272 terms

Patho Exam 1

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Delirium
An acute, reversible organic mental syndrome characterized by confusion, disorientation, restlessness, incoherence, fear and often illusions
Etiology
The study or theory of all factors that may be involved in the development of a disease, including susceptibility of an individual, the nature of the disease agent, and the way in which an individual's body is invaded by the agent: or the cause of the disease
Fetal Alcohol Syndrome
Condition resulting from exposure of a fetus to alcohol; characterized by mental handicaps, growth deficit, and physical disability
Histology
The branch of anatomy that deals with the minute () structure, composition and function of cells and tissues.
Iatrogenic
Induced inadvertently through the activity of a physician or by medical treatment or diagnostic procedure
Idiopathic
Arising spontaneously or from an unknown cause
Morphology
The study of the physical form and structure of an organism; or the form and structure of a particular organism
Pathogenesis
The origination and development of disease or illness; describe the sequence of cellular and tissue events that occurs from the time of first contact with an etiologic agent until the disease becomes evident; disease evolution, it is the story of the disease
Primary Prevention
Actions or activities that prohibit a disease condition from occurring. Primary Prevention - PREVENTS - includes activities provided to individuals to prevent the onset or acquisition of a given disease. The goal of primary prevention is to spare individuals the suffering, burden and cost associated with the clinical condition. Examples: health-protecting education and counseling, car restraints, bicycle helmets; fall prevention and accidents for elderly; immunization
Secondary Prevention
Early detection and treatment of disease through screening. Secondary prevention includes activities that identify and treat asymptomatic persons who have risk factors for a given disease or in preclinical disease. Secondary Prevention SCREENS - mammography and cervical examinations, blood pressure measurement, blood to determine lipid levels.
Senescence
The process or condition of aging or growing old; post-maturational processes the lead to diminished homeostasis and increased vulnerability; used interchangeably with aging, can have cellular senescence
Symptom
An indicator that is reported by an ill individual and is often considered a "subjective" manifestation
Syndrome
A complex of signs and symptoms that occur together or a compilation of signs and symptoms characteristic of a clinical picture or a specific disease state.
Teratogen
Any agent or factor that induces or increases the incidence of developmental abnormalities in a fetus; agents cause physical defects in developing embryo
Tertiary Prevention
Directed at clinical interventions that prevent further deterioration or reduce complications of a disease once it has been diagnosed. Management of a person's disease. TERITIARY - TREATMENT.
Teratogenic Agents
1. Environmental agents that produce abnormalities during embryonic development in utero.
2. Maternal disease or metabolic dysfunction can affect the baby's or embryo in utero environment as well.
Causes birth defects:
a. Direct exposure of the pregnant woman and the baby to the agent
b. Exposure of the soon-to-be pregnant woman with an agent that has a slow clearance rate
c. Mutagenic effects of an environmental agent that occur before pregnancy, causing permanent damage to woman or man' reproductive cells.
Radiation
1. Cause microcephaly, skeletal malformation and mental retardation
2. It is teratogenic and mutagenic and bring the risk of genetic material alteration
Drugs and Chemical Substances
• **Most drugs can cross the placenta and expose the baby to both pharmacologic and teratogenic effects.
• Lipid-soluble drugs ten to cross the placenta more readily and enter the baby's circulation.
• Molecular weight of a drug also influences the rate of transfer and the amount of drug transferred across the placenta (< 500 - easy; >1000 poor)

1. Alcohol
2. Cocaine
Alcohol
a. Most common teratogenic drug used in the U.S.
b. Leading cause of birth defects in certain parts of the U.S
c. Top cause of mental retardation in the U.S.
d. At any dose it is capable of causing neurologic deficits and facial deformities ranging from mild to sever
FETAL ALCHOL SYNDROME:

Description:
4000 children are born in the US each year with this diagnosis. At any dose, alcohol is capable of causing neurologic deficits and facial deformities ranging from mild to severe.
FETAL ALCHOL SYNDROME:

Etiology:
Maternal alcohol consumption.
FETAL ALCHOL SYNDROME:

Pathophysiology:
a. Alcohol adversely affects several cellular functions associated with fetal development: DNA synthesis, protein synthesis, glucose uptake, and the development of neural signaling pathways.
b. ETOH is lipid soluble and has a molecular weight of 600-1000. It can pass across the placental barrier.
c. Baby's ETOH level will be the same as the mom. The harmful effects extend the ENTIRE pregnancy.
FETAL ALCHOL SYNDROME:

Clinical Manifestations:
a. Mild- severe
b. Facial characteristics become more pronounced as the baby develops.
c. Growth retardation, CNS abnormalities, Cognitive abnormalities, intellectual deficits, birth defects
d. Timing and amount of ETOH consumption all play a role.
FETAL ALCHOL SYNDROME:

Timing and amount of ETOH consumption
a. 3 drinks/day has demonstrated decreases in IQ by 4 years of age
b. ETOH consumption during organogenesis has shown skeletal and organ defects
c. ETOH in late gestation - behavioral and cognitive disorders in the absence of physical disorders.
FETAL ALCHOL SYNDROME:

Treatment/Intervention:
IT IS 100% PREVENTABLE.

