Pathophysiology

Denver School of Nursing – ADN & BSN Programs No Laboratory component for this class Pathophysiology BIO 206 & 308 – Day 1 CH1– 3 Alteration to Cellular Bio & Genetic Path

Introductions Intro’s – Please Share with us: 1) What is your name? 2) What city have you resided in the longest? 3) Who or what event influenced you most to enter the field of nursing? 4) What field of nursing do you want to work in? 5) What is your favorite pathological condition?

Pathophysiology For the first “warm up” day of Patho we are going to cover: • 1) Cellular Biology - Ch. 1 • 2) Genes and Genetics Diseases - Ch. 2 • 3) Altered Cell / Tissue Bio - Ch. 3

CH 1. Cellular Biology This whole chapter is a brief summary and review from Anatomy and Physiology • LETS See how much you remember…

CH 1. Cellular Biology • LETS See how much Cell Bio you remember… ~ What are the metaphors for the following images????

CH 1. Cellular Biology • What cellular structure does this represent? Source: http://news.parcel2go.com

CH 1. Cellular Biology • What cellular structure does this represent? Source: http://googleimages.com

CH 1. Cellular Biology • What cellular structure does this represent? Source: http://www.itchmo.com

CH 1. Cellular Biology • The “Circle of Cellular Life”

CH 1. Cellular Biology • What cellular structure does this represent? Source: http://www.itchmo.com

CH 1. Cellular Biology • What cellular structure does this represent? Source: chipotle.com

CH 1. Cellular Biology • LETS See how much you remember… ~ What is the diff between Prokaryotes & Eukaryotes? ~ Membrane composition - Why are Proteins / lipids important? - Endoplasmic reticulum - Ribosomes - Golgi complex - Lysosomes - Peroxisomes - Mitochondria - Cytoskeleton (microtubules + actin)

CH 1. Cellular Biology Source: Huether, McCance Understanding Pathophysiology 4th Ed. 2008

CH 1. Cellular Biology ~ What are the diff types of cellular signaling?

CH 1. Cellular Biology ~ What are the diff types of cellular signaling? 1) Autocrine 2) Paracrine 3) Hormonal 4) Neurotransmitter 5) Neurohormonal secretion 6) Diffusion vs Transport

CH 1. Cellular Biology What are the Different types of cellular signaling? Source: Huether, McCance Understanding Pathophysiology 4th Ed. 2008

CH 1. Cellular Biology • What are the two types of cellular division?

CH 1. Cellular Biology Source: http://www.accessexcellence.org

CH 1. Cellular Biology Source: Houston Biology Project: http://sites.google.com/site/houstonbiologyproject

CH 1. Cellular Biology Source: Indian River State College, http://faculty.irsc.edu/

Break Time!! Image Source: http://www.gilmerfreepress.net

CH 2. Genetics • What does the “universal genetic code” mean?

Genetics

CH 2. Genetics • The “universal genetic code” • All living organisms use precisely the same DNA codes (codons – triplets of bases: A, C, T & G) to specify the production of proteins. • (Only exception being mitochondrial DNA) Source: Huether, McCance Understanding Pathophysiology 4th Ed. 2008

CH 2. Genetics • Codons and AA Source: University of Leicester: www.le.ac.uk

CH 2. Genetics Source: University of Leicester: www.le.ac.uk

CH 2. Genetics Source: http://artedi.ebc.uu.se/course/UGSBR/codonusage1.html

CH 2. Genetics Source: University of Leicester: www.le.ac.uk

CH 2. Genetics – Protein Synthesis • 1) Transcription – from DNA to mRNA • Waiter writes down the order from the customer (DNA) • 2) Gene Splicing (introns and exons) • HnRNA into “functional” mRNA via removal of introns, thus only exons remain. • 3) Translation – from mRNA to AA Chain • The chef (ribosome) translates the order into the meal Source: Huether, McCance Understanding Pathophysiology 4th Ed. 2008

