Anatomy and Physiology Flashcards
How can hormones exert their affect when they bind to a receptor?
1) regulate rate of enzymatic reactions
2) regulate transport of ions and molecules across cell membrane
3) regulate gene expression and synthesis of proteins
4) regulate electrical signalling pathways
What is hyperfunction in endocrine disorders?
Increase in related hormone
What is hypofunction in endocrine disorders?
Reduction in related hormone
Example of hypofunction endocrine disorders?
Hypothyroidism
Hypopituitarism
Diabetes mellitus
Example of hyperfunction endocrine disorders?
Acromegaly
Hyperthyroidism
Which hormones are tyrosine derivatives?
Catecholamines
Thyroid hormones
How are peptide hormones synthesised and stored?
Made in advance
Stored in secretory vesicles
How are steroid hormones synthesised and stored?
Synthesised on demand from precursors, so not stored
How are catecholamine hormones synthesised and stored?
Made in advanced
Stored in secretory vesicles
How are thyroid hormones synthesised and stored?
Made in advanced
Precursor stored in secretory vesicles
How are peptide hormones released from the parent cell?
Exocytosis
How are steroid hormones released from the parent cell?
Simple diffusion
How are catecholamine hormones released from the parent cell?
Exocytosis
How are thyroid hormones released from the parent cell?
Simple diffusion
How are peptide hormones transported in the blood?
Dissolved in plasma
How are steroid hormones transported in the blood?
Bound to carrier proteins
How are catecholamine hormones transported in the blood?
Dissolved in plasma
How are thyroid hormones transported in the blood?
Bound to carrier proteins
Half-life of peptide hormones?
Short
Half-life of steroid hormones?
Long
Half-life of catecholamine hormones?
Short
Half-life of thyroid hormones?
Long
Location of peptide hormone receptors?
Cell membrane
Location of steroid hormone receptors?
Usually cytoplasm or nucleus
Location of catecholamine hormone receptors?
Cell membrane
Location of thyroid hormone receptors?
Nucleus
Response when peptide hormones bind to a receptor?
Activation of second messenger system
Response when steroid hormones bind to a receptor?
Activation of genes for transcription and translation
Response when catecholamine hormones bind to a receptor?
Activation of second messenger systems
Response when thyroid hormones bind to a receptor?
Activation of genes for transcription and translation
Examples of peptide hormones?
Insulin
Parathyroid hormone
Examples of steroid hormones?
Oestrogen
Androgens
Cortisol
Examples of catecholamine hormones?
Adrenaline
Noradrenaline
Examples of thyroid hormones?
Thyroxine (T4)
Where is the hypothalamus located?
The thalamus in the brain
What connects the brain to the pituitary?
A stalk called infundibulum
What are the two parts of the pituitary gland?
Anterior and posterior
Which part of the pituitary is a true endocrine gland?
Anterior
What is the sella turcica?
A bone socket at the base of the skull which houses the pituitary gland
What is the hypothalamic pituitary axis?
A complex function unit that serves as a major link between the endocrine and nervous system
The sella turcica is part of which bone?
Sphenoid
What do neurons do in the hypothalamus?
Synthesis of trophic hormones to release to the pituitary
How are trophic hormones carried to the pituitary?
The hypophyseal portal system
What are tropic hormones?
Hormones that act on other endocrine glands to synthesise or release a hormone
How many tropic hormones does the hypothalamus secrete?
Seven
How many hormones and synthesised and secreted from the anterior pituitary?
Six
What are the six hormones secreted from the anterior pituitary?
Thyroid stimulating hormone
Andrenocorticotropic hormone
Luteinising hormone
Follicle stimulating hormone
Prolactin
Growth hormone
What is endocrine-axis feedback loop?
Where the hormone is regulated by the concentration of hormone in the blood
What is an endocrine axis-driven feedback long loop?
The last hormones in the pathway feeds back to the hypothalamus/anterior pituitary
What is an endocrine axis-driven feedback short loop?
Pituitary hormone feedback to the hypothalamus
Why is the posterior pituitary not a true endocrine organ?
It does not make hormones, only stores them
How many hormones are stored in the posterior pituitary?
Two
Which hormones are stored in the posterior pituitary?
Oxytocin
Antidiuretic hormone
How are hormones transported to the posterior pituitary?
Down nerve cell axons in vesicles
What can cause an endocrine disorder?
Issues with feedback systems
Genetic disorders
Infection or disease (often autoimmune)
Injury to endocrine gland
Endocrine tumour
What is a primary endocrine disorder?
Cause of disorder is in the target endocrine gland
What is a secondary endocrine disorder?
Cause of disorder is in the anterior pituitary
What is a tertiary endocrine disorder?
Cause of disorder is in the hypothalamus
Normal plasma glucose range?
5-7.8mmol/L
Normal plasma glucose range when fasting?
4-5.4 mmol/L
Normal plasma glucose range two hours after eating?
<7.8mmol/L
Factors that affect glucose absorption?
Rate of digestion
Rate of gastric emptying
Rate of absorption in small intestine
How is the liver involved in removing excess glucose?
Blood with high glucose concentration enters hepatic portal system
Blood enters liver
Excess glucose removed, facilitated by insulin
What is glycaemic index?
