Week 3 Flashcards
1
Q
Meiosis is a type of cell division which results in the formation of
A
genetically distinct, haploid gametes
2
Q
Meiosis occurs in the final stages of
A
gametogenesis (the formation of the spermatozoa in males and ovum in females)
3
Q
Mitosis begins with _____.
Mitosis ends with ______.
Meiosis I begins with _____.
Meiosis I ends with _____.
Meiosis II begins with _____.
Meiosis II ends with _____.
A
1 Diploid cell (2n)
2 Diploid cells (2n)
1 Diploid cell (2n)
2 Haploid cells (n)
2 Haploid cells (n)
4 Haploid gamete cells (n)
4
Q
What are the phases of Meiosis?
A
Prophase
Metaphase
Anaphase
Telophase
Cytokinesis
5
Q
The organization of homologous chromosomes as tetrads occurs in what stage of meiosis?
A
Prophase I
6
Q
The exchange of genetic material between non-sister chromatids of homologous chromosomes (Crossover) occurs in what stage of meiosis?
A
Prophase I
7
Q
Crossover/Recombination
A
The exchange of genetic material between non-sister chromatids of homologous chromosomes
8
Q
Chiasma
A
The region where crossover occurs
9
Q
During which phase of meiosis do the tetrads align along the midline of the cell?
A
Metaphase I
10
Q
During which phase does random segregation of the homologous chromosomes to opposite poles occur?
A
Anaphase I
11
Q
In which phase of meiosis is there 1 copy of each chromosome with 2 sister chromatids?
A
Telophase I & Cytokinesis I
12
Q
During which phase of Meiosis do the sister chromatids separate?
A
Anaphase II
13
Q
What occurs during Interphase?
A
The DNA from the chromosome is replicated
14
Q
Which phases of Mitosis & Meiosis contribute to the genetic diversity of gametes?
A
Prophase 1- Crossover between homologous chromosomes
Anaphase I- Random segregation of the homologous chromosomes
15
Q
Meiosis begins with ___ pairs of chromosomes each with ____ chromatids and ends with ___ chromosomes each with ___ chromatids.
A
46 pairs, 2 sister chromatids
23 chromosomes, 1 chromatid
16
Q
Meiosis results in
A
4 haploid gametes with 23 chromosomes
17
Q
Gametogenesis is known as ____ in males & ____ in females.
A
Spermatogenesis
Oogenesis
18
Q
Spermatogenesis results in the formation of
A
4 genetically distinct spermatozoa (Haploid, 23 chromosomes)
19
Q
Oogenesis results in the formation of
A
1 ovum (Haploid, 23 chromosomes) and 3 polar bodies
20
Q
Fertilization of the ovum by sperm results in a
A
Dipoid Zygote (43 chromsomes in 23 pairs)
21
Q
Mitotic division of a Diploid Zygote results in a
A
Embryo (46 chromosomes in 23 pairs)
22
Q
In a Diploid human, ___ chromosomes are donated by the dad and ___ chromosomes are donated by the mom.
A
23
23
23
Q
Centromere
A
Center of the chromosome, holding chromatids together
24
Q
What are all the stages of the cell cycle?
A
Interphase
* Gap 1 (G1)
* S phase
* Gap 2 (G2)
Mitosis (M phase)
* Prophase
* Metaphase
* Anaphase
* Telophase and Cytokinesis
25
What occurs in the G1 phase
Growth and normal metabolic roles. Cellular contents, excluding the chromosomes, are duplicated.
1 Mom chromatid + 1 Dad chromatid
26
What occurs in the S phase
DNA replication
Each of the 46 homologous chromosomes are duplicated into an exact copy containing 2 sister chromatids
(I mom + I dad = X mom + X dad)
27
What occurs in the G2 phase
Growth and preparation for mitosis,
checks for No damage to the replicated DNA & chromosomes, makes repairs.
28
What are the stages of Interphase
G1 (Growth & normal metabolism)
S (DNA Synthesis/ Replication)
G2 (Growth & Preparation for Mitosis, checks for NO damage)
M (Mitosis=PMAT&C)
29
Mitosis
Cell division in eukaryotic somatic cells to form two new Diploid daughter cells.
-The Diploid daughter cells have identical genetic composition as the Diploid parent cell (Each daughter cell receives a copy of every chromosome).
30
Humans have ___ chromosomes, in ___ pairs. Of those, ___ are autosomes, and ___ are sex chromosomes.
46 chromosomes
23 pairs
22 autosomes
1 pair of sex chromosomes
31
Female Sex chromosomes
XX
32
Male Sex Chromosomes
XY
33
In which phase of the cell cycle are DNA replication enzymes active?
S phase
34
During which phase of the cell cycle is a copy of each chromosome made?
S phase
Every chromosome has 2 sister chromatids (II=X)
35
Sister chromatids are linked at the
centromere
36
During which phase of the cell cycle do sister chromatids separate?
M phase
37
During which [hase of the cell cycle do the daughter cells get 1 exact copy of the chromosome?
M phase
38
What is the G0 phase?
Cell Cycle Arrest
39
Prophase
-breakdown of the nuclear membrane
-nuclear envelope dissolves
-spindle fibers appear
-chromosomes condense
-centriole divides and migrates to opposite poles
40
Prometaphase
-Spindle fibers attach to chromosomes via kinetochores at the centromere
41
Metaphase
-chromosomes align at the equatorial plate
-chromosomes are maximally condensed
42
Anaphase
-centromeres divide
-separation/ disjunction of the sister chromatids
-sister chromatids move to opposite poles of the cell
43
Telophase
-nuclear membrane reforms
-chromosomes start decondensing
-spindle fibers disappear
44
Cytokinesis
-cytoplasm divides
-diploid parent cell becomes 2 diploid daughter cells with identical DNA
45
Mitosis is responsible for
the growth and development of an organism
46
_____ is important for cell replacement,
wound healing and growth
Mitosis
47
Result of uncontrolled
mitotic divisions
Cancer
48
Mendel's model organism
peas
49
Phenotype
-Physical expression of a trait
-Manifestation of the trait
-Observable
50
Gene
* Unit of inheritance
* Includes the protein coding region and the regulatory sequence
51
Allele
* Alternative form of a single gene
52
Genotype
* Genetic makeup of individual
* Alleles written in pairs
* (DD, Dd, or dd)
53
Ploidy
* Animals, Human, most plants are diploids
* (note that plants can do interesting stuff)
* Human gametes (ova, sperm) are haploid
54
Organisms typically inherit ___ alleles
2, one from each parent
55
Homozygous/Homozygote
* Both alleles are the same
* Homozygous dominant (DD)
* Homozygous recessive (dd)
56
Heterozygous/Heterozygote
Alleles are different (Dd)
57
Wild type
* Defined as the most frequently
observed allele in a population
* Note, typically, we do not use the
term “wild type” when discussing
human conditions
58
What is a wild type gene usually used for?
