1
Q
What are the characteristics of offspring in asexual reproduction?
A
- Offspring genetically identical
- Generated via mitosis
- Rapid and efficient
- Lack of diversity
- Parthenogenesis - female able to produce an embryo without fertilizing the egg with sperm.
2
Q
What are the characteristics of offspring in sexual reproduction?
A
- Offspring genetically different due to mixing of genes
- Generated via meiosis
- Increases genetic diversity
3
Q
Name the different types of sex determination in mammals.
A
- Chromosome sex
- Gonadal sex
- Phenotypical sex
- Brain sex
4
Q
What is the role of the sry gene in sexual determination?
A
The sry gene, found on the Y chromosome, is a sex-determining gene that:
- Initiates the development of gonads (testes)
- Initiates the production of androgens
- Inhibits passive female development (e.g. by MIH)
5
Q
Describe the initial movement of primoridal cells in an indifferent gonad
A
- Germ cells arise in the allantois
- Migrate to the genital ridges, due to a chemo-attractant gradient
6
Q
What are the downstream effects of the SRY gene in gene expression?
A
- Sox9 is upregulated, contributing to male development.
- Dax1 is inhibited, promoting female development.
- MIH is produced, inhibiting Mullerian duct development.
- wnt4- suppresses the production of androgens
- sf1- Activates MIH and steroid biosynthesis
- wt1- promotes early gonadal development
7
Q
Where are primordial germ cells located in ovaries and testes?
A
Ovaries: Located in the cortex, cells arrest in the 1st meiotic division.
Testes: Located in the medulla, in a cord-like formation, cells arrest in mitosis before meiosis.
8
Q
How does sexual differentiation occur in the reproductive tubes of males and females?
A
Females: Mullerian duct differentiates into fallopian tubes.
Males: Wolffian duct differentiates into vas deferens due to the presence of MIH.
9
Q
What experimental evidence supports sexual differentiation?
A
- Changes to MIH release affects the presence of the Mullerian duct. e.g. in a castrated male- Lack of male androgen leads to passive development into a female with Mullerian duct.
- Castrated male but with androgens develops both ducts because no MIH to inhibit Mullerian, however Wolffian duct still develops due to androgens
10
Q
What is hypothalamic masculinization, and what factors influence it?
A
Hypothalamic masculinization occurs due to exposure to androgens, mainly estrogen, preventing the hypothalamus from dealing with the surge in LH.
~~ Experimental evidence includes injecting dihydrotestosterone and removing testes early in development, showing that this development occurs early in life, and the role of testosterone is significant
11
Q
What are some abnormalities in sex chromosome, hormone response, and hormone production?
A
Sex chromosome abnormalities
- Klinefelter’s syndrome (XXY) and
- Turner’s syndrome (XO)
Androgen insensitivity
- failure to respond to hormones.
Inappropriate hormone production
- Congenital adrenal hyperplasia, produces too much hormone
12
Q
What are the functions of the testes?
A
Production of sperm
Synthesis and secretion of androgens
13
Q
What route does the sperm take through the testis?
A
Seminiferous tubules -> Rete testis -> Efferent duct -> Epididymis -> Vas deferens
14
Q
Describe the structure of the seminiferous tubules
A
Ring of sertoli cells that secrete developed sperm into the lumen
Inbetween these circular structures are Leydig cells that secrete testosterone
15
Q
What are the stages of spermatogenesis?
A
1.Spermatogonia - self renewal cells, maintaining stem cell population
2. Mitosis- production of 2n cells that remain connected to form a syncitium
3. Primary spermatocytes - 4n cells formed at the start of meiosis
4. Meiosis-formation of haploid cells
5. Spermiogenesis - formation of spermatids by structural changes
16
Q
What is spermiogenesis (5) and where does it occur?
A
Spermiogenesis- is the development structural adaptations in sperm, for example the acrosome, flagella, mitochondrial sheath, nuclear compaction and cytoplasmic extrusion
Develops towards the lumen, when sperm are in close contact with Sertoli cells
17
Q
What mechanisms allow for the continuous production of sperm?
A
- A0 Spermatogonia- presence of a stem-cell like sperm cell, continually dividing and producing sperm
- Spermatogenic wave- initiation of spermatogenesis from different places along the seminiferous tubule
- Spermatogenic cycle- Reactivation of the cycle before completion of the previous cycle has occurred, usually reactivates when a quarter of the way through the cycle
18
Q
What are hormonal controls of spermatogenesis?
A
GnRH- from Hypothalamus = release of LH and FSH from the anterior pituitary
LH acts on Leydig cells
FSH acts on Sertoli cells
Testosterone forms part of a negatie feedback cycle on the HP axis
Inhibin, produced by Sertoli cells inhibit FSH release from the anterior pituitary
19
Q
What is the function of Sertoli cells in spermatogenesis?
A
Sertoli cells contribute to the sexual differentiation of the male phenotype
- Control spermatogenesis
- Provide mechanical support
- Produce seminiferous fluid and androgen-binding proteins
- Form the blood-testis barrier.
20
Q
How does temperature affect the testes?
A
External testes
- A temperature 4-7 degrees lower than the body can decrease fertility
Internal testes
- Found in some animals like elephants, adapt to maintain fertility despite internal conditions.
21
Q
What is the significance of the blood-testis barrier?
A
Creation of an immunologically privileged site
Prevent auto-antibody production, maintain a privileged site, and prevent the entry of toxic substances.
Breaking this barrier can lead to infertility.
22
Q
What changes occur in sperm during maturation in the epididymis?
A
- Development of sperm swimming ability
- Surface changes to the sperm head (involving EPPIN and LIPOCALINS)
- Metabolic shifts to fructose usag
- Loss of the cytoplasmic droplet.
EVIDENCE: Sperm sampled from the start and end of the epididymis showed different fertilisation abilities
23
Q
How does sperm move within the epididymis?
A
Sperm passively moves in seminiferous fluid, driven by contractions of smooth muscle in the epididymal wall and the movement of epididymal cilia.
24
Q
What is the composition of seminal fluid, and what are its sources?
A
Seminal fluid- sperm, Na+, K+
Seminal Vesicle- Fructose, prostaglandins, and fibrinogen-like proteins
Prostate gland- Proteolytic enzymes and coagulating enzymes
Bulbourethral gland - mucus
25
Describe the process of erection and ejaculation and its control.
Arteriolar vasodilation = increased blood flow to the corpus cavernosa and corpus spongiosum, causes an erection.
Process is controlled by parasympathetic regulation involving acetylcholine, NO, and cGMP, leading to smooth muscle relaxation.
Ejaculation is controlled by sympathetic mechanisms, leading to smooth muscle contraction in the vas deferens and accessory glands.
26
What are the steps after insemination, and what barriers exist in the female reproductive system?
Barriers include:
- Mucus
Monocytes
- Acidic pH
- Flowback
- Crypts and cervical mucus.
27
What is the life span of gametes, and how does sperm storage vary across species?
The life span of human gametes is 28-48 hours. Sperm storage varies; humans store sperm for 5 days, bats for 186 days, and snakes for 7 years.
28
What is sperm competition, and what mechanisms are involved?
Sperm competition occurs between sperm that are aiming to inseminate the egg
Mechanisms to overcome and 'win' include:
- Numerous sperm for competition
- Last sperm precedence
- Copulatory plugs
- Sperm polymorphism, where different sperm types serve various roles.
29
What is capacitation, and where does it occur?
Renders sperm fertile.
Occurs in the female reproductive tract, in the fallopian tubes (ampulla)
Changes
1. Removal of membrane cholesterol
- changes in membrane permeability, movement of Ca2+ in increases motility
- CRISP-1 inhibitory effect on capacitation, inhibiting uptake of Ca2+ via CATSPER
2. Hyperactivation
3. Protein modifications
- Sperm able to bind to ZP3
- Removal of glycoproteins
4. Increase in intracellular pH
- Promotes acrosome reaction
30
Describe the stages of fertilization, including the acrosome reaction.
1. Progesterone is produced from cumulus oophorus cells surrounding the embryo
2. This increases the amount of Ca2+ uptake, via CATSPER, due to capacitation of the sperm
3. Increasing swimming activity
Acrosome reaction - Release of digestive enzymes such as Acrosin and Hyaluronidase via exocytosis
31
What are the three types of glycoproteins on the Zona pellucida and what are their roles?