US Surgeon General and the Academy of Pediatrics Recommendation - Abstain entire pregnancy.
COCAINE BABIES

Pathophysiology:
a. Decrease in uteroplacental blood flow
b. Maternal Hypertension
c. Stimulates uterine contractions
d. Fetal Vasoconstriction
e. Dose and time dependent
COCAINE BABIES

Clinical Manifestations:
a. Increase preterm births (uteroplacental blood flow)
b. Intrauterine growth retardation
c. Microcephly
d. Neurologic abnormalities
e. Abruptio placenta (maternal hypertension/decrease in uteroplacental blood flow)
f. Limb reduction and urogenital tract defects (hydronephoris, hyospadias and undescended tests, as well as ambiguous genitalia (fetal vasoconstriction)
g. Destructive brain lesions (Strokes, intracranial hemorrhages)
h. SIDS (increase incidence in these children)
COCAINE BABIES

Treatment/Intervention:
IT IS 100% PREVENTABLE.
US Surgeon General and the Academy of Pediatrics Recommendation - Abstain entire pregnancy.
Action potential
Electrical events that travel along an entire neuron by allowing charged ions to flood through channels in the semi permeable membrane around the nerve cell
Active transport
Energy dependent transport of particles across the cell membrane against a gradient
Adenocarcinoma
A malignant tumor of epithelial cells
Anabolism
A constructive metabolic process characterized by the conversion of simple substances into larger, complex molecules
Adenoma
Benign tumor of glandular epithelium cells
Allele
1 or 2 or more alternative forms of a gene located at the same site on homologous chromosomes. Two alleles for each gene. If both alleles are the same they are homozygous. If two different alleles are present the individual is heterozygous for the trait. Ex. Eye color, blood type (a,b and O)
ATP
Principal source of cellular energy; product of a chemical reaction between oxygen and nutrient products such as glucose, fatty acids, amino acids and enzymes
Anaplasia
A neoplasm's loss of differentiation
Aneuploidy
Abnormal chromosome number
Angiogenesis
The generation of new blood vessels
Antiport
System of substances transported in the opposite direction
Apoptosis
Programmed cell death that is prompted by a genetic signal and designed to replace old cells with new; also known as cellular suicide
Atrophy
Decrease in the size of the cell
Autocrine signaling
Occurs when a cell releases a chemical into the extracellular fluid that affects its own activity
Autosomes
Chromosomes other than a sex chromosomes; totals 44 chromosomes in each body cell
Basement membrane
The outer membrane of the vessels that separates the vessel from the tissues of the body
Base pairs
Nitrogen base combinations; DNA base pairs include cytosine, guanine, and adenine and thymine
Benign
Describes a tumor that remains localized and closely resembles the tissue of origin
Blast cell
Any immature cell
Cachexia
A syndrome of unexplained weight loss and tissue wasting related to the stimulation of inflammatory mediators, along with excess energy use, by the proliferating neoplastic cells
Cancer
A term used to describe highly invasive and destructive neoplasms
Caseous necrosis
Distinctive form of coagulation necrosis in which the dead cells persist indefinitely as soft, cheese like debris.
Coagulation necrosis
Acidosis develops and denatures the enzymatic and structural proteins of the cell
Carcinogenesis
A term used to describe the origin, promotion, or development of cancerous neoplasms
Carcinoma in situ
A unique term used to describe carcinomas that are confined to the epithelium and have not yet penetrated the basement membrane
Caseous necrosis
A distinctive yellow, pasty, cheese like necrosis of tuberculosis
Catabolism
A metabolic process through which living organisms break down complex substances to simple compounds, liberating energy for use in work, energy storage, or heat production
Cations
Ions with positive charge
Cell
Smallest component of the living individual
Cell body
Cell structure containing cytoplasm and organelles responsible for the specialized function of cell; also known as soma
Centromere
Structure linking the chromosome pairs of the somatic cells of the body; divides the chromosome into two arms; constant position for each chromosome
Chemical synapses
Transmit impulses across a small gap between cells via stimulation of neurotransmitters
Chromatin
Nuclear genetic material made of DNA; condenses into chromosomes during mitosis
Chromosomes
Double-stranded DNA containing threadlike sections of genes that form an individual's genetic code; most commonly found in the cell nucleus; responsible for reproduction of physical and chemical structures; human somatic cells contain 46 chromosomes; 22 pairs autosomes and 1 pair of sex chromosomes
Coagulative necrosis
Acidosis develops and denatures the enzymatic and structural proteins of the cell; this type of necrosis is characteristic of hypoxic injury and is seen in infracted areas.
Codon
Sequence of 3 nitrogenous bases forms; nucleotide triplet; fundamental triplet code necessary for protein synthesis; basic compounds produced are amino acids
Concentration gradient
Mechanism of passive transport that promotes the movement of particles from an area of high concentration to lower concentration
Cytoplasm
Colloid substance surrounding the cell nucleus composed of water, protein, fats, electrolytes glycogen and pigments
Cytoskeleton
Tubule and filament structures, contributing to cell shape, movement, and intracellular transport; comprised of microtubules, thin, intermediate and thick myofilaments
DNA
Type of nucleic acid containing deoxyribose; usually found in cell nucleus and mitochondria; responsible for the storage of genetic information; made up of four nitrogenous bases, including adenine and guanine, cytosine and thymine
Depolarization
Result of rapid movement of sodium into the cell through sodium channels in the cell membrane
Differentiation
A process of changing the physical and functional properties of a cell to allow greater specificity and functionality to that cell
Diffusion
Movement of particles from an area of high concentration to lower concentration
Diploid
Diploid The number of chromosomes a human body cell contains; 23 pairs of chromosomes, or a total of 46
Dry gangrene
Dry, wrinkled and skin discoloration; arterial blood interference; line of demarcation
dysplasia
The alteration in size, shape, and organization of adult cell types; strongly implicated as a precursor to cancer
Dystrophic calcification
Macroscopic deposition of calcium salts in injured tissue. It is visible to the naked eye and can range from gritty, sandlike grains to firm hard rock material; pathogenesis involves intracellular and extracellular formation of crystalline calcium phosphate; calcium deposits are derived from the bodies of dead or dying cells and circulation/intestinal fluids; examples - advanced atherosclerosis, healed tuberculosis lesions (chronic), aortic valve stenosis in elderly
Electrical synapses
Transmit impulses via passage of current carrying ion through small opening and gaps
Endocrine signaling
Relies on hormones carried in the blood stream to cells throughout the body
Endoplasmic reticulum
Cellular organelle composed of a complex network of tubules; important in the production of proteins and fats and calcium ion regulation; subtypes include rough and smooth
Exon
Segment of DNA coded for protein production
Expressivity
The evidence of the gene in the phenotype
Facilitated diffusion
Assisted movement of substances across the cell membrane; not energy dependent; examples include glucose and insulin
Gamete
Ova and sperm; contain only one of the chromosomal pairs, known as a haploid number
gangrene
Considerable mass of tissue undergoes necrosis; usually from hypoxia, two types dry/wet (gas); see Porth page 108 for in-depth discussion
Genes
Individual units of inheritance located on chromosomes; determine cell protein characteristics
