Transcript Lifecycle histology - U

Lifecycle histology and
miscellaneous topics
Mike Ori
Disclaimer
• Faculty has not reviewed or vetted the
information contained herein.
• If you think this material is any way accurate,
you are mistaken.
• Celebrity voices are impersonated
• Describe the structure of the ovary
• Outer epithelial layer referred to as the
germinal epithelium overlies a connective
tissue capsule called the tunica albuginea.
Underlying this is the parenchyma and stroma
organized into a cortex and medulla.
• Embryologically, where do the primordial
germ cells originate?
• In the yolk sac.
• Whats the difference between an oogonia and
an oocyte
• Oogonia are the result of mitotic expansion of
the primordial germ cells. When they enter
meiosis, they become oocytes
• How many oocytes does a female have in
early fetal life, birth, puberty. How many are
ovulated?
• Fetal – 6 million
• Neonatal – 2.5 million
• Puberty – 400K
• Ovulation – 450
• Distinguish a primordial follicle and a primary
follicle.
• Primordial follicles are more or less the resting
state of the female gamete. They contain a
primary oocyte arrested at prophase I
surrounded by a thin layer of squamous
granulosa cells.
• Primary follicles are entering the active state.
The granulosa cells have plumped up to
cuboidal/columnar and the zona pelucida has
begun to form. As the primary follicle matures,
the theca forms from adjacent stromal cells.
• Distinguish antral from graafian follicles
• Antral follicles have a multi-layer theca, multilayer granulosa, and small fluid filled cavities
called antral cavities.
• Graafian follicles are larger than antral follicles
and the fluid filled spaces have coalesced to form
a lagoon in which the oocyte floats surrounded
by a cloud of granulosa cells (cumulus oophorus).
The cloud is a attached to the wall of the follicle
by a stalk of granulosa cells
• Name the regions of the uterine tube
• (Fimbriae) – infundibulm – ampula – isthmus intramural
• What are the two epithelial cells of the
uterine tubes
• Ciliated cells – move the ovum toward the
uterus
• Peg cells – produce nutritive medium and
enzymes necessary for capacitation
• When and at what stages is the oocyte halted
during meiosis and when does each continue.
• Meiosis I
– Entered in fetal life
– Halted at prophase I
– Completes at ovulation
• Meiosis II
– Entered at ovulation
– Halted at metaphase II
– Completes on fertilization
• What is the second messenger system for FSH
and LH
• They are both Gs linked to cAMP.
• Describe the the two cell theory of hormone
synthesis in the ovary.
• Two cells are required to synthesize estrogen.
• Theca cells overlying the follicle respond to LH
to synthesize androgen (androstenedione).
The androgens diffuse across the basement
membrane of the follicle and enter the
adjacent granulosa cells.
• Granulosa cells respond to FSH to convert
androgen to estrogen.
• What does LH do in both males and females
• It induces the production of androgens
– Androstenedione in females
– Testosterone in males
• Why is [FSH] generally lower than [LH]
• Both FSH and LH are controlled by GnRH and
both are inhibited by estrogen and
progesterone but FSH is also inhibited by
inhibin thus there are more inhibitory inputs
in the FSH pathway.
• Why does LH and FSH decrease in the luteal
phase and pregnancy even though estrogen
levels are high in pregnancy?
• Progesterone is always inhibitory to GnRH thus
the high levels of progesterone in the luteal
phase and during pregnancy prevent FSH and LH
release and subsequently ovulation.
• NOTE: its not completely clear to me if the
estrogen levels are such that inhibition or
induction of GnRH/LH/FSH would occur without
progesterone. I think they are inhibitory levels.
• When does the menstrual cycle begin
• By convention with the first day of menses.
• What are the phases of the menstrual cycle
• Menses (1-~5)
• Follicular/proliferative (1-14)
• Luteal/secretory (14-1)
• What is the purpose of the cervical mucous
glands
• They secrete mucous of varying quality
depending on the hormone milieu. Normally
the mucous is thick and retards entry of both
sperm and micro-organisms into the upper
reproductive tract. When estrogen levels peak
at mid-cycle, the mucous secretions thin and
allow access.
• Describe the epithelium of the cervix. What is
the squamocolumnar junction and why is it
important
• In the endocervical canal, the cervical epithelium
consists of simple columnar epithelium, whereas
in the vagina the cervix is covered with a nonkeratinized squamous epithelium. The
squamocolumnar junction is the point where the
transition is made from columnar to squamous
epithelium. The area surrounding this junction is
called the transformation zone. It is the site of
squamous metaplasia caused by HPV infection
and thus is the site of genesis for most cervical
squamous cell carcinomas
• Describe the glandular structure of the vagina
• The vagina is non-glandular. Secretions from
arousal are due to increased hydrostatic
pressure from congestion of the venous plexus
lining the organ.