ZP1: protein creating cross-linking between ZP2 and ZP3
ZP2: Binds to acrosome-reacted sperm
- Facilitates movement through ZP
ZP3: Binds to acrosome- intact sperm (occurs before ZP2)
- Stimulates Ca2+ influx and acrosome reaction
32
What are the stages of oogenesis in the early fetus, at birth, and during sexual maturity/puberty?
- Early fetus, primordial germ cells undergo mitosis to form oogonia.
- At birth, a primary oocyte with meiosis I arrest is formed within a primary follicle.
- During sexual maturity/puberty, a secondary oocyte with meiosis II arrest is produced, containing the first polar body.
33
What is the role of granulosa cells during antral follicular development, and how does the antrum form in Graffian follicles?
- Granulosa cells play a crucial role in preventing the maturation of the oocyte during antral follicular development by sending signals (cAMP) to keep it in meiosis arrest.
- The antrum in Graffian follicles forms as a fluid-filled central cavity caused by granulosa cells pumping out ions, leading to water movement.
34
What are the stages of ovulation, and what happens during the formation of the corpus luteum?
1. Formation of the stigma
2. Rupture of the follicle releasing follicular fluid and the oocyte,
3. Movement of the oocyte captured by the fimbriae of the oviduct.
The corpus luteum, formed from the remains of follicle granulosa cells, produces progesterone, signaling to the brain and preparing for pregnancy.
35
How is oogenesis hormonally controlled, and what are the roles of LH and FSH?
Release of GnRH from the hypothalamus,
- LH acting on thecal cells for testosterone synthesis
- FSH acting on granulosa cells, promoting continued follicle growth and uterus preparation. Generates negative feedback with inhibin
36
Explain the role of inhibin, estrogen, and kisspeptin in the hormonal control of oogenesis.
Inhibin exerts constant inhibition of FSH production.
Low estrogen has a negative feedback loop, inhibiting GnRH and anterior pituitary action.
High estrogen creates a positive feedback loop, causing an LH surge.
Kisspeptin, released from the hypothalamus, either inhibits (normal estrogen levels) or stimulates (high estrogen levels) GnRH release.
37
What are the effects of the LH surge during oogenesis, and what changes occur in the oocyte?
LH surge leads to
= completion of the first meiotic division, due to withdrawal of cAMP from granulosa cells,
= formation of cortical granules
= increase in collagenase activity in the oocyte.
38
Highlight the similarities and differences between spermatogenesis and oogenesis.
Similarities
- Both involve mitosis and meiosis
- Control by the hypothalamic-pituitary axis (HPA),
- Presence of feedback systems. Differences
- Continuous production of sperm versus the regular release of ova
- Large sperm outputs versus few oocytes released
- Timing and nature of gametogenesis completion. Spermatogenesis occurs throughout adulthood, while oocyte gametogenesis ends at menopause.
39
How do oestrus cycles in sheep, humans, and rodents differ?
Sheep- Start at ovulation, LH surge = ovulation, Luteolysis by Prostaglandin F2α
Human- Start at menstruation, LH surge = ovulation loss of progestorone leads to lining breakdown
Rodents- Start at ovulation, LH surge = ovulation, Progesterone peak caused by adrenal release, luteal phase affected by copulation
40
What is luteolysis and the luteal phase?
Luteolysis- breakdown of the luteum
Luteal phase- formation and regression of corpus luteum
41
What is the role of mechanical stimulation (copulation) in ovulation and maintenance of the corpus luteum?
1. Maintenance of the corpus luteum
- Sensory fibres detect, decrease Dopamine, increases prolactin, corpus luteum maintained
2. Ovulation- in some animals LH surge is not enough, detection leads to increase GnRH and increased LH and FSH
42
What are the functions of the female reproductive tract and how does it structurally change during the ovarian cycle?
Transport gametes to the site of fertilisation
- Changes to be keratinised to protect
Provide a site for implantation
- Increased invaginations to increase SA, increase chance of implantation of egg
43
What changes occur to the cervix in the oetry cycle?
- Mucus consistency changes, in luteal phase is more viscous
- Cervical muscle tone- follicular phase dilated, luteal phase constricted
44
What is the structure of the uterus?
Serosa- outer connective tissue
Myometrium- middle, smooth muscle layer
Endometrium- glandular layer
45
What methods exist for manipulating ovarian cycles, and how do they work?
1. Pregnancy prevention
- Steroidal contraceptives- High progesterone dose and low oestrogen (mimicking pregnancy hormonal levels)
- Increased viscosity of cervical and uterine secretions- Inhibiting movement of sperm
For Induction of synchronous cycling
- Progesterone sponge- absorb hormones, and then removal of sponge co-ordinates start of cycle
- Prostaglandin analogues- for sheep, inducing luteolysis
46
What are the methods and mechanisms of male contraceptives?
1. Hormonal
- Long-acting progesterone suppress GnRH
2. Non-hormonal
- Vasalgel- block vas deferens
- Anti-EPPIN- bind to sperm surface, prevent motility
- Drug- inhibits contraction of vas deferens, so no sperm in seminal fluid
47
What are the hormonal, neuroendocrine and environmental controls of the oestrus cycle?
Hormonal
- oestrogen in follicular phase, LH surge, and progesterone in luteal phase
Neuroendocrine
- HPG axis controlling release of GnRH, LH and FSH
- Feedback controls, inhibin, progesterone and oestrogen
Environmental
- Photoperiod for some seasonal breeders
- Nutritional status,
48
What are the factors affecting fertility?
Age
Genetic factors
Pathological factors
Environmental factors
Physiological factors - hormonal imbalances
49
What are some physiological changes during puberty? (5)
1. Onset of fertility
2. Appearance of secondary sexual characteristics
3. Growth spurt (girls before boys)
4. Changes in body composition
5. Psychological changes.
50
What is the Gonadostat Theory?
Changes in the sensitivity of the hypothalamus and pituitary to gonadotrophins regulate puberty.
True in rodents
51
What is the Hypothalamic Maturation Theory?
It suggests that reactivation of FSH and LH secretion, independent of gonads, triggers puberty
Evidence: following hormonal changes in castrated monkeys, that still showed signs of puberty
Reactivation is due to the removal of the GABA inhibition, and stimulation by glutamate and Kisspeptin
52
What are some factors affecting the age at which puberty occurs?
- Genetic factors
- Size at birth
- Health and nutrition
- Body mass and composition- better nutrition (larger size) leads to earlier onset of puberty
- Pheromones- not in humans however in pigs young pigs exposed to pheromones of male developed. Likewise in mice when exposed to urine (containing pheromones) of dominant male mice
53
What are pheromones, and how do they affect puberty?
Pheromones are chemical signals secreted in urine that can influence the onset of puberty, potentially causing it to occur earlier.
Detected: Vomeronasal organ
54
How does lactation affect ovarian cycles?
1. Lactation leads to a decrease in dopamine
2. Causing an increase in prolactin
3. Increase in beta-endorphin
4. Reducing the release of GnRH
5. Leading to a cessation of ovarian cycles.
Lactation inhibits implantation, however fertilisation of embryo may still occur
55
What are the differences between short-day and long-day breeders in terms of reproduction?
Short-day breeders have a shorter gestation period, mate in autumn and give birth in spring e.g. sheep, while long-day breeders have a longer gestation period and mate and give birth in spring e.g. horses
56
How is light detected and sensed in seasonal breeders?
1. Detection by photoreceptor in the retina, sent and transduced at the Pineal gland to a compound
2. Melatonin is produced in the dark
3. Melatonin inhibits TSH release from Pars tuberalis
4. If TSH is present it would cause Ependemal cells to produce DIO2
5. DIO2 converts T4 -> T3 (active)
6. T3 prevents the release of GnRH
57
What is diapause?
Egg is fertilised however doesn't implant so remains unfertilised
Facultative- delayed few days ,from suckling
Obligatory- delayed months, induced by day length
58
What are the morphological changes in the conceptus after fertilisation in early development?
Cell division
- But smaller in size when in ZP
Cell specialization
- Formation of inner cell mass and trophoblast
Progression from zygote to morula to blastocyst.
59
What is the role of the zona pellucida? (4)
1. Prevents the egg from interacting with the uterus wall too early
2. Helps maintain early cells together
3. Prevents the growth of cells, Compaction of cells
4. Hardens to prevent polyspermy
60
What are the contributions of sperm and egg to the conceptus?
