Exam 2 Flashcards
1
Q
Parenchyma
A
Normal functioning tissue
“Resident cells” - cells that are supposed to be in that area
EX) hepatic cells in liver
2
Q
Stroma
A
Structural framework within tissue
“Stromal”
-structure/framework of cells “scaffolding”
3
Q
Fibroblasts
A
CT cells that form collagenous matrix
- secrete collagen
- -white fiber (protein)
- -very strong
- -supports tissue
4
Q
Cell Classification (based on regenerative ability)
A
Labile cells
Stable cells
Permanent (fixed) cells
5
Q
Labile Cells
A
Regenerate throughout our lifetime
EX) epithelial cells
- highly mitotic
- continuous replicators
only thing that will stop it is overcrowding
-called contact inhibition
6
Q
Stable Cells
A
Stop dividing when growth ceases, but are capable of regeneration if properly stimulated. For these cells to regenerate properly, the underlying structural framework must be intact.
EX) liver cells
- conditional replicators
- will under mitosis ONLY if everything is intact
7
Q
Permanent (fixed) Cells
A
Cells that are unable to divide
EX) muscle cells (heart after MI) and neurons
- NO ABILITY to undergo mitosis
- cannot replenish them
8
Q
Two ways to heal injured tissue
A
Regeneration
- when tissue is replaced from parenchyma cells
- “best case scenario”
Repair
- when fibrous scar tissue fills in gap left by damaged tissue
- “next best thing”
9
Q
Regeneration
A
Process in which damaged cells are replaced with parenchymal and normal structure, and normal function is restored.
10
Q
2 Requirements for Regeneration
A
- The injury must not be too severe
- The tissue must be mitotic (labile or stable)
MUST HAVE BOTH!
11
Q
Repair
A
When the injury is too severe OR the tissue is not mitotic, the parenchymal tissue will be replaced with fibrous connective tissue replacing structure, but sacrificing function
12
Q
Revascularization
A
Whether healing occurs through regeneration or repair, the blood vessels in the area need to be restored. (replace blood vessels when they are lost during injury)
Angiogenesis
New capillaries formed from vessels adjacent to wound.
Dividing endothelia cells form buds or cords that extend into damaged area that eventually meet forming anastomoses
13
Q
Angiogenesis
A
Growing new blood vessels
- normal process, happens every day
- important to growth of tumors
14
Q
Healing Within the Skin
A
- Reepithelialization - replacement of epithelium
- New epithelial cells divide near damage
- New cells move to denuded area
- Cells secrete a new basement membrane as they migrate
- Cells then get anchored to membrane
- Dividing cells now move up towards surface of tissue
- contact inhibition tells them to stay
- overgrowth of epithliod causes large, uprised scar
15
Q
Nervous Tissue Repair
A
Cannot Replace Neurons!
- CNS (Brain and Spinal Cord)
- PNS
16
Q
CNS (nervous tissue repair)
A
If soma intact, some axonal regeneration may begin to occur. However, after 14 days, glial cells form scar tissue that blocks further regeneration.
No function is restored.
- neuroglial cells prevent regeneration
- could cause “rewiring” of brain
17
Q
PNS (nervous tissue repair)
A
If soma and schwann cells are intact, axonal regeneration may occur
18
Q
Factors Affecting Wound Healing
A
Age Nutrition Presence of infection Hormones Blood Supply Size of wound Presence of foreign bodies
19
Q
Age (factors affecting wound healing)
A
YOUNG: increase capacity for repair, but lack reserves for repair combined with an ignorant immune system
OLD: decreased cell replacement potential, decreased immune system
20
Q
Nutrition (factors affecting wound healing)
A
Decreased proteins and fibroblasts prolong the inflammatory phase
Fats: needed for new cell membranes
Carbohydrates: provide energy to leukocytes
Vitamins: C for collagen synthesis
21
Q
Presence of Infection (factors affecting wound healing)
A
Impairs the healing process
- wound contamination
- impaired leukocyte function function (diabetes, certain medications)
22
Q
Hormones (factors affecting wound healing)
A
Corticosteroids decrease capillary permeability, impair phagocytosis, and inhibit fibroblast function, all of which impairs inflammation and healing
23
Q
Blood Supply (factors affecting wound healing)
A
Poor blood supply may result from swelling, cardiovascular disease, etc.