A rating system for foods containing carbohydrates. How quickly food affects blood sugar levels
Foods with a high glycaemic index?
Sugary food/drink
White bread
Potatoes
White rice
Foods with a low/medium glycaemic index?
Some fruits and vegetables
Pulses
Whole grain foods
Is glucose normally excreted?
No
What does OGTT stand for?
Oral glucose tolerance test
What is an oral glucose tolerance test useeld for?
To diagnose diabetes mellitus or to look at insulin resistance
Oral glucose tolerance test procedure?
Fast for 8-12 hours before test
Blood glucose levels measured
Drink 75g glucose
Retest after two hours
Normal OGTT results?
Fast: <6mmol/L
Two hours later: <7.8mmol/L
Diabetic OGTT results?
Fast: >7mmol/L
After 2 hours: >11mmol/L
What type of hormone is insulin?
Peptide
How many amino acids are in insulin?
51
What is the molecular weight of insulin?
6KDa
Basic structure of insulin?
A and B chains held together by disulphide bonds
Is the action of insulin considered anabolic or catabolic?
Anabolic
Where is the pancreas?
Below the liver, behind the stomach
Approximate weight of the pancreas?
100g
What is the head of the pancreas attached to?
Duodenum
What is the tail of the pancreas attaches to?
Spleen
What percentage of the pancreas is exocrine?
98%
What are clusters of exocrine cells in the pancreas called?
Acini
What is exocrine tissue?
Relating to a gland that secretes outwardly through duct(s)
What do exocrine tissues in the pancreas release?
Pancreatic juice
How much pancreatic juice is released per day?
1L per day
What is the pH of pancreatic juice?
8
What does pancreatic juice contain?
Digestive enzymes and bicarbonate to buffer gastric acid released from the stomach
What percentage of the pancreas is endocrine?
2%
What are clusters of endocrine cells in the pancreas called?
Islets of Langerhans
What do islets of langerhans do?
Synthesise and secrete hormones into the blood via the pancreatic vein
Type of cells in the islets of langerhans?
Alpha
Beta
Delta
What percentage of cells in the islets of langerhans are alpha cells?
20%
What percentage of cells in the islets of langerhans are beta cells?
70%
What percentage of cells in the islets of langerhans are delta cells?
5%
What do alpha cells in the islets of langerhans secrete?
Glucagon
What do beta cells in the islets of langerhans secrete?
Insulin
What do delta cells in the islets of langerhans secrete?
Somatostatin
Insulin synthesis process?
1) insulin mRNA translated as a single chain precursor called preproinsulin
2) signal peptide removed during insertion to ER, generating proinsulin
3) in ER C-peptide is removed to form immature insulin
4) insulin and C-peptide packaged into vesicles in the Golgi
5) insulin matures
6) insulin exocytosed when beta cell stimulated
How is insulin stored?
In crystalline form
6 molecules of insulin around two molecules of zinc
Why is insulin stored in crystalline form?
Increased storage capacity
Reduced solubility
Increased half-life
What kind of feedback controls insulin secretion?
Negative
What is the main glucose transporter in humans?
GLUT1
How does glucose stimulate insulin secretion?
1) glucose transported into beta cells through plasma membrane transporters
2) glucose levels in cell increase
3) glucose in beta cells phosphorylated by glucokinase to glucose-6-phosphate
4) most glucose fully oxidised leading to rise in ATP
5) ATP sensitive potassium efflux channels inhibited by ATP
6) channels close
7) cell depolarises
8) depolarisation activates voltage-gated calcium channels
9) increase in calcium leads to exocytosis and release of insulin
Calcium channels in beta cells are controlled by?
Voltage
Potassium efflux channels in beta cells are controlled by?
ATP levels
What type of kinase is glucokinase?
A low-affinity hexokinase
What is glucose phosphorylated to in beta cells?
Glucose-6-phosphate
What kind of pattern is insulin secretion?
Biphasic
Describe biphasic insulin secretion?
Rapid first phase release
Prolonged second phase release
What is the rate limiting step in insulin secretion?
Glucokinase phosphorylation
What type of receptor is the insulin receptor?
Tyrosine kinase
What does insulin promote in the liver?
Glycogenesis
Lipogenesis
Glycolysis
What does insulin inhibit in the liver?
Glycogenolysis
Lipolysis
Gluconeogenesis
What does insulin promote in muscle?
Glucose transport (GLUT4)
Glycogenesis
Glycolysis
Lipogenesis
Protein synthesis
Amino acid transport
Where does insulin act?
Liver
Muscle
Adipose tissue
What does insulin inhibit in muscle?
Lipolysis
Protein catabolism
What does insulin promote in adipose tissue?
Glucose transport (GLUT4)
Lipogenesis
What does insulin inhibit in adipose tissue?
Lipolysis
What is Glycogenesis?
Glucose storage as glycogen
What is Lipogenesis?
Glucose storage as fat
What is glycolysis?
Glucose utilisation
What is glycogenolysis?
Breakdown of glycogen
What is Lipolysis?
Break down of fat
What is gluconeogenesis?
Generation of glucose
What is the main hormone involved in decreasing blood glucose?
Insulin
What is the main hormone involved in increasing blood glucose?
