Case Studies Flashcards
Pattern of Inheritance – Autosomal dominant
Mutation in DNA repair genes
Sickle Cell Disease
- Pattern of Inheritance - Autosomal recessive
- Single base mutation - Beta-globin gene
- Affects hemoglobin - cells “sickle” causing pain
- Aneuploidy (chromosome number that is not 23)
- Chromosomal disorder is trisomy 21
- Occurs due to nondisjunction
- associated with advanced maternal age
- Pattern of Inheritance – X linked recessive
- – the defective gene is located on the X chromosome
- Results in a deficiency of clotting factor VIII
- Pattern of Inheritance - Autosomal recessive
- Single gene - Chromosome 7
- Cystic fibrosis transmembrane regulator (CFTR) - impaired chloride transporters
- Dx: chorionic villa sampling, amniocentesis, sweat test
- 25% chance child will have it, 50% chance child will be a carrier
- Condition caused by the body overheating
- S/S: hyperthermia, altered mental status, N/V, tachy
- Negative feedback inhibition: A type of regulation in which the end produce of a process in turn reduces the stimulus of the same process (Once we get enough of a hormone the body says stop producing) - Try to maintain homeostasis
- Physiological changes resulting from elevated temp:
- — Direct cellular damage
- — Locale effects
- — Systemic effects
- Angina = chest pain
- Infarction = reduction of blood flow and oxygen that causes chest pain
- Troponin & creatine-kinase are biomarkers to detect injury. TIME IS MUSCLE
- Artherosclerosis - thickening of arteries due to plaque
- – heart has to pump harder, increasing BP
- – Increased BP = increase in muscle on the L side o heart = ventricular hypertrophy
- Ventricular hypertophy causes:
1) hypertrophic cardiomyopathy
2) aortic valve stenosis
3) athletic training
- Cannot respond to stress through hyperplasia because the cells are not able to - only can hypertrophy
- -Reperfusion injury - is the assault that occurs when cells/tissues have been deprived of oxygen (for a prolonged period) and then oxygen is reintroduced. –Hypoxia/ischemia is the initial mechanism of cell injury, followed by excess ROS which formed in the absence of/limited oxygen. Additionally due to low metabolic processes, proteins/enzymes such as SOD and catalase have not been produced and are depleted.
- -Mechanism: SOD converts superoxide into hydrogen peroxide and catalase converts hydrogen peroxide into water and oxygen
- -Recruitment of immune cells gives rise to inflammation that can cause more damage over time (phagocytic process of consuming dead tissues but end-up destroying healthy tissues too). Plaque formation, change in complement proteins, change in vasoconstriction/dilation, etc.
- -ROS is present in oxygen environments. When body area has limited or decreased flow, the enzymes that combat the ROS are depleted. When oxygen is restored the excess ROS’ have nothing to counteract or terminate them. Excess ROS causes cell damage, leaking membranes, calcium influx, and ultimately cell death.
- –Antioxidants are natural and synthetic molecules that inhibit the reactions of ROS with biologic structures or prevent the uncontrolled formation of ROS. Antioxidants include enzymatic and nonenzymatic compounds. Catalase can catalyze the reaction that forms water from hydrogen peroxide. Nonenzymatic antioxidants include carotenes (e.g. vitamin A), tocopherols (e.g. vitamin E), Ascorbate (e.g. vitamin C), glutathione, flavonoids, selenium, and zinc.
- Poor oxygenation of tissues = tissue ischemia
- Dry gangrene: no infection, coagulative necrosis
- Wet gangrene: liquefactive necrosis, bacterial infection, pus
- treatment: antibiotics, debridement, maggot therapy
- Gas gangrene: form of wet gangrene. Clostridium bacteria into wounds (eg frostbite) - spread quickly
–Cancer cells do not follow normal growth signals of the cell. Due to genetic damage or mutations to cell
–Due to proto-oncogenes being transformed into oncogenes
–Alters the growth factors of the genes in the cell causing proliferation
• Cancer cells are characterized by: abnormal and rapid proliferation and loss of differentiation
• Growth regulation is lost with cancer cells
• Oncogenes are normally associated with cell growth (proto-oncogenes in normal state, which encode growth factors in the cells) and “mutate” into oncogene state” if they are enzymes that are involved in cell growth, or receptors for cell growth, which become mutated and stay “oN” or over stimulated there becomes unregulated growth which stimulates ongoing proliferation (cancer)
–cells become immortalized because the cancer cells add telomeres to the ends of their chromosomes. Then they continue to divide again and again and they never get so few telomers that the body gives a signal to say it’s time for the cell to die. Resulting in continuous proliferation.
—Terminally Differentiated means the cell lose their ability to proliferate. For example, erythrocytes become differentiated (specialized and no longer divide)
Oncogenic Viruses can induce cancer because they are small particles with DNA or RNA which enter a host cell and become incorporated in its chromosomal DNA take control of replication and produce viral proteins as a result of the invasion.
—There are two vaccines available to protect against HPV: The vaccine stimulates the body to produce antibodies that when encountered by the virus bind to the virus and prevent it from infecting cells. Vaccines contain virus like particles but not the viral DNA and have found to produce strong immunogenic effects
–The retinoblastoma gene or pRB is a tumor suppressor gene. Tumor suppressor genes have genetic mechanisms that protect cells against activated or newly acquired oncogenes. When pRB is inactivated and that genetic signal that inhibits cell proliferation is removed, unregulated growth will begin.
–Oncogenes promote proliferation through secretion of growth factors and hormones
–DNA repair genes fix DNA mutations. This gene is highly associated with the cancer HPNCC
pRB genes act as the break to the cell, it stops the cell at the R point restricts the cell from G0 to G1. pRB is signaled by phosphorylation to release the cell to G1 by receiving signals from hormones or another signal
–When interrupted, cells keep replicating without regard to need for proliferation. The R point is disregarded and the cells replication is not restricted. This leads to a tumor.
–Mutations in tumor suppressing genes such as pRB are generally recessive, in that cells tend to behave normally until there is homologous deletion, inactivation or silencing of both the maternal and paternal genes. This can occur through replication
— Autosomal dominant inheritance pattern.
–A person’s chance of developing colorectal cancer by genetic means increases when that person has the following:
—-Two or more 1st or 2nd degree relatives (or both) with colorectal CA
—-These make up 20% of all patients with colorectal CA a family history of cancer, Crohns or UC diagnosis
Diagnosis of FAP
—-Colorectal cancer is also likely to develop due to long term dietary habits
-CEA (carcinoembryonic antigen) is fetal antigen normally only present during embryonic development
—-Produced by embryonic tissue in the gut, pancreas, and liver and is associated by a number of different cancers
—-Has limited value in screening tests, not specific enough for a diagnosis, but once a malignancy has been diagnosed and shown to be associated with elevated CEA it can be used to assess response to treatment
—-Tumors are named by suffix