-Used in the lab to identify the control allele that is found in the starting strain.
-Wild type usually indicates the functional allele.
59
A gene may be ____ under on environmental condition and ____ under another environmental condition.
functional
deleterious
60
Pedigrees allow us to follow ____ in families
alleles
61
Dominant traits almost always _________ generation
appear in each generation
62
Dominant autosomal traits appear ____ in both sexes
equally
63
Affected individuals of an autosomal dominant trait will have
an affected parent
64
What is the risk of inheriting the disease-causing allele in an Autosomal dominance?
50%
65
Incomplete Penetrance
traits that are inherited autosomal dominant but may not appear in each generation.
The individual has the allele, & they either manifest the trait, or they don't.
Some people who have a mutation do not show any phenotypic manifestations at all.
66
Dominant traits are controlled by the inheritance of ____ allele in order for the trait to manifest
only one allele (the dominant allele)
67
Variable expressivity
"range of possible outcomes"
some individuals with the allele may have severe manifestations; some might be mild. The range can differ within families.
68
A man who has an autosomal dominant trait marries a woman who does not have the trait. What is the probability that any of their children will inherit the trait?
50%
69
Autosomal Dominant Disorders
1. Familial hypercholesterolemia (due to LDL-receptor deficiency)
2. Achondroplasia
3. Huntington's disease
4. Marfan syndrome
5. Lynch syndrome (hereditary non-polyposis colon cancer; HNPCC)
70
Familial Hypercholesterolemia
Autosomal Dominant, Haploinsufficiency
LDLR deficiency
-The LDL Receptor functions to clear LDL-cholesterol from the blood (uptake
into the liver)
- If one copy of LDLR is nonfunctional, not enough receptors exist on liver cell (hepatocyte), and too much cholesterol stays in the blood
71
What is the genetic principle behind Familial Hypercholesterolemia?
Haploinsufficiency
72
Haploinsufficiency
-Haplo (meaning one of the alleles on one chromosome)
-Insufficient (meaning that both alleles are required to avoid disease)
73
Achondroplasia
Autosomal Dominant, Gain of Fx
Fully penetrant disorder
Observable at birth
* FGFR3 gene signals too early & too much. The FGFR3 protein is persistently
active (it is not regulated), it is just “on”
* Premature ossification occurs, causes cessation of bone growth, bones are not as long as they should be, and the person has dwarfism.
* FGFR3 encodes a receptor that responds to fibroblast growth factor hormone
* In response to this signal, cells in the growth plates of the long bones ossify & stop growing
74
Gain of function
Protein does more than it normally should; or acts in an unregulated manner
75
Genetic principle behind Achondroplasia
Gain of Function
(also a fully penetrant disorder)
76
Allelic Heterogeneity
-Other mutations in the same gene can lead to other disorders.
-Different alleles can be found in the same gene.
-Ex: Other mutations in the FGFR3 gene can lead to other disorders that are distinguished from achondroplasia
77
Locus Heterogeneity
Other/Different genes (loci) can cause a similar presentation
Ex: many other genes can cause dwarfism, it is not only attributed to mutations of the FGFR3 gene
78
Huntington disease
Autosomal Dominant
Gain of Function/Attainment of a Novel Fx
Fully Penetrant, Adult onset
* Caused by an expansion of three nucleotides in the exon of the gene that encodes for the huntington protein
-Normally, there is 10–33 repeats of the CAG codon in the gene (we all have it)
-CAG codon codes for the AA glutamine
* If repeats expand too far, it becomes pathogenic
✓If the string of Glutamine AAs in protein is too long → disease
✓Causes neurodegeneration, neuronal death, chorea, neurological manifestations, memory loss
-This area of the genome is sometimes unstable
✓If the repeat becomes longer, it becomes even more unstable
✓Anticipation; disease gets worse in successive generations
79
Genetic principle behind Huntington's Disease
Gain of Fx/ Attainment of Novel Fx
80
Attainment of Novel Function
New function is gained that is not understood
81
Concept of Anticipation
-reserved for Triplet repeat expansion disorders (Huntington's)
-disorder may get worse in successive generations
-disorder may have earlier onset in later generations
82
Marfan Syndrome
Autosomal Dominant
Dominant is Negative OR Haploinsufficiency
-Caused by mutation in the fibrillin gene → different protein produced
-can be caused by different types of mutation in the same fibrillin gene (haploinsufficiency) OR from negative dominance (more severe disorder)
-The protein formed from the mutant gene doesn’t assemble properly with other proteins, causing higher-order structures to not form properly
-Leads to connective tissue problems
-Chest wall deformity
-Tall stature
-Risk of heart defect
-Eye lens subluxation
* Only need one allele with the mutation for this effect to occur, so autosomal
dominant, in this case (the dominant is negative)
83
What is the genetic principle behind Marfan's Syndrome
-Dominant Negative (Both alleles are expressed, but dominant negative interaction leads to manifestation of the trait)
OR
-Haploinsufficiency (loss of expression from one of the fibrillin alleles)
84
Dominant Negative disorders tend to be
More severe
85
Sonic Hedgehog Mutation (SHH)
Autosomal Dominant, Haploinsufficiency
-possible Incomplete Penetrance
-possible Variable Expressivity
-Signaling through SHH controls several essential developmental processes.