Glucagon
What other hormones are involved in increasing blood glucose levels?
Adrenaline
Cortisol
ACTH
Growth hormone
Thyroxine
What type of hormone is glucagon?
Peptide
How many amino acids in glucagon?
29
Glucagon acts on which receptor?
Glucagon receptor
What type of receptor is the glucagon receptor?
GsPCR
Where does glucagon act?
Liver
Adipose tissue
What does glucagon promote in the liver?
Glycogenolysis
Gluconeogenesis
What does glucagon promote in adipose tissue?
Lipolysis for Gluconeogenesis
How does cortisol help increase blood glucose?
Promotes Gluconeogenesis
Breakdown of skeletal muscle protein to provide substrates for Gluconeogenesis
Enhance Lipolysis
Counteracts the affects of insulin
How does exercise affect glucose homeostasis?
Increases glucagon, noradrenaline, adrenaline and cortisol
How is glucagon related to exercise in glucose homeostasis?
Increased glucagon increases Glycogenolysis and Gluconeogenesis in the liver.
Meaning more glucose for anaerobic exercise
How is cortisol related to exercise in glucose homeostasis?
Increases Gluconeogenesis during aerobic exercise when carbohydrate resources are depleting
How does exercise affect fat metabolism?
Increased cortisol, growth hormone, noradrenaline and adrenaline increase lipase enzyme activity which increases Lipolysis
Groups of steroid sex hormones?
Androgens
Oestrogens
Progestogens
What are androgens?
Male sex hormones
What are oestrogens and progestogens?
Female sex hormones
Types of androgens?
Dihydrotestosterone
Testosterone
Types of oestrogens and progestogens?
Oestradiol
Progesterone
What is dihydrotestosterone produced from?
Testosterone by the enzyme 5alfa-reductase
What types of hormones are sex hormones?
Steroids
What does dihydrotestosterone do?
Critical in sexual differentiation of the embryo and subsequent sexual development and maintenance of masculine characteristics
Does dihydrotestosterone act locally or systemically?
Locally
There is testosterone produced?
Testes
Does testosterone act locally or systemically?
Both
What does testosterone do?
Critical for generation of sperm and development and maintenance of masculine characteristics
Where is oestradiol generated?
Ovaries
What is oestradiol generated from?
Androgens by the enzyme aromatase
What does oestradiol do?
Controls the development and maintenance of feminine characteristics and stimulates the growth of the egg follicle
What does progesterone do?
Stimulates the growth of the endometrial lining of the uterus in order to prepare it for pregnancy
What does the hypothalamus synthesise and secrete in relation to the reproductive system?
Gonadotropin-releasing hormone (GnRH)
What does GnRH stand for?
Gonadotropin-releasing hormone
What does the anterior pituitary synthesise and secrete in relation to the reproductive system?
Follicle-stimulating hormone (FSH)
Luteinising hormone (LH)
What does FSH stand for?
Follicle-stimulating hormone
What does LH stand for?
Luteinising hormone
FSH and LH act on the gonads to promote?
Sex hormone production
Gametogenesis
What do the testes produce?
Testosterone
Spermatozoa
What do the ovaries produce?
Oestradiol
Progesterone
Ova
What is gametogenesis?
Production of gametes
What causes puberty?
Signalled by high pulses of gonadotropin-releasing hormone
Average age of puberty onset in males?
12 years old
What does gonadotropin-releasing hormone stimulate the release of?
LH
FSH
What controls the negative feedback loop in the male reproductive system?
Testosterone
Inhibin
What is inhibin?
A peptide hormone that controls the release of GnRH, FSH and LH in a negative feedback loop (along with testosterone)
Hormonal control of the testes?
Diagram of testes?
Key parts of the testes?
Seminiferous tubules
Rete testis
Epididymis
Vas deferens
What happens at the seminiferous tubules?
Site of spermatogenesis
What happens at the rete testis?
Sperm concentrated here
What happens at the epididymis?
Sperm is stored here
What is the vas deferens?
Ducts that transport sperm from the epididymis to the ejaculatory ducts
What cells are present in the seminiferous tubules?
Leydig cells
Sertoli cells
What do Leydig cells respond to?
Luteinising hormone
What do Leydig cells do?
Produce testosterone
What does testosterone make the Sertoli cells secrete?
Production of factors that promote spermatogenesis
What do the Sertoli cells form?
The testes/blood barrier
What do Sertoli cells do?
Provide nutrients and factors to the developing germ cells
What do Sertoli cells respond to?
FSH
What do Sertoli cells secrete?
Chemical signals needed for proliferation and differentiation of germ cells
Inhibin
Seminal fluid
What does seminal fluid contain?
Androgen-binding protein (ABP)
What does Androgen-binding protein do?
Binds testosterone to maintain a high concentration in the tubules which is essential for spermatogenesis
What are germ cells called? (male reproductive system)
Spermatogonia
Process of spermatogenesis?
Spermatogonia divide mitotically and meiotically and then differentiate into spermatozoa
Germ cells move away from basement membrane and towards lumen of seminiferous tubule
Does long does the process of spermatogenesis take?
60-64 days
Where does inhibin act on?
Posterior pituitary
Average age of puberty onset in females?
11 years old
What is menstruation?