Oxygen necessary for collagen synthesis
Necessary to remove debris and waste
24
Q
Size of Wound (factors affecting wound healing)
A
Suturing greatly enhances healing process
25
Presence of foreign bodies (factors affecting wound healing)
Wood, metal, glass, sutures
26
Acquired Immunity
adaptive/specific immunity
- adapts to pathogen every time it encounters one
- developed over lifetime
27
Specificity
Reacts to specific substances
-Antigen, Pathogen
28
Antigen
Molecule that elicits an IR (immune response)
ex) allergies
29
Epitope
Binding site on antigen
| -spot on antigen that immune system can react with
30
Pathogen
disease causing agent
31
Memory
Long-term retention
encounter again = rapid response
32
Tolerance
Ability to distinguish between self and foreign antigens. (Self recognition)
- will attack anything that is foreign, but leave own cells alone
- very important part of immunity
Tolerance depends largely on a group of cell surface proteins known as MHC
33
Major Histocompatibility Complex (MHC)
Protein on surface of cell "ID tag"
*Code for making MHC is on chromosome 6
MHC is also called Human Leukocyte Antigen (HLA)
34
MHC Class I
Molecules found on the surface of all cells
Offer evidence of intracellular abnormalities
-acts as a billboard and gives an idea of what is going on in that cell
-important for transplants
35
MHC Class II
Molecules made by antigen presenting cells (APC)
Offer evidence of extracellular activities
-Macrophages - eat something and display as a trophy
36
Phagocytes
neutrophils and macrophages
37
Lymphocytes
B cells and T cells
38
B lymphocytes
Responsible for Humoral Immunity (Antibody Molecules)
Plasma cells: antibody synthesis
-"antibody factory" - kicks out a lot of antibodies (2000/second/cell)
Memory B: long lived immunity
-hang out and if encounter pathogen again - IR is quick
39
T lymphocytes
Responsible for cell mediated immunity
Produced in bone marrow and thymus: maturation occurs in thymus
-T cells learn hat they should attack and what they should leave alone
40
T Lymphocyte Subgroups
Helper T/CD4
Memory T
Cytotoxic
41
Helper T
(also called CD4)
Recognizes MHC II from APC's
Direct the immune response via cytokine release
-"commander in chief", "conductor", "quarterback"
42
Memory T
Long term retention
-strike pathogen faster if it returns
43
Cytotoxic
(also called T/CD8/Killer T)
Recognizes MHC I
Destroy via perforin
- checks out cells to see if they are doing what they are supposed to
- drills holes in cell membrane
44
B lymphocytes (more details)
Antibody-mediated immunity (Humoral Immunity)
Create antigen specific antibodies
Maturation occurs in red bone marrow
45
Antibodies
Y-shaped protein molecules that provide a means for linking defenses to pathogen
-do not do destruction themselves, but plant a "kiss of death"
Have fragment of antigen binding (FAB) (variable region) that attaches to foreign epitopes.
-changes all of the time - lots of shapes
```
Have FC region (constant region) for single, simple binding site
-doesn't attach - determines class of antibody
```
46
The antibody response to an antigen
Production of masses of antigen-specific antibodies that bind to that specific antigen
47
Antibodies: How they Destroy
1. Attracting IS cells
2. Agglutination
3. Activate Complement
48
Attracting IS cells (antibodies)
Opsonization
- "to prepare to eat"
- hook onto anything where shapes match
- makes it easier for phagocytes to get ahold of it
49
Agglutination (antibodies)
Clumping
- "bigger bite" for macrophages - easier to eat
- makes it harder for pathogen to get into cells
50
Activate Complement (antibodies)
To form Membrane Attack Complex (MAC)
- activated in a cascade
- -end product is called MAC
- -involves 30 different proteins
- DESTROYS the cell!