-SHH signaling is required for many things, including midline of body, and brain formation.
-Loss of one functional copy of SHH can cause holoprosencephaly (brain)
86
Genetic Principle behind SHH mutation
Incomplete Penetrance
Variable Expressivity
87
Variable Expressivity
People with the same mutation can have mild presentation or very severe presentation
88
Lynch syndrome
Autosomal Dominant, 2-hit hypothesis
Loss of Heterozygosity
Hereditary non-polyposis colon cancer
-Lynch syndrome is caused by inheritance of a mutation in one allele of a gene
that functions in the DNA mismatch repair pathway
-This pathway is comprised of a family of MMR/MSH genes, a type of tumor suppressor gene called “caretakers” because they take care of the genome
-The person who is born with this mutation is heterozygous
-adult onset after a 2nd mutation occurs in
a somatic cell >mutations>cancer
88
A new-born baby is diagnosed with holoprosencephaly after MRI shows incomplete separation of the 2 hemispheres of the brain. Genetic analysis reveals a mutation in the SHH gene. Which of the following best explains the genetic inheritance of the disorder in this patient?
Haploinsufficiency
89
Most cancers are ____ in nature
sporadic / idiopathic
90
Cancer is _____ hereditary
Rarely
91
Dominant disease alleles are typically only inherited in the Homozygous/Heterozygous state.
Why?
Heterozygous
-Dominant disease alleles are very rare
-Dominant disease alleles will be more severe when homozygous (some are lethal)
92
Heterozygous vs Homozygous Familial Hypercholesterolemia (LDLR defect)
✓Autosomal Dominant (heterozygous) adult-onset high cholesterol
✓Autosomal Dominant (homozygous) childhood onset high cholesterol
*Homozygous is more severe
93
Heterozygous vs Homozygous Huntington Disease
✓The very few homozygous people ever seen have childhood onset seizure & movement disorders (homozygous is typically lethal)
✓Heterozygous Adult onset, causes neurodegeneration, neuronal death, chorea, neurological manifestations, memory loss
94
Heterozygous vs Homozygous Achondroplasia (FGFR3 gain of function mutation)
✓Autosomal Dominant Heterozygous Dwarfism
✓Autosomal Dominant Homozygous is lethal either perinatal or during fetal development
95
Loss of Heterozygosity
Inheritance of a mutation in a tumor suppressor gene can lead to cancer when a 2nd mutation occurs in a somatic cell
96
If both parents are heterozygous carriers for a recessive disorder, what are the chances their child will inherit the recessive allele from both parents?
25% aa
50% Aa (be a carrier)
25% AA
97
For autosomal recessive traits, an individual must inherit a non-functional, disease-causing allele from ____ parents for the trait to manifest
Both
✓A person who inherits just one disease allele is a “carrier” and we say that the functional allele is “haplo-sufficient”, so the disease does not manifest
✓The functional allele is dominant for the trait, and the person appears normal
✓The functional allele “masks” the presence of the non-functional
variant.
98
A person who inherits just one disease allele is a ____ and we
say that the functional allele is ____ so the disease will not manifest.
carrier
haplo-sufficient
99
In a family, multiple generations are likely/unlikely to exhibit the trait for most autosomal recessive traits.
unlikely
100
Genes that display haploinsufficiency are likely to cause ____ traits
Dominant
101
Most enzyme deficiencies are Dominant/Recessive
Recessive
(autosomal recessive or x-linked recessive)
102
Autosomal Recessive Disorders
1. Tay Sachs disease (deficiency of an enzyme)
2. Phenylketonuria (deficiency of an enzyme)
3. Cystic fibrosis (deficiency of a chloride ion channel)
4. Alpha-1 antitrypsin deficiency (deficiency of a protease inhibitor)
5. Sickle cell disease (homozygosity for a structural variant of hemoglobin)
103
Tay Sachs Disease
Autosomal Recessive, Deficiency of an Enzyme
-Deficiency of hexosaminidase A activity (HEXA) that causes a buildup of specific ganglioside (lipid-sugar molecule) in the lysosome in the CNS tissues
-loss of both alleles=Tay Sachs; loss of one allele=haplosufficient, no disease
-Progressive, inexorable decline of central nervous system * Person is unaffected at birth, but at around 6 mo’s of age decline occurs and then deterioration
104
PKU Phenylketonuria
Autosomal Recessive, Deficiency of an enzyme
-Deficiency of the phenylalanine hydroxylase enzyme resulting in the inability to degrade the amino acid phenylalanine (Phe)
-mutation in 1 allele=haplosufficient, mutation in both alleles=PKU
-Phe builds up in serum (converted to phenylacetate, and phenylpyruvate), hence the suffix on the name “ketonuria”
-Too much Phe in circulation causes disease, goes to brain, reduces ability for other AAs to get into the brain, neurological impairment
-Prevents Phenylalanine>Tyrosine
-Typically diagnosed at birth
-Easy to diagnose, and if identified, is treatable via dietary restriction
105
Cystic Fibrosis
Autosomal Recessive, Deficiency of an Cl- ion channel
- The CFTR gene encodes a channel that allows Cl- to cross the cell membrane
-Sodium Na+ follows Cl- to balance charges, If NaCl is on one side of the membrane, then water will follow.
-If the system is set up to pump Cl- into a luminal space (say lungs, or pancreatic duct, then those areas will become hydrated
-If the system is set up to allow Cl- to cross back into the sweat pore, then Na+ is conserved (salt conservation, excess)
-1 allele is haplosufficient, 2 mutant alleles=CF
-People with CF experience pancreatic insufficiency, pulmonary infections, high salt content in sweat, absence of the vas deferens
106
What is the 2/3 carrier risk principle?