When the uterine lining is shed if fertilisation does not take place
Phases of the menstrual cycle?
Follicular phase
Ovulatory phase
Luteal phase
Menstruation
What happens in the follicular phase?
A follicle develops into a mature follicle
What is a follicle? (reproductive)
Small structure in the ovary that contains one immature egg (oocyte)
What is a mature follicle? (reproductive)
Fluid-filled sac containing the oocyte
How long does the follicular phase last?
9-23 days
What happens in the ovulatory phase?
Release of the oocyte
How long does the ovulatory phase last?
1-3 days
What happens in the luteal phase?
The development of the corpus luteum
Where is the thyroid gland found?
Anterior neck, below the larynx
What is an enlarged thyroid gland called?
Goitre
Shape of the thyroid gland?
Butterfly-shaped
What connects the two lobes of the thyroid gland?
Isthmus
What are the two thyroid hormones?
Thyroxine (T4)
Triiodothyronine (T3)
What does T3 stand for?
Triiodothyronine
What does T4 stand for?
Thyroxine
XX see chromosomes create?
Female
XY see chromosomes create?
Male
What causes testes for form in an embryo?
SRY gene activates a transcription factor that activates the pathway at around 7 weeks
What does the SRY gene do?
The SRY gene provides instructions for making a protein called the sex-determining region Y protein
What are the names of the two sets of ducts in an embryo that are to do with sexual differentiation?
Wolffian ducts
Mullerian ducts
Which embryo ducts develop into the male reproductive tract?
Wolffian ducts
Which embryo ducts develop into the female reproductive tract?
Mullerian ducts
What does SRY induce the expression of?
Anti-mullerian hormone (to get rid of Mullerian ducts)
Testosterone
Dihydrotestosterone
How is dihydrotestosterone produced?
From testosterone by the enzyme 5a-reductase
What does dihydrotestosterone do?
Sexual differentiation in embryo and subsequent sexual development and maintenance of masculine characteristics
Where does dihydrotestosterone work?
Locally
Where is testosterone made?
In the testes
What does testosterone do?
Generation of sperm and development and maintenance of masculine characteristics
Where does testosterone work?
Systemically and locally
What does oestradiol do?
Controls the development and maintenance of feminine characteristics and stimulate the growth of the egg follicle
What does progesterone do?
Stimulates the growth of the endometrial lining of the uterus in order to prepare it for pregnancy
What does the hypothalamus secrete (reproductive endocrinology)?
Gonadotropin-releasing hormone (GnRH)
What does the anterior pituitary secrete (reproductive endocrinology)?
Follicle stimulating hormone (FSH) and Luteinising hormone (LH)
What is GnRH?
Gonadotropin-releasing hormone
What is FSH?
Follicle stimulating hormone
What is LH?
Luteinising hormone
Male gonads?
Testes
Female gonads?
Ovaries
Principle functions of gonads?
Produce steroidal sex hormones Gametogenesis
What causes puberty?
High pulses of gonadotropin-releasing hormone
What does the release of GnRH do?
Stimulates the release of FSH and LH from the pituitary gland
Hormonal regulation of the male reproductive system?
Hypothalamus secretes GnRH -> GnRH causes pituitary gland to secrete FSH and LH -> FSH acts on testes to begin spermatogenesis and LH to produce testosterone -> testosterone and inhibin control release of GnRH and FSH/LH through a negative feedback mechanism
What is inhibin?
A peptide hormone that controls the release of GnRH and FSH/LH
What do the seminiferous tubules do?
Site of spermatogenesis Make up 80% mass of the testes
What do the rete testis do?
Sperm are concentrated here
What does the epididymis do?
Store sperm
What does the vas deferens do?
It is duct that transports sperm from the epididymis to the ejaculatory ducts
Two main types of cell in the seminiferous tubules?
Leydig cells Sertoli cells
What do leydig cells do?
Respond to LH to produce testosterone
What does testosterone do to the Sertoli cells?
Stimulates the production of factors that promote spermatogenesis
Where are the leydig cells located?
Surround the seminiferous tubules
Where are the Sertoli cells located?
Beneath the basement membrane of the seminiferous tubules and form the blood/testes barrier
What do Sertoli cells do?
Provide nutrients and factors to developing germ cells Respond the FSH to produce chemical signals for proliferation and differentiation of germ cells Secrete inhibin Secrete seminal fluid which contains androgen-binding protein (ABP) that binds testosterone to maintain a high concentration in tubules
What is ABP?
Androgen-binding protein It binds testosterone to maintain a high concentration in the seminiferous tubules
Process of spermatogenesis?
Germ cells called spermatogonia divide mitotically and meiotically and differentiate into spermatozoa Germ cells move away from the basement membrane, towards the lumen of seminiferous tubules
How long does spermatogenesis take?
60-64 days
How many sperm on average are made per day?
30 million
Hormonal control of spermatogenesis?
Hypothalamus releases GnRH -> GnRH causes release of FSH and LH from pituitary gland -> LH acts on leydig cells to produce testosterone -> testosterone and FSH act on Sertoli cells to facilitate spermatogenesis and release inhibin -> testosterone acts on hypothalamus and pituitary as a negative feedback mechanism whereas inhibin only acts on the pituitary
Hormonal control of female reproductive system?