CH 2. Genetics – Protein Synthesis • Figure 2-5 (p. 40) Source: Huether, McCance Understanding Pathophysiology 4th Ed. 2008

CH 2. Genetics • Mutations • “Any inherited alteration of genetic material.” • A massive diversity of Mutations exist: • Polymorphisms • Point Mutation • Base pair substitution* • Deletion • Insertion • Frameshift mutation* • Inversion *Focused on in text book Source: Huether, McCance Understanding Pathophysiology 4th Ed. 2008

CH 2. Genetics • Mutations • Polymorphisms – “many forms” = changing of genes • Point Mutation = Base pair substitution – 1 base pair replaces another • Frameshift mutation – Insertion or deletion of base pairs (as long as not a multiple of 3) causing a shift in the “reading frame” thus causing a huge alteration in AA sequence. • Inversion – an entire section of DNA is reversed Source: Huether, McCance Understanding Pathophysiology 4th Ed. 2008

CH 2. Genetics • Mutations Point Mutation A point mutation is a simple change in one base of the gene sequence. This is equivalent to changing one letter in a sentence, such as this example, where we change the 'c' in cat to an 'h': Original The fat cat ate the wee rat. Point Mutation The fat hat ate the wee rat. Source: http://www.genetichealth.com

CH 2. Genetics • Mutations Insertion  Mutations that result in the addition of extra DNA are called insertions. Insertions can also cause frameshift mutations, and general result in a nonfunctional protein. Original The fat cat ate the wee rat. Insertion The fat cat xlw ate the wee rat. Source: http://www.genetichealth.com

CH 2. Genetics • Mutations Deletion Mutations that result in missing DNA are called deletions. These can be small, such as the removal of just one "word," or longer deletions that affect a large number of genes on the chromosome. Deletions can also cause frameshift mutations. In this example, the deletion eliminated the word cat. Original The fat cat ate the wee rat. Deletion The fat ate the wee rat. Source: http://www.genetichealth.com

CH 2. Genetics • Mutations Insertion  Mutations that result in the addition of extra DNA are called insertions. Insertions can also cause frameshift mutations, and general result in a nonfunctional protein. Original The fat cat ate the wee rat. Insertion The fat cat xlw ate the wee rat. Source: http://www.genetichealth.com

CH 2. Genetics • Mutations Inversion In an inversion mutation, an entire section of DNA is reversed. A small inversion may involve only a few bases within a gene, while longer inversions involve large regions of a chromosome containing several genes. Original The fat cat ate the wee rat. Insertion The fat tar eew eht eta tac. Source: http://www.genetichealth.com

CH 2. Genetics • Mutation • Mutagens – agents that increase the frequency of mutations. • EX) radiation, nitrogen mustard, vinyl chloride, alkylating agents, formaldehyde & sodium nitrite. • Spontaneous mutations (mutation in absence of mutagens) are very rare events. Source: Huether, McCance Understanding Pathophysiology 4th Ed. 2008

CH 2. Genetics • Polyploidy • Euploid Cells – cells with multiple of the normal number of chromosomes (greekeu = good / true) • Gametes Euploid = Haploid • Somatic Cells = Diploid • > Diploid = Polyploid • Interestingly, some liver, bronchial and epithelial tissues are physiologically polyploid. • However a zygote that is triploidy or tetraploidy will spontaneously abort, or rarely be stillborn. (Triploidy 1:10,000 births) . Source: Huether, McCance Understanding Pathophysiology 4th Ed. 2008

CH 2. Genetics • Aneuploidy • A cell that does not contain a multiple of 23 chromo’s • Trisomic / Trisomy = 3 copies of one chromosome • Often survivable (13, 18, 21 / Trisomy 21 causes what disease? Trisomy 16 leading cause of trisomyabortuses yet incombatable with life thus not seen in live births) • Monosomy = the presence of only one copy of a given chromosome in a diploid cell. • Monosomy of ANY chromosome is lethal ( Generally “Loss of genetic material induces a much greater consequence than duplication of genetic material”) • Usually a consequence of nondisjunction during meiosis (Text book says also in Mitosis – which is FALSE) . Source: Huether, McCance Understanding Pathophysiology 4th Ed. 2008