If an autosomal recessive disorder is fully penetrant and easily identifiable, and both parents are carriers, there is a 2/3 carrier risk in their child.
107
Alpha-1 Antitrypsin Deficiency (AATD)
Autosomal Recessive, Deficiency of a protease inhibitor
1. In the lungs, neutrophils are always working to fight infection
2. Neutrophils must be able to migrate through tissues to get at invading bacteria
3. Neutrophils secrete ELASTASE, which is a protease enzyme that degrades the elastin (part of the connective tissue that allows lungs to stay elastic)
4. This helps neutrophils to migrate
5. Hepatocytes (liver cells) express and secrete AAT into the blood
6. The AAT travels in the blood to the lungs to protect lung elastase from destruction by our immune system
108
____ is the founding member of the Serine protease enzyme.
Trypsin
109
Trypsin is the founding member of the ____ protease enzyme.
Serine
110
Gene that encodes Alpha 1 Antitrypsin
SERPINA1 (Serine Protease Inhibitor)
111
What are the 2 alleles of Alpha 1 Antitrypsin (AAT) and which one leads to A-1Antitrypsin Deficiency?
-M allele
-Z allele (causes AATD)
✓It doesn’t bind very well to elastase (loss of function)
✓It is degraded more quickly and not much is made (loss of function)
✓BUT… sometimes, it polymerizes in the hepatocyte when it is synthesized (recognize this as attainment of novel function)
112
Diseases caused by Homozygosity of the Alpha-1 Antitrypsin Deficiency Z allele
COPD (adult onset)
-due to loss of Fx of the protease inhibitor
Liver Disease (pediatric)
-due to Attainment of Novel Fx polymerization of the protein during its production in the rough ER, causing hepatocellular damage
113
Sickle Cell Disease
Autosomal Recessive
-single base pair mutation in the DNA causes a single AA change in the protein
-Glutamate 6 to a Valine causes the Hb protein to polymerize and sickle shape of RBCs
-Glu is hydrophilic and Val is hydrophobic
114
Heterozygote advantage
In the heterozygous state,
the person has a slightly
increased probability to
survive a malaria infection
✓Heterozygote advantage
✓Selective pressure
115
Pseudodominance
A recessive allele mimicking a dominant pattern.
Ex: SCD may appear to be dominant, but its actually autosomal recessive. In some populations, sickle cell allele is found at a relatively high frequency (because of selective pressure from malaria). So, in people of ancestries that had malaria exposure, there is a relatively
higher likelihood that the spouse of an affected person might be a carrier 1/8 chance.
116
Reasons you'd see pseudodominance
-high frequency of the recessive allele
-consanguinity
-Luck of happening to see it
117
Codominance
Both alleles are expressed, both alleles are detected.
-Both maternal and paternal alleles are expressed
-Can both be equally detected
-The ABO blood groups are best example
118
Sickle Cell Trait is an example of ____.
Codominance.
-In a carrier trait, the person expresses both, and both can be detected
✓HbA (the normal allele)
✓HbS (the sickle allele)
-Both are expressed=codominance
119
The ovum can only contribute a ___ sex trait to a zygote. Sperm can contribute ____ sex trait to a zygote.
X (females are XX)
X or Y (males are XY)
120
During embryonic development, one of the X chromosomes is deactivated, known as _____ to ensure that males and females have _____ gene expression.
X-inactivation
balanced
121
Mechanism of X-inactivation
-The X-chromosome that is to be inactivated choses itself. Typically the choice is random: inactivation could be either from the maternal or the paternal origin.
* It expresses an RNA from a gene called XIST
* The XIST RNA then coats the chromosome that expressed it
* Other proteins then help
* Most of the genes on that X-chromosome are then silenced
* All daughter cells from this cell maintain the same inactivated X-chromosome
122
Hemizygous
A person who has only one copy of a gene rather than the usual two copies. Most males are hemizygous for traits on the X & Y chromosomes as they only have one of each.
*Males are more likely to have autism or intellectual disabilities
123
Recurrence risk for X-linked recessive disorder
Normal Father (XY) x Carrier mother (Xx◘)
124
Recurrence risk for X-linked recessive disorder
Affected Father (x◘Y) x Normal mother (XX)
125
Recurrence risk for X-linked recessive disorder Affected Father (x◘Y) x Carrier mother (x◘X)
126
X-linked Disorders
-G6P dehydrogenase deficiency
-Inability to detect red-green color
-Hemophilia A
-Hemophilia B
-Lesch-Nyhan syndrome
-Duchenne muscular dystrophy
127
Glucose 6-phosphate dehydrogenase deficiency (G6PD deficiency)
X-linked Disorder
-Hemolytic anemia due to oxidative damage in RBCs
-Caused by exposure to:
1. Sulfa drugs
2. Primaquine
3. Fava beans
4. Other exposures that increase oxidative stress in the blood.
-G6PD mutations can be driven to relatively high frequency in the population due to environmental pressures.
-G6PD is needed for NADPH production. NADPH is needed to maintain glutathione in its reduced (active) form. Glutathione is needed to protect the RBC membrane from oxidative damage.
-G6PD is required for glucose entry into the PP shunt.
-Complete loss of G6PD is lethal.
-Mutational variants in G6PD that decrease protein stability, or reduce (but not eliminate its function) will impact the red blood cell.
128
In the RBC, ____ is required for detoxification of reactive oxygen species
NADPH
129
People with G6PD deficiency are sensitive to ________.
oxidizing agents
130
Red-Green Color blindness
X-linked Disorder
*Inability to differentiate between red and green colors
*X-linked, so relatively common in males and relatively rare in females
*Example where gene duplications/deletion may provide a mechanism for genetic disease
*Inappropriate crossing over during meiosis may lead to loss of a gene
*Genetic Principle: deletion/duplication mutation can occur at hot spots in the genome due to repetitive regions.