51
Five main types/CLASSES of antibodies
```
IgG - immunoglobin G
IgA - immunoglobin A
IgM - immunoglobin M
IgD - immunoglobin D
IgE - immunoglobin E
```
52
IgG - immunoglobin G
Principle circulating antibody
Only one to cross placenta
Binds to macrophages
(secondary response antibody)
53
IgA - immunoglobin A
Secreted in saliva, breast milk, respiratory, and urogenital tract
Protects mucous membranes (from invasion)
54
IgM - immunoglobin M
```
In plasma
Star Shaped (very big!)
```
(Primary/First antibody produced)
55
IgD - immunoglobin D
Found on B lymphocyte
Needed for B cell activation
(Dumb!)
(Function unknown)
56
IgE - immunoglobin E
Found on mast cells in allergic response
| important for allergies
57
Long Term Immunity
First antibody response to antigen takes about a week. It peaks at about 12 days and then tapers off.
Second and subsequent challenges produce faster rise in antibody production, which is retained at higher levels for a longer time. (increases antibodies immediately)
58
Immune System Diseases (types)
Autoimmunities - loss of tolerance
Hypersensitivity - overreaction
Immunodeficiencies - insufficient response
59
Autoimmune Diseases
- Result from breakdown in the integrity of immune tolerance such that a humoral (B cell) or cellular (T cell) immune response is mounted against host cells antigens
- Etiology = idopathic
- Ability of immune system to distinguish foreign from native antigens is responsibility of MHC complexes
- Current Theories: Genetic (chromosome 6), hormonal (more women affected), environmental
60
Molecular Mimicry
When similarities exist between foreign and self antigens sufficient enough to trigger IR
("mistaken identity" - antibodies attack similar shapes of own cells)
61
Select Autoimmune Disorders (listed)
```
Graves' Disease
Insulin-Dependent Diabetes Mellitus
Myasthenia Gravis
Rheumatoid Arthritis
Systematic Lupus Erythematosus (SLE)
Multiple Sclerosis (MS)
```
62
Graves' Disease
Autoantibodies bind to TSH receptors = hyperthyroidism
| eyes bulge, weight loss, anxiety
63
Insulin-Dependent Diabetes Mellitus
Beta cell destruction
| Type 1 - immune system attacks Beta cells of Pancreas - need insulin injections
64
Myastenia Gravis
Autoantibodies block/destroy ACh receptors
| antibody hooks onto ACh receptors at neuromuscular junction; progressive muscle weakness and then paralysis
65
Rheumatoid Arthritis
Immune response targeting synovial membranes
66
Systematic Lupis Erythematosus (SLE) is also called ___ ?
| nickname
"Great Imitator"
67
Etiology of SLE
Idiopathic
- Genetic (chromosome 6, African Americans more often)
- Environmental (UV light, sunlight, stress = increased flare ups)
- Hormonal (estrogen - more in women)
68
Statistics of SLE
1 in 2,500 general population
1 in 700 females
1 in 250 black females
*understand trends, not numbers
Age - women 20-40 are most affected (peak instance)
69
Pathogenesis of SLE
Autoantibodies produced against a variety of targets
Multisystem disease characterized by remission and exacerbation. (exacerbations triggered by sunlight and stress)
Ag/Ab complexes deposit in basement membrane of tissues triggering inflammation and clogging organs
70
Signs and Symptoms of SLE
Depend on target and vary widely
Common Sites:
90% SKIN involvement
90% JOINT involvement
50% KIDNEY involvement
Sometimes causes pericarditis, endocarditis, and other HEART problems (~25%)
71
Diagnosis of SLE
ANA and S&S
| ANA=anti-nuclear antibodies which are the antibodies against DNA/RNA
72
Treatment of SLE
Control symptoms and reduce the immune response.
