pathology Flashcards
etiology
causes of disease
pathogenesis
mechanism of disease
morphologic changes
structural alterations induced in the cells and organs that are characteristic of a disease or diagnostic of an etiologic process
clinical manifestations
functional consequences of morphological changes
etiology can be be broken down into two classes
genetic
acquired (environmental)
evolution of disease
etiology
pathogenesis
morphologic changes
clinical manifestations
pathogenesis breakdown
the sequence of cellular, biochemical, and molecular events that follow the exposure of cells or tissues to an injurious agent.
progress
clinical course and outcome
symptom
departure from normal function, appearance, or sensation. experienced by patient and indicitive of dsease. subjective
sign
any abnormally indication of disease. discoverable by clinician at examination of patient. objective
is a sign or symptom more objective
sign
sign or symptom, skin rash
sign
do you palpatate a sign or a symptom
sign
Hypermedia
Active process resulting from arteriolar dilation and increased blood inflow. Occurs at sites of inflammation or in exercising skeletal muscle.
Tissues are redder than normal because engorgement with oxygenated blood.
Congestion
Passive process resulting from impaired outflow of venous blood from a tissue.
Have n=abnormal blue red color that stems from the accumulation of deoxygenated hemoglobin.
Long standing chronic congestion
Inadequate tissue perfusion and persistent hypoxia may lead to parenchyma cell death and secondary tissue fibrosis. Elevated intravascular pressures may cause edema or rupture the capillaries
Edema
Accumulation of interstitial fluid within tissues.
Ansarca
Severe generalized edema marked by profound swelling of subcutaneous tissue and accumulation of fluid in body cavities
Fluid movement between vascular and interstitial spaces is governed by
Vascular hydrostatic pressure
Colloid osmotic pressure.
Increased movement of water into the interstitium
Increased hydrostatic pressure or decreased colloid osmotic pressure
How is excess edema fluid removed
By lymphatic drainage and returned to the bloodstream by way of the thoracic duct
Transudate
Protein poor edema fluid that accumulates because of increased hydrostatic pressure or reduced intravascular colloid
Exudate
Protein rich inflammatory edema fluid
Non inflammatory causes of edema
Increased hydrostatic pressure
Reduced plasma osmotic pressure
Lymphatic obstruction
Sodium retention
Causes of increased hydrostatic pressure
Mainly caused by disorders that impair venous return.
What does reduction of plasma albumin concentrations lead to
Decreased colloid osmotic pressure and loss of fluid from the circulation
Nephrotic syndrome
Most important cause of albumin loss is from th blood.
Either by sever liver disease or protein malnutrition
Route fluid should normally take if things are working properly (ie no blockage)
Fluid drawn out of interstitial fluid to the lymph to the lymph duct to blood
What effect does excessive salt retention have to result in edema
Increases hydrostatic pressure and reduces plasma osmotic pressure.
Hemorrhage
Extravasation of blood from vessels, most often the result of damage to blood vessels or defective clot formation
Hematoma
Hemorrhage that accumulates in a tissue.
Results can range from trivial to fatal
Hemarthrosis
Bleeds in the joints
Petechiae
Minute hemorrhages in skin,
1-2 mm in diameter
mucous membranes or serous always surfaces.
Causes include low platelet count, defective platelet function, loss of vascular wall support
Purpura
Slightly larger hemorrhages
3-5 mm
Can result from same disorders as petichae as well as trauma, vasculitis, and increased vascular fragility
Eccymoses
Larger 1-2. Cm subcutaneous hematoma
Bruises
Extravasated red blood cells are phagocytosed and degraded by macrophages.
What determines the clinical relevance of hemorrhages
Volume of blood being lost
Site of hemorrhage
Normal hemostasis
Series of regulated processes that culminate in the formation of a blood clot that limits bleeding from an injured vessel
Thrombosis
Formation of blood clot in non traumatized , intact vessels
What does hemostasis involve
Platelets
Clotting factors
Endothelium
Sequence of events leading to hemostasis
Arteriolar vasoconstriction Primary hemostasis (platelet plug) Secondary hemostasis (deposition of fibrin) Clot stabilization and resorption
Endothelium
Potent endothelium derived vasoconstrictor
Arteriolar vasoconstriction
Occurs immediately after injury and markedly reduces blood flow to the area.