131
Red-green color blindness is explained by
unequal intragenic recombination between a pair of X chromosomes
132
Hemophilia A & Hemophilia B
* Bleeding disorder; improper hemostasis; inability to clot
-Blood clots fail to form; or form too slowly * Both are X-linked disorders
* Hem A and B mostly occurs in males due to 1 X chromosome & hemizygous
* Females are extremely unlikely to inherit
a pathogenic variant from both parents
-Female carriers may exhibit symptoms, but they are usually less severe compared to a male
If a carrier female is affected, it could be the result of non-random X-inactivation
133
Lesch-Nyhan Syndrome
X-linked disorder caused by deficiency of an enzyme
Caused by pathogenic mutation of the gene encoding the hypoxanthine-
guanosine phosphoribosyl transferase (HGPRT) enzyme
-Inability to salvage purines- guanine & adenine
-Used to make GTP, ATP, dGTP, dATP
-Inability to salvage these bases causes excessive disposal
-End product of purine disposal is uric acid (sodium urate)
-ndividuals have excessive uric acid production
-Leads to severe intellectual disability, seizure, and self-destructive behavior, severe form of gout that presents in early childhood
134
Associated Organs Digestive System
Tongue
teeth
salivary glands
pancreas
liver
gallbladder
135
Processes of digestion
ingestion
secretion
mixing & propulsion
digestion
absorption
defecation
136
Largest serous membrane in the body, lining the abdominal cavity
Peritoneum
137
Intraperitoneal vs Retroperitoneal
Intra- suspended in the abdominal cavity
Retro- attached to Posterior wall
138
Parietal peritoneum vs Visceral peritoneum
Parietal peritoneum – an outer layer which adheres to the anterior and posterior abdominal walls. Lines abdominopelvic cavity.
Visceral peritoneum– an inner layer which lines the abdominal organs.
139
a large apron-like fold of visceral peritoneum that hangs down from the stomach
Greater omentum
140
What ligaments are composed of the lesser omentum?
hepatogastric, hepatoduodenal ligaments
141
connects the lesser curvature of the stomach and the proximal end of the duodenum to the liver
lesser omentum
142
5 major peritoneal folds
greater omentum
falciform ligament (attaches ventral wall)
lesser momentum
mesentery
mesocolon (transverse & sigmoid)
*all attach to the posterior wall except falciform ligament
143
Falciform Ligament
144
Transverse Mesocolon
Sigmoid Mesocolon
145
Lesser omentum
Greater omentum
146
The peritoneal cavity sits between the _____ & _____.
Parietal peritoneum (outer)
Visceral peritoneum (inner)
147
What are the 4 distinct layers of connective tissues in the GI Tract?
Mucousa (inner)
Submucosa
Muscularis externa
Serosa (outer)
148
Alimentary canal
esophagus to anal canal
149
3 components of the mucosa
epithelium
lamina propria (blood, glands, lymph)
muscularis mucosae
150
3 functions of the mucosa
protection
absorption
secretion
151
-dense irregular connective tissue
-larger blood & lymph vessels
-some glands
-parasympathetic ganglia
-postganglionic fibers
-innervates muscularis mucosae
-part of enteric nervous system
Submucosa
152
What are the 2 layers of the muscularis externa
Inner circular
-compresses & mixes contents
-forms sphincters
outer longitudinal
-propels contents forward
-thicker in the Large intestine
153
What is the function/role of the muscularis externa
Peristalsis
-Slow, rhythmic contraction of muscle layers
-Controlled by enteric nervous system
154
Which plexus is
-part of the enteric nervous system
- has Parasympathetic ganglia & postganglionic fibers
-Innervates the muscularis mucosae
Submucosal plexus
155
Which plexus is
-part of the enteric nervous system
-has Parasympathetic ganglia & postganglionic fibers
-located between the inner circular muscle & outer longitudinal muscle layers
-innervates the muscularis externa
Myenteric plexus
156
Which layer of GI Tract tissues is continuous with the mesentary and lining of the abdominal cavity?
Serosa
157
This layer of the GI Tract tissue attaches part of the GI tract without a a serosa to the body wall
Adventitia
158
Connects pharynx to stomach
esophagus
159
Barret's disease affects the ______.
GERD affects the ______.
-esophagus
-esophagus, pharynx, etc. as stomach contents move up into the esophagus
-Both specifically affect the lamina propria layer of the mucosa of the esophagus
160
The mucosa layer of the esophagus is made up of what type of cells
Nonkeratinized stratified squamous epithelium
161
Layers of tissue in the esophagus
Adventitia (outer)
Muscularis (longitudinal)
Muscularis (circularr)
Submucosa
Mucosa (inner)
162
The muscularis externa layer of the esophagus contains different muscle types.
The upper 1/3 is ______.
The middle 1/3 is _____.
The lower 1/3 is ______.
Upper 1/3 Striated muscle
Middle 1/3 striated & smooth muscle
Lower 1/3 smooth muscle
163
Barret's esophagus
-lower esophagus undergoes metaplasia, a change in the differentiation of cells
-Stratified squamous cells convert to secretory simple columnar epithelium
164
GERD
Gastroesophageal reflux through the
lower esophageal sphincter
-Allows gastric acid into the lower esophagus
-Higher risk of developing dysplasia
-Risk of developing adenocarcinoma
165
What are the 4 regions of the stomach?
Cardia (opening)
Fundus (upper "bubble" area)
Body
Pylorus (end sphincter)
166
Which glands are located in each part of the stomach
-Carida
-Fundus
-Body
-Pylorus
Cardiac glands
Fundic/Gastric glands
Fundic/Gastric glands
Pyloric glands
167
What are the longitudinal mucosal & submucosal folds of the stomach?
Rugae
168
Functions of the stomach
-Mixing & gastric secretions
partial digestion of food, production of chyme
-very little absorption
some water, lipid soluble drugs, & alcohol
169
The stomach has ___ layers in the muscularis externa. What are they?
3
inner oblique
middle circular
outer longitudinal
170
Gastric/Fundic glands have relatively ___ pits, and ___ glands.
short pits
long glands
171
Cells within the Gastric/Fundic Glands and what they secrete.