• Why do vaginal squamous epithelia synthesize
glycogen? What controls glycogen synthesis
and how would this impact the vaginal tract
with age?
• The glycogen synthesized in the vaginal mucosa is
released into the lumen when the cells are
sloughed. The glycogen is fermented to lactic
acid by symbiotic bacterium, creating an low pH
environment that is hostile to many pathogenic
species. Synthesis is controlled by estrogen.
• Thus as women age, the pH of the vagina should
increase, leading to an increase in candida
infections however, in reality (or up to date at
least) this increase in candida infection does not
occur…go figure
• Mammary glands are glorified versions of
what?
• Apocrine sweat glands…put that way, what’s
all the fuss about?
• If sperm were vegetarian, what kind would
they be?
• Frutitarians as they consume fructose for fuel
• Describe the structure of a seminiferous
tubule
• The seminiferous tubule is divided into a basal
and adlumenal compartment. Spermatogonia
lie within the basal comparment and give rise
to the spermatocytes of the adlumenal
compartment. Sertoli cells rest against the
basement membrane of the tubule and
extend through to the adlumenal
compartment. Leydig cells lie outside the
tubule in the testicular stroma.
• What is the function of leydig and sertoli cells
• Leydig cells respond to LH to produce
testosterone.
• Sertoli cells secrete androgen binding protein
which effectively traps testosterone within the
seminiferous tubule thus ensuring that high
the levels of testosterone required to support
spermatogenesis are maintained.
• Describe the regulation of GnRH, FSH, and LH
in males
• Testosterone feeds back to inhibit GnRH, FSH,
LH. Inhibin secreted by sertoli cells feeds back
on FSH only.
• Differentiate spermatocytogenesis from
spermiogenesis
• Spermatocytogenesis refers to the production
of spermatocytes.
• Spermiogenesis refers to the maturation of
spermatids into spermatazoa.
• Which cell is responsible for the blood testes
barrier
• That would be the sertoli cell.
• Is it me or does sertoli sound like a plumber?
• What are the functions of the sertoli cell
• Support
– Physical support for spermatogenic series
• Protection
– Blood testes barrier
• Nutrition
– Regulate nutrients available to spermatocytes
• Phagocytosis
– Spermatocyte and spermatid castoffs
• Secretion
– ABP
– Inhibin
• What’s the difference between testis, testes,
and testicle?
• Testis = testicle = singular
• Testes = plural
• So what does that mean for estes?
• What is the normal sperm count and at what
level is a man considered sterile?
• Normal 100 million/ml
• Sterile < 20 million/ml
• What are the components of semen and
where are they synthesized.
• Testes
– Sperm
• Seminal vesicles (50%)
– Fructose
– Prostaglandins
– Proteins
• Fibrinogen
• Prostate (50%)
– Proteins
• Fibrinolysin
– Citric acid
– Acid phosphatase
• Fructose levels in ejaculate are assays for the
function of what?
• The seminal vesicles.
• What are the three regions of the male
urethra
• Prostatic
• Membranous (very short)
• Penile/spongy
• What is the difference between emission and
ejaculation
• Emission is the movement of sperm into the
urethra by sympathetic contraction of the
smooth muscle of the ducts and glands
• Ejaculation refers to the expulsion of sperm
from the penis by contraction of the
bulbospongiosis muscle.
• Which vessel is responsible for erection in
males and females?
• Deep artery of the penis/clitoris
• At what point are sperm able to fertilize an
ova?
• Only after capacitance in the uterine tubes.
• Why is the blood testis barrier important? Is
there an analogy in females?
• The blood testes barrier prevents the
activation of an immune response against the
antigenically different sperm
• To me it seems like the inherent isolation of
the oocyte by the granulosa cells serves the
same purpose
• How is dihydrotestosterone formed?
• DHT is formed from testosterone by 5-alpha
reductase
• What are the target tissues for DHT and
testosterone
• DHT
– Scrotum
– Penis
– Prostate
• Testosterone
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Muscle
Bone
Skin
Adipose
Brian
liver
• Men have estrogen at levels equivalent to
certain times in the menstrual cycle of
females. Why are men not feminized?
• Men have a much higher quantity of
testosterone than women such that the T:E
ratio is about 1000:1 in men and 70:1 to 6:1 in
females. It is believed that the ratio is an
important factor in response to the sex
steroids.
