MicroBiology and Pathophysiology
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| Neoplasm | group of cells with single
progenitor and mutation(s) leading to growth
advantage and proliferation
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| Oncology | study of cancer
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| Neoplasia | new growth
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| Malignant | neoplasm with invasive capability
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| Benign | neoplasm confined to a location
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| Cancer | crab
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| Carcinoma | epithelial origin - 80% cancers
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| Sarcoma | mesenchymal origin
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| Tissue name + oma | usually benign exceptions being lymphoma, thymoma, melanoma
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| Differentiation - resemblance to normal |
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| Anaplasia | “backward formation”
– Pleomorphic - variable size and shape
– Variable and bizarre nuclei
– Loss of polarity / organizational pattern
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| Undifferentiated or anaplastic tumor cells | no longer resemble tissue of origin
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| Dysplasia | disorderly but non-neoplastic
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| Metastasis | Secondary implant of tumor
discontinuous with primary tumor; Not all cancers have this ability; Sentinel lymph node
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| Dissemination via: | Seeding within body cavity (invasion of cavity)
– Lymphatic spread (favored by carcinomas)
– Hematogenous spread (sarcomas (venous))
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| Epidemiology | incidence, geography, environment, age, hereditary, preneoplastic lesions
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| Classic model of carcinogenesis - 3 stages | 1. initiation 2. promotion 3. progression
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| Initiation | - rapid, un-repaired first mutation; irreversible
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| Promotion | - proliferation, then an “epigenetic” process (chemical but not genetic) affects gene expression, fosters development, ends with carcinogenesis; cell “transformed” to malignant
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| Progression (continued development after malignancy) | - acquisition of further mutations required for metastasis
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| What are the hallmarks of cancer? | Self-sufficient in growth signals (unregulated);Inhibitory signals ignored; Evasion of cell death; Limitless replicative potential; Angiogenesis; Ability to invade local tissues (and spread); Altered metabolic pathways;Immune system evasion
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| Carcinogenic agents | virus, radiation, chemicals
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| Grade/Staging | Grades - malignancy and Stage - of development
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| Grade - of malignancy | - of Malignancy - I-IV reflect increasing anaplasia
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| Stages of development | - of Development based on size of tumor, extent of lymph spread, metastases or not
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| TNM system | T1-4, NO-3, MO-1
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| AJC method | 0- IV
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| Infectious Agents | Prions, Viruses, Bacteria, Fungi, Protozoa, Helminths (Ectoparasites)
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| Prions | abnormally folded proteins, BSE - bovine spongiform encephalopathy -
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| accumulation of prion protein causes | neural spongiform damage
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| Viruses | Intracellular parasites, DNA or RNA genome, surrounded by capsid; Transient or persistent (Chronic or latent); Can be tumor-causing
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| Bacterial shapes | Sphere, rod, spiral
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| Gram Staining | positive or negative (easier vs. harder to treat)
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| Bacterial factors | Obligate intracellular, facultative intracellular, or extracellular; Projections: Flagella, pili; Colonize skin and GI tract >3000 types in normal gut! Estimated 10 m - 1 b types; shapes, aerobic or anaerobic, gram staining, shapes- sphere, rod, spiral
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| Gram positive factors | one layer, thick, absent outer membrane, possible periplasmic space, petidoglycan, teichoic acid and lipotechoic acid, less lipid, no porin proteins, more penetrable permeability, less resistance to molecules
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| Gram negative factors | two layers, thin, outer membrane, periplasmic space, porin proteins, more lipid, less peptidoglycan, less permeability of molecules, lipopolysaccharide, peptodoglycan, lipoportei
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| Eukaryotic | have membrane bound organelles
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| Prokaryotic cells (inc. bacteria) | are much smaller and simpler, with no separate organelles
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| Fungi | Food!, Antibiotics, Fermentation; Thick walls and membranes; Yeast or Hyphae
Superficial or Deep infxns; Endemic or Opportunistic
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| Protozoa | single-celled, replicate intra or extra- cellularly , major problem in developing countries
