Exam 3 pathopharm Flashcards
overactivity of thyroid (Excessive amounts of thyroid hormones are produced and released into the circulation)
Hyperthyroidism (thyrotoxicosis)
accompanied by opthalmopathy (or dermopathy) and diffuse goiter. Onset between 20-40 years more likely in women. Characterized by abnormal stimulation of thyroid gland by thyroid-stimulating antibodies that act through the normal TSH receptors.
Graves’ Disease
6 causes of hyperthyroidism
- Graves’ Disease
- Multinodular Goiter
- Adenoma of the thyroid
- Thyroiditis
- Iodine-containing agents
- Thyroid Crisis (thyroid storm)
acutely exaggerated manifestation of the thyrotoxic state. Life-threatening.
Thyroid Crisis (thyroid storm)
what are the s/sx of hyperthyroidism
Increased body temperature, tachycardia, thin skin, palpitations, hypertension, flushing, intolerance to heat, amenorrhea, weight loss, and goiter, lose weight, sweat, hot, red, increased metabolic rate
what are the treatments for hyperthyroidism?
Directed toward reducing the level of thyroid hormone. Accomplished with eradication of the thyroid gland with radioactive iodine, through surgical removal of part or all of the gland, or with the use of drugs that decrease thyroid function and thereby the effect of the thyroid hormone on the peripheral tissues.
administered to block effects of the hyperthyroid state on sympathetic nervous system.
They are given in conjunction with antithyroid drugs (propylthiouracil and methimazole) that act by inhibiting the thyroid gland from using iodine in thyroid hormone synthesis and by blocking the conversion of T4 to T3 in the tissues.
Beta-adrenergic blocking drug
underactivity of thyroid- can be congenital (from mom)
Hypothyroidism
Congenital causes of hypothyroidism
absence of the thyroid gland.
lack of suff iodine in the diet to produce the needed level of TH
Lack of suff fxning thyroid tissue due to tumor or autoimmune disorders
lack of TRH related to a tumor of disorder of the hypothalamus
Acquired causes of hypothyroidism
Hasimoto thryoiditis (MOST common cause)--> thyroid gland may be totally destroyed by immunologic process (women) Thyroidectomy
3 manifestations of hypothyroidism
Hypometabolic state
Myxedematous fluid
Myxedematous coma
characterized by gradual onstet of weakness and fatigue, tendency to gain weight despite loss of appetite, cold intolerance. Skin becomes dry and rough and hair becomes coarse and brittle. Increased blood levels of carotene give skin yellowish look.
Hypometabolic state
is most obvious in the face and can collect in interstitial spaces of almost any body structure. The tongue is enlarged and voice becomes hoarse and husky. Carpal tunnel and entrapment syndromes are common, impairment of muscle function with stiffness, cramps, and pain.
Myxedematous fluid
life-threatening, end-stage expression of hypothyroidism: coma, hypothermia, CV collapse, hypoventilation, severe metabolic disorders including hyponatremia, hypoglycemia, and lactic acidosis
Myxedematous coma
Tx of hypothyroidism: Levothyroxine Thyroid Desiccated Liothyronine Liotrix
- synthetic salt of T4
- prepared from dried animal thryoid galnds and contains both T3 and T4.
- Synthetic salt of T3
- Synthetic preparation of T4/T3 in a standard 4:1 ratio.
Disorder of the adrenal cortex;: Excessive anterior pituitary secretion of ACTH. Usually a tumor. something wrong with HPAxis (check CRH levels)
Cushing’s Disease/Syndrome
S/Sx of Cushing’s Disease
Excessive level of cortisol weight gain (truncal obsestiy, moon face) glucose intolerance/ DM Polyuria Muscle wasting/weakness Weak integumentary tissues
TX of Cushing’s Disease
CRH: stimulates release of ACTH from anterior pituitary- used to diagnose Cushing’s disease
- Primary adrenal cortical insufficiency
2. Severe hypotension and vascular collapse
- Addison Disease
2. Addison Crisis
Stimulate an increase in glucose levels for energy. used systemically in endocrine disorders.When produced as a part of stress response, these hormones aid in regulating the metabolic functions of the body and in controlling inflammatory response.