Surface Mucous cells-- mucus
Mucous neck cell-- mucous
Parietal cell (eosinophilic)-- HCl & intrinsic factor (glycoprotein)
Cheif cell-- Pepsinogin & gastric lipase
G cell-- Gastrin
172
Pepsinogen is produced by _____ cells and then turned into ____.
Chief cells
pepsin
173
Intrinsic Factor, or Glycoprotein, is secreted by ___ cells and is essential for ____ absorption
Parietal cells
vitamin B12
174
Lack of intrinsic factor (glycoprotein) results in
pernicious anemia & vitamin B12 deficiency
175
_____ stimulates the parietal cells & HCl secretion
Gastrin via activation of the Gastrin receptor on Parietal cells
176
G cells, also known as _____, secrete ____ which stimulates ____ cells to secrete ____.
Enteroendocrine cells
Gastrin
Parietal cells
HCl
177
Chronic Peptic Ulcers damage the entire thickness/layer of ______ in the stomach or duodenum. Peptic ulcers are most often due to _____.
mucosa
Helicobacter Pylori infection
178
Complications of Chronic Peptic Ulcers
1. Perforation
-Complete opening to peritoneal cavity
2. Hemorrhage
-Tissue necrosis can involve a large artery
3. Obstruction
-Repeated attempts at repair can result in progressive fibrous scarring
-Can result in narrowing or complete obstruction of lumen
179
Parts of the small intestine
duodenum
jejunum
Ileum
180
-Principle site for digestion & absorption
-longest component of the digestive tract
Small intestine
181
What are the tissue & cell specializations that increase surface area for absorption in the small intestine?
Plicae circularis (circular folds)
Villi
Microvilli (brushborder on the villi)
182
Villi contain
Central lacteals, or lymphatic capillaries that absorb dietary fats
183
The duodenum begins at the _____ and ends at the _____.
Pylorus of the stomach
duodenojejunal junction
184
The dudodenum contains ____ glands which protects the mucosa from the acidic stomach contents entering the duodenum
Submucosal Brunner's glands
185
Distinguishing characteristics of the Jejunum
-Numerous plicaecircularis
–Long prominent villi
-Increase in goblet cells
-No submucosal glands
186
Distinguishing characteristics of the Ileum
–Peyer's patches (Aggregated nodules of lymphatic tissue in lamina propria)
187
Types of cells in the small intestine & their function
Enterocytes-- absorption & digestive enzymes
Goblet cells-- mucous secretion
Enteroendocrine/G cells-- produce hormones Gastrin, Cholecystookinin CCK, Secretin, Motilin, GIP
Paneth cells-- secrete antimicrobial substances Lysozyme & alpha-defensins
188
Which hormones can Enteroendocrine/G-cells of the small intestine produce?
-Gastrin
-Cholecystokinin CCK
-Secretin
-Motilin
-GIP
189
Distinctive features of the Large intestine
1. Taeniacoli (TC)
-3 thickened prominent bands of the outer longitudinal muscularis externa layer
2. Haustracoli (HC)
-Visible sacculations between TC External surface of cecum and colon
3. Omentalappendices (OA)
-Small fatty projections of the serosa -Outer surface of colon
190
Functions of Large intestine
- Reabsorption of water & electrolytes
- Elimination of waste
191
Thin, finger-like extension
of the cecum
Appendix
192
Distinguishing characteristic of the Appendix
Numerous lymphatic nodules
193
Appendicitis
-inflammation of the appendix
-results from blockage of the opening to the cecum (scarring, thick mucous, stool)
194
The internal anal spincter is ___ while the external anal sphincter is ___.
circular muscularis externa
striated muscle
195
Hirschsprung disease
-Congenital aganglionic megacolon (swollen)
-absence of ganglion cells in distal colon
-Lack of peristalsis
-obstruction/ stool builds up from no movement
-constipation
-abdominal distension
196
The left & right hepatic ducts drain into the _____.
common hepatic duct from the liver
197
The common hepatic duct (liver) and the _____ duct from the _____ drain into the common bile duct.
cystic duct
gall bladder
198
The common bile duct and the pancreatic duct enter the _____ through the _____.
duodenum
sphincter of oddi
199
What are the 4 lobes of the liver?
1. Right
2. Left
3. Caudate (upper)
4. Quadrate (lower)
200
Liver blood supply
201
Hepatocytes
liver cells
202
Bile canaliculi
small ducts that collect bile from hepatocytes and drain into the main bile ducts
203
Sinusoids
highly permeable blood capillaries between hepatocytes that drain into the central vein
204
Portal Triad (liver)
Bile duct
Hepatic artery
Hepatic portal vein
205
Gallbladder function
stores & concentrates bile
206
Pancreatic components
Exocrine 99%
Endocrine 1%
207
Exocrine functions of the pancreas
produce enzymes to break down:
-carbs (amylase)
-proteins (trypsin, chymotrypsin, carboxypeptidase, elastase)
-lipids (lipase)
-nucleic acids (ribonuclease & deoxyribonuclease)
208
Endocrine cells & secretory products
Alpha--glucagon
Beta-- insulin
Delta-- somatostatin (inhibits secretion of glucagon & insulin)
F cells-- pancreatic polypeptide (inhibits somatostatin secretion)
209
Mediastinum
central compartment of the thoracic cavity
210
What structures does the mediastinum contain
heart
great vessels
trachea
esophagus
thymus
thoracic duct
phrenic nerve
cardiac nerves
lymph nodes
211
Boundaries of the mediastinum
sterum to vertebral column
1st rib to the diaphragm
between the lungs
(the heart cavity)
212
Pericardium
membrane that surrounds the heart and
the root of the great vessels
213
Pericardial cavity
*A narrow space between the visceral (inner) and parietal (outer) layers of the serous pericardium
*Filled with a thin film of lubricating fluid
214
Pericardium components
Fibrous (tough connective tissue outer layer)
Serous (thin parietal layer & visceral layer/epicardium/inner-most layer)
215
3 layers of the heart wall
Endocardium
Myocardium
Pericardium
Serous Pericardium
-Visceral pericardium
(Pericardial cavity)
-Parietal pericardium
Fibrous Pericardium (outer-most layer)
216
Prevents blood from flowing back into the Right atrium when the Right ventricle contracts
Tricuspid valve
217
Fibers responsible for conducting electrical impulses through
the heart
Purkinje Fibers
218
structure in the right atrium responsible for generating impulses
SA node
219
structure between the atria and ventricles responsible for
generating impulses
Bundle of HIS (Atrioventricular bundle)
220
Flow of electrical impulses through the heart
SA>AV>Bundle of His>Right & Left Bundle branches>Purkinje Fibers
221
Semilunar valves
Aortic Valve
Pulmonary Valve
-NOT attached to the chordae tendinae
222
Atrioventricular Valves
-Tricuspid valve (right)
-Bicuspid/Mitral valve (left)
Both attached to the chordae tendinae
223
Which vessels supply the heart muscle & tissues with oxygenated blood?