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| Protozoa causing diseases | Toxoplasmosis, malaria, giardia, amoebic dysentary, African sleeping sickness, cryptosporidium, trichomonas
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| Helminths | parasitic worms, complex life cycles, roundworms, tapeworms, flukes
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| Ectoparasites | insects, arachnids, live on or in skin
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| modes of identifying | staining, antibodies, molecular techniques
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| Major contributing Factors to emerging infectious diseases | human behavior, environmental changes, adaptive pathogens
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| Bioterrorism danger based on | transmissibility, mortality, ease of production, effectiveness of therapy
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| Categories of bioterrorism | A - high risk; anthrax, small pox B- moderate; salmonella, e.coli C- emerging threats
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| Transmission routes of entry (and protective factors) | skin - pricks, bites, wounds, burns , GI - fecal contaminated food or water; respiratory - inhaled microbes, Urogenital - urethra - BL-KD, Vaginal
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| protective factors of skin | - Keratin, pH, fatty acids
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| protective factors of GI tract | acid, mucus, enzymes, peptides, flora, IgA
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| protective factors of respiratory | hair, mucus, cilia, macrophages
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| protective factors of urogenital | tube length, urine flow
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| protective factors of vaginal | pH, flora, secretions
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| Infx, dz spread within the body through | direct invasion - secrete lytic enzymes(some ext. cellular bacteria, fungi, helminths) blood or lymph spread (viruses, most bacteria, some protozoa, all helminths) cell to cell (most viruses)
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| Every fluid or tissue that is normally secreted, excreted, or shed is used by microorganisms to leave the host for transmission | Skin, saliva, respiratory droplets, feces, blood, STIs, vertical transmissions
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| how do microorganisms cause disease? Viral mechanisms | directly enter host cells, replicate at host's expense, bind to specific cell types, cytopathic effects, evade immune system
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| cytopathic effects | prevent synthesis of critical molecules, induce apoptosis, trigger immune attack of affected cells, transform infected cells into benign or malignant tumor cells,
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| How do bacterial mechanisms cause dz? | adhere to host cells, enter cells (intra. cellular b.) or travel btw cells, produce toxins, evade immune system; injurious immune response - hypersensitivity( delayed immune reaction, antibody complex formation)
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| immune evasion techniques | antigenic variation(mutation, genetic shuffling, diverse serotypes, inactivating antibodies, resisting phagocytes,(resist binding of cells, inhibit or kill) suppressing adaptive responses
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| HSV 1, 2, VZV (3) | live in nerves, destroy infected cells - Herpes, Human Papilloma Virus, Varicella and Zoster
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| CMV (5) HHV 6, 7 | live in WBCs in blood, KD, glands; enlarge infected cells - cytomeglovirus and shingles chicken pox
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| EBV (4) HHV 8 | live in lymphoid tissue, infect T or B lymphocytes only - Kaposi syndrome
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| Gene | - hereditary factor that reacts with environment resulting in a trait
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| Allele | - variant of a gene (you inherit two alleles for each gene, one from each parent)
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| Trait - quantifiable characteristic eg eye color | quantifiable characteristic eg. eye color
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| Chromosome | - strand of DNA encoded with genes (humans have 22 pairs plus 2 sex chromosomes = 46)
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| Locus - location of a specific gene on a chromosome | location of a specific gene on a chromosome
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| Heterozygous (hybrid) | - alleles of a particular gene are non-identical
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| Homozygous | - alleles of a particular gene are identical
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| Autosomes | - “non-sexual” chromosomes
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| X- (and Y-) linked - | locus for gene is on sex chromosome
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| Dominant | - only one allele of a gene necessary to express the trait
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| Recessive | both alleles of a gene must be identical to express the trait
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| Genotype - | genetic constitution of an individual made up of alleles
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| Phenotype - | end result of genetic and environmental factors giving the clinical state of an individual
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| hereditary | derived from one's parents
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| congenital | present at birth ; Not always genetic, eg congenital syphilis
Not all genetic disorders are congenital, eg Huntington’s disease