• What is SRY
• SRY is the sex determining region gene on the
y chromosome. It induces development of
leydig and sertoli cells
• Explain the role of hormones in the
development of the male and female
reproductive tracts
• Male
– SRY on Y induces sertoli and leydig cells.
– Single DAX1 on X promotes testes development
– Leydig derived testosterone induces survival of the mesonephric
ducts
– Sertoli derived anti-mullerian hormone causes the regression of
the paramesonephric ducts
– DHT causes the differentiation of the prostate and male external
genitalia
• Female
– Two DAX1 genes on X promotes ovary formation
– Lack of testosterone allows degeneration of mesonephric duct
– Lack of AMH allows maturation of paramesonephric duct
• What percent of pregnancies are unplanned
and what is their disposition.
• 50% unplanned
• 25% aborted (1/2 of unplanned)
• What are the roles of mifiprex and cytotek in
abortion?
• They are used for medical abortions.
• Mifiprex is a progesterone antagonists that
causes degeneration of the endometrium
• Cytotek is a PGE2 agonist that causes
contraction of the myometrium.
• Define cytogenetics
• The study of chromosomes, their structure,
and their inheritance
• Define euploidy and aneuploidy
• Euploidy is the state of having an exact
multiple of the haploid number of
chromosomes. 1n, 2n, 3n, etc
• Aneuploidy is the state of having a nonintegral number of chomosomes. 2n+1 of 47,
XXY
• Describe the structural rearrangements of
chromosome
• In gross terms rearrangements may be balanced or
unbalanced. In the latter there is loss or gain of
genetic material
• Deletion – loss of genetic material
• Duplications – gain of genetic material
• Inversions – swapping material within the same
chromosome
• Translocations – movement of material to other
chromosomes
• Robersonian translocations – Joining of two acrocentric
chromosomes to form a single chromosome
• List the descriptive locations of the
centromere
• Metacentric – near the middle
• Sub metacentric – off-center
• Acrocentric – on one side
– 13,14,15,21,22
– Robertsonian translocations possible
• If a person has a robertsonian translocation of
13 and 21 what is their pheonotype. What is
the pheonotype of their offspring?
• The carrier will be normal as they still have the
full complement of 13 and 21. Their offspring
may have downs if the robertsonian
chromosome is assorted into the gamete
along with the normal chromosome 21.
• In broad terms describe the differences
between sex chromosome abnormalities and
autosomal chromosome abnormalities
• Sex chromosome
– abnormalities of stature and sexual maturation
– Turner = short
– Klinefelters = tall
• Autosomal
– Mental retardation
– Birth defects
• During pregnancy the total number of
erythrocytes increases and yet the mother
may be technically anemic. Why?
• Erythrocytes increase 33% but volume
increases 45-50%. Thus more RBC are
distributed in an even larger volume.
• What are the phases of fetal development
with regard to teratogens?
• Preimplantation
– 0-14 days
– All or nothing
• Organogenesis
– 15-60 days
– All organ systems
• Growth and differentiation
– 61-term
– Brain
• What are the principles of teratology
• Timing
– Exposure timing must be consistent with defect
• Genetic susceptibility
– Maternal and fetal
• Tissue access
– Must have access to the fetus
• Pattern of malformation
– Must be consistent
• Dosage effects
• What categories of disorders are screened for
in the newborn screening in Arizona
• Amino acid disorders
– PKU – CNS damage, limit phenylalanine
– MSUD – CNS damage, limit branch chain ketoacids
• Fatty acid disorders
– MCAD – liver heart damage, avoid fasting
• Organic acid disorders
• Hemoglobinopathies
– Sickle cell
– Thalasemia
• Others
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Biotinidase deficiency – biotin cycling, exogenous biotin supplements
Galactosemia – liver toxicity, limit lactose
Congental adrenal hyperplasia – 21-OHase salt wasting
Hypothyroidism - cretinism
Cystic fibrosis – pancreatic enzymes, treatment programs
• What principles are used in determining the
tests on the newborn screen
• Must be common disease
• Must be treatable
• Cost effective, sensitive, specific test must be
available
• Describe the phases of labor
• Phase I effacement and dilation
– 4cm dilation until full effacement and dilation
• Phase II – delivery of infant
– Cardinal movements of labor
• Phase III – placenta delivery
• What are the cardinal movements of labor
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Engagement
Descent
Flexion
Internal rotation
Extension
External rotation
Expulsion
Don’t forget I enjoy extremely expensive
equipment
• Outline the role of CRH in parturition
• Increases exponentially through term.