Sperm
- haploid nucleus
- centrioles
- non-coding RNA
Egg
- mitochondria
- cytoplasm
- haploid nucleus
- most organelles.
61
What is compaction, and why is it important?
- Compaction is the process where blastomeres polarize and adhere to each other
- Polarization occurs due to arrangement of actin filaments and Wnt signalling
- Leading to asymmetric division and the generation of two populations of cells, apical and basal.
- Which will determine the inner cell mass and trophoblast
62
What is cavitation?
Cavitation is the process where blastomeres pump out Na+ ions into an inner cavity, creating a blastocoel as water moves in
Outer cells forming the trophectoderm and inner cells forming the inner cell mass.
63
How does control of gene expression change during embryogenesis?
Maternal RNA and proteins control the first divisions until the formation of the blastocyst, with timing dependent on the stability of maternal RNA and length of time between divisions.
64
What is epigenetic regulation, and what are some examples?
Heritable changes in gene expression without changes in the DNA base sequence (not mutations)
Examples:
- DNA methylation
- Histone modifications
- Non-coding RNAs.
65
What is genomic imprinting, and how does it affect embryogenesis?
Genomic imprinting is the pattern of genetic marks (epigenetics) that differ between oocytes and sperm, leading to differences between the mother and father, which can affect fetal and placental growth.
Evidence: in breeding experiments between M/F horses and M/F donkeys, production of either a mule or hinny
Example IGF 2 from paternal increase size
H19 maternal
66
What are Parthenogenetic, Gynogenetic and Androgenetic embryos? And what do they show
Parthenogenetic - one M and F nuclei
Gynogenetic- Both F = no placenta
Androgenetic - Both M = no embryo
They show imprinted genes where only one working is inherited from either the father or the mother
67
What is dosage compensation?
Inactivation of one X chromosome in each cell
Carried out by condensation with a non-coding RNA (Xist) forming a Barr body
68
What are the reasons for embryo implantation?
- Acquire more resources (nutrients and gases)
- Form the placenta for exchange of nutrients, gases, and waste between the mother and the developing embryo.
69
What hormone plays a crucial role in determining the implantation window?
Dependent on the hormonal profile, particularly requiring adequate levels of progesterone and estrogen.
70
Describe the changes in the uterus during the pre-receptive and receptive phases of implantation.
During the pre-receptive phase, the uterus is estrogen-dominant with high progesterone receptors, a negative charge on the membrane, a thick mucin coat, and long microvilli.
In the receptive phase, it becomes progesterone-dominant with lower progesterone receptors, thin mucin coat, short microvilli, and pinopodes for fluid absorption
71
What enzymes and factors are involved in the process of embryo hatching and implantation?
1. trypsin (protease) by the embryo to break down the zona pellucida.
2.Factors like LIF and OPN from uterine glands also play roles in facilitating implantation ,by preparing the uteirne lining
3. Integrins - attach blastocyst to lining
4. MMPs - remodelling of endometrium
72
What factors determine embryo spacing in the uterus?
Embryo spacing depends on maternal factors like
- muscle contractions
- fluid levels
- uterine crypt structure
- vascular flow
- embryonic factors like folate metabolism.
73
What are the two types of implantation, and how do they differ?
Invasive implantation involves breaking through the epithelium and developing in the uterine wall
Non-invasive implantation occurs within the lumen of the uterus without breaking through the epithelium.
74
What is decidualization, and what role does it play in implantation?
- Only occurs in invasive implantation
- Decidualization is the process where stromal cells differentiate into decidua,
- Provide a supportive environment for implantation and facilitating the maternal recognition of pregnancy.
- Inflammation like response, angiogenesis, and VEGFs
- With NK cells to stop embryo from penetrating too far
75
How do different species ensure the maintenance of the corpus luteum during early pregnancy? (4)
1. Neuro-endocrine links- increase prolactin or increase GnRH
2. Inhibition of luteolytic factors like PGF2α - by release of oxytocin or oestrogen from oocyte
3. Secretion of luteotrophic factors like hCG
4. Formation of additional corpus luteum through hormones like PMSG (horses).
76
What are the different pathologies associated with invasive implantation?
Accreta- breakdown of endometrium
Increta- breakdown of myometrium
Percreta- breakdown of serosa
77
What are the different modes of vertebrate prenatal nutrition?
- Lecitrophy- nutrients from yolk
- Epitheliophagy- nutrients from uterine lining
- Oophagy- eating unfertile egg
- Embryophagy- eats embryo
- Placentrophy- absorption across the placenta
78
What are the roles of the placenta?
- Exchanges nutrients and waste
- Provides protection from trauma and teratogens
- Offers immunological protection
- Secretes hormones
79
What are the mechanisms of exchange across the placenta?
Simple diffusion
Facilitated diffusion
Active transport
Receptor-mediated endocytosis.
80
What are teratogens?
Teratogens are external influences that can lead to abnormal development in embryos, such as:
- radiation
- physical trauma
- microorganisms
- hyperglycemia
- chemicals.
81
How does the placenta protect against teratogens?
1. Acts as a physical barrier
2. Immunomondulates effects from teratogens
82
What are the 4 foetal membranes?
The yolk sac
Amnion
Chorion/ Trophoblast
Allantois
83
What is the immunological function of the placenta?
Prevent rejection of the foetus by modulating maternal immune responses
- Reduced expression of MHC I, Expression of non-classical MHC that isn't very variable, promote Th1 -> TH2 response
Acting as a physical barrier against foreign tissue, no transfer of blood, so immunologically privileged site
84
What are the endocrine functions of the placenta?
Supports pregnancy by secreting hormones like hCG, eCG, and steroids
- Prepares for lactation with placental lactogens
- Initiates birth with steroids, prostaglandins, and relaxin.
85
What is the role of progesterone in pregnancy? (5)
1. Maintenance of the endometrium
2. Prevention of uterine contractions
3. Immune modulation
4. Development of mammary glands
5. Regulation of the menstrual cycle
86
How can estrogen's role in pregnancy be described?
Maintained at high levels during pregnancy, even higher than progesterone in some species like mares (horses).
- Uterine growth and development
- Mammary gland development
87
What is the luteoplacental shift?
Transition from progesterone secretion by the corpus luteum to the placenta, a process observed in humans but not all animals.
88
What are some cardiovascular changes during pregnancy?
Increased cardiac output
Decreased total peripheral resistance
Changes in blood pressure
Increased blood volume
Postural/heart compression.
89
How does pregnancy affect blood volume?
Pregnancy triggers vasodilation and pooling of blood, leading to an increase in blood volume.
This is regulated by hormonal pathways such as the ADH and RAA pathways.
90
What are some haematological changes during pregnancy?
1. Increased erythropoiesis
2. but a greater increase in blood volume, 3. Causes decrease in red blood cell concentration and haemoglobin levels, a condition known as = physiological anaemia.
91
How does pregnancy affect urinary function?
Increases renal blood flow, leading to an increase in glomerular filtration rate (GFR) and urine output.
Hormones like relaxin and nitric oxide (NO) contribute to vasodilation.
92
What respiratory changes occur during pregnancy?
Increases oxygen demand, compensated by an increase in tidal volume.
Progesterone increases airway dilation, and some degree of hyperventilation may occur.
93
What metabolic changes occur during pregnancy? (4)
- Increase in PTH
- Gestational diabetes
- Increased lipolysis
- Placental lactogens
94
How does pregnancy affect calcium mobilization? (4)
- Increased parathyroid hormone (PTH) secretion
- leading to increased reabsorption (upregulate enzyme converting VitD to active)
- Retention of calcium (calbindin @kidney)
- Increased mobilization by osteoclasts.
95
What thyroid changes occur during pregnancy?
Increases thyroid-binding proteins due to oestrogen, leading to an increase in total T3 and T4. HCG binding to TSH receptors, due to their similar structure, also activates the thyroid gland.
96
What gastrointestinal changes may occur during pregnancy?
Pregnancy may lead to intestinal or liver hypertrophy, and compression may cause increased intragastric pressure and reflux.
97
How can foetal growth be measured?
Ultrasound to look at size
Direct - post mortem
Indwelling methods
Weight measurements
98
What are the ways in which growth can be abnormal?