Corticosteroids and NSAIDS
Immunosuppressants in SEVERE cases
73
Multiple Sclerosis (MS)
Demylenation of axons in the CNS and optic nerve
74
Etiology of MS
Idiopathic
- Genetics/ancestry
- Hormones (2x more common in women)
- Viral
- Environmental (more vitamin D decreases risk for MS - it interacts with chromosome 6)
Age - 20-40 is peak incidence
75
Pathogenesis of MS
Autoimmune destruction of the myelin sheath = CNS lesions - infilm and scarring (gliosis) depending on area of demylination
76
Common S&S of MS
Has many different symptoms
- Visual impairment
- Muscle weakness
- Ataxia (loss of coordination)
- Speech
- Mental impairment
Characterized by remission and exacerbation (usually caused by stress but really unknown)
77
Diagnosis of MS
(hard to diagnose because of many symptoms)
Evoked potentials (EEG and flashed lights should evoke certain action potentials at certain speeds - if slower than normal, MS likely)
MRI
S&S
78
Treatment/Prognosis
Palliative
Corticosteroids (reduce inflammation)
Interferon
Immunosuppressants (dangerous)
Vitamin D (low levels in etiology of MS; increase in dose to go into remission faster)
Prognosis varies widely
(treat as early as possible!)
79
Hypersensitivity Reaction
Abnormal immune response to a relatively harmless environmental agent, an allergen (exogenous antigen)
80
Hypersensitivity Reaction - Type 1
Anaphylactic-type reaction (immediate hypersensitivity reactions)
- Mediated by IgE and mast cells
- Clinical examples: hay fever, bronchial asthma, anaphylactic shock, food allergies, and latex glove allergies.
81
Hygiene hypothesis (hypersensitivity)
Lack of exposure to antigens increase susceptibility
82
Etiology of hypersensitivity
Idiopathic
- Genetics (runs in families)
- Environment
83
Pathogenesis of hypersensitivity
Reactions require presentation, meaning they must have been exposed to antigen previously to show symptoms
84
Hypersensitivity - FIRST exposure
Allergen is processed by the immune system
Plasma cells produce antibodies (IgE) against the allergen.
IgE becomes fixed on mast cells. They are now termed "sensitized mast cells".
85
Hypersensitivity - SECOND exposure
Allergen binds with IgE causing degranulation of mast cell and release of histamine.
Histamine causes vasodilation and increased capillary permeability resulting in the signs and symptoms of the allergic response.
86
Herminthic Therapy
Involves the use of hook worms
87
Anaphylaxis
(Anaphylactic Shock)
Severe life threatening systematic hypersensitivity
Examples: penicillin, bee stings, food (nuts, shellfish)
88
(anaphylaxis) SECOND exposure results in:
Systemic vasodilation (decreases BP)
Bronchospasm (smooth muscle contracts and blocks airflow - minutes count!)
Increases capillary permeability
89
Treatment of anaphylaxis
EPI pen
- epinephrine
- vasoconstricts
- bronchodilator
90
S&S of anaphylaxis
```
Skin - urticaria (hives)
Eyes - conjunctivitis (red/runny)
GI Tract - nausea (vomiting, diarrhea)
Nose - runny, sneezy
Bronchopulmonary - coughing/wheezing (edema)
```
91
AIDS is a disease cause by:
infection with human immunodeficiency virus (HIV)
92
AIDS is characterized by:
Profound destruction of Helper T cell directed immune response with resultant opportunistic infections, causing death
(The primary disease lowers the victims immunity, and a secondary, unrelated disease produces the symptoms that cause death)
93
Opportunistic Infection
An infection caused by pathogens that do not usually cause disease in a healthy immune system
94
AIDS was first recognized in:
June 1981 in the LA area
95
HIV was first isolated in
1983
96
HIV/AIDS Statistics - US
Number of new HIV infections in 2009 = 0.5 million
Number of people living with HIV/AIDS = 1 million, (including more than 0.5 million with AIDS)
Number of AIDS deaths since the beginning of the epidemic = 0.5 million
70% of these new infections occur in men and 30% occur in women
In 2010, the age group 20-24 accounted for
the highest rate of new HIV diagnosis
By race, 45 percent of the new infections in the US occur among African Americans
21% of people are infected with HIV and do not know (about 1 in 5)
97
Racial and ethnic minorities are disproportionally affected
Although black people represent only about 1 in 8 Americans, 1 in every 2 living with HIV in the US, is black
98
HIV/AIDS Statistics - worldwide
In 2010, there were 34 million people infected (living with HIV/AIDS) worldwide, and 1.8 million deaths
Globally, women account for 50% of infections
Since inception, >30 million have died
90% of HIV infections are in poor countries
2/3 are in Africa
-Hardest hit region is sub-saharan Africa - accounts for 68% of all infections worldwide
In 2005, 1 person died every 13 seconds. That is 23 people every 5 minutes.