Hypothalamus secretes GnRH -> GnRH causes pituitary gland to secrete FSH and LH -> FSH and LH stimulate ovaries to produce oestrogen for follicular development and ovulation -> oestrogen controls release of GnRH and FSH/LH through a negative feedback mechanism
Menstrual cycle definition?
The monthly cycle of release of the oocyte and the preparation of the endometrial lining of the uterus for pregnancy which is then shed if fertilisation does not take place
What are the three phases of the menstrual cycle?
Follicular phase Ovulatory phase Luteal phase
Main cells of the follicle?
Granulosa cells Theca cells
What do theca cells do?
Respond to LH and synthesise testosterone
What do granulosa cells do?
Respond to FSH to synthesise oestradiol from testosterone They acts as nurse cells to the oocyte
How many follicles develop each month?
10-25
What causes all but one of the follicles to die?
A drop in FSH
What causes follicle growth?
FSH increase
What hormone causes ovulation?
LH increase
Why happens during ovulation?
The oocyte is released into the Fallopian tube
What is the corpus luteum?
The follicle after the oocyte has been released The granulosa cells greatly enlarge
What does the corpus luteum do?
Produces progesterone which stimulates the growth of the endometrial lining to prepare for pregnancy It also releases oestrogen and inhibin
Hormonal control of menstrual cycle?
Hypothalamus releases GnRH -> GnRH stimulates pituitary to releases FSH and LH -> FSH and LH stimulate follicles to produce low levels of oestradiol and also produce inhibin -> low levels of oestradiol inhibit GnRH to keep FSH and LH levels low causing menstruation -> LH and FSH levels increase which increase oestradiol which thickens the uterine lining -> GnRH is secreted causing LH and FSH levels to rise -> resulting in ovulation around a day later -> LH stimulates growth of corpus luteum -> corpus luteum releases oestradiol and progesterone that blocks GnRH and LH and FSH causing endometrium to further develop
What does the combined pill contain?
Oestrogen and a progestogen (synthetic progesterone)
How does the contraceptive pill work?
Suppresses the release of FSH and LH
What does human chorionic gonadotropin (HCG) do?
Generated by the developing embryo to ensure survival of corpus luteum
Where does fertilisation occur?
In the Fallopian tube
When can fertilisation occur?
Within a couple of days of ovulation
What is the zona pallucida?
the thick transparent membrane surrounding a mammalian ovum before implantation
How does fertilisation occur?
Sperm binds to zona pallucida -> triggers acrosomal reaction causing acrosomal enzymes to be released -> enzymes digest a path through zona pallucida -> when a sperm penetrates zona pallucida a reaction occurs to harden the zona pallucida to prevent entry of more sperm -> sperm DNA (the head) enters the oocyte which is now called a zygote
What is a zygote?
The cell formed by the union of two gametes
Fertilisation to implantation?
Zygote undergoes mitotic division resulting in 16-32 totipotent cell conceptus -> after 3/4 days conceptus reaches uterus -> totipotency is lost and conceptus differentiates and develops into blastocyst -> blastocyst embeds in wall of uterus
What are trophoblasts?
A layer of tissue surrounding the blastocyst Provides nutrients to the developing embryo for the first three months
What do trophoblasts release and why?
Human chorionic gonadotropin (HCG) to ensure survival of corpus luteum so it can continue to produce progesterone and oestradiol for the first three months to maintain the pregnancy
What do pregnancy tests detect?
HCG
How soon can a pregnancy test work?
After implantation (6-12 days after fertilisation)
What happens to trophoblasts at 3 months?
They differentiate into the placenta and stop making HCG and instead produce progesterone and oestradiol Placenta takes over the job of corpus luteum which degenerates due to fall in HCG
Name a common cause of miscarriage around 3 months?
When the switch between the corpus luteum and the placenta goes wrong
Where is oxytocin produced?
Hypothalamus and then stored in posterior pituitary
Process of oxytocin release?
Baby pushes against cervix causing activation of stretch receptors -> stretch receptor send message to hypothalamus to release more oxytocin This is positive feedback
What does oxytocin do?
Causes contractions of smooth muscle of the uterus pushing baby further down birth canal
Why may oxytocin be given to a patient?
To induce labour To accelerate labour To stop bleeding after deliver (routine after caesarean-delivery)
What type of receptors do LH and FSH bind to?
GPCR
Process of oogenesis?
1) during foetal development oogonia divide mitotically
2) 7 months after conception then stop dividing
3) a third differentiate into primary oocytes
4) start to replicate their DNA ready for meiosis
5) cells wait in meiotic arrest until puberty
6) at puberty cells undergo meiotic division
7) second meiotic division occurs after ovulation and is completed after fertilisation
When does oogenesis begin?
During foetal development
What does the contraceptive implant contain?
Progestogens (etonogestrel)
Ovulation disordered account for what percentage of infertile couples?
25%
How can endometriosis cause infertility?
Tissue that usually only grows in the uterus starts to grow in other areas. This growth may obstruct the tubes or affect the lining of the uterus.
Uterine or cervical causes of infertility?
Benign polyps or tumours
Uterine abnormities
Cervical stenosis
Abnormal mucus
What is the most common cause of female infertility?