Non-proportionate = Genetic factors may lead to disproportionate growth
Size = large or small
99
What are the 3 key influences affecting foetal growth?
- Foetal
- Maternal
- Placental
100
What are the two foetal influences on growth?
Foetal genome - genetic diseases e.g. trisomy, or genetic inheritance can lead to larger size
Endocrine action of the foetus
- Glucocorticoids leads to smaller foetus
- Increase in GH has no effect
- IGF-II effects rate, however most experience catch up growth
101
What are the 5 maternal influences on foetal growth?
1. Uterus size
- Pony in thoroughbred led to larger offspring
2. Nutrition effect
3. Parity between child number
- first child smaller than the rest up until a certain point, dependent on age also
4. Socio-economic influences
- healthcare
5. Disease
- Diabetes leads to larger foetus
102
What are the 4 placental influences on foetal growth?
1. Weight of placenta
2. Vascularization of the placenta
- low vascularization shows brain-sparing effect
3. Transport of nutrients
4. Placental adaptions and structure
- upregulation of transport proteins
103
Why is foetal growth important in the long term?
Foetal programming
- Low birth weight linked to development of cardiovascular disease, potential epigenetic changes
Long term health
104
How is fluid balance in the foetus maintained?
Intake
- Absorb some through the skin
- Swallow some form surrounding amnion
- Produce lung liquid
- Intra-membranous exchange
Outtake
- removal via the urethra
- Placental exchange
105
How is the foetal cardiovascular system different to the adult system?
Circulation
- foetus has 3 shunts
--Ductus venosus-- bypasses liver
-- Ductus arteriosus - bypasses lungs
-- Foramen ovale - bypasses the lungs (hole in heart)
- Resistance in foetus and placenta run in parallel
106
How does gas transfer occur in the foetus?
1. Foetal haemoglobin has a higher affinity (2α and 2γ), less responsive to 2,3- DPG
2. Foetus has high Hb conc
3. Difference between maternal and foetal blood promotes diffusion
107
Describe the mechanism of haemopoiesis in the foetus
1. Cortisol released from adrenal gland
2. Forms the aorta- gonad- mesonephros (AGMs)
3. Region maturates the haematopoietic stem cells
4. Switch to liver and spleen
5. Then switch to bone marrow closer to birth
108
What endocrine molecules are present in foetal development? (3)
Cortisol rise -> from foetal adrenal gland
- Increase in PNMT enzyme to convert NA to A
Leptin - fat deposition
TH - CNS development
Adrenaline -> lung and metabolic development
109
What respiratory changes occur in the foetus?
Increase in elastin for expansion
Surfactant synthesis - cortisol, adrenaline and TH
Breathing movements
110
What changes to the gut occur in the foetus?
1. Structural changes
- increase in smooth muscle
2. Increased secretion of digestive enzymes
3. Increase in glycogen deposition
4. Increase in gluconeogenic enzymes
- PEPCK , G6Pase
111
What hormonal changes occur in parturition?
- Progesterone decline
- Increase in prostaglandin
- Increase in oxytocin from posterior pituitary gland
- Corticotropin-releasing hormone (CRH) increases
- Relaxin is produced by the placenta
112
What are the phases involved in the remodelling of the cervix?
Phase 1: Progesterone (softening)
= loss of collagen cross-linking, by inhibiting collagenolysis
Phase 2: Oestrogen (ripening)
= Increase in elastin, hyaluronic acid secretion (lubricant), slacking of pelvic ligaments
Phase 3: Dilation and contractions
Phase 4: Postpartum repair
113
What are the role of prostaglandins in reproduction?
1. Increase of PGF2α and its receptors
- Causes action potentials and contractions
2. Luteolytic factor, breaking down the corpus luteum, decreasing progesterone levels
3. Modulate release of embryo and fertilisation
4. Induce parturitions by promoting contractions
114
What is the role of oxytocin in parturition?
Secreted from the posterior pituitary due to the Ferguson reflex (pressing of the baby in the uterus)
- causes uterine contractions
- causes contraction of cells in the mammary gland
115
What is the role of the foetal HPA axis?
- Helps maturation of the foetus
- Signals foetal stress to initiate parturition
Evidence:
Veratrum californicum (teratogen plant), eaten by mother leads to long gestation period (delayed birth), as well as lambs developing cyclopia and lacking pituitary
116
How can birth be artificially hastened?
Glucocorticoids - promote the maturation of foetal lungs
Prostaglandins- soften and ripen the cervix for birth
Oxytocin - initiate and strengthen contractions
117
What is the anatomy of the secretory ducts of the mammary gland?
Mesh of myoepithelial cells surround an area of milk-secreting alveoli
Seen as glandular lobes
- During pregnancy area becomes full of milk
118
What is the composition of milk? (4)
Lactose
Protein
Lipids
Ions (Ca2+, phosphate, Mg2+, K+) but low Fe2+ and Na+
119
How is lactose in the maternal milk formed?
1. Hormonal environment (e.g. prolactin)
2. Production of α-lactalbumin
3. Alters specificity of enzyme (galactosyl transferase)
4. Catalyses UDP-galactose+glucose → Lactose and UDP
5. Lactose is stored in the Golgi
6. Causes the movement of water in via osmosis
120
Describe the type and organisation of proteins in milk
20-80% found as caseins
- Remain in colloid suspension with calcium aggregates, repelling them away from each other
Albumins and globulins are found dissolved
121
What are the two forms of milk released?
Foremilk- for rehydration, lower conc of proteins and lipids
Later milk- for energy, contains more lipids
122
What is the role of milk in the foetus?
Lowers blood pressure
Reduces blood clotting
Builds up an immune system
123
What is the role of the gastric hormone rennin?
Contains a protease (chymosin)
Causes the coagulation of casein
Makes digestion of milk slower
So that more nutrients are taken up
124
What are and what's the role of somatomammotrophins?
- Peptide hormones from the anterior pituitary e.g. GH or prolactin. Or from the trophoblast e.g. lactogens
Role
- Body growth
- Luteotrophic
- Anti-insulin
- Drives maternal behaviour
- Suppression of the ovarian cycle
125
What are maternal physiological changes that occur in preparation for lactation? (6)
1. Mammogenesis
- growth of mammary glands
2. Lactogenesis
3. Galactopoiesis
- maintenance of milk production
4. Ejection
5. Mammary involution
- apoptosis of mammary epithelial cells
6. Lactational anoestrus
- species specific, effect of lactation on ovulation or pregnancy development
126
What are the two phases of mammogenesis?
1. Pubertal mammogenesis
- significant growth, allometry >1
- proliferation of mammary epithelial cells and ductal structures
2. Pregnancy- induced mammogenesis
- Lobule development of alveoli, due to progesterone and placental lactogens
127
What hormonal changes allow for lactogenesis?
Increase in
- glucocorticoids
- Prolactin
Decrease in
- Oestrogen
- Progesterone
128
What factors are involved in galactopoiesis?
Local:
- Increase in suckling frequency, causing a decrease in the pressure in the mammary gland
- Decrease in inhibitory protein (inhibiting production), due to loss of milk
Reflex:
- Neuro-endocrine sensing, decrease in dopamine and increase in prolactin
129
What hormone drives ejection of milk?
Oxytocin
- As well as being conditioned to a certain stimuli e.g. baby crying
130
What occurs in mammary involution?
Apoptosis of excess epithelial mammary cells
Re-organisation of duct cells
131
What is lactational anoestrus?
Species-specific e.g. cows
Suckling induced inhibition of pregnancy
- due to increased prolactin levels
132
What are the benefits of breast-feeding?
For infant
- reduced risk of autoimmune disease
- better development
For mother
- promotes uterine involution
- period of postpartum infertility
- reduced risk of ovarian cancer?
133
What respiratory changes occur in the foetus leading up to and after birth?
-Lung liquid is produced by the lungs
- needs to be removed
- Breathing using muscles
- Production of surfactant
134
How is lung liquid removed?
30% reabsorbed when foetus is moved through birth canal
Reabsorption via lymphatics
- Liquid follows movement of Na+ , stimulated by adrenaline of b-adrenergic receptors
135
What factors triggers the onset of breathing?
Asphyxiation/ Hypoxia
Cold temperature
- Evidence is the delivery of a lamb into warm bath showed delayed breathing
Mechanosensitive
136
What are the struggles with the first breath and how are they overcome?
