Disorders of Cellular Development
Genes and Genetic Disorders
University of San Francisco
Dr.M.Maag
©2003 Margaret Maag
Class 1 Objectives
• Upon completion of this lesson, the student will be able to
 identify the basic cellular processes, which influence
our health.
 compare and contrast cellular adaptation processes.
 describe the processes associated with aging and list
the current theories.
 determine syndromes associated with chromosomal
defects.
 explain the difference between autosomal dominant
and recessive defects.
Cellular Reproduction
• Meiosis: formation of gametes
– Sperm and egg cells
• Mitosis: nuclear division of somatic cells
– A two-phase process:
• cellular division
• cytokinesis: cytoplasmic division
• Before cell divides it has an “interphase” or “growth
phase”
Somatic Cell Cycle
• Four phases
– S phase = DNA synthesis
– G2 phase = RNA and protein synthesis
– M phase = mitosis (nuclear and cytoplasmic
division)
– G1 phase = the time between M phase &
DNA synthesis
• See Fig. 1-23 McCance & Heuther (2002)
p. 25
– Time: 12 to 24 hours
Do you know?
• Which adult cells do not replicate and divide?
– Nerve cells
– Lens cells of the eye
– Muscle cells
• Which adult cells do replicate and divide?
– Epithelial cells: rapidly (< 10 hrs.)
– Intestinal
– Lung
– Skin
• Clinical implications?
Do you know?
• During which phase of pregnancy are fetal cells most
vulnerable to injury?
• Pre-Embryonic = 0 - 3 weeks
– teratogens cause spontaneous abortion
• Embryonic = 3 - 8 weeks
•
•
•
•
all organ systems are formed
angiogenesis: CVS activates pump at 3rd week
critical period for morphogenesis
teratogens cause major congenital anomalies
• Fetal = 9 - 40 weeks
• period of rapid growth
What Stimulates Cell Division?
• “Social control genes” and protein growth factors
– Survival of the whole organism vs. survival or growth of
individual cells
• Chemical signals, or “growth factors,” such as
cytokines (peptides)
– Relay messages within and between the cells
– Epidermal growth factor
– Insulin-like growth factor
• Clinical implications?
See McCance & Huether Table 1-4p.
26
7
Cellular Adaptations

•
•
•
Atrophy = decrease in cell size & proliferation
Hypertrophy = increase in cell size
Hyperplasia = increase in rate of cell division
Dysplasia = abnormal shape, size,and
organization
• Metaplasia = reversible replacement of one
cell with another
Cellular Injury
• Can occur d/t hypoxia, toxins, or infections
– Hypoxia: a result of ischemia (decreased
blood supply)
• Low oxygen environment
• Low hemoglobin or RBC
• Oxidative enzymes (e.g. cytochomes)
– Anoxia: no oxygen at all
– Injury d/t extreme energy sources or
chemical agents
Cellular Injury
• Assessment:
– Fever d/t PGEs and TNF
– Tachycardia d/t fever
– Pain d/t obstructions, pressure, bradykinins
• Increased cellular enzymes in blood
– LDH, CK, ALT, AST, Amylase, Aldolase,
Alkaline Phosphate
Cellular Death
• Common clinical types:
– Gangrene d/t severe hypoxia
• Dry, Wet, or Gas
– Fat: seen in the breast
– Caseous: seen in TB with granuloma
– Liquefaction: seen in the brain
– Coagulation: inside the heart
Necrosis
• Necrotic cell death occurs when injurious stimuli to
the cell are too intense or prolonged
• ‘Severe injury’ induced cell death initiated by
inflammatory cytokines
– stimulates immune & inflammatory response
– characterized by cellular swelling
– due to prolonged hypoxia or infection
Apoptosis
“A Dropping Off ”
• Important programmed capacity of genome to induce
cell suicide and the elimination of ‘unwanted’ cells
– e.g. preneoplastic, aged or damaged cells
– Unlike necrosis; affects scattered single cells
• Controlled by intrinsic cellular mechanisms or by
extra-cellular signals
– Hormones, UV Radiation, Chemotherapy, Viruses
– Pharmacological blockade of the calcium channels (e.g.
Nifedipine) can inhibit apoptosis
Aging
• Developmental, irreversible, and a universal
programmed process on the cellular & molecular
level
– Atrophy of skeletal muscle
– Loss of “elastin”
– Decreased immunity, increased autoimmunity
• Aging does not always equal pathology
– Primary vs. Secondary Aging
• Life span today is between 80-100 years
• Women tend to outlive men
Theories
• Longevity and health between
– Genetic
– Sex hormones
– Social Class
• General Categories of Aging
– Damage accumulation
– Genetic control of human lifespan
Basics Of Genetic Inheritance
• DNA & RNA are genetic blueprints for cell
development
• Both are nucleic acids
• What is the action of DNA vs. RNA?
• DNA carries genetic code & is mainly found in the
nucleus & mitochondria
• RNA transcribes genetic code from DNA & carries the
code to the cell’s cytoplasm.
• RNA makes proteins
RNA
• http://www.nytimes.com/packages/html/scie
nce/20030121_RNA/sci_RNA_01.html
How Do Chromosomes Interact?
• 22 pairs of autosomes (haploid)
• Plus 1 pair of gametes
– (sperm and egg cells)
– (xx or xy)
• 44 + 2 = 46 (diploid)
Plain Genetics!
