What is pathology
The scientific study of disease. Determining what is the etiology (cause) of the disease. What morphologic changes are at the molecular level.
What is pathophysiology
the functional changes associated with or resulting from disease or injury
What are two major classes of etiologic factors
- Genetic: inherited mutations/disease associated gene variants
- Acquired: infectious, nutritional, chemical, physical
Most common disorders are multifactorial and arise from the effects of various ____triggers on a genetically susceptible individiual
external
What are examples of aqcuired patholical diseases
- caries
- cardiovascular disease
- Traumatic ulcer
- syphillic uveitis
- chancre (syphillis)
Ex of genetic factors
- Amelogenesis imperfecta
- APC Gene mutation
- Marfan syndrome
- Familial adenomatous polyposis
- Crouzon syndrome (mutation of growth factor receptor 2 - FGFR2)
What does nicotine cause
- blood to thin
- more blood to flow
- excess neutrophils to fight off but produce elastase which causes damage if too much
- reactive oxygen species cause tissue damage
- emphysema
what are morphologic changes
They refer to the structural alterations in cells or tissues that are either ch. of a disease or diagnostic of an etiologic process.
what are morphologic changes with a diseased kidney
- shrunken glanular surface
- decreased function
- smaller size
- high urine protein
What are functional consequences (pathophysiology)
- Virtually all forms of disease start with molecular or structural alterations in cells.
- The end result of structural changes in cells and tissues are functional abnormalities which lead to the clinical manifestations of disease as well as its progress
What is the diff between signs and symptoms
Symptom: exp and reported by the patient
Sign: discovered by the physician during examination or by a clinical scientist by means of an invitro examination of the patient.
A ____ is an abnormal mass of tissue, the growth of which exceeds and is uncordinated with that of the normal tissues and persists in the same excessive manner after cessation of the stimuli which evoked the change
neoplasm
How can benign and malignant tumors be distinguished
- Degree of differentiation
- Rate of growth
- Local invasivness
- distant spread
What is a benign tumor (leiomyoma)
- small
- well demarcated
- slow growing
- noninvasive
- nonmetastic
- well diffrentiated
What is a malignant tumor (leiomyosarcoma)
- large
- poorly demarcated
- rapidly growing with hemorrhage and necrosis
- locally invasive
- metastatic
- poorly differentiated
If its a glandular origin it would be____ if blood vessels prefix would be _____. If its benign it would end with ____. If malignant it wound end with ____. If smooth muscle it would be ___. IF striated muscle it would be
adeno; hemangio
-oma; sarcoma
leiomyoma; rhabdomyoma
Epithelium has a maturing process and is constantly being turned over. Mouth normally has no ____ except parakeratin on gingiva, hard palate and lingual dorsum
keratin
Dysplasia are \_\_\_\_\_ Hyperkeratosis is \_\_\_\_ Psuedoepitheliomatous hyperplasia refers to \_\_\_\_\_ Acanthosis refers to\_\_\_\_\_ Papillary refers to \_\_\_\_
atypical, cancer like cells
excess surface keratin
bening sq epithelium, that has strong proliferation that looks like its invading. “fake cancer: appearance”
thickened from extra number of cells.
thickened from excess spinous layer
Long blunted finger like surface projections
Prominent nucleoli shouldnt be that obvious. As cell starts to divide it might divide unusually; this would be called a ____ polymorphism
nuclear
Dysplasia refers to _____ and can be a precursor to malignancy.
non malignant cellular growth
What are causes of dysplasia
- chronic irritation
- chemical agents
- cigarrete smoke
- chronic inflammatory irritation
What are characteristics of dysplasia
- disorganized, structureless maturation and spatial arrangement of cells
- atypical cells without invasion
- acanthosis in the epithelium
The differentiation of parenchymal tumor cells refers to the extent to which they ____
resemble their normal forebears morphologically and functionally
What is a well differentiated squamous cell carcinoma
looks like normal tissue but behaving completely differently. Its a cancer but looks like normal epithelial structure
what is a poorly differentiated SCCA
still some semblance of the tissue of origin.
what is carcinoma in situ
Within it’s place. Stayed in original area that it should be in, but hasn’t broken in; doctor should look to see if any other structures are affected in area. Do MRI or CT.
what is metaplasia. What is ex of this
- Replacement of one cell type with another. Ex is squamous metaplasia
- Cervix: changes due to HPV infection
- Barrett’s esophagus (chromic irritaiton from reflux). Can have dysplasia –>adenocarcinoma
What is anaplasia
“Backward formation” implying dedifferentiation, or loss of the structural and functional differentiation of normal cells.