Genotype
Genetic makeup of an individual
Glycolipid
Sugar bound to lipid head of the plasma membrane
Glycoprotein
Regulate cell movement across the matrix, provide a place for attachment of the cells to the matrix, and prompt the cell to function
Golgi complex
Cellular organelle with a membranous structure; prepares substances by the endoplasmic reticulum for secretion out of the cell; folding and condensing - remember trash compactor
Haploid
Cells containing single chromosomes rather than pairs; chromosome number total 23 (22 autosomes, 1 sex chromosome); characteristic of gametes
Homozygous
Identical alleles on each chromosome
Heterozygous
Different alleles on each chromosome
Hydrophilic
Likes water
Hydrophobic
Doesn't like water
Hydrostatic forces
Force promoting fluid movement between extracellular compartments; promotes movement of fluid based on the pressure gradient; also known as filtration pressure
hyperplasia
An abnormal multiplication or increase in the number of normal cells of a body part
Hypertrophy
Increase in cell size
hypoxia
*understand the difference between hypoxia and infarction. Hypoxia is an inadequate supply of oxygen to tissue that is below physiologic levels despite adequate perfusion of the tissue by blood.
Infarction
Occurs when an artery supplying an organ or part of the body becomes occluded and no other source of blood supply exists.
Integral protein
Form of transmembrane protein; forms a channel in the plasma membrane for transport of ions
Intron
Segment of DNA not involved in protein expression
Karyotype
Picture of arranged, paired, like chromosomes in order from largest to smallest
Ligands
Molecules that bind to specific receptors; involved in signal transduction
Liquefaction necrosis
Occurs when some of the cells die but their catalytic enzymes are not destroyed
Lysosomes
Cellular organelles comprised of small sacs surrounded by membrane; responsible for hydrolytic digestion of cellular debris
Malignancy
Invasive and destructive cellular growth
Meiosis
Process of sex cell (gamete) division; cell division resulting in gametocytes containing half (haploid) the number of chromosomes found in a somatic cell
Mendelian pattern of inheritance
Predictable trait transmission based on autosomal dominant or recessive genotypes
mRNA
Template for protein synthesis; depends on a codon sequence based on that of the complementary strand of DNA; cytoplasmic area where protein is made in amino acid sequences
Metaplasia
Changing of one cell type to another
Metastases
Process that occurs when neoplasms are spread to distant sites often by way of the lymphatics or blood vessels
Metastatic calcification
Occurs in normal tissue as the result of increased serum calcium levels (hypercalcemia), examples Paget disease, cancer with bone metastasis
Mitochondria
Cellular organelle containing enzymes involved in oxidative physphoylation; principal producer of the cellular energy source ATP
Mitosis
Process of reproduction of nuclear chromosomes in somatic cells; reproductive phases include protophase, protometaphase, metaphase, anaphase, and telophase; results in the creation of daughter cells with the same chromosome number and genetic makeup as the cell of origin
Monosomy
One copy of a chromosome, in place of a normal pair, the result of nondisjuncture
Mutation
Change in genes or sequence of base pairs that make up the chromosomes; genetic alteration perpetuated in subsequent cellular divisions
Mutator genes
Genes that repair mutated DNA and protect the genome
Neoplasia
The irreversible deviant development of cells resulting in the formation of neoplasms
Nondisjunction
Failure of chromosome separation during meiosis or mitosis; results in an unequal number of chromosomes
Nucleus
Round mass of protoplasm within the cytoplasm of the cell; surrounded by a nuclear envelope enclosing structures responsible for mitosis during cell division
Oncogenes
Cancer causing
Osmosis
Movement of water across a concentration gradient; water movement to an area of higher concentration of particles (less water content) from an area of lower concentration of particles (more water content); regulated by concentration of particles that do not diffuse across the semi permeable membrane
Osteoma
Tumors that arise from bone cells
Oxidative stress
Potential source of cellular damage by exposure to reactive oxygen species
Oxidative phosphorylation
Oxygen is required by the mitochondria for oxidative phosphoylation and the production of ATP.Remember the cell uses thinks such as free fatty acids and glycerol in oxidative phosophorylation to produce ATP.
Paracrine signaling
Hormone effects restricted to the local environment; enzymes rapidly metabolize the chemical mediators and therefore they act mainly on nearby cells.
Paraneoplastic syndrome
Hormonal, neurological, hematological, and chemical disturbance in the body not directly related to invasion by the primary tumor or metastasis, i.e. anemia, Cushing Syndrome
penetrance
Ability of a gene to express a mutation, influences the effects of mutation
Peroxisomes
Cellular organelle made up of small membrane enclosed sacs; promote cell survival by oxidation of oxygen free radicals
Phenotype
Genetic traits that are apparent or observable
Primary active transport
Process requiring the direct use of energy in the form of ATP
Proteosome
Large cellular organelle that recognize abnormally folded or formed proteins; involved in proteolysis;
Proto-oncogene
Normal genes in the body with a vital role in regulating cell function (proliferation
Receptor
A cytoplasmic or cell surface protein molecule structured to bond specific factors
Recessive
Trait caused by a particular allele that does not manifest itself in the presence of other alleles that generate traits dominant to it
RNA
Nucleic acid that contains sugar; responsible for control of protein synthesis; made up of the four nitrogenous bases, adenine and guanine, cytosine and uracil
Sex chromosome
X or y; the genetic determinants of the sex of an individual
Signal transduction pathway
Mechanism of cellular communication; initiated by bing of ligand to receptors and resulting in an action through subsequent communication events.
Single gene trait
Characteristics passed on by the transmission of a single gene
Soma
Cell body; component of cell comprised of cytoplasm and organelles responsible for specialized function of the cell; somatic - relating to soma, or body
Symport
System of substances transported in the same direction
Synaptic Signaling
Occurs in the nervous system, where neurotransmitters act only on adjacent nerve cells through special contact areas called synapses.
Telomerase
An enzyme that adds length to the telomere, the chromosomal time clock
Transcription
Transfer of genetic code from one type of ribonucleic acid to another; based on the nucleotide sequence of a complementary DNA template
tRNA
Involved in production of proteins with specific amino acid arrangements through interactions with mRNA
Translation
Process involved in the production of protein from amino acids
Translocation
Exchange of a section of chromosome from one to another; often occurs during meiosis; able to be transferred to subsequent generations
Transmembrane proteins
Proteins extending through the plasma membrane, contacting both the intracellular and extracellular components
Trisomy
Presence of three copies of a chromosome in place of a normal pair; the result of nondisjuncture
Tumor markers
Substances that may detached in cells or body fluids and can provide clues to the presence, extent and treatment response of certain neoplasms
Tumor suppressor genes
Genes that prohibit over proliferation of cells and regulate apoptosis
Wet gangrene
Cold, swollen, and pulseless, moist, black and skin undertension, liquefacation occur, malodorous, venous return interference.
Marfan's Syndrome:

Etiology
Rare degenerative, generalized disease of connective tissue. Affects men and woman equally with an incidence of about 1 in 20,000 people in the U.S. Marfan's Syndrome is a result from elastin and collagen defects and causes ocular, skeletal and cardiovascular anomalies.
Marfan's Syndrome:

Pathophysiology:
Autosomal dominant trait. Mutation in a single allele of a gene located on Chromosome 15. Patients are heterozygous for the mutation (one gene with mutation, other gene is normal in the patient). It has been mapped to a specific chromosome location - chromosome 15. On this chromosome, more than 20 mutation have been identified that can occur in a gene that codes for fibrillin, a component of connective tissue.

Fibrillin is a glycoprotein component of connective tissue found abundantly in large blood vessels, ocular ligaments. You see functional and structural changes.
Marfan's Syndrome:

Clinical Manifestations:
1. Skeletal malformation: increased height, long extremities, arachnodactyly (spiderlike appearance on hands/fingers), chest depression (pectus excavatum), chest protrusion (pectus carinatum), chest asymmetry, scoliosis, kyphosis, arched palate, join hypermobility.

2. Ocular: lens displacement, cataract formation, nearsightedness, and retinal detachments. Seventy- five percent have crystalline lens displacement (ectopia lentis), the ocular hallmark of Marfan's Syndrome. Quivering of the iris with eye movement (iridondonesis). Most patients are severely myopic, many have retinal detachment, and some have glaucoma.

3. Cardiac: valve and aorta dysfunction.
> Valvular - anatomic defect producing redundancy to the leaflets, stretching of the chordate tendineae, and calcification of the mitral annulus. MVP progress to MVR (backflow of blood from the LV to LA).
> Aorta - dilation of the aortic root and ascending aorta - aortic regurgitation (backflow into LV), aortic dissection, and rupture.

4. Thin body build with little subcutaneous fat, striae over the shoulders and buttocks. Spontaneous pneumothorax, inguinal and incisional hernias, dilation of the dural sac.
Marfan's Syndrome:

Diagnosis:
1. Based on positive family history in one parent and typical clinical features.
2. Radiographs for skeletal abnormalities
3. Echocardiogram
4. DNA Analysis
Marfan's Syndrome:

Treatment/Intervention:
-No established treatment exists
-S/S symptomatic treatment: Surgical repair of aneurysms and ocular deformities, surgical replacement of aortic and mitral valve, mechanical bracing for orthopedic support
Marfan's Syndrome:

Nursing Thoughts
1. High school kids and sports - risk of sudden death - good physicals and history
2. National Marfan Foundation - Nursing education critical
3. Need regular medical follow- due to potential complications for weak joints and ligaments; cataracts and retinal detachment, severe mitral valve insufficiency
Genetic mutations
Genetic mutations are either a point mutation, which involves a single base pair substitution or a framework mutation, which often changes the genetic code dramatically.

- A sequence of DNA (codon) is required to code for each amino acid.
Point mutation
cause the affected codon to signify an abnormal amino acid.