Glucocorticoids
What are the actions of Glucocorticoids
- Enter target cells and bind to cytoplasmic receptors
- initiate many complex runs respon. for anti-inflmm and immunosupp. effects
- Hydrocortisone, cortisone, prednisone have some mineralocorticoid activity.
3 Indications for the use of Glucocorticoids
- short-term tx of many inflm disorders
- to relieve discomfort
- give the body a chance to heal from the effects of inflm
Affect electrolyte levels and homeostasis. Play essential role in regulating potassium and sodium levels and water balance. Aldosterone secretion is regulated by rennin-angiotensin mechanism and by blood levels of potassium. Increased levels of aldosterone promote sodium retention by distal tubules of kidney while increasing urinary losses of potassium
Mineralcorticoids
Male and female sex hormones
Androgens
growth hormone excess in adulthood (called gigantism in childhood). Exaggerated growth of the ends of the extremities
Acromegaly
GH-secreting adenomas, most of which are benign. When the production of excessive GH occurs after the epiphyses of the long bones have closed, as in the adult, the person cannot grow taller, but the soft tissues continue to grow. This is the cause of what?
Acromegaly
CAN a father pass on an X linked disease to the son?
NO
graphic method for portraying a family history of an inherited trait. Constructed from a carefully obtained family hx and useful for tracing pattern of inheritance for a particular trait.
Pedigree
ordered display of chromosomes
Karyotype
A person’s physical characteristics
Phenotype
A person’s genetic material
Genotype
associated with the X chromosome, are those in which an unaffecyed mother carries one normal and one mutant allele on the X chromosome. She has a 50% chance of transmitting the defective gene to her sons who are affected, and her daughters have a 50% chance of being carriers of the mutant gene. Because of a normal paired gene, female heterozygotes rarely experience the effects of a defective gene.
Sex-linked disorders
single mutant allele from affected parent is transmitted to offspring regardless of sex. Affected parent has a 50% chance of transmitting the disorder to each offspring
Autosomal Dominant Disorders
manifested only when both members of the gene pair are affected. Usually, both parents are unaffected but are carriers of the defective gene. Their chances of having an affected child are 1/4; of having a carrier child, 2/4; and of having a noncarrier unaffected child ¼.
Autosomal Recessive Disorders
If two parents are both carriers of a genetic condition with a recessive inheritance pattern, there is a one-in-four chance that each child will be affected. So on average, one-quarter of their children will be affected. There is also a one-in-two chance that each child will be an unaffected carrier, like the parents. Examples of genetic conditions that show a recessive pattern of inheritance are cystic fibrosis, sickle-cell disease, Tay-Sachs disease and phenylketoneuria.
Recessive Inheritance
trait is seen much more often in males. bc a father can give a son only a Y chrome, trait is NEVER transmitted from a father to a son.The gene can be transmitted through a series of carrier females, causing the appearance of one or more “skipped generations.The gene is passed from an affected father to all his daughters
X linked Inheritance
the variation in a phenotype associated with a particular genotype. This can be caused by modifier genes
Expressivity
Examples of expressivity
Von Recklinghausen's disease. Neurofibromatosis 1 Autosomal dominant Long arm of chrom 17 disease varies from dark spots on the skin to malignantneurofibromas, scoliosis, gliomas, neuromas.
specific genotype who also express the expected phenotype
Penetrance
Individual who has the gene for a disease but does not express the disease
ex: Retinoblastoma (eye tumor in children) demonstrates this (90%)
Incomplete Penetrance
cells and organisms are those containing more than two paired (homologous) sets of chromosomes.