Malignant neoplasms that are composed of ____cells are said to be anaplastic which is a hallmark of ______
undifferentiated; gone back to its embryonic presentation; malignancy
A _____ neoplasm remains localized as its site of origin. It does not have the capacity to infiltrate, invade or metastasize to distant sites, as do malignant neoplasms
benign
_____ are secondary implants of a tumor that are discontinuous with the primary tumor and loc in remote tissues.
Metastases
What are the seq of events that happen with invasion
- tumor cells detach from each other
- secrete proteolytic enzymes degrading the BM.
- Binding to proteolytically generated binding sites and tumor cell migration follow.
- Reverse process when they infiltrate new site
____ spread is more typical of carcinomas. ____ spread is favored by sarcomas
lymphatic; hematogenous
The most common location of hematogenous metastasis is in the ____ and ___because all portal area drainage flows to the liver and all caval blood flows to the lungs.
liver and lungs
HOw do we stage cancers?
- T refers to the extend of the primary tumor: from the earliest (Tis = carcinoma in situ) to the most advanced (t4 = tumor directly invades other organs or structures)
- N refers to lymph node involvement. From N0 to N2
- M refers to distant mets absent or present
How do we grade it?
Based on how its behaving to see how long they will be able to live. A higher grade type of lesion would be less differentiated bc it would behave ratically when it looks abnormal.
3 types of oral cancer in _____Env factors could be the cause of this. Most common age range of age related cancer is ____
men; 55-75
there is up to _____ DNA modification events per cell per day
500,000
What is the molecular basis of cancer
- Acquired env. DNA damaging agents
- failure of DNA repair
- Mutations in the genome of somatic cells.
- Unreg cell proliferation
- clonal expansion
- tumor progression
- malignant neoplasm
- invasion and metastasis
Mutations that occur in the non germ cells are called ___ mutations because they are occuring in our body or “soma.”
somatic ; if genetic every single cell has a mutation
what is the clonal expansion principle
a tumor can result if a mutation results in sufficient production of clones.
What are principles of tumor progression and generation of heterogeneity
New subclones arise from the descendants of the original transformed cell by multiple mutations. With progression, the tumor mass becomes enriched for variants that are more adept at evading host defenses and are likely to be more aggressive.
What are hallmarks of cancer
- Self sufficiency in growth signals: Tumors can proliferate w/o external stimuli
- Insensitivity to anti-growth signals
- Evade apoptosis: Tumors may be resistant to programmed cell death
- Limitless replicative potential
- Sustained angiogenesis
- Tissue invasion and metastasis
Oncogenes are:
What proto-oncogenes get mutated into. They are genes that promote autonomous cell growth in cancer cells.
What role does VEGF play
- Promotes angiogenesis
- Inc vascular permeability
- stimulates endothelial cell migration/proliferation
What are mechanisms that tumor cells dev to evade immunocompetent hosts
- Selective outgrowth of antigen negative variants; strongly immunogenic subclones may be eliminated
- Loss/reduced exp of MHC molecules: They then escape attack by T cells.
- Apoptosis of cytotoxis T cells
- Lack of co-stimulation
- Immunosuppression: suppresses host immune responses
- Antigen masking: cell surface antigens of tumors can be masked from immune system by glycocalyx molecules such as sialic acid containing mucopolysaccharides.
What are 4 classes of reg genes that can lead to tumor formation if mutated or targeted by transformed cells
- MYC
- p53
- TNF; regulate programmed cell death
- BRCA1 and BRCA2: involved in DNA repair
What is the Ras oncogene
Ordinarily, Ras plays an important role in signaling cascades downstream of growth factor receptors. Point mutation of RAS family genes is the single most common abnormality of proto oncogenes in human tumors.
-15-20% of all human tumors contain mutated versions of Ras proteins.
The chromosomal ____ is what causes it to proliferate and cause Burkitt’s lymphoma at ABL locus.
translocation
What is the mechanism of the BCL-2 oncogene
There is a translocation of a gene to the heavy chain locus. Lymphocytes start to build up because BCL-2 can no longer cause apoptosis which can form to a lymphoma. Tumors associated with this grow very slow.
What are Anti-VEGF therapies? how does it work
potential anti cancer treatments:
- neutralize monoclonal antibodies against VEGF or its receptor
- small molecule tyrosine kinase inhibitors of VEGF receptors
- soluble VEGF receptors which act as decoy receptors for VEGF
- Ribozymes which specifically target VEGF mRNA.
Amplification or over expression of this gene has been shown to play an impt role in dev and progression of breast cancer
HER2/NEU