Problems
- Collapsed alveoli, has to overcome larger pressure (-40cmH2O)
- High surface tension
Solution
- Surfactant reduces surface tension
- upregulation of PNMT conversion to adrenaline for contractions
- deiodinase enzyme converts T4 to T3
137
What circulatory modelling occurs at birth in the neonate?
1. More blood low to the lungs, that are now functioning
2. Closure of the foramen ovale, 1/3 people don't fully fuse
3. Closure of ductus arteriosus and venosus
- no more prostaglandins for vasodilation keeping vessels open
138
Describe neonatal thermoregulation
Unable to shiver or sweat due to lack of development
Use Brown adipose tissue (BAT)
- Presence of uncoupling protein 1 (UCP1) which makes metabolism less efficient and energy is released as heat
Produces T3 to drive metabolism which can release heat
139
How does nutrition change from a foetus to a neonate?
Dependent on own liver glycogen stores as milk can take a few days to come
- uses fat for metabolism
- increase in the secretion of pancreatic amylase which breaks down starch
140
What liver, adrenal and thyroid changes occur from a foetus to a neonate?
Liver
- Inefficient at removing bilirubin, hyperbilirubin leads to jaundice
Adrenal gland
- remodelled, involution occurs, due to a lower demand of steroids
Thyroid gland
- Degradation of type 3 deiodinase which would degrade T3, however in neonate T3 levels rise
141
What are the 3 areas of the small intestine and their roles?
Duodenum - enzymatic breakdown
Jejunum - enzymatic breakdown
Ileum - absorption
142
What is the structure of the large intestine?
1. Caecum
2. Ascending colon
3. Transverse colon
4. Descending colon
5. Sigmoid colon
6. Rectum
7. Anus
143
What is the cross-sectional structure of the small intestine? (5)
1. Epithelium
2. Mucosa
- Lymphoid aggregates - protection
3. Submucosa
Submucosal plexus - nerve network
Submucosal gland- Brunner's gland in the duodenum
4. Muscular externa
- Circular and longitudinal
- Myenteric plexus - controlling contraction
5. Serosa
144
Describe the blood supply to the gut and specifically the vili
24% of cardiac output
Linked to the liver by the hepatic portal
Under ANS control, more blood in parasympathetic stimulation
Vili
- Counter current exchange movement, around the lacteal found in the middle
145
Describe the mechanism of cell turnover in the gut
Stem cells are found in the crypts of Lieberkuhn
1. Tight junctions form between cells
2. Old cells are pushed up and released
- Barrier is not compromised throughout the process
146
What are the components of the enteric nervous system?
Parasympathetic travelling in the vagus nerve - release ACh
Sympathetic with ell body located in the thorax -release Noradrenaline
Sensory neurones in the gut
- Intrinsic primary afferent neurones (IPANs)
- General visceral afferent fibres
- Intestinofugal afferent neurones
147
What are the roles of the sensory neurones in the gut?
Intrinsic primary afferent neurones (IPANs)
- responsible for peristalsis, and mixing
- Initiates reflexes
General visceral afferent fibres
- conveys pain
- vagovagal reflexes
Intestinofugal afferent neurones
- Long range inhibitory reflexes
- Short circuits neurones in the ENS
148
How does gut smooth muscle contraction occur?
Ca2+ entry by calcium induced calcium release
- Facilitated by the presence of caveolae - indents that increase the surface area
1. Ca2+ binds to calmodulin
2. Activates MLCK
3. Pi added to myosin
4. binds to actin and causes contraction
149
What triggers peristalsis?
1. Local stretching detected by enterochromaffin cells
2. Release seretonin
3. ENS fibres are stimulated
4. Myenteric promotes contraction on oral side of bolus and dilation of anal side of bolus
150
What is the basal electrical rhythm and what causes it?
Slow phasic waves of depolarisations
Caused by the interstitial cells of Cajal (ICCs)
151
How do slow waves generate contractions?
- Spikes of depolarisations can be generated by L-type VG Ca2+ channels
- Help the cells reach the threshold for contraction
152
What is segmentation?
Contractions causing mixing of constituents
153
What neurocrine transmission acts on the gut?
ACh- acts on muscarinic receptors, exciting the muscle
NO and VIP - Relaxes smooth muscle
Noradrenaline - promotes contraction of sphincters and smooth muscle
154
What are the six key peptide hormones secreted from enteroendocrine cells?
Secretin
Gastrin
Cholecystokinin
Incretins
Motilin
Ghrelin
155
What is the role of secretin?
Secreted from S cells in response to acid
- Increases pancreatic secretions (mainly increase the bicarbonate conc)
- Inhibits gastric acid secretion
- Causes contraction of the pyloric sphincter
156
What is the role of gastrin?
Secreted from G cells in response to the presence of amino acids and peptides
- Increases gastric acid secretion from parietal cells
157
What is the role of cholecystokinin (CCK)?
Secreted by I cells in response to fat digestion and fatty acids
- Stimulates gall bladder contractions
- Increases pancreatic secretions, mainly the amount of digestive enzymes
- Inhibits gastric emptying (pause)
- Promotes satiety on NTS
158
What is the role of incretin?
GIP and GLP-1 are secreted from K and L cells respectively after a meal
- Increase insulin secretion from the pancreas
- GLP-1 agonists can be used to treat diabetes
- GIP inhibits gastric motility
- Used to suppress appetite at NTS
159
What is the role of motilin?
Secreted from M cells, in response to fasting
- Initiates the migrating myoelectrical complex
160
What is the role of ghrelin? And where is it secreted from?
Secreted by endocrine cells in the stomach in response to fasting
- Stimulates appetite
- Promotes GH release from the anterior pituitary
161
What is potentiation?
When cells have receptors for many signals, sum exceeds the response to each messenger
162
What are the roles of saliva? (4)
Lubrication
Defence
- Lysosyme
- Lactoferrin (removes Fe)
- Proline-rich proteins bind to plant tannins
Bufferin
- HCO3-
Digestion
- presence of enzymes
163
Describe the process of saliva secretion
1. Acinar cells produce the primary secretion
- Contains high amounts of NaCl
2. Duct cells modify to produce secondary secretion
- retain Na+ for K+
- Retain Cl- in exchange for bicarbonate
3. Myoepithelial cells
- contract to force saliva into the ducts
164
How is saliva secretion controlled?
Anticipatory (cephalic phase)
Parasympathetic- open more acinar channels, vasodilation
Sympathetic - release adrenaline to contract myoepithelial cells
WORK SYNERGISTICALLY
165
Describe the structure of the oesophagus
Upper 2/3 surrounded by striated muscle
Lower 2/3 surrounded by smooth muscle
Upper oesophageal sphincter- remains at a higher resting pressure, and pressure increases when food passes through it
Lower oesophageal sphincter - tonically contracted, controlled by ENS, prevents heat burn. Disease can lead to lack of control and distension of the oesophagus
166
What are the actions involved in emesis?
Salivation increase
Retroperistalsis
Lowering of intrathoracic pressure
Retching if UOS is closed, however eventually relaxes
167
What is the structure of the stomach and their roles?
Fundus - air bubble
Body - acid secretion
Antrum- contraction
Pyloric sphincter- controls emptying rate
168
What causes gastric motility?
ICCs generating slow waves in the antrum and body
169
What is retropulsion?
Increasing contractions causes closure of sphincter
Causes mixing and helps break up larger particles as part of the antral mill
- Causes the formation of chyme
170
What is the migrating myoelectric complex and its role?
Wave of contractile activity that occurs hours after a meal (clearing signal)
- Initiated by motilin
171
What are the various ways in which gastric emptying is controlled? (6)
1. ANS controlling release of NO which affects constriction of the pyloric sphincter
2. Migrating myoelectric complex- inbetween meals allows for clearing
3. Excess acid - triggers negative feedback loop
4. Duodenal stretch
5. Ileal break
- Lowers stomach activity
6. High concentrations of peptides and amino acids
172
What are the roles of the oxyntic glands?
Parietal cells - secrete HCl
Chief cells - secrete zymogen (e.g. pepsinogens)
Intrisic factor production, for VitB12 uptake
Calves- secrete chymosin to coagulate milk
173
What are the roles of gastric acid?