99
AIDS: Life Expectancy
Sub-Saharan Africa sees reduction in life expectancy
US:
- In 2003 - a 20 year old diagnosed had a life expectancy of 49 years old
- In 2008 - a 30 year old diagnosed had a life expectancy of 69 years old
100
HIV: virus structure
1. Core of 2 strands of RNA with 3 transcription enzymes
2. These are surrounded by core proteins/capsid (p24)
3. Glycoprotein/Capsid - outer protein coat (gp120). This binds to CD4 and CCR5 on helper T cells
4. At least 2 different types of the virus
- HIV-1: around the world, most concerning, transmitted easier, progresses quicker
- HIV-2: not as easy to transmit, mostly in Africa (west), slower progressed
101
More on the HIV virus
1. It is a retrovirus, its genetic material is carried on RNA, and it changes the coding to DNA by reverse transcriptase
(it is also a lentivirus - attacks immune system)
2. Once it produces DNA from RNA, its DNA is integrated into the host cell's DNA
3. There, it can take over the cell's protein machinery and start making copies of itself
4. Replication of HIV
102
8 Steps of Replication (HIV virus)
1. HIV binds to CD4 and CCR5
2. Uncoating of virus
3. Reverse transcriptase makes viral DNA
4. Integration into cell's DNA (via integrase)
5. Transcription of viral DNA to make messenger RNA
6. Translation of mRNA to produce HIV polyprotein
7. Cleavage into individual proteins (protease)
8. Assembly and release of new HIV virus from host cell
103
Why is HIV so devastating?
| Host Cell Functions and HIV Properties
Host Cell Functions
- recognize foreign antigens
- stimulate B cell response (antibody mediated)
- stimulate CTL ("killer T")
- stimulate macrophages
HIV Properties
- host choice
- replication rate
- mutation rate
- escapes detection (NEF)
104
Primary HIV Infection
1. Some develop mono-like symptoms early - fatigue, fever, swollen glands, headache, night sweats, myalgia (muscle pain), sore throat, nausea, vomiting
2. Lasts 2-4 weeks
3. During this stage there is a large amount of HIV in the blood and the immune system begins to respond to the virus by producing HIV antibodies. This process is known as SEROCONVERSION. If an HIV antibody test is done before seroconversion is complete, then it may not be positive.
(takes 1-3 months for antibodies to show up in the blood)
105
Clinically Asymptomatic Stage
1. Lasts for an average of 10 years, and is free from major symptoms, although there may be lymphadenopathy. The level of HIV in the blood is low, but people remain infections and HIV antibodies are present.
2. Research has shown that HIV is not dormant during this stage, but is very active in the lymph nodes. A test is available to measure the small amount of HIV that escapes the lymph nodes. This test which measures HIV RNA (HIV genetic material) is referred to as the VIRAL TEST LOAD.
106
Symptomatic HIV/Progression to AIDS
1. As the immune system fails, symptoms develop. Initially many of the symptoms are mild, but as the immune system deteriorates the symptoms worsen.
2. Symptomatic HIV infection is mainly caused by the emergence of opportunistic infections that the immune system would normally prevent.
107
Classification of HIV Infection
Based on the CD4 (TH cells) count per microliter of blood.
- Category 1: more than 500
- Category 2: 200 to 499
- Category 3: less than 200
108
AIDS defining illnesses/Identifier Diseases/Opportunistic Infections
As CD4 count decreases, susceptibbility to opportunistic infections increases. These are some examples:
1. Kaposi's sarcoma
2. Pneumocytis pneumonia (PCP)
3. Tuberculosis
4. Candidiasis
5. Cryptosporidium
6. Wasting Syndrome
109
Kaposi's Sarcoma
Cancer of the endothelial cells that line small lymph vessels (KSHV = Karposi's Sarcoma Herpe's Virus - causes transformation of epithelial cells)
- used to be rare
- lymph vessels fill with blood and lesions appear on the surface of skin, and also internally
110
Pneumocytis Pnemonia (PCP)
Caused by a fungas
111
Tuberculosis (TB)
MDR strains from lack of compliance
- #1 cause of death in persons with AIDS (1/2 of people with AIDS has TB)
- In people with AIDS, TB moves outside of the lungs to other parts of the body
112
Candidiasis
Thrush.