Left coronary artery
Right coronary artery
224
Which structures do the Right coronary artery supply?
–Right atrium
-Right ventricle
–SA node
-AV node
–InterAtrial septum
–Portion of the left atrium
–The posterior-inferior 1/3 of the interventricular septum
–Portion of the posterior left ventricle
225
Which structures do the Left coronary artery supply?
–Most of the left atrium
--Most of the left ventricle
–Anterior (front) two-thirds of the
interventricular septum
–The atrioventricular bundle of His
-Right & Left Bundle branches
226
Flow of blood through the heart
Right Atrium (deoxygenated)
Tricuspid valve
Right ventricle
Pulmonary valve
Pulmonary trunk & arteries
Lungs (pulm. capillaries for oxygen)
Pulmonary veins (Oxygenated)
Left atrium
Bicuspid/ Mitral Valve
Left Ventricle
Aortic Valve
Aorta
Systemic arteries
Systemic capillaries (loses Oxygen)
Superior or Inferior Vena Cava or Coronary Sinus
Right Atrium
227
3 layers of blood vessels
tunica intima
tunica media
tunica adventitia
228
Thin sheets of elastic fibers with spaces for diffusion of nutrients to the tunica media
Internal elastic lamina
External elastic lamina
229
Endothelium function in blood vessels
influences blood flow
secretes vasoactive substances
assists with capillary permeability
230
Basement membrane function in blood vessels
-anchors the epithelium to underlying tissue
-guides cell movement during tissue repair
231
Tunica media
-middle layer of blood vessel wall
-smooth muscle
-elastic fibers
-connective tissue
232
tunica media function
-stretch & recoil
-regulate blood flow, BP, & homeostasis
233
tunica adventitia
-outer most layer of blood vessel wall
-dense connective tissue
234
tunica intima
-inner most layer of blood vessel wall
-where blood flows
-simple squamous endothelium
-basement membrane of collagen fibers
235
Arteries carry ____ blood ____the heart.
Veins carry ____ blood ____ the heart.
oxygenated
away
deoxygenated
toward
236
Types of Arteries
Elastic Conducting Arteries
Muscular Distributing Arteries
237
Elastic Contributing Arteries vs
Muscular Distributing Arteries
Elastic Conducting Arteries:
-Contain abundant sheets of elastic fibers in the tunica media (Aorta and its direct branches)
-Ability to recoil helps to maintain BP when the heart is relaxed
Muscular Distributing Arteries:
-Distribute blood to the organs
-Abundant smooth muscle fibers in the
tunica media helps to regulate blood flow
238
3 types of capillaries and where they're found
1)Continuous (lungs, Brain/CNS)
2)Fenestrated (glands, kidneys)
3)Sinusoids (Liver, spleen)
239
small thin-walled vessels that participate in the exchange of substances between the blood and tissues
capillaries
240
endothelial cells with large pores and incomplete or absent basement membranes
sinusoid capillaries
241
endothelial cell wall with small pores
fenestrated capillaries
242
vessels with collapsible walls
veins
243
small veins across which exchange of
nutrients and wastes and white blood cell emigration occur
venules
244
The microcirculatory unit is made up of
capillaries (oxygenated)
venules (deoxygenated)
245
Extension of the tunica intima that permits unidirectional flow of blood
valve
246
contain smooth muscle in the tunica adventia to assist in blood return to the heart
Large veins (Inferior vena cava)
247
Blood vessels (largest to smallest) oxygenated >deoxygenated (smallest to largest)
Elastic Arteries
Muscular Arteries
Arterioles
Capillaries
Postcapillary Venules
Muscular Venules
Veins
248
The tunica externa is thickest in ___.
veins
249
There is NO tunica externa or tunica media in ___.
capillaries
250
There is NO tunica media in ___.
postcapillary venules
(and capillaries)
251
Parts of the Aorta
Ascending Aorta
Aortic Arch
Descending Aorta
Thoracic Aorta
Abdominal Aorta
252
Upper limb circulation from Aorta to Hand
Ascending Aorta
Aortic Arch
Brachiocephalic Trunk
Subclavian Artery
Axillary Artery
Brachial Artery
Radial & Ulnar Arteries
253
Types of Veins
Deep Veins
Superficial Veins
254
Serve as important access points when drawing blood
Superficial Veins
255
____ veins accompany arteries and connect with ____ veins
Deep
Superficial
256
Flow of blood in veins of the upper limb from hand to heart
venous plexus of the hand
Cephalic & Basilic veins
Subclavian vein
Superior Vena Cava
257
Major Systemic Circulation Veins
Superior Vena Cava
Inferior Vena Cava
258
Which veins flow into the Superior Vena Cava
Right & Left Brachiocephalic Veins
259
Which Veins flow into the Inferior Vena Cava
Right & Left Common Illiac Veins
260
What vessels make up the Coronary Circulation
Right Coronary artery
Left Anterior Descending Artery
261
Cardiovascular Disease
any disorder of the heart & circulatory system
(coronary artery disease, stroke, Heart attack)
262
Coronary Artery Disease
-due to a build up of fatty deposits and cholesterol on the inner walls of the artery
-can eventually lead to stenosis or narrowing of the arteries and, eventually, blockage.