Mediated by endothelin
Effect is transient and bleeding would resume if not for activation of platelets and coagulation factors
Neoplasia
New growth
Transformed because they continue to replicate regardless of regulatory influences that control normal cells
Benign tumor
Microscopic and gross characteristics remain localized
Malignant tumor
Lesion can invade and destroy adjacent structures and metastasize
Two components of tumors
Parenchyma (neoplasticism cells)
Stroma (supporting, host derived non neoplastic, made up of connective tissue, blood vessels and host derived inflammation cells
Parenchyma of neoplasm function
Largely determines its biologic behavior
Where tumor derives its name
Stoma funciton
Crucial to the growth of the neoplasm. Carries blood support
Nomenclature benign tumors
Suffix oma to cell type from cell type tumor arises
Adenoma
Benign epithelial neoplasms that produce gland like structure and those derived from glands but lacking a glandular growth pattern
Paillomas
Benign epithelial neoplasms growing on any surface that produce microscopic or macroscopic fingerlike fronds
Polyp
Mass that projects above mucosal surface to form a macroscopically visible structure
Sarcoma
Malignant neoplasms arising in solid mesenchymal tissues or its derivatives
Leukemia’s and lymphomas
Malignant neoplasms arising from mesenchymal cells of the blood
Leukemia is blood based
Lymphoma is more solid tissue
Carcinomas
Malignant neoplasms of epithelial cells
Adenocarcinomas
Carcinomas that grow in a glandular pattern
Squamous cell carcinomas
Carcinomas that produce squamous cells
Three features benign and malignant tumors can be distinguished
Differentiation and anaplasia
Local invasion
Metastasis
Differentiation
Extent to which neoplasms resemble their parenchyma cells of origin both morphologically and functionally
Anaplasia
Lack of differentiation
Anaplastic
Tumors composed of undifferentiated cells
Anaplastic morphological features
Pleomorphism
Nuclear abnormalities
Atypical mitoses
Loss of polarity
Pleomorphism
Variation in size and shape
Capsule of benign tumors
Rim of compressed fibrous tissue. Largely made of extracellular matrix deposited by stromatolites cells
Metastasis
Spread of tumor to sites that are physically discontinuous with primary tumor and unequivocally marks tumor as malignant
Metastasis pathways
Seeding within body cavities
Lymphatic spread
Hematogenous spread
Typical metastasis pathway of carcinomas vs sarcomas
Lymphatic spread is favored by carcinomas
Hematogenous spread is favored by sarcomas
Pattern of lymph node involvement depends on
Site of primary neoplasm and natural pathways of local lymphatic drainage
Paraneoplastic syndromes
Symptom complexes in cancer patients that cannot be explained by local invasion, metastasis, or elaboration of hormones
Hypercalcemia and paraneoplastic syndrome
Can be due to tumor production of pth related protein
Cushing syndrome and paraneoplastic syndrome
Arising as parneoplastic phenomenon usually related to ectopic production of acth or acth like polypeptides by cancer cells.
Grading
Based on degree of tumor cells and sometimes on number of mitoses or architectural features
Staging
Based on size of primary tumor, extent of spread to regional lymph nodes, and the presence or absence of distant metastases
Environmental influences of cancer
Smoking Alcohol consumption Reproductive history (estrogen stimulation) Diet Infectious agents
Acquired conditions that predispose cancer
Chronic inflammation
Immunodeficiency
Precursor lesions
Precursor lesions
Localized disturbances of epithelial differentiation that are associated with an elevated risk for developing carcinoma
Oncogenes
Genes that induce a transformed phenotype when expressed in cells by promoting increased cell growth.
Oncoproteins
Encoded oncogenes that serve functions similar to counterparts but are constitutively active.
RAS
Most commonly mutated oncogene in tumors
Commonly activated by point mutations which interfere with breakdown of GTP (which is essential to inactivate RAS).
Cell is forced into continuously proliferation state
ABL
Proto oncoprotein that has tyrosine kinase activity that is dampened by internal negative regulatory domains.
Activates growth factor signaling pathways
MYC
Functions by activating the transcription of other genes
Genes activate include growth promoting genes whose products drive cells into the cell cycle
Cell cycle oncogenes
2 categories
Gain of function mutations to promote cell cycle
Loss of function mutations (of inhibitors) promote cell cycle
Tumor suppressor genes
Apply brakes to cell proliferation.
Disruptions of these genes render cells refractory to growth inhibitions and mimics growth promoting effects of onco genes
RB
Negative regulator of the cell cycle - directly or indirectly inactivated in most human cancers
First tumor suppressor gene to be discovered
Two hit hypothesis
Familial vs sporadic
In familial cases - children inherit one defective copy of RB gene, other is normal. Then normal RB gene is lost as result of somatic mutation
In sporadic cases - both alleles are lost by somatic mutation
TP53
Most commonly mutated gene in human cancer
P53 is transcription factor that prevents neoplastic transformation by activation of temporary cell Ceylon arrest, permanent arrest, or apoptosis
Maintains integrity of genome
Mutant allele
Tumor cells evasion of cell death mechanisms
Loss of TP53 function
Overexpression of anti apoptosis members of bcl2 family
Quiescence
Activation of temporary cell cycle arrest
Senescence
Induction of permanent cell cycle arrest