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| Important to know about genes | every cell has all genes, same DNA, 20-39,000 human genes, 99.5% idential in all humans, DNA organizes in chromosomes, chromosomes organized into genes, genes code for proteins mostly, DNA made up of base pairs
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| Base pairing - | adenine can form two hydrogen bonds with Thymine; Cytosine can form three hydrogen bonds with Guanine
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| DNA | 2 complementary strands, sequence of one determines the other - double helix
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| RNA | single stranded, may form secondary structures, participate in protein synthesis, 3 classes - messenger RNA, transfer RNA, ribosomal RNA
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| Genetic code | based on sequence of mRNA which is made up of nucleotides while proteins are made up of amino acids; must be specific relationship btw the nucleotide sequence and amino acid sequence, 3 N (a codon) for one amino acid
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| Essential amino acids | cannot be made by the body; must come from food - Nine: histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine
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| Nonessential amino acids | produced by the body; Alanine, asparagine, aspartic acid and glutamic acid
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| conditional amino acids | non usually essential except in times of illness & stress. Arginine, cysteine, glutamine, tyrosine, proline, serine, glycine, ornithine,
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| genetic mutations | permanent change, point mutation aka "missense" nonsense mutation, framshift, Trinucleotide repeat eg. Fragile X
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| other alterations | sequence and copy number variations (polymorphisms, SNPS & CNVs); epigenetics(methylation) non coding RNA ( regulatory )
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| Genomic Imprinting | inherit only one working copy, depending on gene one is epigenetically silenced through the addition of methyl groups during egg or sperm formation - imprinting improperly can lead to 2 active/inactive copies - abnormals, cancer, etc.
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| Angelman Syndrome (AS) | Severe congenital mental retardation, unusual facial appearance, and muscular abnormalities ; Caused by abnormal function of a gene on chromosome 15; Maternal deletion
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| Prader- Willi Syndrome (PWS) | Obesity, low muscle tone, cognitive disabilities, and incomplete pubertal development; Loss of several genes on the chromosome 15; Paternal deletion
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| Mendel's Laws (Principles) | Segregation, Independent Assortment, Means - (The above principles include the simple assumption that one allele is dominant to another)
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| Segregation - M.law | gene pairs segregate (become alleles) when forming gametes (a parent will give only one copy to a child, a child is half and half of each parent)
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| Independent Assortment- M. law | genes for different traits assort independently of one another;
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| Means - M.law | Characteristic ratios of phenotypic classes, such as 3:1
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| Single gene defects | autosomal recessive, autosomal dominant, X linked
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| AR inheritance: If both parents are carriers of the recessive allele for a disorder, all of their children will face the following odds of inheriting it: | AR: Autosomal Recessive Inheritance;
25% chance of having the disorder
50% chance of being a healthy carrier
25% chance of being healthy and not carrying the recessive allele at all
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| AR diseases - both parents carriers | Examples: sickle cell anemia, cystic fibrosis, albinism, beta-thalassemia
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| AR Inheritance: If one parent is a carrier and the other has a recessive disorder, their children will have the following odds of inheriting it: | 50% chance of being healthy carrier, 50% change of having disorder
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| Autosomal Dominant AD | disorders caused by dominant alleles, inheriting just one copy of D allele is enough to cause disorder, people who are heterozygous are not healthy carriers(Aa) they have disorders just like homozygous individuals (AA)
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| AD inheritance - if only one parent has a single copy of a dominant allele for a dominant disorder, their children will have the following odds of inheriting it | 50% inheriting disorder, 50% being entirely normal
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| AD diseases | Huntington, polydactyly, familial hypercholesterolemia, Marfan syndrome, achondroplasia dwarfism
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| X linked Disorders - recessive | Hemophilia, Duchenne muscular dystrophy, red green color blindness
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| Mutation induced disorders - Marfan, Ehler Danlos, Cystic Fibrosis, Familial hyperCHL, PKU, Galactosemia, TaySachs, Neimann Pick, hereditary tumors | Structural protein encoding genes, Receptor or channel encoding genes, enzyme encoding genes, lysosomal and glycogen storage dz, cell growth regulating genes
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| chromosomal disorders | Trisomy 21 - Down, Klinefelter Syndrome (XXY), Turner Syndrome (X)
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| Klinefelter Syndrome (XXY) | Sterility, testicular atrophy, gynecomastia