Chromosomal Polyploidy
A somatic cell that does not contain a multiple of 23 chromosomes. This is usually the result of nondisjunction, an error in which homologous chromosomes or sister chromatids fail to separate normally during meiosis or mitosis
Chromosomal Aneuploidy
is the presence of only one copy of any chromosome; often lethal
Monosomy
cell containing three copies of one chromosome; infants can survive with this of certain chromosomes; most common 13, 18, 21; Down syndrome
Trisomy
5 environmental factors for disease
- Teratogens
- Radiation
- Chemicals
- Drugs
- Infection
When undifferentiated, rapidly dividing cells mutate, they form rapidly dividing tumors. A neoplasm or tumor that is harmful, resisting treatment, threatening to produce death
Malignant Tumors (cancers)
the more differentiated a cell is when it mutates, the more likely it will become a 1; if poorly differentiated cells mutate, the tumor is more likely to become a 2
- Benign tumor
2. Malignant tumor
tissue name + carcinoma
Epithelial tissue
tissue name + sarcoma
Mesenchymal Tissue
effects of malignant tumors on the organ system include?
inflammation and damage, which ultimately lead to organ failure. In all cases the organ cannot function optimally, and is unable to secrete the normal/typical amount of hormones.
benign tumors may cause ? of normal organ secretions
overproduction
Grow rapidly, not encapsulated, invasive, poorly differentiated, high mitotic index, can spread distantly (metastasis)
Malignant
Grow slowly, well-defined capsule, not invasive, well differentiated, low mitotic index, do NOT metastasize
Benign
Growth of new vessels to provide blood supply to cancer
Advanced cancers can secrete these factors (VEGF)
Not likely to occur in small cancers, as cancers grow they need there own blood supply for oxygen and nutrients
Angiogenesis
environmental risk factor for cancer;
Multipotent carcinogenic mixture
Linked to cancers of the lung, lower urinary tract, aerodigestive tract, liver, kidney, pancreas, cervix uteri
Linked to myeloid leukemia
Tobacco
environmental risk factor for cancer;
Emission from x-rays, radioisotopes, and other radioactive sources
Exposure causes cell death, gene mutations, and chromosome aberrations
Bystander effects
Poor gene repair
Changes in gap junction intercellular communication
Ionizing Radiation
environmental risk factor for cancer;
Causes basal cell carcinoma, squamous cell carcinoma, and melanoma
Principal source is sunlight
Ultraviolet A (UVA) and ultraviolet B (UVB)
Promotes skin inflammation and release of free radicals
Ultraviolet Radiation
environmental risk factor for cancer;
Risk factor for oral cavity, pharynx, hypopharynx, larynx, esophagus, and liver cancers
Cigarette/alcohol combination increases a person’s risk
Alcohol Consumption
environmental risk factor for cancer; Carcinogenic types of human papillomavirus
High-risk HPV
Sexual Reproductive behavior
environmental risk factor for cancer;
Reduces cancer risk
Decreases insulin and insulin-like growth factors
Decreases obesity
Decreases inflammatory mediators and free radicals
Increased gut motility
Physical activity
environmental risk factor for cancer;
Asbestos
Dyes, rubber, paint, explosives, rubber cement, heavy metals, air pollution, etc.
Radon
Occupational Hazards
environmental risk factor for cancer;
Xenobiotics
Toxic, mutagenic, and carcinogenic chemicals in food
Activated by phase I activation enzymes
Defense mechanisms
Phase II detoxification enzymes
(Ex: cooking of fat, meat, proteins/ mold by-products)
Diet
How do you determine tumor grading?
Cell Differentiation
- classifies cancer cells
- degree of microscopic abnormality
- struc and growth pattern of the cells–how differentiated they are
- determines the tumor growth and spread potential
Increased nuclear size, loss of differentiation- act embryonic-very little differentiation. divide more frequently; replicate easily; rapid growth; the more of this=the more serious the cancer
Anaplasia
vary in size and shape
Pleomorphism
Oncogenic virus is one that can induce cancer. How many DNA viruses have been implicated in human cancers
4
pathogenesis squamous cell carcinoma of the cervix and anogenital region. Cervical cancer can be viewed as an STD, caused by transmission of it
HPV
member of herpes virus, has been implicated in pathogenesis of Burkitt hymphoma, nasopharyngeal cancer, B-cell lymphoma, nasopharyngeal cancer, B-cell lymphomas in immunosuppressed (AIDS) and some cases of Hodgkin lymphoma.
Epstein- Barr Virus (EBV)
Chronic HBV and HCV infection with hepatocellular carcinoma due to immunologically mediated chronic inflammation leading to persistent liver damage, regeneration, and genomic damage. The regeneration process is mediated by a vast array of growth factors, cytokines, chemokines, and bioactive substances produced by immune cells that promote cell survival, tissue remodeling, and angiogenesis.