Fungal
Is present in body, but with AIDS can get "out of check"
113
Cryptosporidium
Protozoa that causes severe diarrhea
| -Happens in healthy or poor immune system, but people with AIDS will not recover from it
114
Wasting Syndrome
Loss of lean body mass
| -with AIDS, the metabolic rate is faster than normal
115
AIDS Transmission
HIV is found in blood, semen, vaginal fluid, CSF, tears, and saliva, but it seems that sufficient virus for transmission is limited to the blood, semen, vaginal secretions, and breast milk
Best suited sites for establishment of infection after exposure appear to be the cardiovascular system, open wounds of the skin, the penis, the vagina, and rectum.
(Tissue injury/STDs pose greater risk)
116
Transmission Routes (HIV/AIDS)
1. Blood to blood
- 10-15% IV drug use
- transfusions, needle sticks <1% since 1985
2. Sexual
-75-85% (all types)
--M to M - 77% of HIV+ men
--M to F - 86% of HIV+ women
--F to M - 12% of HIV+ men
(it is much easier for a male to give to a female than the opposite)
3. Perinatally (mom to baby - crosses the placenta and found in breast milk)
- WITHOUT treatment - 20-30% during delivery and 5-20% during breastfeeding
- WITH treatment - 1-3%
117
Prevention of Transmission (HIV/AIDS)
1. If infected, do not have vaginal, oral, or anal intercourse (positive prevention strategy)
- If not infected, use ABCs
2. If have intercourse, effective whether HIV+ or HIV-, use effective barrier, latex condoms. (NO N-9 - can increase transmission)
3. Blood and Blood products - must be tested for HIV
4. Care in the handling of needles/use universal precautions/needle exchange
5. If infected, females who are pregnant, need treatment
6. Circumcision - New 2007 Guideline - WHO AIDS Cheif, Kevin deCock, Strongly advises circumcision (can decrease transmission by 51-60% (heterosexually))
118
Treatment (HIV/AIDS)
HAART - Highly Active Anti-viral Therapy/ Antiretroviral Therapy (ART)
-attempts to keep virus low
1. Reverse transcriptase inhibitors - AZT
2. Protease inhibitors bind to active sites of HIV-1 protease
3. Fusion inhibitors - inhibit HIV from binding to Helper T's
4. Integrase inhibitors - inhibit insertion into DNA
5. CCR5 antagonists - fusion inhibitor
119
When to start treatment for HIV/AIDS
Offer to all regardless of CD4
| -500 microliters or below - strongly recommend!
120
When to switch treatment for HIV/AIDS
- ART - "3 drug cocktail"
| - toxicity or tolerance (viral load test)
121
Compliance is Critical (HIV/AIDS)
or resistance will develop
64% are non-compliant
14% say side effects are too awful
122
Vaccine for HIV/AIDS
HIV vaccine 2009 - only 31% effective (reduces transmission by 31%)
Difficulties
- HIV mutates
- Vaccines trigger Ab formation
123
Neoplasm
(New growth) - Abnormal mass growing by uncontrolled proliferation that serves no useful purpose or function
-may be malignant (cancer) or benign
124
Oncology
The study of tumors
125
Benign
"kind" - growth is slow, orderly, and localized
126
Malignant
"with malace or intent to cause harm" - characterized by rapid, disordered, uncontrolled growth by aggressive invasion into adjacent normal tissues and ability to metastasize.