CH 2. Genetics • Aneuploidy • Partial trisomy – an extra portion of a chromosome is present in each cell. (Less severe consequences) • Chromosomal Mosaics – the body has two or more different cell lines (Thus different karyotypes in different cells of the same organism / patient) . Source: Huether, McCance Understanding Pathophysiology 4th Ed. 2008

CH 2. Genetics • Examples of Aneuploidy (In Somatic Chromosomes) • Trisomy 13 – Patau Syndrome • One in 10,000 live births • Trisomy 18 – Edwards Syndrome • One in 3,000 live births (Increases with maternal age) • Trisomy 21 – Down syndrome • Women < 30 y/o risk of 1:1,000 = 0.1% • Women > 35 y/o risk of 1:1,000 = 0.1% • Women > 45 y/o risk of 3% - 5% Source: Huether, McCance Understanding Pathophysiology 4th Ed. 2008

CH 2. Genetics • Trisomy 13 – Patau Syndrome Some physical characteristics are flattened facial features, malformed and low-set ears, cleft lip and/or palate, prominent heels, and genital malformations. Often there are problems with the nervous system, including forebrain development, spinal cord development, mental retardation, and seizures. Vision and eye problems are common, as well as respiratory and heart defects. Approximately 45% of Patau syndrome babies die within the first month of life, while the number increases to 70% in the first 6 months. Source: Lucina Foundation: http://www.lucinafoundation.org

CH 2. Genetics • Trisomy 18 – Edward Syndrome Patients with trisomy 18 can range from mildly to severely affected. Some characteristics of this syndrome are clenched hands, shield chest with short sternum, short neck, and small jaw. Heart defects are typical of trisomy 18, including ventricular septal defects, atrial septal defects, and coarctation of the aorta. Also common are omphaloceles (externalized GI) and renal pathology Source: Lucina Foundation: http://www.lucinafoundation.org

CH 2. Genetics • Trisomy 21 – Down Syndrome Down syndrome is a chromosomal disorder which causes physical and intellectual delays in development and occurs when there are 3 chromosome 21's, resulting in 47 total chromosomes instead of the normal 46. The most common clinical features are short neck and flat face, upward slanting eyes, low muscle tone and a single crease across the palm of the hand. Congenital heart defects accompany Down syndrome in about 40% of the cases. Vision and hearing problems are also common. Source: Lucina Foundation: http://www.lucinafoundation.org

CH 2. Genetics • Examples of Aneuploidy (In Sex Chromosomes) • Trisomy X – Most Common Aneuploidies Effect 0.1% births • Triplet of X in all cells. No physical abnormalities. Do have sterility, menstrual irregularity and sometimes MR. (5 or > X increases MR, and introduction of physical defects) • Monosomy X – Turner Syndrome • Results in a total of 45 chromosomes. (45,X) • 15-20% of spontaneous abortions, only 0.5% survive to term. If survive, short stature with pathoneumonic webbing of the neck, widely spaced nipples, reduced carrying angle, Also aortic coactation is common, usually sterile but with no MR. • Klinefelter Syndrome (47,XXy) • Moderate MR, Have general male appearance but usually sterile, with gynecomastia and incomplete secondary male maturation. Long limbs also common. 1:1,000 male births, Increased freq qMateral age. Source: Huether, McCance Understanding Pathophysiology 4th Ed. 2008

CH 2. Genetics • Mode of Inheritance – the pattern in which a genetic disease is inherited through generations. Usually studied via pedigree charts. • 1) Autosomal Recessive • 2) Autosomal Dominant • 3) X – Linked Recessive • 4) X – Linked Dominant . Source: Huether, McCance Understanding Pathophysiology 4th Ed. 2008

Pathophysiology