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| Trisomy 21 - Down Syndrome | Prenatal - nuchal thickening, distinct appearance, mental disorders, increased risks
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| Turner Syndrome (X) | Sterility, webbed neck, aortic coarctation
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| Dysostoses | aplasia, missing, extra, abnromal fusion
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| dysplasia | osteogenesis Imperfecta (brittle bones OI) Achondroplasia(dwarfism - inherited or spontaneous mutation, osteopetrosis - bones like stones
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| bones made of up | minerals and collagen
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| Acquired bone disorders | osteoporosis , Paget disease, Rickets, osteomalacia, hyperparathyroidism
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| Osteoporosis | loss of bone mass, can be regional(disuse), increased susceptibility to fracture, post menopausal - trabecular bone, compression fractures(vertebral collapse) senile or age related - cortical bone, fractures or weight baring bones - neck
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| causes of osteoporosis | primary - post menopausal, old age; secondary - endocrine disorders, GI disorders(absoprtion) drug exposures (steroids, chemicals, alcohol)
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| Paget disease | frenzied osteolysis , disordered rebuilding, resulting gain in bone mass - decreasing incidence, inflammatory response - may have viral trigger
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| RIckets and Osteomalacia | Vitamin D deficiency - children/deformity ; adults/under mineralization, fracture risk
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| PTH | regulates CA - activates osteoclasts, increased serum levels - entire skeleton affected, increased fracture risk, bone deformity, joint problems, reversible
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| Most common bone pathology of fractures | complete/incomplete, closed/compound; comminuted "pulverized" displaced
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| healing fracture | soft tissue callous, bony callous, remodeling
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| osteonecrosis | avascular necrosis - common in femoral head, knee shoulder ankle wrist - pn in joint first symptom, interruption in blood flow (infarction) due to trauma, inflammation, steroid use or unknown causes
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| osteomyelitis | bone and marrow inflammation caused by infection - common agents in include pyogenic or pus forming bacteria such as strep, e.coli, salmonella and TB, staph
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| osteoma | benign usually head and neck middle age, cosmetic or mechanical problems
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| osteoid osteoma and osteoblastoma | benign usually male - teens painful
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| osteosarcoma | malignant, rare, incidence peaks in teens and elderly
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| Osteochondroma | common, benign, long bones stop growing with rest of bone - early adult, teens
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| chondroma | benign, middle age, short tubular bones
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| chondrosarcoma | malignant, rare, usually in males +40 - painful
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| fibrous and fibroosseous tissue | fibrous cortical defects and nonossifying fibroma - development abnormalities, asymptomatic
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| fibrous dysplasia | benign - asymptomatic or deforming depending upon location
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| Ewing sarcoma | malignant, painful , tubular and flat bones
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| primitive neuroectodermal tumor | malignant, painful , tubular and flat bones
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| Giant cell tumor (GCT) | benign, aggressive, males and females 20-40, painful, often around knee
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| Metastases - any cancer can go to bone | most common bone malignancies
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| Joint disorders | osteoarthritis, RA, Juvenile RA, gout pseudogout, infectious arthritis, tumor
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| OA - aka degenerative joint disease (DJD) | articular cartilage underlying bone - primary due to age, secondary trauma, deformity dz, obesity
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| RA | systemic, inflammatory autoimmune - synovitis under cartilage underlying bone, 3x5 more females, genetic predisposition, usually symmetric affecting small joints, nodules, deformity, RA factor (Ab) immune complexes
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| Gout | acute arthritis due to uric acid crystal deposits 1% pop. more in males
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| Infectious arthritis | suppurative (septic) Lyme arthritis
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| Joint tumors and lesions | ganglion and synovial cysts - TGCT -
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| Soft tissue = not epithelial | bone, cartilage, CNS, blood, lymph
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| Tumors and tumor like lesions in soft tissue | adipose- liposarcoma, lipoma, fibrous tissue - fibrohistiocytic(dermal), skeletal mm - Rhabdomyosarcoma, Smooth mm - leiomyoma, synovium - synovial sarcoma
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| How do microorganisms cause disease? | bacterial mechanisms & injurious immune response (hypersensitivity - delayed reaction of immune system,; antibody complex formation.