127
Metastasis
Spread of cancer to locations distant from the origin
Only occurs in malignant tumors, not benign
128
Primary Site (tumor)
Origin (original location of cancer cells_
1 CELL loses control and forms a tumor
129
Secondary Site (tumor)
Site of metastasis
Does not have to change tissue type
-Example: breast cancer tissue found in bone will look like breast tissue
130
Cancer Statistics
1. Second ranking cause of death in North America
2. 25% of population has some form
- 15% of those die as a result
3. Most common = skin cancer
4. Cancer Incidence/Deaths (US) - Estimated 2011
- Males
- -1. prostate/lung
- -2. lung/prostate
- -3. colon/colon
- Females
- -1. breast/lung
- -2. lung/breast
- -3. colon/colon
131
Naming of Tumors
"-oma" = tumor (used for benign tumors)
carcinoma = glands and epithelial
sarcoma = muscle and (CT) bone, adipose, cartilage
-(used for malignant tumors)
Some Prefixes:
- "adeno-" = gland
- "chondr-" = cartilage
- "lipo-" = fast
- "sarco-" = muscle
- "osteo-" = bone
132
Modes of Metastasis
Blood
Lymph
Seeding (movement of cancer in body cavities because of gravity)
SITES: bone, brain, liver, lungs (areas of high blood flow)
133
Carcinogenesis/Oncogenesis
Cell growth control system failure
| All cancers are thought to be due to genetic mutation
134
Cancer-Associated Genes (listed)
Proto-oncogenes
Oncogenes
Tumor Suppressant Genes (TSGs)
135
Proto-oncogenes
Genes that control responsible cell proliferation ("go button")
Tells cells when to begin growth
136
Oncogenes
Mutated proto-oncogenes = unlimited mitosis
137
Tumor Suppressant Genes (TSGs)
Safeguard against irresponsible growth ("stop button")
Produce a protein that tell the cell to exit cycle
EX) p53
138
What do TSGs do?
1. DNA repair
| 2. Trigger apoptosis
139
Neoplasia, or uncontrolled cellular proliferation, can result either from:
1. mutations that "turn on/amplify" that stimulate growth
| 2. Mutations that result in loss of tumor suppressor genes and their products that inhibit cellular growth
140
Multi-hit model of Carcinogenesis:
More than one mutational event is required in the development of cancer
141
3 Steps Involved in Carcinogenesis/Tumor Cell Transformation
1. INITIATION - mutations the result of exposure of a cell or cells to a carcinogen, which permanently alters its genetic material
- virus, radiation, and some chemicals
2. PROMOTION - mitagens. A substance that involves induction of unregulated growth in initiated cells.
- hormones, alcohol, most chemical exposure
3. PROGRESSION - Tumor cells acquire malignant characteristics via accumulated genetic mutations ac
142
Complete carcinogen
Substance that is both initiator and promoter, such as "tobacco smoke"
Has both MUTAGENS and MITAGENS
143
Etiological Factors in Carcinogenesis (listed)
Radiation
Chemical Exposure
Genetics
Viral
144
Radiation (Etiological Factors in Carcinogenesis)
2 Sources:
- Ionizing Radiation
- UV Radiation
145
Chemical Exposure (Etiological Factors in Carcinogenesis)
Alcohol, coal tar, cigarette smoke, radon, asbestos, etc.
146
Genetics (Etiological Factors in Carcinogenesis)
Currently >50 cancers are considered inherited (parents give you the mutations)
BRCA1 and BRCA2 mutations - early onset breast and ovarian cancers
147
Viral (Etiological Factors in Carcinogenesis)
Oncogenic viruses - HPV, KSHV, HBV, EBV
148
Adaptive Cell Responses
HYPERPLASIA - increased mitosis in response to specific growth stimulus
HYPERTROPHY - increase in cell size due to an increased demand
METAPLASIA - conversion of one cell type to another
ANAPLASIA - undifferentiated; cells lose specialization
DYSPLASIA - Disordered cell growth. Cells are variable in size, shape, and structure. Usually a precursor to tumor, precancerous lesion/carcinoma in situ
149
Pleomorphism
The condition of dysplasia
150
Benign Tumor Characteristics
CELL STRUCTURE: normal; well differentiated; nuclear cytoplasm ratio (n/c) = 4:1
TISSUE STRUCTURE: organized, resembles tissue in which it grows
GROWTH RATE: above normal. Growth fraction = ~3%
INVASION: local by expansion
METASTASIS: never
CAPSULE: often = well circumscribed/demarcated (makes for easier removal)
PROGNOSIS: depends on: site, size, and products
151
Malignant Tumor Characteristics
CELL STRUCTURE: bizarre and anaplastic; pleomophic (many shapes); nuclear to cytoplasm ration 1:1; mitotic figures are present; hyperchromatic (stain darker)
TISSUE STRUCTURE: unorganized
GROWTH RATE: measured by growth fraction = % of cells that are dividing. Slow growers = 10% GF (aggressive)
ANGIOGENSIS: Vascular Endothelial Growth Factor (VEGF)
INVASION: collagenase - enzyme to dissolve surrounding tissue; underexpression - of E. cadheren = loss of cohesion; loss of contact inhibition - overgrow and form mounds
CAPSULE: rare or incomplete