Polycystic ovary syndrome
How does PCOS cause infertility?
Increased androgen and LH secretion
Symptoms of PCOS?
irregular periods or no periods at all
difficulty getting pregnant (because of irregular ovulation or no ovulation)
excessive hair growth (hirsutism) – usually on the face, chest, back or buttocks
weight gain
thinning hair and hair loss from the head
oily skin or acne
What is premature ovarian insufficiency?
Premature loss of ova due to genetic problems or environmental insults, such as, chemotherapy
What does surgery for infertility usually do?
Unblocks any blockages. Can be used in males and females
What is a varicocele?
A varicose vein in the testicles that interferes with sperm development
Types of assisted conception?
Intrauterine insemination (IUI)
In vitro fertilisation (IVF)
What is intrauterine insemination?
Sperm is placed in the uterus using a fine plastic tube
What is in vitro fertilisation?
Sperm and egg are mixed outside the body and out back into the uterus
Do egg/sperm donors have to provide information about this identity?
Yes, since 1st April 2005
Average length of the menstrual cycle?
24-35 days
How long does the zygote stage last?
First 24 hours after union of egg and sperm. Ends when the first cell division takes place
When does the zygote become an embryo and until when?
24 hours-8 weeks after fertilisation
When does the embryo become a foetus?
8 weeks
What do ovulation tests detect?
LH
Signs of ovulation?
Changes in cervical fluid (usually watery/stretchy when ovulating)
Increase in body temperature
Changes in cervical position or firmness
During ovulation the cervix is?
High, soft and open
Before and after ovulation the cervix is?
Low, hard and closed
What percentage of total body mass is the brain?
2%
What percentage of the body’s total resting energy is used for the brain?
20%
Can the adult CNS regenerate?
No
Who discovered evidence of the blood brain barrier?
Ehrlich and Lewandowsky
How was evidence for the blood brain barrier founded?
Intravenous injection of dyes that stained other tissues but not the brain
What is the blood brain barrier?
A network of blood vessels that form a physical and chemical barrier between the brain parenchyma and systemic circulation
Main type of cell that makes up the blood brain barrier?
Brain capillary endothelial cells
Cells involved in the blood brain barrier?
Brain capillary endothelial cells
Pericytes
Astrocytes
Neuronal cells
Anatomy of brain capillary endothelial cells?
Have tight junctions, which prevent paracellular transport of small and large (water soluble) compounds from the blood to the brain
Function of pericytes at the blood brain barrier?
Phagocytosis
Barriers to drug delivery across the blood brain barrier?
1) endothelium surrounded by basement membrane
2) tight junctions
3) enzymatic barriers
4) efflux barriers
Enzymatic barrier to drug delivery across the blood brain barrier?
Various enzymes highly expressed in brain capillary endothelial cells which convert some drugs their inactive metabolites
Examples of drugs that are converted to inactive metabolites by enzymes at the blood brain barrier?
Arachidonic acid
Testosterone
Progesterone
Desipramine
Efflux barriers to drug delivery across the blood brain barrier?
Efflux pumps are P-glycoprotein and multidrug resistance-associated proteins
They recognise a wide variety of drugs
Transport pathways across the blood brain barrier?
1) paracellular aqueous pathway
2) transcellular lipophilic pathway
3) transport proteins
4) receptor-mediated transcytosis
5) adsorptive transcytosis
What types of molecules can cross the blood brain barrier via the paracellular pathway?
Water-soluble agents
What types of molecules can cross the blood brain barrier via the transcellular lipophilic pathway?
Lipid-soluble agents
Examples of drugs/molecules that cross the blood brain barrier via transport proteins?
Glucose
Amino acids
Nucleosides
Vinca alkaloids
Cyclosporin
Azathioprine
Examples of drugs/molecules that cross the blood brain barrier via receptor-mediated transcytosis?
Insulin
Transferrin
Examples of drugs/molecules that cross the blood brain barrier via adsorptive transcytosis?
Albumin
Other plasma proteins
Passive diffusion across the blood brain barrier depends on?
Molecular weight
Lipophilicity
What molecular weight can diffuse across the blood brain barrier?
<400/500Da
Ideal logP to permeate the blood brain barrier?
1.5-2.5
Can polar/charged molecules permeate the blood brain barrier?
Generally not
What percentage of small drug molecules do not cross the blood brain barrier?
98%
What percentage of large drug molecules do not cross the blood brain barrier?
100%
Four categories of CNS disorders that consistently respond to small, lipophilic drugs?
Affective disorders
Chronic pain
Epilepsy
Migraine
Ways that it may be possible to bypass the blood brain barrier?
Intrathecal
Nose to brain
How are brain capillary epithelial cells different to other capillary cells?
Don’t have pores
What is in the telencephalon?
Cerebral hemispheres
White matter
Subcortical structures
What is in the diencephalon?
Thalamus
Hypothalamus
Other structures
Parts of the brain stem?
Midbrain
Pons
Medulla oblongata
What day of gestatIon are the six divisions of the adult CNS apparent in the foetus?
50 days
What is the initial embryonic structure of the brain?
Neural tube
Basic embryonic development of the brain?
Neural tube -> primary brain vesicles -> secondary brain vesicles -> adult brain structured and neural canal regions
What are the three primary brain vesicles?