- Delays gastric emptying by triggering a negative feedback loop
- Solubilize Ca2+ and iron
- Activates pepsinogens
- Destroys ingested microbes
174
How does the composition of gastric acid vary?
When flow is low, during fasting
- Mainly NaCl
When flow is high, after a meal
- Mainly HCl
Showing conservation of energy, because ATP is required to pump out H+
175
What hormones and neurotransmitters control acid secretion?
Promoters
- Gastrin
- Histamine - released from enterochromaffin-like cells, acts on H2 receptors increases cAMP
- ACh vagus nerve
Inhibitors
- Somatostatin - reduces cAMP
- Secretin
- Prostaglandins - promotes bicarbonate and mucus production
176
How is digestion regulated and how are they linked to acid secretion?
Cephalic - feed-foward, small increase in acid secretion
Gastric phase - when food enters stomach, big increase in acid secretion
Intestinal phase- Vagovagal reflexes, decrease in acid secretion
177
How is the lining protected from ulcer formation?
Secretion of mucus and bicarbonate
- presence of bicarbonate leads to pH7 mucus
178
How is pancreatic secretion different to salivary secretion?
In pancrea
- no myoepithelial cells
- Duct is where most of the water is secreted
- Pancreas secretes zymogens
- Zymogens are packaged into vesicles, with pancreatic secretory trypsin inhibitor (PSTI)
179
How are pancreatic secretions controlled?
Secretin and CCK
- secreted in response to low pH
Secretions need to increase to buffer the acidic conditions
180
How is the mucosal lining adapted for absorption?
Fold of Kerckring (increasesx3)
Vili (increases x10)
Microvili (increases x20)
181
How does absorption of carbohydrates occur?
Glucose and galactose in by SGLT1
Fructose on the GLUT5
All leave out of GLUT2 on the basolateral membrane
182
How are proteins digested?
Pepsins break them into polypeptides
Trypsins break them into peptides
Brush border peptidases break them into amino acids
183
Describe the process of calcium absorption
1. Ca2+ diffuses into the cells
2. Binds to calbindin which ferries it across the cell
3. Movement out by active transport
184
Describe the absorption mechanism of iron
1.Iron reductase turns Fe3+ → Fe2+
2. H+/ Fe2+ cotransporter (DMT1) takes up iron
3. Ferried across the cell (due to its charge)
4. Ferroportin transports iron out
5. When in blood is bound to transferrin
Storage → Hepcidin blocks ferroportin, leading to accumulation and binding to ferritin, however, iron is lost when cell is shed
185
Describe the absorption of water
Standing gradient model
1. Na/K ATPase found near the intracellular cleft
2. Increases gradient near tight junction
3. Drives water movement
4. Water flows down through the tight junction to the capillaries
186
Why do we need extrinsic nervous control of the gut?
- Feed-forward mechanisms
- In response to food intake etc.
- ANS- sympathetic control of gut motility and blood supply
- In response to fight or flight
- Presence of striated muscle in the upper 2/3 of the oesophagus as well as the external anal sphincter
- Generation of long distance reflex (vagovagal)
- Short-circuits the ENS, and is much faster
187
What is the cause and response of the gastro-colic reflex?
Cause: stretch of the stomach
Response: Activates peristalsis
188
In what ways does gut smooth muscle resemble cardiac muscle?
- Pacemaker component (ANS and ICCs)
- No resting potential
- Don’t require extrinsic activation, however can be influenced by it
- Small muscles cells that are mononucleate
- Form a syncitium,by joining together using gap junctions
- Use extracellular calcium and not internal stores, these contribute to the calcium induced calcium release.
189
Describe the similarities and differences between ICCs and pacemaker (SAN) cells
Similarities
- Modified cells that no longer contract
- Electrically connected via gap junctions
- Spontaneously generate signals
Differences
- ICCs produce slow waves, while SAN produce action potentials
- Slow waves are much slower than the depolarising waves generated by SAN
- Distribution of cells are different, SAN more localised, ICCs more widespread
190
Describe the importance of CFTR channels
Dysfunctional CFTR = thickened mucus
- malabsorption
- fatty stools, steatorrhea
Overexpression leads to diarrhoea
e.g. V.cholera secreting CTX, increasing cAMP increasing CFTR
191
What are the physiological consequences of vomiting? (5)
Metabolic alkalosis
Hypovolaemia
Damage to oesophagus
Dental erosion - due to acidity
Hypokalaemia
192
Describe the structure of the liver
Composed of many lobules
- Sinusoid mixes hepatic blood from the artery and vein
- Bile canaliculi transports bile in a counter current direction, towards the bile duct
193
What are the functions of the liver? (5)
1. Carbohydrate metabolism
- Carries out gluconeogenesis
- Statin inhibits synthesis of cholesterol
2. Bile formation
3. Storage of vitamins
4. Destruction and detoxification
5. Kupffer cells
- Filter blood, remove damaged erythrocytes
194
What occurs in carbohydrate metabolism?
1. Broken down by amylase and enzymes to form glucose
2. Taken up by SGLT2
3. Transported to liver
- Immediate energy use
- Glycogen store
- Fat store
195
What occurs in protein metabolism in the liver?
Protein synthesis
- produce a range of plasma proteins e.g. albumin, clotting factors and transport proteins
Protein degradation
- targeted ubiquitination
Urea cycle
- conversion of ammonia to urea
Transmination and deamination
196
What is the role of bile? (3)
1. Promotion of fat absorption
2. Excretion of waste
- Heavy metals and excess cholesterol
3. Protection
- IgA and antioxidant tocopherol
197
What is the role of the gall bladder and the enterohepatic circulation? and what hormones are involved?
Gall bladder- collects bile
CCK
- after a meal promotes gall-bladder contractions and relaxation of the Sphincter of Oddi causing emptying into the duodenum
- This can then be moved back into the hepatic circulation
198
How are fats digested and absorbed?
1. Triglycerides are partially broken down by gastric lipase
2. Forms emulsion droplets
3. Broken down by pancreatic lipase
4. FA combines with bile salts to form micelle
199
What is the role of micelle? And what do they contain (4)
Move fats to the brush border for diffusion
Contains:
- Bile salts
- FA
- Cholesterol
- Soluble vitamins
200
How is fat exported from the gut?
1. FA binds to FA binding protein (FABP)
2. Deliver to the ER and converted to triglycerides
3. Combine with chylomicrons
4. Move into lacteal (lymphatics)
201
What occurs in fat metabolism?
1. Lipoprotein lipase breaks down chylomicrons
2. Re-synthesised to free FA
3. FA can be used by muscle, or converted to triglycerides in adipose tissue
4. Liver can use FA to make ketone bodies
202
What are reflexes in the intestine?
Gastroileal reflex
- Feed-forward mechanism triggered by stretching of ileum
- Causes emptying of ileum
Colonileal reflex
- Feed-foward response to stretch of colon
- Stops emptying of the ileum
203
What are the structures of the large intestine?
Caecum
Ascending colon
Transverse colon
Descending colon
Sigmoid colon
Rectum
Anus
204
What are the ridges and muscles in the large intestine?
Haustra- Non-permanent invaginations, caused by partial contracting circular smooth muscle
Taenia coli- longitudinal smooth muscle
205
What triggers large intestinal motility?
- Contractions due to slow waves from ICCs
- High amplitude propagating contractions (HAPCs)- mass movement
- Associated with the relaxation of the haustra
206
What mechanisms occur during defaecation?
1. Relaxation of the internal anal sphincter (IAS)
- Smooth muscle
- Under autonomous control, carried out by VIP and NO
2. Relaxation of the external anal sphincter (EAS)
- Striated muscle, under somatic control
207
What diseases cause changes in defaecation?
Hirschsprung's disease- Lack of ENS, means relaxation of IAS can't occur. Leading to congenital megacolon
Chagas disease- caused by a parasite that damages the NS, leads to lack of sphincter control
208
What are the common sources of food for gut flora?
Fibre
- Cellulose hard to breakdown by the body
Lactose
- bacteria able to use lactose to produce H2, which can be detected in the breath
Raffinose (carb)
- found in beans
209
Why is potentiation important in gastric acid secretion?
Allows production of acid only when various conditions are all met
- ACh - from ENS sense whether rest of the body is ready
- Gastrin - sense stretch of the stomach
- Somatostatin - inhibits secretion when pH is low
210
What are the causes of ulcerations?