• Manufactured in placenta and effects mother
and fetus
• Fetal
– CRH  /\ cortisol  lung maturation 
phospholipid surfactants in lungs  release to
amniotic fluid  proinflammatory  effacement
of cervix, /\ prostaglandins, /\ contractility
• Outline the changes in the myometrium
through term
• Myometrial cells are hypotrophic in the resting
uterus. Estrogen causes hyperplasia and
hypertrophy of the cells.
• Ion channel changes increase excitability as term
nears
• Increased synchronicity during labor (3rd tri?)
allows coordinated waves of contraction
proceeding from the fundus
• Oxytocin receptor concentration /\ during term
reaching zenith in labor
• List important teratogens
•
TORCH organisms
– Rubella – hearing loss, eye abnormalities
– CMV – Blueberry muffin, cerebral calcifications
•
Maternal
– Diabetes – spine, lower extremities, heart, kidneys
– PKU – CNS development issues
– Hyperthermia – CNS development issues
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Medications
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Anticonvulsants – various – hydantoin, valproic acid
Lithium – tricuspid valve defect (ebsteins )
Vitamin A – Ear defects, CNS, Thymus
Warfarin – Nasal hypoplasia, epiphyseal stippling
Recreational drugs
– Alcohol – FAS
– Cocaine – Vascular disruption, miscarriage, fetal cerebral infarcts
• Compare omission and commission
• Omission = withholding care
• Commission = withdrawing care
• From WikiAnswers
– Act of Commission is the doing of an act that causes harm. Example: I dug a
hole in the road and you fell into it. I am liable because I dug the hole which
caused you injury.
– Act of Omission is the failure to do something which failure causes harm.
Example: I saw a hole in the road, I knew it was there, I failed to cover it up or
failed to warn you about it and you fell in. I did not do what a prudent person
would have done to keep someone from harm.
• Why does commission have two M’s? They have different Latin roots.
• C + omission <> comission
• C + omission = commission
• Distinguish multifactorial disorders from single
gene disorders
• Single gene disorders occur when a disease is
attributable to a defect in a single gene. Diseases
caused by the confluence of many different genes
are referred to as multifactorial disorders.
• Single gene disorders often appear earlier in life
than multifactorial. Appearance order rule of
thumb is
– Cytogenetic at birth
– Single gene in childhood
– Multifactorial adulthood
• Define qualitative, discrete, and quantitative
traits
• Qualitative = discrete = trait absent or present
in binary fashion. E.G. cleft lip
• Quantitative traits are distributed along a
spectrum. Disease occurs at an defined point
along the spectrum. Height and intelligence
are quantitative traits.
• Predict the impact of genetics on a disease
using the relative risk ratio.
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•
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Recall that RR = (familial)/(population).
RR=1 = no genetic link
RR > 1 = increasing genetic link
RR autism = 150
RR diabetes = 12
Therefore autism has a stronger genetic link
than diabetes
• Describe the risk threshold model for
multifactorial behaviors
• Within a population it is assumed that there is a
continuous distribution of genetic liability for
many traits. At the highest end, people exceed
the risk threshold and are therefore affected.
• As a person moves farther along the spectrum,
disease severity increases and genetic liability
increases.
• In this model, increasing severity equates to
increased likelihood of trait in offspring due to
increased genetic liability in the adult.
• In the risk threshold model, what factors
affect a persons risk of disease
• Increasing relatedness to someone with the disease.
– Parents > grand parents >> 2nd cousin
• Increases with the number of affected relatives
• Increases with increasing severity of the disease
• When sex linked, offspring of probands of the less
commonly affected sex are higher. I.e. If your mom is
color blind, and you’re male, you’re color blind. If
you’re female and dad is color blind, you will be aat
least a carrier and will exceed the risk threshold only if
mom is color blind (100% likely) or a carrier (50%
likely).
• Distinguish learning disability from intellectual
disability. Also, define the standard deviation
for intelligence tests
• Intellectual disability occurs when the
following criteria are met
– full scale IQ is < 2SD from the mean
– Deficits in adaptive behavior
– Occurs before 18
• Learning disabilities occur when there is a 1SD
deviation between scores regardless of FSIQ.
• 1 SD is 15 IQ points
• Define the levels of intellectual disability and
detail their expected reading and working
levels
Level
IQ range
Reading (grade )
Work/living
Mild
2-3 SD (55-69)
3-6
Independent
Moderate
3-4 SD (40-54)
1-3
Supported
Severe
4-5 SD (25-39)
Survival
Group home
Profound
< 25
None
Assisted for all care
Note that each step falls off 1 SD.
• What common medical school past-time can
lead to mental retardation in offspring
• Alcohol consumption leading to FAS
• Based on his beard, what movie roles could Dr
Weil be typecast for?
•
•
•
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Moses
Santa Claus
Whaling captain
Villian (comic book type)