Prosencephalon
Mesencephalon
Rhombencephalon
What is the forebrain primary brain vesicle?
Proscencephalon
What is the midbrain primary brain vesicle?
Mesencephalon
What is the hindbrain primary brain vesicle?
Rhombencephalon
What are the five embryonic secondary brain vesicles?
Telencephalon
Diencephalon
Mesencephalon
Metencephalon
Myelencephalon
What secondary brain vesicles does the prosencephalon become?
Telencephalon
Diencephalon
What secondary brain vesicle does the mesencephalon become?
Stays as mesencephalon
What secondary brain vesicles come from the rhombencephalon?
Metencephalon
Myelencephalon
What is the mesencephalon?
Midbrain
What is the metencephalon?
Pons
Cerebellum
What is the myelencephalon?
Medulla oblongata
When does folding of the cerebral hemispheres begin during embryonic development?
Six months
What are the five lobes of the brain?
Frontal
Parietal
Temporal
Occipital
Insula
What are sulci?
Grooves on the cerebral hemispheres
What are gyri?
Bumps on the cerebral hemispheres
What are fissures?
Deep sulci
What does the central sulcus separate?
Frontal lobe from parietal lobe
What does the parieto-occipital sulcus separate?
Occipital lobe from parietal lobe
What does the lateral sulcus separate?
Parietal and frontal lobes from the temporal lobe
What does the median longitudinal fissure separate?
The two hemispheres
What does the transverse cerebral fissure separate?
Cerebral hemispheres from the cerebellum
What is the prefrontal cortex involved in?
Complex cognitive, such as:
Differential conflicting thoughts
Consequences of actions
Task managing
Social control
Personality
Working memory
Object recall
What disorders can be associated with the prefrontal cortex?
Schizophrenia
ADHD
Substance misuse disorders
Motor areas of the brain?
Primary motor cortex
Premotor cortex
Frontal eye field
Broca’s area
Purpose of the primary motor cortex?
Allows conscious control of precise, skilled, skeletal muscle movements
What is in the primary motor cortex?
Large pyramidal cells project to contralateral motor neurons, to control the opposite side of the body
What Brodmann area is the primary motor cortex?
4
Where is the premotor cortex?
Frontal lobe
Anterior to the primary motor cortex
Premotor cortex function?
Receives processed sensory information
Involved in planning movements
Where is the frontal eye field?
Frontal lobe
Anterior to premotor cortex
Purpose of the frontal eye field?
Controls voluntary eye movements
Where is Broca’s area?
Frontal lobe
Anterior to inferior premotor cortex. Usually in the left hemisphere
Purpose of Broca’s area?
Controls speech production
Purpose of the primary somatosensory cortex?
Responsible for conscious awareness of the overall somatic sensation of the other side of the body
What lobe of the brain are motor areas found?
Frontal cortex
What lobe of the brain area the sensory areas found?
Parietal
Where is the sensory association cortex found?
Parietal lobe
Posterior to primary sensory cortex
Purpose of the sensory association cortex?
Integrated different sensory inputs to sensory recognition
Two auditory areas of the brain?
Primary auditory cortex
Auditory association area
Sensory areas of the brain?
Primary somatosensory cortex
Sensory association cortex
Primary auditory cortex
Auditory association area
Gustatory cortex
Vestibular cortex
Olfactory cortex
Areas in the occipital lobe?
Primary visual cortex
Visual association area
Purpose of Wernickes area?
Understanding language
Three types of white matter fibres?
Association
Commissural
Projection
How are white matter fibres classified?
According to their types of connections
What are white matter association fibres?
Connections within one hemisphere of the cerebral cortex
What are white matter commissural fibres?
Connections between hemispheres
What are white matter projection fibres?
Connections between cortex and caudal areas
An example of commissural white matter?
Corpus callosum
Examples of projection white matter?
Internal capsule
Corona radiata
What are the basal forebrain nuclei?
A cholinergic system located anterior and dorsal to the hypothalamus
Function of the basal forebrain nuclei?
The basal forebrain cholinergic nuclei provide the main cholinergic input to prefrontal cortices, the hippocampi, and amygdala. These structures are highly relevant for the regulation and maintenance of many cognitive functions, such as attention and memory
Types of neurons in basal forebrain nuclei?
Cholinergic
Function of the basal ganglia?
Its main function is related to motor refinement, acting as a tonically active break, preventing unwanted movements to start. Much of this involves reducing the excitatory input to the cerebral cortex. This prevents excessive and exaggerated movements.
The five nuclei of the basal ganglia?
caudate nucleus
putamen
subthalamic nucleus
globus pallidus
substantia nigra
Examples of deep grey matter?
Basal forebrain nuclei
Basal ganglia
The thalamus forms the superior lateral walls of which ventricle?
Third ventricle
What is the only sensory input that does not pass through the thalamus?
Olfactory
Where is the thalamus located?
Between the cerebral cortex and the midbrain
Function of the thalamus?
relay motor and sensory signals to the cerebral cortex
Overall function of the hypothalamus?
To maintain homeostasis
Hypothalamic functions?
