3
WEEK 1: CELLULAR BIOLOGY AND ALTERATIONS
Week 1 Instructor Comment:
Retinoblastoma
• Retinoblastoma is a rare cancer that occurs only in children. It develops either as a
hereditary disease, due to an abnormality of the RB1 gene, or sporadically (70% of
cases). Located on chromosome 13q14, the RB1 gene is responsible for encoding pRb,
which is a tumor suppressor protein. In the heritable form, the RB1 gene mutation is
inherited through germinal cells, with a second mutation occurring in somatic retinal
cells. The noninherited type of retinoblastoma occurs as a result of two mutations in
the somatic retinal cells. The tumor arises from the inner surface of the retina and then
spreads into the retina, resulting in leukocoria—a white appearance to the red reflex,
commonly called cat-eye reflex—which is most often first identified by the child’s
parents.
• Normally the RB1 gene (pRB) governs the passage of the restriction point in the cell
cycle, thus regulates cell proliferation.
Germline mutations are inherited, whereas somatic mutations are acquired.
• Tumor suppressors are a class of genes that work to limit cell growth, and they are
important for tumor suppression by preventing DNA synthesis until mutations are
corrected; preventing cell division if DNA replication introduces new mutations, and
inducing programmed cell death when damage cannot be repaired. RB or
retinoblastoma protein is one example of a tumor suppressor. They act in the G1/S
checkpoint, thereby inhibiting progression to DNA synthesis. RB activity is regulated
by many signals, including growth factors and cell differentiation. Clinically,
retinoblastoma appears in the first years of life--shining light on the eye gives off an
abnormal white reflection. Bilateral retinoblastoma is always due to inherited RB
mutations.
• Retinoblastoma is a rare cancer that occurs only in children. It develops either as a
hereditary disease, due to an abnormality of the RB1 gene, or sporadically (70% of
cases). Located on chromosome 13q14, the RB1 gene is responsible for encoding pRb,
which is a tumor suppressor protein. In the heritable form, the RB1 gene mutation is
inherited through germinal cells, with a second mutation occurring in somatic retinal
cells. The noninherited type of retinoblastoma occurs as a result of two mutations in
the somatic retinal cells. The tumor arises from the inner surface of the retina and then
spreads into the retina, resulting in leukocoria—a white appearance to the red reflex,
commonly called cat-eye reflex—which is most often first identified by the child’s
parents.
Normally the RB1 gene (pRB) governs the passage of the restriction point in the cell
cycle, thus regulates cell proliferation.
Germline mutations are inherited, whereas somatic mutations are acquired.
Page 1 of 32
, 3
References:
Quinonez, S. C., & Barsh, G. (2019). Pathophysiology of disease: An introduction to
clinical medicine (8th ed.). McGraw-Hill.
Tkacs, N. C., Herrmann, L. L., & Johnson, R. L. (2021). Advanced physiology and
pathophysiology: Essentials for clinical practice. Springer Publishing Company, LLC.
• The retinoblastoma (RB) gene was identified when studying a rare disease, familial
retinoblastoma. RB gene is a tumor suppressor gene, their products and possible
mechanisms is loss of their function contributing to unregulated cell growth. Patients
who are carriers of retinoblastoma trait have a higher risk of developing
retinoblastoma often in both eyes, and are also at great risk for developing
osteosarcoma and other soft-tissue sarcomas. About 60% of retinoblastomas occur
sporadically virtually in only one eye, and such patients are not at increased risk for
other forms of cancer.
Reference:
Kumar, V., Abbas, A. K., Fausto, N., & Aster, J. C. (2015). Robbins and Cotran
pathologic basis of disease, professional edition (9th ed.). Elsevier.
• Retinoblastoma is a tumor originating from the nuclear layer of the primary retinal
photoreceptor cells, genetically determined. It develops due to a mutation in
chromosome 13 in the q14 band. It is the most common, originally malignant
intraocular change in childhood and accounts for 10-15% of cancer cases occurring in
the first year of life. Usually, this cancer manifests itself as a leukocoria in a child
under two years of age. It can be multifocal on both sides in a congenital form, and the
risk of secondary cancers. Diagnosis of retinoblastoma requires indirect
ophthalmoscopy and research using imaging diagnostics techniques: ultrasonography
(USG), magnetic resonance imaging (MRI), or computed tomography (CT). If left
untreated, it leads to metastasis and death of the child. With the advancement of
medicine, survival with modern treatment methods is> 95%. More and more often, it is
possible to save the mutant eye enucleation surgery. An interdisciplinary team's
immediate referral to an ophthalmologist's oncologist and proper management is
necessary to optimize the visual effect and survival.
