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Pathology
study of disease
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pathophysiology
study of physiological processes leading up to disease
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etiology
study of CAUSE of disease
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idiopathic
no identifiable cause
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syndrome
concurrent sets of s/sx
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prognosis
predicted course and outcome
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remission
symptoms subside or diminish
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exacerbation
worsening of symptoms
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relapse
returns wks/mths after cessation
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complication
onset of another disease or abnormal state
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Anabolism
cellular functions which require energy
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Catabolism
- energy-releasing process (transferred to ATP in the mitochondria)
- -proteins to amino acids
- -lipids to fatty acids (ketoacids) and glycerol
- -carbs to monosaccharides (glucose)
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passive transport
- no energy expenditure
- -diffusion....blood vessels
- -filtration...glomerulus (kidneys)
- -osmosis....cell membrane (depends on solution tonicity)
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isotonic
similar osmolarity as serum
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hypotonic
- decrease in osmolarity
- -shift of fluid from solution into cells, from vessels into tissues
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hypertonic
- increase osmolarity
- -shift of fluid out of cells, from tissues into vessels
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mediated transport
- can be passive or active
- -passive-(facilitated diffusion) involves transport proteins
- -active
- *energy expenditure
- *lg. molecules or movement against a concentration gradient
- *endocytosis-(pinocytosis, phagocytosis)
- *exocytosis- secretion (hormones)
- *membrane potential (depolar/repolarization)
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hormonal signaling
hormones secreted by endocrine cells travel via bloodstream to target cells
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paracrine signaling
- localized
- -neurotransmitters at synapses
- -coagulation factors
- -hypothalmic releasing factors...pituitary
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autocrine signaling
self stimulation (interleukins)
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4 types of tissues
- -epithelial
- -muscle
- -connective
- -nervous
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epithelial tissue
- -forms sheets that cover the body's outer surface, lines internal surfaces and forms glandular tissue
- -regenerative
- -malignant tumors-carcinomas
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connective tissue
- -most abundant tissue; binds organs and tissues together, support, storage site
- -regenerative
- -malignant tumors-sarcomas
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muscle tissue
- -contractile tissue
- -important source of body heat
- -skeletal muscle(striated; voluntary)- non-regenerative
- -cardiac muscle(striatved;involuntary)-non-regenerative
- -smooth muscle(non-striated;involuntary)-regenerative
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nervous tissue
- -highly specialized cells (neurons) and supporting cells (neuroglia) that receive and transmit electrical impulses very rapidly across junctions called synapses;designed for communication purposes
- -non-regenerative
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hypoxia
- -lack of oxygen
- -single most common cause of cellular injury
- *systemic injury
- •Decreased amt oxygen in the air
- •Loss or interference with hemoglobin function
- •Decreased rbc production
- •Diseases of respiratory & cardiovascular systems
- •Poisoning
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ischemia
- -cellular injury
- -reduces blood supply (decrease oxygen, decrease waste removal)
- -localized injury
- -ex. occluded blood vessel
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Toxic injury (cellular injury)
- •Free radicals – injurious chemical bond formation generates unpaired, unstable electrons that disrupt cellular function. Most susceptible to damage: cell membranes ≠ transport, signaling
- DNA in mitochondria = decreased energy = aging
- •smoking, pollution, herbicides, radiation
- •antioxidants (Vit A,C,E) – to protect against damage
- •Chemicals agents – alcohol, lead, arsenic, CO, drugs
- •toxic substances damages cell membrane ® increased permeability
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physical injury (cellular injury)
- •Mechanical – trauma, surgery
- •Thermal - electrical injuries, ionizing radiation, extremes of temperature
- •Extremes of temperature
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infectious injury (cellular injury)
•Biological – pathogens multiply, trigger immune/inflammatory
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Deficit injury (cellular injury)
•Oxygen, water, nutrients, decreased waste removal
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atrophy (cellular adaptation)
- -lack of use (broken limb-muscle)
- -muscles shrink-decrease hormone/growth..poor nutrition
- -ex. skin changes (ischemia) that occur on the legs and feet of an individuals with poorly controlled diabetes mellitus
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hypertrophy (cellular adaptation)
- -impt in NON-REGENERATIVE tissues (cardiac and skeletal)
- -ex. myocardium in response to prolonged elevated BP
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hyperplasia (cellular adaptation)
- -increase demand on REGENERATIVE tissue
- -ex. development of a callus on the hands of an individual involved in heavy physical labor
- -ex. breast enlargement at puberty
- -ex. enlargement of the prostate gland w/age
- -ex. Thyroid gland’s response to hypersecretion of TSH
- -ex. Liver’s response to chronic alcohol abuse
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metaplasia (cellular adaptation)
- -change-adaptative strategy from chronic irritation (acid reflux)
- -if continued on...=dysplasia
- -ex. Changes that occur over the years in the respiratory tract of a smoker
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dysplasia (cellular adaptation)
- -disorderly-tissue dysfunction
- -ex. Changes responsible for an abnormal Pap smear
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anaplasia (cellular adaptation)
total dysfunction
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passive transport
- -(Facilitated diffusion)
- -Involves transport proteins
- -no energy expenditure
- -water and solutes through semipermeable barrier
- •Diffusion
- •Filtration
- •Osmosis
- *depends on solution tonicity
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active transport
- •Energy expenditure
- •Large molecules or movement against a concentration gradient
- •Endocytosis - (pinocytosis, phagocytosis)
- •Exocytosis - secretion
- •Membrane potential (depolar/repolarization)
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congenital (perinatally acquired disease)
- –appear at birth or shortly after, may be multifactorial in combination with an inherited disorder but typically not caused by genetic or chromosomal abnormalities
- •usually result from some failure in development during the embryonic stage/first 2 months of pregnancy
- Can not be transmitted to offspring
- •Inadequate oxygen
- •Maternal infection - rubella
- •Drugs - thalidomide
- •Alcohol – fetal alcohol syndrome
- •Malnutrition
- •Radiation
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Hereditary (familial)
- -result of metabolic breakdown cause by a lack of direction from a missing or compromised gene or chromosomal segment
- •Chromosomal disorders
- -additions, deletions, translocations
- •Genetic disorders
- -gene responsible for the production of a protein (enzyme or structural type) is missing or defective results in the accumulation of toxic metabolites®cellular dysfunction and alternations leasing to disease or death
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Use of genes to treat or prevent disease.
