Pathophysiology

• A,C,T,G:
• Adenine and Guanine (double carbon-nitrogen rings - purines)
• Cytosine and thymine (single carbon-nitrogen rings - pyrimidines)

• pentose sugar molecule
• deoxyribose
• phosphate molecule

Complementary base pairing of adenine with thymine and guanine with cytosine: A-T and G-C.

It travels along the single DNA strand and adds the correct nucleotides to the free end of the new strand while proofreading each strand as it goes. It essentially ensures the accuracy of DNA replication.

The inherited alteration of genetic material.

An agent that incrases the frequency of mutations. (radiation, chemicals, etc.)

Certain areas of some chromosomes that have particularly high mutation rates. The sequence of cytosine followed by guanine (CG) is highly susceptible to mutation and accout for a large percentage of disease-causing mutations.

cell nucleus

on ribosomes in the cytoplasm

• sugar molecules
• phosphate groups
• nitrogenous bases

RNA has the sugar molecule ribose rather than deoxyribose and has the base uracil rather than thymine. So it is C,A,G,U rather than C,A,G,T.

The process by which RNA is synthesized from DNA template to form mRNA.

The process by which RNA directs the synthesis of a polypeptide. mRNA interacts with tRNA which has a site for the attachment of amino acids (which mRNA does not have). Ribosomes bind to the mRNA then the tRNA to initiate base pairing between mRNA and tRNA. Then the amino acids can be translated into peptide bonds that will eventually be released into the cytoplasm to perform its required functions.

23 pairs in diploid cells.

The autosomal pairs (22 of the 23) of chromosomes in males and females are identical in appearance (homologous). The remaining pair of chromosomes are the sex chromosomes which have 2 homologous X chromosomes in females, and a nonhomologous pair, X and Y, in males.

When there is 3 copies of each chromosome (incompatible with life)

A somatic cell that does not contain a multiple of 23 chromosomes as a result of nondisjunction (an error in which chromosomes fail to separate normally during meiosis or mitosis.)

A cell containing 3 copies of one chromosome. This is an example of aneuploid.

Monosomy is worse because the loss of chromosome material has more serious consequences than the duplication of chromosome material.

Down syndrome

has the karyotype 45,X. Has no Y chromosomes and is female

2 X chromosomes and 1 Y chromosome (47,XXY karyotype) - male appearance, sterile, may have gynecomastia.

cri du chat syndrome (cry of the cat). Where broken chromosomes and loss of DNA occures without appropriate spontaneous repair.

Not for the carrier. there is no loss or gain of genetic material - only a backwards expression of the genes. Problems ony occur in the offspring of individiduals carrying the inversion. Offspring may then have chromosome deletions or duplications.

The long arm of the X chromosome is broken

Homozygous

Heterozygous

The genetic makeup or composition of the genes at a given locus.

the outward appearance of an individual based on their genotype.

homozygous (aa)

• 1) Principle of segretation: homologous genes separate from one another during reporduction and each reproductive cell carries only one of the homologous genes.
• 2) Principle of independent assortment: the hereditary transmission of one gene has no effect on the transmission of another.

The union of one normal homozygous recessive parent and one affected heterozygous dominant parent. (Dd + dd) There is a 50% chance of passing it on to offspring. Diseases are rare because rarely do 2 affected parents mate.

• 1) 2 sexes exhibit the trait in equal proportions and are equally likely to pass on the trait to offspring.
• 2) No skipping of generations. If a child has a disease, one of the parents must have it also.
• 3) Heterozygous individuals transmit the trait to about half of their children. However, it is still possible that all or none of the children may have the trait.

The probability that subsequent children will have the disease.

When 2 or more offspring present symptoms of an autosomal dominant disease when there is no family h/o the dz. Due to mutations that occured during embryonic development that efffected all or part of the germline but few or none of the somatic cells of the embryo.

Penetrance: The % of individuals with a specific genotype who also exhibit the expected phenotype.

Incomplete Penetrance: the person with the gene for a dz may no exhibit the diz phenotype but still be able to transmit the dz to the next generation. (ie. retinoblastoma)

When two heterozygous carriers for a dz reproduce and pass on the recessive trait to their offspring who then is homozygous affected. 25% recurrence risk.

Usually have delayed age of onset, incomplete penetrance, and variable expressivity

• 1) males and females are affected equally
• 2) consanguinity is often present (inbreeding)
• 3) dz is seen in siblings but usually not in their parents
• 4) 1/4 of teh offspring of carrier parents will be affected.

Males

• 1) more often affects males
• 2) never transmitted from father to son because a father can only give a son a Y chromosome.
• 3) can have the appearance of "skipped generation"
• 4) gene is passed from an affected father to all his daughters, who, as phenotypically normal carriers, transmit it to about half their sons, who are then affected. (skipped generation affect)

the number of NEW cases of a dz reported during a specific period divided by the number of individuals in the population.

• The proportion of the population affected by a dz at a specific poin in time.
• It is determined by both the incidence rate and the length of survival period in affected individuals.