Hepatitis B Virus (HBV)
Causes Kaposi sarcoma in persons with AIDs
Human Herpes Virus 8 (HHV-8)
only known retrovirus to cause cancer in humans- associated with form of T-cell leukemia. It is attracted to CD4+ T cells, which is the major target for cancerous transformation. The virus requires transmission of infected T cells by way of sexual intercourse, infected blood, or breast milk
Human T-cell Leukemia Virus-1 (HTLV-1)
Helicobacter Pylori; gastric adenocarcinoma and gastric lymphomas are what?
Bacterial causes of cancers
Degree of cancer spread (3)
- Local 2. Regional 3. Distant
Clinical staging for Carcinoma: Stage 1: Stage 2: Stage 3: Stage 4:
Stage 1: confined to the original organ
Stage 2: Locally invasive
Stage 3: Spread to regional sites (Lymph nodes)
Stage 4: Spread to distant sites (metastasis)
Tumor grading: GX: G1: G2: G3: G4:
GX: Grade cannot be assessed (undetermined grade)
G1: Well-differentiated (Low grade)
G2: Moderately differentiated (Intermediate grade)
G3: Poorly differentiated (high grade)
G4: Undifferentiated (high grade)
Tumor grading is used to identify 4
- How differentiated the cells are
- How much the cancer cells have spread
- the size of a solid tumor
- the involvement of lymph nodes
Can damage or destroy some neoplastic cells;T cells recognize the abnormal cells and destroy them
Antibodies form in response to parts of the abnormal cell protein
Cancer’s effect on blood cells
Risk for developing serious infections
Neutropenia
Increases risk for bleeding
Thrombocytopenia
increases vascular permeability; mitogenic for endothelial cells of blood vessels.When it is overexpressed, it can contribute to disease. Solid cancers cannot grow beyond a limited size without an adequate blood supply; cancers that can express this are able to grow and metastasize
Vascular Endothelial Growth Factor (VEGF)
Systemic treatment that enables drugs to reach the site of the tumor as well as distant sites. It may be used as primary form of treatment or as part of a multimodal treatment plan.
Chemotherapy
It is the primary treatment for most hematologic and some solid tumors, including choriocarcinoma, testicular cancer, acute and chronic leukemia, Burkitt lymphoma, Hodgkin disease, and multiple myeloma
Chemotherapy
Triggering suicide of cancer cells
Apoptosis
Chemo suppresses bone marrow function and formation of blood cells, leading to anemia, neutropenia, and thrombocytopenia.
Anorexia, nausea, vomiting
Alopecia/hair loss
Toxicity to all cells
acute (after a few days), intermediate(within weeks), or long term( months-years)
Adverse effects of Chemotherapy
Goals of Cancer treatment: Destroying cancer cells through several methods
Surgery to remove them; stimulation of the immune system to destroy them; radiation therapy to destroy them; drug therapy to kill them during various phases of the cell cycle.
exert their action during a specific phase of the cell cycle
Cell cycle specific
exert effects throughout all phases of the cell cycle
Cell cycle-nonspecific
React chemically with portions of the RNA, DNA, or other cellular proteins
Alkylating Agents
Have chemical structures similar to those of natural metabolites
Antimetabolites
Not selective only for bacterial cells; toxic to human cells
Antineoplastic Antibiotics
Drugs that kill cells as the process of mitosis begins
Mitotic Inhibitors
Used in cancers that are sensitive to estrogen stimulation
Hormones and Hormone Modulators
Treat chronic myeloid leukemia (CML) and CD117-positive unresectable or metastatic malignant GI stromal tumors (GIST)
Cancer Cell Specific Agents
Chemotherapy induced nausea and vomiting (CINV)
Prevention of CINV is most effective; tx is very difficult once it has begun; tx Pt PRIOR to administration of chemotherapy; select meds to control nausea/ vomiting.
promote the synthesis of various types of major blood components by promoting the growth, or differentiation, and function of their precursor cells in the bone marrow
Hematopoietic Drugs
