inflammatory cytokines in action
67
What is one of the key factors in making capillaries leaky during inflammation?
Damaged tissues release histamineS
68
What are the 2 types of necrosis associated with the pancreas?
Liquefactive necrosis (when the pancreas breaks itself down with its own enzymes) and enzymatic fat necrosis (when pancreatic enzymes break down surrounding fat)
69
Key mediator of apoptosis
Caspases (enzymes) They activate proteases (break down cytoskeleton) and endonucleases (break down DNA)
70
Cytochrome C and apoptosis
Cytochrome C activates caspases, thus turning on apoptosis. Normally Cytochrome C is trapped in mitochondria and held there by _Bcl2_ which is stabilizing the mitochondria.​ Bcl2 is knocked out when there is so stimulus which will result in apoptosis (DNA damage, hormone changes, etc.), allowing for caspases to leak out.
71
Hemotoxylin
Basic dye which binds to acids (like DNA)
72
Eosin
Acidic dye which binds bright pink to proteins (like those found in cytoplasm)
73
Gram Stain Stains bacteria background yellow/ positive purple and pink
74
Periodic acid-Schiff (PAS) Stains fungi and glycogen background light pink/ positive magenta
75
Grocott methenamine silver stain (GMS) stains fungi background green/ postive black
76
Acid Fast Stains mycobacteria, actinomyces background blue/ positive red
77
IHC Immunohistochemical stain Antibodies combine with enzyme and produce a color when bound to certain antigens Background negative blue/ positive brown and red
78
Steps to neutrophil entering interstitial space
1. Marginalization 2. Rolling 3. Adhesion 4. Transmigration
79
Key cytokines for ending inflammation
IL-10, TGF-B
80
Sarcoma vs Carcinoma
S: Malagnancy of mesenchymal tissue (ex. bone, cartilage, fat etc.) C: Epithelial tissue (breasts, lung, stomach, etc.)