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| Bacterial mechanism | adhere to host cells, enter cells or travel btw, produce toxins, evade immune system
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| Adverse drug reactions |
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| Heavy metal toxicity - symptoms of most common | lead exposure is absorped through LU or GI tract; organic is absorbed through skin - BONE, BLOOD, MARROW, NS, GI and KIDNEYS - targets; effects anemia to pain to peripheral neuropathy and encephalopathy
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| how are toxins excreted | Through excretory derivatives(polar water soluble ) bile, feces, serum, kidneys, urine
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| how and why is CO dangerous | result of incomplete combustion, safe in small amounts, displaces 02 from hemoglobin and binds to hemoglobin for long time, decreased 02 supply, can cause death
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| Xenobiotics - | exogenous chemicals that may be absorbed by the body through inhalation, ingestion, or skin contact
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| 2 phages of the Liver & reactions | Metabolizing reactions occur in 2 phages - I (hydrolysis, oxidation or reduction(cytochrome p450) and II - glucuronidation, sulfation, methylation, and conjugation with gulathione (GSH)
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| Endotoxins | end products of metabolism, bacterial endotoxins.
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| lipid soluble toxins are stored in | adipose tissue and contribute to increased toxic load with weight loss
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| Liver Detoxification pathway - Cytochrome 450 - catalyzes reactions that | are either detoxify xenobiotics or active them into active compounds that cause cellular damage if not removed or processed further (both product ROS)
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| ROS | reactive oxygen species capable of causing cellular damage
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| Liver Detoxification pathway- Cytochrome 450 | participates in metabolism of many common drugs such as acetaminophen, barbiturates, anticonvulsants, and alcohol; activity varies widely due to genetic and environmental factors - smoking fasting and alcohol use can effect activity
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| air pollutants can cause | increased airway reactivity, decreased lung function, inflammation of LU, infection, hypoxia, mortality
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| Lead toxic effects | hemolytic anemia, lead colic, kidney tubule inflammation, neuritis, encephalopathy, seizures, delayed development, intellectual impairment, lead lines
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| Toxic metals - Mercury | Inorganic - dental fillings, organic - fish - manifestation of toxicity depend on type and level of exposure, age and health of exposed person.
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| Signs of severe Mercury poisoning | tremors, inflammation of the gums, salivation excessive, psychiatric symptoms such as excitability, insomnia, and shyness (MAD HATTER)
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| Vitamins are | organic substances not synthesized by the body but necessary in the diet to prevent metabolic disorders
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| Deficiencies of any of the water soluble or fat soluble vitamins and trace elements necessary to a health diet cause | characteristics effects of "deficiency states"
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| Vit. A deficiency | night blindness, low immunity
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| Vit. D deficiency | Rickets in kids, osteomalacia in adults
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| Vit. E deficiency | hemolysis, vision and neurological problems
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| Vit. K deficiency | bleeding tendency
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| Vit. B1 - Thiamine | Beriberi ( nerves, heart, muscles)
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| Vit. B2 - Riboflavin | cheilosis, stomatitis, glossitis, dermatitis
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| Vit B3 - niacin | dementia, dermatitis, diarrhea
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| Vit B5- pantothenic acid | fats, hormones, cholesterol metabolism
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| Vit. B6 - pyridoxine p5p | anemia, inflammation, morning sickness
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| Vit B7 -biotin | alopecia, skin rash
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| Vit. B9 - folate | anemia, birth defects
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| Vit. B12 - cobalamin | anemia, neuropathies
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| VIt. C | scurvy
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