Sickle cell anemia is an example of a point mutation. Single amino acid substitution which causes significant dysfunction.
Framework mutation
addition or removal on 1 or more bases, which changes how the DNA is sequenced and read.
X-Linked Recessive

sex-linked disorders
Genetic disorders located on the sex chromosomes, X or Y are called sex-linked disorders
X-Linked Recessive

Majority of disorders are linked to the X chromosome or X-linked and are usually ____.
Majority of disorders are linked to the X chromosome or X-linked and are usually RECESSIVE.
X-Linked Recessive

Females have XX so they are usually the ____.
Females have XX so they are usually the CARRIERS.
X-Linked Recessive

Males have only 1 X so they usually are likely to be ____ by the disorder.
Males have only 1 X so they usually are likely to be AFFECTED by the disorder.
X-Linked Recessive

Dad has defective gene on the X chromosome, known as X-linked recessive, all daughters will be ____ and sons will be ___.
Dad has defective gene on the X chromosome, known as X-linked recessive, all daughters will be CARRIERS and sons will be UNAFFECTED.
X-Linked Recessive

Mom has defective gene on the X chromosome and passes it on, it is X-linked dominant, her daughters will have a ____% chance of being carriers, and her sons will have a ____% chance of being affected.
Mom has defective gene on the X chromosome and passes it on, it is X-linked dominant, her daughters will have a 50% chance of being carriers, and her sons will have a 50% chance of being affected.
X-Linked Recessive

Two examples:
Hemophilia and x-linked severe combined immunodeficiency (XSCID) or "bubble boy disease". X-linked disorders with mom carrying the defect and only males expressing disease.
Fragile X syndrome

Description:
Sex-linked genetic disorder that follows Mendelian inheritance pattern. Long repeating sequences of three nucleotides, called triplet repeats. Most common cause of familial mental retardation. Repeat sequence CGG.
Fragile X syndrome

Pathophysiology:
- Located on the long arm of the X chromosome, a nucleotide mutation in the FMR1 gene has been identified as the molecular basis of the syndrome.

- Variable trinucleotide repeat of the nitrogen base combination of cytosine-guanine-guanine (CGG).
Fragile X syndrome

Typical allele
55 repeats
Fragile X syndrome

Premutation
55-200 repeats
Fragile X syndrome

Full mutation
> 200 repeats

Impaired ability to produce the fragile X mental retardation protein (FMRP).
Fragile X syndrome

Clinical Manifestations:
- Distinctive facial features, connective tissue problems, and macroorchidism (enlarged testicles)

- Cognitive impairment and behavioral difficulties (distinguishing characteristics)

- Males are affected/Woman carriers
> Female carriers can have mild cognitive or behavioral defects, premature ovarian failure, fragile -X associated tremor/ataxia syndrome (FXTAS)
> Males affected are usually unable to live independently
Fragile X syndrome

Diagnosis:
Genetic screening
Fragile X syndrome

Treatment:
- No cure
- Clinical manifestation driven
> Stimulants - manage distractibility/hyperactivity/impulsivity
> Antidepressants - manage anxiety, OCD behavior, mood changes
> Antipsychotic - aggression
Chromosomal Disorders
Chromosomal defects are usually due to an abnormal number of chromosomes OR alteration in the structure of one or more chromosomes.
Aneuploidy
means there is an abnormal number of chromosomes (more or less than 46).

There can be 2 reasons for aneuploidy
1. Nondisjunction
2. Anaphase lag
Nondisjunction
•Chromosomes separate during first and second phase meiosis in a process known as disjunction

•Fail to separate - nondisjunction
o Unequal number of chromosomes between cells
o Timing of nondisjunction determines the number of cells involved
o MOSAICISM - refers to the combination of cells with the regular chromosome number and those with altered chromosome numbers.
o Risk of nondisjuncture increases with parental age
Anaphase Lag
1 chromosome lags behind and is therefore left out of a newly formed cell nucleus. One daughter cell with normal number of chromosomes and one with a deficiency of one chromosome.
MONOSOMY
cell with one copy of a chromosome instead of two.

- If occurs with autosomes - deathIf occurs
- with sex hormones - significant physical and mental defects
- Example- Turner Syndrome
TRIOMY
refers to the presence of 3 copies of chromosomes in a cell.

- Large chromosomes affected - death
- Chromosome 21 - Down's Syndrome
POLYSOMAL
too many chromosomes ( common and less debilitating)
Alteration in the structure of one or more chromosomes.
1. Severity depends on chromosomal rearrangement

2.Gene locations are described by their location on the long arm (q arm) or the short arm (p arm) of the chromatid ( one copy of a chromosome formed by DNA replication that may be joined to the other copy(sister chromatid) at the centromere.
TRANSLOCATION
The interchanging of genetic material between nonhomologous chromosomes.

It affects the persons off spring who inherit the defective chromosome.
Robertsonian translocation
the long arm of the two nonhomolous chromosomes fuse at the centromere forming a single chromosome. Confined to 13, 14, 15, 21, and 22 because of the short arms of these chromosomes. The short arms are usually lost during subsequent cell division.
A common Robersonian translocation involves...
A common Robersonian translocation involves the fusion of the long arms of chromosomes 21 and 14. An offspring who inherits a gamete carrying the fused chromosome receives an extra copy of the long arm of chromosome 21 and thus develops Down's Syndrome (3-5% of cases).
Reciprocal translocation
Reciprocal translocation is where large segment of DNA breaks from one chromosome and reattaches to a different chromosome (often during meiosis)
INVERSIONS
Two breaks on a chromosome, followed by the reinsertion of the missing fragment at its original site but in inverted order. Example chromosome a,b,c,d,e becomes, a,e,b,d,c

No loss or gain of genetic material

Balanced alteration of chromosome structure - no physical effects

Problems will be evident in offspring of individuals carrying the inversion.
DELETIONS
Break in the arm of the chromosome resulting in a fragment of DNA with no centromere. (associated with cancer, good example - retinoblastoma)

Example - Cri du chat syndrome - caused by a deletion of part of the short arm of chromosome 5. The name means "cry of a cat". Low birth weight, severe mental retardation, microcephaly (smaller than normal head), heart defects, and typical facial appearance.
DUPLICATIONS
Extra copies of a portion of DNA. Chromosomal aberration

Less serious consequences than deletions
Trisomy 21 (Down's Syndrome)

Description:
Chromosomal disorder .
Trisomy 21 (Down's Syndrome)

Pathophysiology:
- Trisomy 21 is an aberration in which chromosome 21 has 3 copies instead of 2. The extra chromosome originates from the mother more than 90% of the time.