- •Replacing a mutated gene that causes disease with a copy of the gene from a healthy donor.
- •Inactivating, or “knocking out,” a mutated gene that is functioning improperly.
- •Introducing a new gene into the body to help fight a disease oftentimes via viruses
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genetic disorder transmission
- Autosomal dominant: presence of disorder/trait (phenotype) ID’s individuals with the dominant gene
- •phenotype will be the same (always be expressed) whether homozygous (DD) or heterozygous (Dd); only 1 copy of gene needed for expression
- •diseased person will always have at least one affected parent
- •if both parents are homozygous, all offspring will be affected
- •if diseased parent is heterozygous, varies 50-75%
- •no carriers
- •male & female offspring affected equally
- *Hunginton disease
- *Marfan syndrome
- *Familial hypercholesterolemia
- *Polydactyly
- *Achondroplasia
- -Autosomal Recessive
- Both parents must pass on recessive gene ® homozygous child with the expressed trait/disease
- •carriers result when offspring receives 1 gene
- •Offspring have 25% chance of being affected if have 2 carrier parents
- •male & female offspring affected equally;
- •consanguinity a factor (families, ethnic groups)
- *Sickle cell disease
- *Cystic fibrosis
- *PKU
- *Tay-Sachs
- *Albinism
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Benign Tumors
- -Above-normal growth rate
- -Encapsulated(non-invasive)
- -Differentiated cells of normal size, shape
- -Orderly tissue structure
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Malignant Tumors (cancer)
- •Rapid, unceasing growth
- •Infiltrative, invasive
- •Loss of differentiation; anaplasia
- •Disordered,irregular
- •metastatic*
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Cancer risk factors (controllable)
- All cancers caused by cigarette smoking and heavy use of alcohol could be prevented completely
- •ACS est. 169,000 deaths caused by tobacco use
- •1/3 will be related to overweight or obesity, physical inactivity and poor nutrition and could be prevented
- •Cancers related to infectious agent (HBV, HPV, HIV, H. pylori) could be prevented through behavioral changes, vaccines or antibiotics
- •Many of the >1 million skin cancers could be prevented by protection from sun’s rays and avoiding indoor tanning
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Cancer risk factors (cont.)
- -----Heredity (inheritance of CA susceptibility genes)
- •BRCA1, BRCA2, HER2, NF-1, WT-1, p53
- ---Environmental factors
- •chemical agents (benzene, asbestos, dyes)
- •pesticides/herbicides (agent orange)
- •meds (diethylstilbestrol-DES)
- •air pollutants
- •radiation (UV, Xrays, sunlight)
- •Microorganisms (chronic infections-HBV, HCV, HIV, HTLV-1, EBV, HPV, HHV8, H. pylori, Schistosoma mansoni)
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tumor cell markers
"altered tissue antigens"(BRCA1, BRCA2, HER2, AFP, CEA, CA125)
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cancer grading
- -Determines the degree of abnormality of the neoplasm. Microscopic exam of the tumor to determine degree of differentiation. Grades I to IV.
- •Grade I – (well-differentiated) less aggressive and serious
- •Grade IV (anaplastic)–
- most aggressive and serious
-Grading and staging are used to plan treatment and to help determine prognosis
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cancer staging
- -Process of finding out the extent and spread of the disease.
- -TNM system of the American Joint Committee on Cancer (AJCC) most commonly used
- •T (tumor) – size of primary tumor & local spread
- •N (nodes) –involvement of regional lymph nodes
- •M (metastasis) - extent of metastatic involvement
- -The stage of a cancer does not change over time, even if the cancer progresses
- -Survival statistics and treatment by stage info of specific cancer types refer to the stage when the cancer was first diagnosed
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cancer treatment
- -Goals of cancer treatment methods fall into three categories: curative, control, palliative
- Surgery -debulking, majority of tumor removed
- Radiation therapy -idea is that the rapidly proliferating and poorly differentiated cells are more likely to be injured by ionizing radiation than normal cells. Injurious to rapidly ¸norm cells (bone marrow, GI tract lining)
- Chemotherapy -systemic treatment that allows drugs to reach the primary tumor as well as distant tumor sites. Most effective when used in combination (cocktail)-individually effective against the tumor and synergistic w/ea other
- Immunotherapy -anti-tumor immune response
- Anti-angiogenesis -stop tumors from making new blood vessels
-- Side effects: GI, bone marrow, hair, skin, reproductive tract
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