METASTASIS: 3 Routes - blood, lymph, seeding. Common sites: areas of high blood flow (bone, brain, liver, lungs)
PROGNOSIS: depends on site, stage, and response to treatment
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Liver Metastasis
Common due to hepatic portal system, which drains GI Tract
Parentineal cells likely to set up second site in liver b/c of this pathway
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Cancer kills by:
Spreading to vital tissue, replacing parenchymal tissue, compressing, obstructing, and destroying normal tissue
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Lung Metastasis
Common via lymph or venous
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Bone and Brain Metastasis
Via systemic circuit
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Tumor Effects
1. Tissue destruction
2. Obstruction/Compression
3. Infection
4. Anemia
5. Pain
6. Cachexia ("wasting" syndrome involving general weakness, fever, weight loss, can pallor)
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Cancer Diagnosis
An attempt to accurately identify the site of origin and the type of cells involved.
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Steps to Cancer Diagnosis
1. Diagnostic Tests/S&S - imaging studies, scans
2. Biopsy - removal of tissue for microscopic evaluation (cannot diagnose cancer until biopsy is done)
3. Tumor Markers - substances that can be found in abnormal amounts in the blood, urine, or tissues of some patients with cancer. Limited Use. Different markers in different cancers. Used for screening, monitoring, diagnosis, and prognosis
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A cancer is typically undetectable until...
it contains more than 1 billion cells!
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Different Tumor Markers
CA 125: ovarian cancer
-present in high numbers when cancer is advanced. Not useful as a screener because it is found too late. Used to monitor treatment.
PSA: elevated with prostate CA > 10 ng/mL = abnormal
- currently the only screening marker (detects early)
- problem: too many false positives
p53 mutations: colon CA cells shed in stool
-new area - high cost limits use
HER-2/neu: an oncogene in breast CA indicates aggressive growth likely
-codes for protein that becomes receptor on breast cancer cells
Estrogen receptors/progesterone receptors: Determines treatment in breast cancer
- intracellular receptors
- have drugs that block receptors and can cause some breast cancers to shrink
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Strain
Stretching injury to a muscle or musculotendinous unit cause by mechanical overloading.
- usually the result of excessive stretch or unusual contraction
- pain, stiffness, and swelling are present
common sites of injury: lower back, cervical spine, elbow, and shoulder
treatment: application of heat and massage. if serious, traction and bed rest
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Sprain
Involves the ligaments surrounding a joint. Pain and swelling subside more slowly.
Caused by abnormal or excessive movement of the joint.
Symptoms: pain, rapid swelling, heat, disability, discoloration, and limitation of function
Ankle joint is most common site of sprains (foot turns inwards). Also common in knees and elbows.
May see a chip on an x-ray
Four grades, 1-4
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RICE
Rest
Ice
Compression
Elevation
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Classification of Fractures: Open/compound
When bone fragments have broken through the skin
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Classification of Fractures: closed
When bone fragments have not broken through the skin
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Classification of Fractures: greenstick
Only one side of the bone broken; bent. Seen in children because bones are more resilient
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Classification of Fractures: comminuted
Has more than two pieces (shatter)
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Classification of Fractures: compression
Two bones squeezed or crushed together. Vertebrae are common site
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Classification of Fractures: impacted
Fracture pieces wedged together
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Five Stages of Healing (fracture)
1. Hematoma formation
2. Cellular Proliferation
3. Callus Formation
4. Ossification
5. Remodeling
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Fat Emboli
When the fat in the medullary cavity is released into venous blood = pulmonary embolism
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Osteosarcoma
Seen in long bone metaphysis, typically by knee or elbow
Peak incidence is in adolescence