- Zollinger- Ellison syndrome
- NSAID (non-steroidal anti-inflammatory drug)
- H.pylori burrows into the mucus
211
How can gastric acid secretion be suppressed?
1. Anti-histamine (ranitidine, cimetidine)
- Act on H2 receptors
2. Proton pump inhibitor (PPI), e.g. Omeprazole
212
What are the similarities between kidney and intestines?
1. Both have SGLT1
- Drives movement of water, along with sodium and glucose
2. Presence of ENaC and K+ channels
3. Epithelial cells have microvili
4. Both act as barriers
5.
213
What are the two feedback mechanisms generated by CCK?
Detect: Long chain FA
CCK causes
Negative feedback
1. Gall bladder contractions
2. Bile is released
3. Fat products absorbed by micelles
4. More long chain FA
or
Positive feedback
1. CCK causes greater pancreatic secretions
2. Greater triglyceride digestion
3. More long chain FA
214
What are the breakdown steps of bilirubin?
1. Haem broken down to
2. Biliverdin
3. Bilirubin (yellow)
= Bruising and if ...
In the liver converted to Urobilinogen
4. Stercobilin formed by oxidation (faeces)
5. Urobilin found in urine
215
What are the structures of foregut fermenter stomachs?
1. Reticulorumen
- Fermenting
2. Omasum
- absorption
3. Abomasum
- Secrete acid and pepsinogens
216
What are the two forms of contraction in the reticulorumen?
Primary contractions
- waves sent down vagus nerve
- triggered by stretch
Secondary contractions (belching)
- follows primary contractions
- movement of gas up the oesophagus
217
What is rumination?
1. Food is moved up the oesophagus
2. Remasticated
3. Swallowed back down
218
What are the steps in cellulose fermentation?
1. Extracellular digestion of monosaccharides by microbes
2. Microbes break monosaccharides to pyruvate
3. Regeneration of NAD+ and production of ATP
4. Produce lactate or VFA
219
What are 3 examples of volatile fatty acids and their role?
Acetate (2C)
- metabolised to fat
Propionate (3C)
- turned into glucose
Butyrate (4C)
- converted to ketone bodies
220
Describe the membrane across which VFA are absorbed in cows?
@ the stomach wall
- Stratified squamous epithelial cells form syncytium by forming gap junctions
1. Stratum corneum
- keratinised protective layer
2. Stratum granulosum
- VFAH diffuse in
3. Stratum basale
- moved out into ECF
221
How is urea metabolised?
1. Urea is released from the liver
2. Moved to the salivary glands
3. Enter the rumen
4. Microbes break urea to ammonia
222
What are the negatives of hindgut fermenters?
Smaller distal colon
- Used for absorption
Greater loss of nitrogen
223
What is coprophagy?
- Ingestion of faeces to improve nitrogen use efficiency
1. Soft pellets with envelope
2. Reingest pellets
3. Pass intact to the stomach where they undergo fermentation
e.g. rabbits and guinea pigs
224
What are the negatives and positives of foregut and hindgut fermenters?
Foregut
- takes longer, but digestion is more complete
- food stored for safer times
- more efficient nitrogen use efficiency
Hindgut
- faster transit time can ingest more food
- better for when food quality is good
225
What are the factors affecting metabolic rate?
- Sleep
- Fasting
- Post-prandial thermogenesis (following a meal)
- Temperature
- Exercise
- Growth
- Pregnancy
- Hormone imbalances
226
How can basal metabolic rate (BMR) be measured?
Indirect calorimetry
- At rest
- 12-14hrs after a meal
- Thermoneutral environment
227
What is the respiratory quotient and what are the values for fat and carb?
Rate of CO2 production/ Rate of O2 consumption
Fat metabolism = 0.7
Carbohydrate metabolism = 1
Normal metabolism = 0.82
228
What are the two types of fat and their distribution?
Essential - myelin sheath and phospholipids
Storage - lipids in adipose tissue
Patterning
Android - abdominal fat
Gynoid - fat on hips and thighs (worse)
229
What are methods of measuring body fat?
1. BMI
- mass (kg)/ height (m)^2
2. Underwater weighing
- based on density and amount of displacement (Mg-F)
3. Skin fold test
4. Bioelectrical impedance analysis
5. CT and MRI scanning
6. Dual energy X-ray absorptiometry (DEXA)
230
What is the endocrine response to fasting?
Short term control
- Insulin
- Glucagon and adrenaline
Long term control
- Cortisol and GH
-- FGF21
231
What is the role of glucagon and when is it released?
Released from α cells in the islets of Langerhans
Stimulation for release:
- Low insulin and glucose levels
- Sympathetic stimulation
- Presence of amino acids
Effect:
- promotes gluconeogenesis
232
What are the stages of metabolism following a meal?
Post prandial (immediately after)
- Carbohydrates oxidised for energy
- RQ approaches 1
Post-absorptive period
- Glucagon levels rise
- Protein catabolism
- use fats
- RQ drops
233
What are the stages of metabolism in fasting?
Phase I (days)
- Glucagon increases
- T3 drops
- Insulin is low
Phase II (a week later)
- Glucagon normal
- Insulin low
- Metabolism of fat occurs (FGF21)
Phase III (few days before death)
- Cortisol significantly increases
- Fat reserves are low
- Death when over half of protein is metabolised
234
What are two examples of protein- energy malnutrition?
Kwashiorkor - development of oedema due to low levels of plasma protein, caused by oxidative stress
Marasmus - calorie deficient of all macronutrients
235
What are the pathological problems associated with obesity? (5)
- Type II diabetes
- Obstructive sleep apnoea
- CVD
- Gall stones
- Colorectal cancer
236
What key peptides control appetite?
Ghrelin
- promotes hunger as an anticipatory response
- stimulates release of GH
Cholecystokinin (CCK)
- release is stimulated by the presence of long chain FA in the duodenum
- promotes satiety
GLP1 and PYY
- secreted L cells in the jejunum and colon
- released after a meal, may regulate next meal
237
What other controls are there for appetite?
- Intestinal stretch
- Dehydration
- Levels of glucose CSF and blood
- Alcoholic drinks
- Choice of food
- Company
238
What are the control points in the brain for appetite? (3)
1. Ventromedial nucleus (VMN)
- satiety centre
2. Lateral Hypothalamic area (LHA)
- lesions cause weightloss, hunger centre
3. Arcuate nucleus
- master centre for weight regulation
- Ghrelin and leptin
4. Nucleus Tractus Solitarius (NST)
- CCK and secretin
5. Paraventricular (PVN)
- Integrates signals, controls release of CRH and TRH
239
How was leptin discovered?
Parabiosis- fusion of rats showed that there's a movement of a hormone between the two rats
ob mouse = unable to produce leptin but can react, so weight is reduced
normal/db mouse = produced leptin, but unable to respond to it, causing normal mouse to lose weight
240
What is the role of leptin? And what are associated pathologies?
- Peptide hormone formed from adipose tissue
- Signal satiety and inhibit hunger
- Activation of Leptin receptors leads to fat oxidation
- Secretion is constant as levels of fat don't vary massively
Obese - commonly due to leptin resistance
Congenital leptin deficiency - lack of leptin production
241
How is appetite suppressed by the arcuate nucleus?
1. Leptin and insulin diffuse past the BBB
2. Act on POMPC neurone
3. Release α-MSH
4. Acts on Melanocortin-4 receptor (MC4-R)
242
How is appetite stimulated by the arcuate nucleus?
1. Ghrelin activates NPY/AgRP neurone
2. Causes release of NPY and AgRP
NPY- acts on Y5-R
AgRP - inhibits MC4-R
243
What is the role of the paraventricular nucleus (PVN) and the Nucleus Tractus solitarius (NTS)?
PVN (hypothalamus)
- Release Corticotropin releasing hormone (CRH)
- Causes the release of ACTH
- Produce oxytocin and vasopressin
NTS (medulla oblongata)
- stimulates non-exercise activity thermogenesis (NEAT)
244
What is non-exercise activity thermogenesis (NEAT)?
Heat lost by various mechanisms that don't include exercise
e.g. fidgeting
245
How can obesity be treated?