- Most Down's Syndrome patients exhibit 47 chromosome instead of the normal 46.

- Studies have shown the abnormality results from deterioration of the oocyte (primitive egg) which can be caused by age or the cumulative effects of environmental factors (radiation/viruses)

- Tremendous amount of aging research being conducted with Down's Syndrome. Patient's who live into adult life - They have pre-mature senile dementia (similar to Alzheimer's)

- Increase incidence of leukemia, acute and chronic infections, DM, and thyroid disorders
Trisomy 21 (Down's Syndrome)

Clinical Manifestations:
a. Produces mental retardation, characteristic facial features and distinctive physical abnormalities.

b. Associated with heart defects and other congenital abnormalities including:
Duodenal obstruction, clubfoot, imperforate anus, cleft lip and cleft palate, Hirschsprung's disease (congenital colon enlargement), myelomeningocele, and pelvic bone abnormalities.

c. 44% die in the first year due to congenital heart disease

d. Birth - the baby are more lethargic with 1 or more of the following: slanting, almond-shaped eyes, protruding tongue, small, open mouth, single, transverse crease on the pal (simian crease), small white spots on the iris (Brush field's spot), small skull, flat nose bridge, flattened face, small ears, short neck with excess skin.

e. Short stature, short extremities,

f.Hands/feet - broad, flat and squarish
Trisomy 21 (Down's Syndrome)

Diagnosis:
1st Trimester screening - nuchal translucency (NT) - thickness of the nape of the neck - common finding in Down's. Completed between 10 and 14 weeks.

2nd Trimester screening - ultrasound patterning - combination of below
o Short humerus
oShort femur
o Echogenic cardiac foci (LV)
o Echogenic bowel (bright areas in the intestine)

2nd Trimester amniocentesis - amniotic fluid, fetal cell analysis, fetal karyotype - chromosomal abnormalities
Trisomy 21 (Down's Syndrome)

Treatment:
Focus on independent living skills. Clinical manifestation treatment- cardiac, GI complications.
Turner's Syndrome

Description:
The presence of a single X chromosome and no homologous X or Y chromosome, so the individual has a total of 45 chromosomes. It causes a set of symptoms known as Turner Syndrome.
Turner's Syndrome

Pathophysiology:
The person has no Y chromosome so people with Turner's syndrome are females.
Turner's Syndrome

Clinical Manifestations:
- Based on abnormality and point in time of nondisjuncture

- Skeletal abnormalities - short stature, short fingers, short neck, cleft palate, webbing of the neck in 50 % of the cases,

- Soft tissue abnormalities - lymphatic obstruction, low hairline, widely spaced nipples

- Organ abnormalities - cardiac (15-20% have narrowing of the aorta) , kidney, hearing loss

- Reproductive problems (estrogen deficiency), hypothyroidism, deafness, osteoporosis, sparse body hair

- Usually sterile and gonad streaks rather than ovaries. These streaks of
connective tissue are susceptible to cancer
Turner's Syndrome

Diagnosis:
Ultrasound - 14-16 weeks

- HYGROMA - large, septated, cyst on the back of the neck, edema short femur and narrow aortic arch

- 99% abort spontaneously
Turner's Syndrome

H&P
o Behavior delays development as an infant

o Feeding problems - crying

o Newborns will have puffy hands and feet from lymphedema, extra nuchal skin from the remaining cystic hygroma and heart defects,

o Gonad failure - delayed puberty and infertility

o Premature menopause
Turner's Syndrome

Treatment
Varied based on phenotype

Teenagers with Turner syndrome are typically treated with estrogen to promote the development of secondary sex characteristics.
Klinefelter's Syndrome

Description:
Individuals with at least two X chromosomes and a Y chromosome in each cell (47, XXY karyotype).
Klinefelter's Syndrome

Pathophysiology:
Abnormal ovum carrying an additional X chromosome (XX) is fertilized by a normal male sperm (Y)

Nondisjunction of the X chromosome in the mother and the frequency of the disorder rises with maternal age.

Individuals who have XXXY and XXXXY karyotypes and also consider Klinefelter's Syndrome (degree of physical and mental disabilities increases with the additional X chromosome).
Klinefelter's Syndrome

Clinical manifestations:
The presence of a single Y chromosome which causes the undifferentiated gonads to become tests, always produce a male.

infertile (usually sterile)

Scant public hair, atrophic testes and a small penis

Feminine features - lack of facial hair, female hip shape, and breast development (gynecomastia)

Tall, slim eunuchoid stature

Moderate degree of mental impairment
Key Multifactorial Inheritance Disorder Points:
• Pattern of inheritance of common health problems and rarer conditions caused by combination of genetic and other factors (environmental, natural aging process, lifestyle health practices, exposure to toxins)

• Multifactorial Disorders do not always develop despite suggested presence of a faulty gene (s).

• The inherited faulty gene(s) predisposes the person but unless "other" factors are present the condition may not develop.

• Having 1 or more biological relatives develop a conditions, especially at younger ages, is usually an indication that one could be at risk.

• The faulty gene is USUALLY autosomal dominant inheritance
Some conditions that are related to genetics playing a role

Birth defects:
Neural tube defects are congenital malformations that produce defects of spine or skull. Failure of neural tube closer between days 24-28 after conception
Some conditions that are related to genetics playing a role

Cardiovascular Conditions:
HPTN, high cholesterol,

Genetic influences range from single gene to complex interactions with genes/environment.