Reference:
Budny, A., & Grochowski, C. (2018). Retinoblastoma. Journal of Education, Health
and Sport, 8(7), 204-213. http://dx.doi.org/10.5281/zenodo.1299573.
• The tumor suppressor genes controlling these processes include many cell cycle
inhibitors and regulators. When a tumor suppressor is inactivated or turned off, the
likelihood of cancer development is increased. As such, the actions of a normally
functioning tumor suppressor will inhibit proliferation, but upon loss of its function,
unregulated growth can occur. More than half of all cancers in humans have mutations
in the TP53 tumor suppressor gene, illustrating its vital importance in maintaining
Page 2 of 32
, 3
genome integrity and eliminating irreversibly altered cells. When the p53 protein is not
functional, DNA damage goes unrepaired, and mutations accumulate in cells, leading
to other cancer cell characteristics. RB1 represents an additional tumor suppressor
gene, and its product, pRb, can stop the cell cycle in G1. The consequence of losing
this function is underscored by the typical findings of RB1 mutations in
retinoblastoma, osteosarcoma, and carcinomas of breast, lung, and colon.
Reference:
Quinonez, S. C., & Barsh, G. (2019). Pathophysiology of disease: An introduction to clinical
medicine (8th ed.). New York, NY: McGraw-Hill.
• Multiple checkpoints are present within the cell cycle machinery to ensure the cell
undergoes division appropriately. Cell cycle progression is the ability to halt the cycle
when necessary. If a cell experiences alterations to its DNA through damage or
mutations, the cell must be prevented from proceeding through cellular division and
not produce daughter cells with the same genetic alterations. Additionally, cells must
ensure that the necessary nutrients and building blocks are present before proceeding
through division steps. One regulatory protein of cell division, the retinoblastoma
protein (pRb), inhibits the cell cycle from progressing through G1 checkpoint, also
known as the restriction point; by binding and inhibiting the activity of necessary
transcription factors. As cyclin D levels rise in response to growth factor—and
nutrient-induced signaling—the cyclin D–activated CDKs phosphorylate pRb, leading
to a change in its structure; this structural shift causes the release of the bound
transcription factors and allows the cell to continue through G1.
Reference:
McCance, K. L., & Huether, S. E. (2019). Pathophysiology: The biologic basis for disease in
adults and children (8th ed.). Elsevier.
ADHD
• Neuroimaging studies provide much information that currently allows us to expand the
neurobiology of ADHD. The neuroimaging studies show disorders of several other
brain areas, particularly the anterior cingulum, the dorsolateral and ventrolateral
prefrontal cortex, the orbitofrontal cortex, the superior parietal regions, the caudate
nucleus, the thalamus, the amygdala, and the cerebellum.
• A consequence of leakage of lysosomal enzymes during chemical injury is an
enzymatic digestion of the nucleus and nucleolus occurs, halting DNA synthesis.
Page 3 of 32
, 3
Reference:
Kasparek, T., Theiner, P., & Filova, A. (2015). Neurobiology of ADHD from childhood to
adulthood: Findings of imaging methods. Journal of Attention Disorders, 19(11), 931–943.
doi: 10.1177/1087054713505322
• Down syndrome, Turner Syndrome, and Klinefelter Syndrome are all examples of
chromosomal disorders that occur from a literation in the chromosome number.
Sex-linked disorders frequently are associated with the X chromosome and are
predominantly recessive.
The Punnett square can be utilized to describe possible combinations that can occur
with the transmission of single-gene dominant and recessive traits.
The genetic information needed for protein synthesis is encoded in the DNA contained
in the cell nucleus.
• A phenotype is the set of characteristics or the clinical presentation of an individual,
which results from the particular genotype.
Crossing over involves the exchange of genetic material between two homologous
chromosomes during meiosis.
Messenger RNA carries the instructions for protein synthesis.
• The kind of genetic mutation that results in the change of an amino acid sequence in
the protein sequence is best described as a missense mutation.
Semi conservative replication relates to the concept that as DNA is copied, one
original and one newly formed copy of the DNA is inherited together in each of the
progeny cells.
Reference:
McCance, K. L., & Huether, S. E. (2019). Pathophysiology: The biologic basis for disease in
adults and children (8th ed.). Elsevier.
LVH
• Heart failure occurs when the heart is unable to pump enough blood to meet the
body's needs. The left ventricle is more prone to develop heart failure than the right
ventricle due to its workload and vulnerability to ischemic and other injuries. In left-
sided heart failure with reduced ejection fraction, the Frank-Starling mechanism stays
intact, but over time the end-systolic and end-diastolic volumes increase, the chamber
dilates, and the ventricular wall thins.
Reference:
McCance, K. L., & Huether, S. E. (2019). Pathophysiology: The biologic basis for disease in
adults and children (8th ed.). Elsevier.