• incidence rate of the dz among individuals exposed to a risk factor
• incidence rate of the dz among individuals NOT exposed to risk factor

Normal, bell-shaped distribution

When a dz does not follow the bell-shaped distribution. They are either present or absent regardless of inheritance patterns expected.

the person appears "normal" or has less chance of developing the dz

The person is affected by the dz. Has more of the dz-causing genes and environmental factors.

identical with the same genetic makeup

fraternal with different genetic makeup much like any other siblings.

If both members of a twin pair share a trait (cleft palate) they are concordant traits. It they do not share the trait, they are doscordant traits.

Biochemical barriers

Collectins produced and secreted in the lungs.

Bactericidal/permeability-inducing protein (BPI)

Antimicrobial lectins

redness, pain, swelling, heat

• 1) vasodilation
• 2) increased vascular permeability and leakage of fluid out of the vessel.
• 3) WBC adherence to the inner walls of vessels and their migration thru vessel walls to the site of the injury. (diapedesis)

The Complement System because it can destroy pathogens directly and can activate or collaborate with every other component of the inflammatory response.

• 1) classical pathway: activated by the antigen-antibody immune complex. (efficient activation of this pathway requires concurrent binding of C1 to at least 2 antibody molecules)
• 2) Lectin pathway: activated by bacterial carbohydrates.
• 3) alternative pathway: activated by gram-negative bacterial and fungal cell wall polysaccharides.

• 1) anaphylatoxic activity resulting in mast cell degranulation.
• 2) leukocyte chemotaxis
• 3) opsonization (tagging of micro-organisms for destruction or cell lysis)
• 4) cell lysis

• 1) prevent the spread of infection to adjacent tissue
• 2) traps microorganisms and foreign bodies at the site of inflammation for removal by infiltrating cells (neutrophils and macrophages)
• 3) forms a clot to stop bleedin
• 4) provides a framework for future repair and healing.

Production of fibrin clot.

• Produced from the Kinin cascade.
• Causes dilation of blood vessels, acts on PGEs to stimulate nerve endings and induce pain, causes smooth muscle cell contraction, increases vascular permeability, and may increase leukocyte chemotaxis.

Primary circulating WBCs. They are neutrophils, eosinophils, and basophils.

Expressed primarily on macrophages.

They facilitate the recognition and phagocytosis of bacterial pathogens, damaged cells, altered soluble lipoproteins associated with vascular damage.

histamine, chemotactic factors, and cytokines

H1 receptors: proinflammatory, present on smooth muscle cells, especially those of the bronchi, cause bronchoconstriction when stimulated.

H2 receptors: anti-inflammatory, suppresses leukocyte fxn, abundant on parietal cells of the stomach mucosa and induces secretion of gastric acid as part of the normal physiology of the stomach.

Neutrophils

increase vascular permeability and neutrophil chemotaxis. Also induce pain.

Process by which a cell ingests and disposes of damaged cells and foreign material.

• 1) opsonization, recognition of the target and adherence of the phagocyte to it.
• 2) engulfment (ingestsion or endocytosis) and formatio of phagosome
• 3) fusion wit lysosomal granules withing phagocyte (phagolysosome)
• 4) destruction of the target

alpha₁-antitrypsin

Macrophages and lymphocytes

To remove debris in sterile lesions (burns) and phagocytosis of bacteria in nonsterile lesions.

Phagocytes that are produced in the bone marrow, enter the circulation and travel to the inflammatory site where they develop into macrophages. Thus, they are the small precursor to macrophages.

Larger, more active phagocytes that are important cellular initiators of the inflammatory response. They can appear at the site within 24 hours of neutrophil infiltration. But usually arrive 3-7 days later. They are good for long defense because they can survive and divide in the acidic inflammatory site or where there is low oxygen.

• 1) speed (neutrophils arrive 1st)
• 2) active life span (macrophages survive longer)
• 3) chemotactic factors (not attracted by the same factors)
• 4) enzymatic content of their lysosomes
• 5) role in the immune response (macrophages are involved in activation of the "adaptive immune system", not neutrophils.)
• 6) role in would repair (macrophages play a larger role to initiate healing)

eosinophils

basophils

recognition and elimination of cells infected with viruses as well as cancer cells.

Interleukin-1: it acts on receptors of the hypothalamus to affect the body's thermostat.

During acute inflammation, there is leukocytosis or an increase in circulating leukocytes (primarily neutrophils). This makes an increase in the number of immature neutrophils (bands) that migrate to the site of inflammation and show up in higher quantity on blood draws.

CBC with differential - to show fibrinogen and bands: there will be increase in blood levels of fibrinogen (acute-phase reactant), and bands because of an increase in immature neutrophils migrating to the inflammatory site.

Sedementation rate - with increased fibrinogen levels comes an enhanced erythrocyte formation. The erythrocytes start to stack leading to an increased sed rate of erythrocytes.

Fibroblasts because they synthesize and secrete collagen and otehr connective tissue proteins.