Strong association between high levels of LDL cholesterol and atherosclerotic disease

• Mutations of genes regulating update of cholesterol from the blood (LDLR, ARH genes)

• Binding of apolipoprotein B-1000 to the LDL receptor (APOB-100)

• Syntheses and clearance of cholesterol (ABCG5 and ABCG8 genes)

• 4 specific disease with identified single gene defects contribute to hypercholesterolemia (family choesterolemia, familial ligand-defective apolipoprotein B-100, and sitosterolemia)
Some conditions that are related to genetics playing a role

Hypertension
contributes to increased risk of CVA, MI, HF, and renal failure.

• Single gene mutation leading to impaired renal salt handling demonstrate mendelian inheritance patterns in affected individuals

• Complex polygenetic influences of gene-gene and gene-environment interactions.
Some conditions that are related to genetics playing a role

CVA
2 genes (STRK1 and STRK2) have been associated with twice the risk of MI and CVA.

• Mutations in gens regulating the clotting cascade
Some conditions that are related to genetics playing a role

Neurologic/psychiatric conditions:
Alzheimer's Disease in later life, schizophrenia, bipolar disorder
Some conditions that are related to genetics playing a role

Skin conditions:
psoriasis, moles, eczema
Some conditions that are related to genetics playing a role

Cancer:
breast, ovarian, bowel, melanoma and prostate
Some conditions that are related to genetics playing a role

Metabolic:
diabetes
Some conditions that are related to genetics playing a role

Muscular/skeletal:
arthritis, rheumatic disorders, osteoporosis
Some conditions that are related to genetics playing a role

Respiratory:
asthma, allergies, emphysema
There have been a few multifactorial diseases where the environmental trigger has been identified. Hence, health prevention and education become the key:

Folate deficiencies:
Lack of folate in the developing baby's environment has been linked to the chance the baby will have a neural tube defect such as spinal bifida. During a woman's pregnancy she can significantly reduce the number of babies born with the condition by taking supplemental folate.
There have been a few multifactorial diseases where the environmental trigger has been identified. Hence, health prevention and education become the key:

High dietary cholesterol:
High dietary cholesterol is a factor in increased risk for heart disease. It can lead to obesity and increase risk for DM. Exercise is an effective intervention as is diet control.
Are you at risk for cancer?

Age
as you age increases so does your risk especially over 65. This is due in part to the aging senescence changes such as hormonal changes, changes in the immune system, and accumulation of free radicals over the years. It is the SINGLE MOST IMPORTANT FACTOR IN CANCER DEVELOPMENT
Are you at risk for cancer?

Gender
depending on the cancer you can see gender specificity. Women tend to have higher numbers of breast cancer and obviously uterine cancer. Men more testicular cancer etc.
Are you at risk for cancer?

Genetics
15% of cancers account for this variation - We see a family relationship in cancers such as breast, ovarian, lung, colon and prostate
Are you at risk for cancer?

Immune System
there are some viruses that increases your risk: Epstein Barr Virus( EBV), g human cytomegalovirum, HIV
Are you at risk for cancer?

Chemicals
Exposure to certain chemicals can increase your chances of developing some forms of cancer
Are you at risk for cancer?

Race
different cancers effect different races differently
Are you at risk for cancer?

Smoking
lung, bladder, esophageal, gastric laryngeal, oropharyngeal and pancreatic - if you chew the tobacco then include oral and esophageal cancer and if someone who lives with you smoke - your chances for lung and bladder cancers increase
Are you at risk for cancer?

ETOH (alcohol)
liver and esophagus and put it with cigarette and you can climb to the head of the class in cancer risk factors
Are you at risk for cancer?

Diet
high fat, low fiber - lots of preserved meat and pickled food
Are you at risk for cancer?

Job and where you live
Your job and where you live also influence it

Ex. Mesothelioma due to asbestos exposure
Cancer Notes

CAUTION: Teach your patient to remember these
C - change in bowel or bladder habits
A - sore that does not heal
U - unsusual bleeding or discharge
T - thickening or lump in breast or elsewhere
I - indigestion or difficulty in swallowing
O -obvious change in wart or mole
N - nagging cough or hoarseness
Cancer Notes

Cachexia
a condition of general ill health and malnutrition, marked by weakness and emaciation, it is often caused by products of the tumor itself as well as a hypermetabolic state of the cancer cells.
Cancer Notes

Anaplasia
lack of differentiated features. Indicated by variations in cell size and shapte within a tumor, enlarged nuclei, abnormal mitoses and bizarre-looking giant cells.
Cancer Notes

Carcinogen
agents and substances capable of inducing cancer.
Cancer is associated with ____ expression of cellular genes that normally regulate cell proliferation and differentiation. It is a disorder of gene expression.
Cancer is associated with ALTERED expression of cellular genes that normally regulate cell proliferation and differentiation. It is a disorder of gene expression.
Benign Versus Malignant Tumors:

Level of Differentiation

Benign
Closely resembles tissue of origin; well differentiated; cluster
Benign Versus Malignant Tumors:

Level of Differentiation

Malignant
Undifferentiated; does not resemble tissue of origin
Benign Versus Malignant Tumors:

Proliferation

Benign
Rate of growth is usually slow
Benign Versus Malignant Tumors:

Proliferation

Malignant
Rate of growth can be rapid and depends on the level of differentiation; a greater lack of differentiation is associated with extensive and rapid proliferation/growth
Benign Versus Malignant Tumors:

Invasion of Adjacent Tissues

Benign
Does not invade adjacent tissues
Benign Versus Malignant Tumors:

Invasion of Adjacent Tissues

Malignant
Invasive; apparent spread to adjacent tissues
Benign Versus Malignant Tumors:

Spread to Distant Sites (Metastasis)

Benign
No
Benign Versus Malignant Tumors:

Spread to Distant Sites (Metastasis)

Malignant
Yes
Tumor terminology

-oma
used to indicate a benign tumor

Adenoma is a benign tumor of glandular tissue
Tumor terminology

-carinoma
used to indicate a malignant tumor of epithelial origin

Adenocarcinoma - is a malignant tumor of the glandular issue
Tumor terminology

-Sarcoma
used to indicate a malignant tumor of the mesencyhmal (nerve, skeletal, muscle) origin
Tumor terminology

Exceptions to the rules (there always are!!)
Lymphomas, hepatomas, melanomas - highly malignant depite their oma suffix

Leukemia - malignant growth of WBC
Normal cell phenotype
Predictable relationship with adjacent cells

Cell growth and cell death are proportional

Cellular signaling is required for them to do their work and growth within the space allotted

Normal apoptosis
Cancerous Cell phenotype
Do not follow the rules

Proliferate despite lack of growth-initiating signals from the environment

Achieve immortality and unlimited replication

Lose their differentiation features-lose their function

Genetically unstable, new mutations at a much faster rate than normal cells

Invade local tissue and destroy adjacent cells

Migrate
Proto-oncogenes
100+ different proto-oncogenes that code for components of cellular growth-activating pathways

When they are overactive it promotes cell proliferation and predisposes to cancer
Tumor suppressor genes
The function varies, but all appear to inhibit proliferation or induce apoptosis in defective cells

Both copies of the tumor suppressor genes must be inactivated for cancer to develop

A person who inherits a defective copy to a tumor suppressor gene has a higher incidence of cancer than one who has two normal copies

Genetic mutations are the cause of tumor suppressor genes to stop functioning: chromosome deletions, point mutations, or chormosme loss through disjunction
Tumor suppressor genes

Rb gene
codes for a large protein in the cell nucleus that has been labeled the master break of the cell cycle
Tumor suppressor genes

P53 gene
most common tumor suppressor gene defect. Approximately 50% of human tumors lack functional p53. Inhibits cell cycling. Mutation stops the check and balance on genetically unstable and/or damaged cell division. The other important point to remember- p53 mediates chemotherapy and radiation-induced cell death. It triggers p53 mediated apoptosis.
Metastatsis
Cancer cells escape their tissue of origin and initiate new colonies of cancer in distant lands

Escape the basement membranes of the tissue of origin, move thru the extracellular space and penetrate the basement membrane of the vessel. Travels the highways and byways of the blood vessels and lymphatic system. Then it reaches its destination it has to go through the basemembrane yet again. Once it sets uphome - need food and a blood suplly and learn how to live in a different environemtn. The more poorly differentiated the cell is the better it adapts to its new surroundings. Nasty little buggers.
Patterns of spread

Tumor markers
tumor markers are proteins found in blood and other body fluids; are released by either the tumor or by body as a defense in response to tumuor; they can be oncofetal antigens (carcinoembryonic antigen (CEA) or alphafetoprotein (AFP) hormones , isoenzymes, tissue-specific protein (PSA is a famous one) or cytokines - CRP, IL-2, TNF ;useful as an indicator for further diagnostic evaluation and to track the tumor burden. Indicate progression and proliferation. Examples: Ca125- ovarian, uterus, cervix, and pancreas. PSA- prostate
Patterns of spread

Angiogenesis
process of forming new blood vessels. Late stage cancer -angiogenesis usually occurs. Trigger is not fully understood. Tumor may secrete endotheial growth factor (VEGF) in response to hypoxia or other signal. New blood supply provides nutrients and oxygen to help the tumor thrive. Inhibt angiogenesis -you limit tumor growth and metastatis -lots of research ongoing.
Patterns of spread

Grading
classifies cancer based on degree of abnormality of cells when examined under microscope. It utilizes a Roman Numeral number
Patterns of spread

Grade I
Grade I - cell is slightly different than normal (mild dyplasia)
Patterns of spread

Grade II
Grade II - cell more abnormal; moderately well differentiated (moderate dysplasia)
Patterns of spread

Grade III
Grade III - cell clearly abnormal, poorly differentiated (severe dysplasia)
Patterns of spread

Grade IV
Grade IV - cells anaplastic (immature) and undifferentiated (cell origin difficult to determine)
Patterns of spread

Staging tumor
TNM Classification
Patterns of spread

Staging tumor

TX
Primary tumor cannot be evaluated
Patterns of spread

Staging tumor

T0
No evidence of primary tumor
Patterns of spread

Staging tumor

T1
Size or extent of the primary tumor
Patterns of spread

Staging tumor

NX
Regional lymph nodes cannot be evaluated
Patterns of spread

Staging tumor

N0
No regional lymph nodes involvement
Patterns of spread

Staging tumor

N1,2,3
Involvement of regional lymph nodes (number and/or extent of spread)
Patterns of spread

Staging tumor

MX
Distant metastasis cannot be evaluated
Patterns of spread

Staging tumor

M0
No distant metastatsis
Patterns of spread

Staging tumor

M1
Distant metastasis (cancer has spread)
Cancer Treatment:

Radiation
it is used to kill a tumor, reduce tumor size, relieve obstruction or decrease pain. Causes lethal injury to DNA so it can destroy rapidly multiplyin cancer cells; radiation therapy also kills normal cells. You can have brachytherapy (internal radiation) or teletherapy ( external radiation)
Cancer Treatment:

Chemotherapy
give a cytotoxic medication and chemicals to promote tumor cell death - usually IV by can be oral intrathecal, topica, intraarterial, intracavity and intravesical . Chemo disrupts cell cycle in various phases, interferes with cellular metabolism and reproduction.
Cancer Emergencies:
Spinal cord compression, superior vena cava syndrome, DIC, cardiac tamponade
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