– If the blockage remains and is not
cleared within 12 hours, this will result in cell death (necrosis) in the area.
– When this process occurs in the heart
it is a heart attack or myocardial infarction (MI).
263
Myocardial Infarction
Heart attack
264
Tests used to identify MI
Electrocardiogram (ECG)
Nuclear scan
Coronary Angiography
265
Symptoms of MI
* Radiating chest pain or discomfort
* Upper body discomfort in one or both arms, the neck, jaw, or
stomach
* Shortness of breath
* breaking out in a cold sweat
* Nausea & vomiting
* light-headedness
* unusual tiredness
266
MI symptoms in diabetic
MI or myocardial ischemia (deficient supply of blood) can occur SILENTLY
-occur without any symptoms due to associated nerve damage
267
Cardiac Biomarkers are mostly ___ & ___ and are present due to the release of _____ components into the blood.
enzymes
proteins
intracellular
268
Cardiac Biomarkers
Cardiac Troponin
CK-MB
269
Necrosis of a small portion of the heart cells due to prolonged blockage of an artery of the heart by plaque and blood clot is called
Myocardial Infarction
Heart Attack
270
Cardiac Biomarkers of the PAST
* Lactate dehydrogenase (LD/LDH)
* Aspartate aminotransferase (AST)
* Myoglobin
* Creatine kinase
271
Lactate Dehydrogenase
-MI Biomarker of the PAST
-acute MI
-LDH levels rise 10Hours After
-Peak @ 24-48 hours
-Last up to 8 days
-non-specific for cardiac tissue (also in pancreas, kidneys, stomach, RBCs, & platelets)
-In cardiac tissue, LDH1 & LDH2 are present.
272
Aspartate Aminotransferase (AST)
-MI Biomarker of the PAST
-found in heart & liver
-catalyzes transfer of alpha-amino group between Asparatate<>Glutamate
273
Myoglobin
-can be used with troponins and CK-MB for MI diagnosis
-present in heart & skeletal muscle
-short plasma 1/2 life (disappears quickly)
274
Creatine Kinase Isoenzymes & Locations
-present in skeletal muscle, myocardium (middle layer), brain, some visceral tissues
-catalyzes Creatine<>Phosphocreatine
CK-MM =Muscle
CK-BB =Brain
CK-MB =Mainly Heart
275
LD, LDH, AST, CK or Myoglobin are no longer the cardiac biomarker of choice in the diagnosis of MI because they are
Non-specific for MI
276
Cardiac Biomarkers Used for MI
CK-MB
Troponin
277
CK-MB levels begin to rise _____, Peak ____, and return to baseline about ____ later.
Rise 3-6 Hours after MI
Peak ~12-24 Hours after MI
Return to Normal ~48-72 hours after MI
278
If levels of CK-MB return to normal then rise again, this indicates _____.
re-infarction
279
CK: CK-MB ratio improves/decreases specificity for use in diagnosis of MI.
improves
280
The ____ the ratio of CK-MB:CK, the _____ likely MI has occured.
Higher CK-MB: CK
More likely MI
281
Ratio of CK-MB: CK indicates MI
2.5-3 CK-MB : 1CK
282
Troponin subunits
TnC
TnT
TnI
283
The _____ is attached to tropomyosin. Tropomyosin sits in the groove between ___ filaments in striated muscle.
Troponin Complex (TnC, TnT, TnI)
Actin
284
Which Troponin isoforms are used as biomarkers for MI
TnT
TnI
285
A patient is suspected to have MI. Laboratory analysis of the patient’s serum indicates a high 0%
total CK with CK-MB/CK ratio of 1.0. This suggests damage to
Skeletal Muscle
*Must be 2.5 or higher for MI
286
Heart-type fatty acid binding protein (H-FABP) is still being researched as a cardiac biomarker. It aids in the intracellular uptake of long-chain fatty acids in the myocardium. H-FABP is small in size & released rapidly after MI.
H-FABP & TnT can be measured together to evaluate MI within ____ hours of MI.
4-12 Hours
287
TnI and TnT level begin to rise ____ hours after MI. May persist for up to ___ days after MI.
3-6 Hours
10 days
288
Which of the following would be the ideal cardiac biomarker 5 days after the onset of clinical symptoms?
TnI or TnT
289
T/F: Normal Troponin levels 12 hours after chest pain means MI is unlikely.
True, it may be Angina
290
Angina
a type of chest discomfort caused by poor
blood flow through the blood vessels of the heart
muscle with NORMAL cardiac troponin levels
291
Elevated CK-MB values may be seen in
– Significant skeletal muscle injury
– Cardiac injury other than MI
* Blunt chest trauma like sports injury
* Some surgical procedures
* Cocaine abuse
292
Elevated Troponin levels may be seen in
– myocarditis (inflammation of the heart muscle)
– an arrhythmia (abnormal heart rhythm)
– pulmonary embolism (blood clot lodged in the lung)
– high blood pressure (hypertension)
293
MI definition
1) Evidence of a significant increase (PEAK) in Troponin or CK-MB concentration with time
2) Evidence of ischaemia: a sudden
reduction of heart muscle blood supply
3) Symptoms of MI
-Chest pain or discomfort
-Shortness of breath
-breaking out in a cold sweat
-nausea
-light-headedness
-upper body discomfort in one or both
arms, the neck, jaw, or stomach
294
A 48 year old male with a history of hypertension and high serum cholesterol presents to the emergency department with chest pains for about 2 hours. He describes a substernal (below the sternum) chest pressure “like an elephant on my chest” associated with shortness of breath and diaphoresis. His ECG result is consistent with myocardial infarction. Which of the following laboratory results would be expected?
Elevated myoglobin, normal troponin I, and normal CK-MB
*2 Hours