Page 4 of 32
WEEK 1: CELLULAR BIOLOGY AND ALTERATIONS
Week 1 Instructor Comment:
Retinoblastoma
• Retinoblastoma is a rare cancer that occurs only in children. It develops either as a
hereditary disease, due to an abnormality of the RB1 gene, or sporadically (70% of
cases). Located on chromosome 13q14, the RB1 gene is responsible for encoding pRb,
which is a tumor suppressor protein. In the heritable form, the RB1 gene mutation is
inherited through germinal cells, with a second mutation occurring in somatic retinal
cells. The noninherited type of retinoblastoma occurs as a result of two mutations in
the somatic retinal cells. The tumor arises from the inner surface of the retina and then
spreads into the retina, resulting in leukocoria—a white appearance to the red reflex,
commonly called cat-eye reflex—which is most often first identified by the child’s
parents.
• Normally the RB1 gene (pRB) governs the passage of the restriction point in the cell
cycle, thus regulates cell proliferation.
Germline mutations are inherited, whereas somatic mutations are acquired.
• Tumor suppressors are a class of genes that work to limit cell growth, and they are
important for tumor suppression by preventing DNA synthesis until mutations are
corrected; preventing cell division if DNA replication introduces new mutations, and
inducing programmed cell death when damage cannot be repaired. RB or
retinoblastoma protein is one example of a tumor suppressor. They act in the G1/S
checkpoint, thereby inhibiting progression to DNA synthesis. RB activity is regulated
by many signals, including growth factors and cell differentiation. Clinically,
retinoblastoma appears in the first years of life--shining light on the eye gives off an
abnormal white reflection. Bilateral retinoblastoma is always due to inherited RB
mutations.
• Retinoblastoma is a rare cancer that occurs only in children. It develops either as a
hereditary disease, due to an abnormality of the RB1 gene, or sporadically (70% of
cases). Located on chromosome 13q14, the RB1 gene is responsible for encoding pRb,
which is a tumor suppressor protein. In the heritable form, the RB1 gene mutation is
inherited through germinal cells, with a second mutation occurring in somatic retinal
cells. The noninherited type of retinoblastoma occurs as a result of two mutations in
the somatic retinal cells. The tumor arises from the inner surface of the retina and then
spreads into the retina, resulting in leukocoria—a white appearance to the red reflex,
commonly called cat-eye reflex—which is most often first identified by the child’s
parents.
Normally the RB1 gene (pRB) governs the passage of the restriction point in the cell
cycle, thus regulates cell proliferation.
Germline mutations are inherited, whereas somatic mutations are acquired.
Page 1 of 32
, 3
References:
Quinonez, S. C., & Barsh, G. (2019). Pathophysiology of disease: An introduction to
clinical medicine (8th ed.). McGraw-Hill.
Tkacs, N. C., Herrmann, L. L., & Johnson, R. L. (2021). Advanced physiology and
pathophysiology: Essentials for clinical practice. Springer Publishing Company, LLC.
• The retinoblastoma (RB) gene was identified when studying a rare disease, familial
retinoblastoma. RB gene is a tumor suppressor gene, their products and possible
mechanisms is loss of their function contributing to unregulated cell growth. Patients
who are carriers of retinoblastoma trait have a higher risk of developing
retinoblastoma often in both eyes, and are also at great risk for developing
osteosarcoma and other soft-tissue sarcomas. About 60% of retinoblastomas occur
sporadically virtually in only one eye, and such patients are not at increased risk for
other forms of cancer.
Reference:
Kumar, V., Abbas, A. K., Fausto, N., & Aster, J. C. (2015). Robbins and Cotran
pathologic basis of disease, professional edition (9th ed.). Elsevier.
• Retinoblastoma is a tumor originating from the nuclear layer of the primary retinal
photoreceptor cells, genetically determined. It develops due to a mutation in
chromosome 13 in the q14 band. It is the most common, originally malignant
intraocular change in childhood and accounts for 10-15% of cancer cases occurring in
the first year of life. Usually, this cancer manifests itself as a leukocoria in a child
under two years of age. It can be multifocal on both sides in a congenital form, and the
risk of secondary cancers. Diagnosis of retinoblastoma requires indirect
ophthalmoscopy and research using imaging diagnostics techniques: ultrasonography
(USG), magnetic resonance imaging (MRI), or computed tomography (CT). If left
untreated, it leads to metastasis and death of the child. With the advancement of
medicine, survival with modern treatment methods is> 95%. More and more often, it is
possible to save the mutant eye enucleation surgery. An interdisciplinary team's
immediate referral to an ophthalmologist's oncologist and proper management is
necessary to optimize the visual effect and survival.