- Diet and exercise
- Orlistat (pancreatic lipase inhibitor)
- Surgery (gastric bypass)
- GLP-1 agonists (Ozempic), suppresses appetite
- DNP - mitochondrial uncoupler (e.g. UCP3), can lead to death
246
Describe the role of Prostaglandins in reproduction
Fertilisation
- Promotes constriction of smooth muscle and movement of egg and sperm to fertilise
Establishment of pregnancy
- In invasive pregnancy, promotes decidualisation
Parturition
- Softens and remodels cervix for parturition, increase in matrix metalloproteinases (MMPs) to breakdown collagen
- Promotes uterine contractions
- Promotes CRH production causing release of cortisol
Neonate
- Causes closure of ductus venosus and arteriosus shunts
- Lack of prostaglandins leads to BAT breakdown
247
What is the role of cortisol in parturition? (4)
1. Promote foetal lung development
- Surfactant production from alveolar type II cells
2. Uterine contractions - increase connexins across myometrium
3. Stress response
- Regulate emotional response and pain perception
4. Promotes production of prostaglandins
5. Foetal haematopoiesis
248
What is the role of VitB12 in the body?
- Crucial for thymine synthesis in DNA replication
- Cofactor that regulates transfer from Me-Tetrahydrofolate to homocysteine to form methionine. Leaving Tetrathydrofolate for thymidine synthesis
249
What is the role of LIF? (3)
1. Promote binding of trophoblast to the uterine membrane
- Promote expression of ErbB on trophoblast and HB- EGF on membrane
2. Promote decidualisation in invasive implantation
- Controls inflammatory response to increase blood flow and vasodilation
3. Wound healing
- promotes migration and proliferation of fibroblasts and keratinocytes
250
How can maternal recognition of pregnancy occur?
1. Neuro-endocrine link
- copulation stimulates luteotrophic factors such as prolactin
2. Inhibition of luteolytic factors
- inhibit production of PGF2α, either by oestrogen or decreasing oxytocin
3. Secretion of luteotrophic factor
- e.g. human chorionic gonadotropin (hCG)
4. Formation of another corpus luteum
251
What is syngamy?
Fusion of the sperm and egg nucleus
252
Compare exocrine and endocrine secretions from the pancreas
Exocrine into ducts or cavities
- Pancreatic secretions for digestion, HCO3- (Secretin), Digestive enzymes(CCK)
Endocrine, commonly into blood
- Glucagon from α cells
- Insulin from β cells
- Somatostatin from delta cells, regulates balance between insulin and glucagon + stops stomach acid secretion
253
What is the role of insulin?
- In muscle and adipose promotes the uptake of glucose by translocating GLUT4 receptors to membrane
- Stimulates amino acid uptake and protein synthesis
- In liver promotes glucose oxidation and glycogen synthesis. INHIBITS gluconeogenesis
254
How is the secretion of cortisol controlled/regulated? What factors effect its secretion?
- Release is from the zona fasciculata in the adrenal cortex
- Controlled by HPA axis
Hypothalamus -> CRH
Anterior pituitary -> ACTH
Adrenal glands secrete
Factors
- Own negative feedback control
- diurnal pattern
- Stress response
- Maternal cortisol influences foetal cortisol
- Foetal adrenal development
255
How does VFA absorption vary between humans and cows? (4)
1. Absorption location
- Human = colon
- Cow = Rumen and omasum
2. Breakdown
- Human = microbial
- Cow = microbial and fermentation
3. Sources of VFA
- Human = dietary fibre + starch
- Cows = fibrous plant material (grass)
4. Efficiency
- Humans = low, hindgut fermentation
- Cows = high, foregut
256
In what conditions is somatostatin released?
1. Following a meal- High levels of amino acids and glucose
= Inhibits gastrin, secreting and CCk
2. High GH levels
= Inhibits GH, negative feedback
3. Pathology
= Treat acromegaly
257
Describe the types of glands in the stomach and what they produce
1. Oxyntic glands- secrete HCl, digestive enzymes (pepsinogens) e.g. lipase, amylase, intrinsic factor
2. Pyloric glands – secrete mucus
3. Cardiac glands - produce mucus and HCO3-
258
What are the changes which occur to the oocyte immediately following sperm entry?
- Cortical reaction
- Oocyte completes meosis II
- Paternal pronucleus unwinds
- Metaphase plate established
- Syngamy
259
What is the role of melanocortin receptor 4 (MC4-R) and Y receptor type 5 (YR5)?
MC4-R
- Promotes energy expenditure e.g. thermogenesis, regulates glucose and lipid metabolism
Y5R
- Promotes food seeking behaviour
260
What is hypophysectomy and what does it cause to the development of reproductive organs?
- Removal of the pituitary gland
Anterior - lack of LH, FSH and prolactin
Pituitary - lack of oxytocin
= Influences fertility
= Reduced development of reproductive organs
261
Describe 5 types of hypoxia
1. Hypoxic hypoxia - due to lack of O2 e.g. at altitude
2. Circulatory(stagnant) hypoxia - localised e.g due to ischaemia and heart attack, lack of flow
3. Anaemia hypoxia - due to lack of Fe and RBC
4. Histotoxic hypoxia - cells unable to utilise e.g. cyanide poisoning
5. Metabolic hypoxia - due to high demand from tissues
262
How can diabetes effect weight regulation?
Increase in weight due to lack of insulin response
- Insulin along with leptin suppress appetite
- Dysregulation of lipid metabolism, increase fat deposition
263
What are the components of bile?
- Water
- Bile salts
- Cholesterol
- Enzymes
- Vitamins
264
What are the output afferents from the enteric nervous system? (3) And what are their roles ?
Intestinofugal afferent neurones (IFANs to CNS)- long range inhibitory reflexes
Intrinsic Primary afferent neurones (IPANs - LOCAL)
- peristalsis and mixing, initiate reflexes
General visceral afferent fibres to CNS
- Vagovagal reflexes, conveys pain
265
What are the 6 key forms of movement in the GIT?
1. Deglutination
2. Retropulsion
3. Peristalsis
4. Phasic contractions
5. Segmentation
6. Migrating Myoelectric complex
266
How do prostaglandins control secretions from the pancreas?
Indirectly controls
Control the blood flow to the pancreas
So controls delivery of hormones
Can reduced digestive enzyme release
267
Outline the similarities and differences between the antrum and the blastocyst
Similarities
- Both have fluid filled cavity
- Both have differentiated layers
- Both are influenced by hormones
Differences
- B influenced by progesterone, F by FSH
- Origin B from follicular embryo, F from follicle
- Outcome B ends in implantation, F leads to ovulation
- Genome B both parents undergoing mitosis, F only maternal, arrested in meiosis
268
What are 4 pieces of evidence for the role of hormones in spermatogenesis?
1. Hypophysectomy (removal of pituitary) led to lack of
2. Exogenous application stimulated spermatogenesis
3. Knockout of hormone receptors, reduced spermatogenesis
4. Endocrine disorders (hypogandism) reduced spermatogenesis
269
What hormones are involved in lactation?
1. Oxytocin - causing ejection
2. Prolactin - promoting galactopoiesis, lactational anoestrus
3. Progesterone + Placental lactogens- promote mammogenesis
4. Cortisol - promotes lactogenesis and mammogenesis
270
What neuronal stimulation is there on the pancreas?
EXTRINSIC
VIP - increases digestive secretion
ACh - binds to muscarinic, also secretes digestive enzymes
NA - on α2 inhibits secretion
INTRINSIC (ENS)
- VIP and ACh
271
What are the roles of somatostatin? (Location/ Response)
Location
- Delta cells pancreas
- D cells GIT
Response
- Inhibits pancreatic secretions (insulin + glucagon)
- Inhibits gastric secretions
272
What is the role of leptin?
- Suppress appetite (α-MSH, MC4-R)
- Activate AMK pathway (fatty oxidation at mitochondria)
- Mitochondrial biogenesis
- Increase insulin insensitivity (more efficient FA oxidation)
273
What are the roles of LIF and OPN?
LIF
- Implantation
- Embryonic stem cell maintenance
- Immune system modulation
OPN
- Bone remodelling
- Differentiation of T helper cells
- Wound healing
274
Name 4 somatomammotrophins
Prolactin - Ant Pit
- Promote lactation
HG - Ant Pit
- Promote growth, starvation suppress
IG-1 - Liver
- mediate GH
Placental lactogen - Placenta
- Increase blood sugar
Physiology
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