Male
Female
A B
A B
A = Recessive
A A
B A
A B
B B
B = Dominant
Eye Color
• http://www.athro.com/evo/gen/genefr2.html
Principle of Dominance
• One gene may “mask” another gene when the 2 are found
together on a heterozygote
• The “dominant” gene’s characteristics are observable
• The concealed gene is called “recessive”
• Genes for a “recessive” occur in heterozygotes who carry
1 copy of the gene, but do not express the disease.
Normal Female Karotype
Normal Male Karotype
Chromosomal Defects
• Causes miscarriages (1 in 12 conceptions and 50% of
first trimester spontaneous abortions)
• Turner’s Syndrome: 1: 2,500 births; females with short
stature (4ft, 8”); abnormal sexual development;
intelligence not effected
• Klinefelter’s Syndrome:1:500 BIRTHS Tall stature;
delayed puberty; (47: xxy); moderate mental
impairment; small firm testes; gynecomastia
Turner’s Syndrome
Kleinfelter’s Syndrome
Autosomal Dominant Defects
• Huntington’s Chorea
– Abnormal motor function as a result of degeneration
of the basal ganglia & cortical neurons
– 1:10,000; occurs in middle adulthood
– Defective gene inherited from one parent
– http://www.kumc.edu/hospital/huntingtons/
Autosomal Dominant Defects
• Marfan Syndrome: genetic disorder affecting the
connective tissue
• Chromosome 15: “Fibrillin gene” is affected
– skeleton, lungs, eyes, heart and blood vessels can be
affected
– 200,000 in USA
– 25% of the cases are “de novo” cases
– 50:50 chance of passing it on to offspring
Autosomal Recessive Defects
•
•
•
•
Largest category of mendelian disorders
Cystic Fibrosis: 1: 2,500 WHITES IN U.S.;
abnormal sodium transport  airway & pancreatic
duct obstruction
Sickle Cell Disease 1: 400 African Americans
PKU: 1:12,000 worldwide; Lack enzyme to convert
phenylalanine to tyrosine; can lead to mental
retardation; screened at birth: Guthrie’s test
Hematological Slide
Sickle Cell
Sex-Linked Defects
• Hemophilia “A”: X-linked recessive disorder resulting from an error in the
gene coding for coagulation factor 8
– boys inherit defective gene on the X chromosome from mother
– mother is heterozygous for disorder (without symptoms)
– spontaneous bleeding after a minor wound
– BLEEDING INTO JOINTS CAUSING PAIN & DISABILITY
– factor 8 replacement: frozen plasma concentrate
• Hemophilila “B”: X-linked disorder
– lack of factor 9
Sex Genetics!
Male
Female
X Y
X X
X X
X Y
X Y
X X
e.g. Hemophilia A
Sex-Linked Defects
• Duchenne’s muscular dystrophy: a defect in a single protein in
the muscle fibers
• Causes progressive muscle weakness  muscle cells breakdown
& are lost
• Is seen before age 11
• Mainly males
What Stimulates Cell Division?
• “Social control genes” and protein growth factors
– Survival of the whole organism vs. survival or growth of
individual cells
• Chemical signals or “growth factors” such as
cytokines (peptides)
– Relay messages within and between the cells
– Epidermal growth factor
– Insulin-like growth factor
• Clinical implications?
See McCance & Huether Table 1-4p.
26
34
Case Study
A 6-month old is admitted to the ER with a
diagnosis of recurrent pneumonia. The nurse
notes a resp. rate of 50, heart rate of 170, and
temperature of 102 F. The client is retracting
substernally with bilateral wheezes and
rhonchi. The mother states that this is her
son’s 3rd admission since birth for
pneumonia. She also mentions that he hasn’t
been gaining weight liker her older child had a
6-months of age.
NCLEX Questions
1. A child with progressive cystic fibrosis for 2
years is in the ER with significant
respiratory distress. What physical
characteristics would the nurse anticipate to
see in this client?
a) Low-set ears
b) Gray appearance
c) Clubbed fingernails
d) Jaundice
NCLEX Question
2.
a.
b.
c.
d.
The nurse involved in genetic counseling for the family of a
mother with Huntington’s Disease is asked if they have a
chance of developing the same disease process? What would
be the nurse’s best response?
If the mother alone has the disease, they have a 2:4 chance
of inheriting the disease.
Both parents must have the disease for the offspring to inherit
the disease.
The disorder is a spontaneous disruption of the
neurotransmitters with no inheritance principles.
If the mother has the disease, they a 1:4 chance of inheriting
the same disorder.
NCLEX Question
3.
a.
b.
c.
d.
Which response is best when a nurse is asked by a
family member why a client with Huntington’s
Chorea would be given thickened liquids?
The client is at risk for dehydration.
The client is at risk for aspiration.
The client may have difficulty chewing.
The client may have pain on swallowing.
References
• Hansen, M. (1998). Pathophysiology:
Foundations of disease and clinical
intervention. Philadelphia, PA: Saunders.
• Hogan, M., & Hill, K. (2004). Pathophysiology:
Reviews and rationales. Upper Saddle River:
New Jersey, NJ: Prentice Hall.
• Huether, S. E., & McCance, K. L. (2002).
Pathophysiology. St. Louis, MO: Mosby.