Reference:
Budny, A., & Grochowski, C. (2018). Retinoblastoma. Journal of Education, Health
and Sport, 8(7), 204-213. http://dx.doi.org/10.5281/zenodo.1299573.
• The tumor suppressor genes controlling these processes include many cell cycle
inhibitors and regulators. When a tumor suppressor is inactivated or turned off, the
likelihood of cancer development is increased. As such, the actions of a normally
functioning tumor suppressor will inhibit proliferation, but upon loss of its function,
unregulated growth can occur. More than half of all cancers in humans have mutations
in the TP53 tumor suppressor gene, illustrating its vital importance in maintaining
Page 2 of 32
, 3
genome integrity and eliminating irreversibly altered cells. When the p53 protein is not
functional, DNA damage goes unrepaired, and mutations accumulate in cells, leading
to other cancer cell characteristics. RB1 represents an additional tumor suppressor
gene, and its product, pRb, can stop the cell cycle in G1. The consequence of losing
this function is underscored by the typical findings of RB1 mutations in
retinoblastoma, osteosarcoma, and carcinomas of breast, lung, and colon.
Reference:
Quinonez, S. C., & Barsh, G. (2019). Pathophysiology of disease: An introduction to clinical
medicine (8th ed.). New York, NY: McGraw-Hill.
• Multiple checkpoints are present within the cell cycle machinery to ensure the cell
undergoes division appropriately. Cell cycle progression is the ability to halt the cycle
when necessary. If a cell experiences alterations to its DNA through damage or
mutations, the cell must be prevented from proceeding through cellular division and
not produce daughter cells with the same genetic alterations. Additionally, cells must
ensure that the necessary nutrients and building blocks are present before proceeding
through division steps. One regulatory protein of cell division, the retinoblastoma
protein (pRb), inhibits the cell cycle from progressing through G1 checkpoint, also
known as the restriction point; by binding and inhibiting the activity of necessary
transcription factors. As cyclin D levels rise in response to growth factor—and
nutrient-induced signaling—the cyclin D–activated CDKs phosphorylate pRb, leading
to a change in its structure; this structural shift causes the release of the bound
transcription factors and allows the cell to continue through G1.
Reference:
McCance, K. L., & Huether, S. E. (2019). Pathophysiology: The biologic basis for disease in
adults and children (8th ed.). Elsevier.
ADHD
• Neuroimaging studies provide much information that currently allows us to expand the
neurobiology of ADHD. The neuroimaging studies show disorders of several other
brain areas, particularly the anterior cingulum, the dorsolateral and ventrolateral
prefrontal cortex, the orbitofrontal cortex, the superior parietal regions, the caudate
nucleus, the thalamus, the amygdala, and the cerebellum.
• A consequence of leakage of lysosomal enzymes during chemical injury is an
enzymatic digestion of the nucleus and nucleolus occurs, halting DNA synthesis.
Page 3 of 32
, 3
Reference:
Kasparek, T., Theiner, P., & Filova, A. (2015). Neurobiology of ADHD from childhood to
adulthood: Findings of imaging methods. Journal of Attention Disorders, 19(11), 931–943.
doi: 10.1177/1087054713505322
• Down syndrome, Turner Syndrome, and Klinefelter Syndrome are all examples of
chromosomal disorders that occur from a literation in the chromosome number.
Sex-linked disorders frequently are associated with the X chromosome and are
predominantly recessive.
The Punnett square can be utilized to describe possible combinations that can occur
with the transmission of single-gene dominant and recessive traits.
The genetic information needed for protein synthesis is encoded in the DNA contained
in the cell nucleus.
• A phenotype is the set of characteristics or the clinical presentation of an individual,
which results from the particular genotype.
Crossing over involves the exchange of genetic material between two homologous
chromosomes during meiosis.
Messenger RNA carries the instructions for protein synthesis.
• The kind of genetic mutation that results in the change of an amino acid sequence in
the protein sequence is best described as a missense mutation.
Semi conservative replication relates to the concept that as DNA is copied, one
original and one newly formed copy of the DNA is inherited together in each of the
progeny cells.
Reference:
McCance, K. L., & Huether, S. E. (2019). Pathophysiology: The biologic basis for disease in
adults and children (8th ed.). Elsevier.
LVH
• Heart failure occurs when the heart is unable to pump enough blood to meet the
body's needs. The left ventricle is more prone to develop heart failure than the right
ventricle due to its workload and vulnerability to ischemic and other injuries. In left-
sided heart failure with reduced ejection fraction, the Frank-Starling mechanism stays
intact, but over time the end-systolic and end-diastolic volumes increase, the chamber
dilates, and the ventricular wall thins.
Reference:
McCance, K. L., & Huether, S. E. (2019). Pathophysiology: The biologic basis for disease in
adults and children (8th ed.). Elsevier.
Page 4 of 32