Controls the autonomic nervous system
Physical response to emotion
Body temperature
Hunger and satiety
Water balance and thirst
Sleep-wake cycles through the suprachiasmatic nucleus
Endocrine system
Another name for the suprachiasmatic nucleus?
Biological clock
What does the suprachiasmatic nucleus control the release of?
Melatonin from the pineal gland
What does the pineal gland secrete?
Melatonin
Three regions of the brain stem?
Midbrain
Pons
medulla oblongata
The spinal cord enters the skull though which opening?
Foramen magnum
What is the medulla oblongata responsible for?
Vital functions e.g. Cardiac, respiratory
Some reflexes
Where is the reticular activating system found?
Midbrain, pons, medulla oblongata and part of the thalamus
Purpose of the reticular activating system?
Levels of wakefulness and enables people to pay attention
Purpose of the cerebellum?
Coordinate movements (memory movements e.g. cycling)
Posture
Equilibrium
What lines the ventricles of the brain?
Ependymal cells
What are brain ventricles filled with?
CSF
How many brain vertricles are there?
4
Names of the brain ventricles?
Lateral (1 and 2)
Third ventricle
Fourth ventricle
What connects the lateral ventricles to the third ventricle?
Intraventricular foramen
What connects the third ventricle to the fourth ventricle?
Cerebral aqueduct
What shape are the lateral ventricles?
C-shaped
Where are the lateral ventricles found?
The cerebral hemispheres
What separates the lateral ventricles?
Septum pellucidum
Where is the third ventricle found?
Diencephalon (epithalamus, thalamus, subthalamus, and hypothalamus)
Where is the fourth ventricle found?
Hindbrain
What connects the ventricles to the subarachnoid space?
Three openings:
Paired lateral apertures in the sides and median aperture in the roof
What are ventricles in the brain?
Continuous central hollow cavities that lie deep within the brain. Filled with CSF and lined by ependymal cells
Purpose of ependymal cells?
Move CSF by cilia
What protects the brain?
Skull
Meninges
Cerebrospinal fluid
Blood-brain barrier
Purpose of the meninges?
Cover and protect the CSF
Protects blood vessels
Contains CSF
Forms partitions in the skull
How many layers of the meninges?
Three
What are the three layers of the meninges?
Dura mater
Arachnoid mater
Pia mater
How does penicillin cross the blood-brain barrier to treat meningitis?
The BBB integrity is disrupted due to inflammation so it can get through
How many bones make up the skull?
22
How many bones in the skull are facial bones?
14
How many bones in the skull are cranial bones?
8
What is the strongest layer of the meninges?
Dura mater
What does arachnoid mater look like?
Web-like
What is the dura mater made up of?
Two layers of fibrous connective tissue
Where are dural venous sinuses found?
Between the two layers of the Dura mater
Function of the dural venous sinuses?
Drain blood away from the brain to the heart
What are sections of dura mater called?
Dural septa
The four dural septa?
falx cerebri
tentorium cerebelli
falx cerebelli
diaphragma selae
Purpose of dural septa?
Limit excessive movement of the brain
Where is the falx cerebri located?
between the two cerebral hemispheres
Where is the falx cerebelli located?
separates the two hemispheres of the cerebellum
Where is the tentorium cerebelli located?
separates the occipital and temporal lobes of the cerebrum from the cerebellum and brainstem
What is the diaphragma sellae?
flat piece of dura mater with a circular hole allowing the vertical passage of the pituitary stalk
Where is the arachnoid mater found?
The middle layer of the meninges
What are the layers of the meninges?
Dura
Arachnoid
Pia
What separates the dura mater from the arachnoid mater?
Subdural space
What does the subarachnoid space contain?
CSF and large blood vessels
What are arachnoid villi?
small protrusions of the arachnoid mater into the outer membrane of the dura mater
Purpose of arachnoid villi?
CSF reabsorption
one-way valves for the flow of CSF into venous blood
Where is pia mater found?
The innermost layer of the meninges
Anatomy of pia mater?
Delicate vascularised connective tissue that clings tightly to brain
Where is CSF produced?
Choroid plexuses
Where are choroid plexuses located?
In brain ventricles
Where is the subarachnoid space?
Between arachnoid and pia mater
Composition of CSF?
Water solution formed from blood plasma. It has less protein and different ion concentrations to blood plasma. Kept at a constant volume
Purpose of CSF?
Gives buoyancy to CNS structures
Protects CNS from trauma
Nourishes brain
Carries chemical signals
How is the composition of CSF controlled?
Ependymal cells use ion pumps. They also cleanse CSF by removing waste
What is the normal volume of CSF?
~150ml
How often is CSF replaced?
Every eight hours
Circulatory path of CSF?
1) produced in ventricles by choroid plexus
2) flows through ventricles and into subarachnoid space via median and later apertures
3) flows through subarachnoid space
4) absorbed into dural venous sinuses via arachnoid villi
What causes hydrocephalus?
Obstructions in CSF circulation or drainage
Why is hydrocephalus less likely to cause brain damage in newborns?
Unfused skull bones allow enlargement of head
How to treat hydrocephalus?
Draining with a ventricular shunt to abdominal cavity (ventriculoperitonel shunt)
What is the epidural space?
Cushion of fat and network of veins in space between vertebrae and spinal dura mater
Where do the dural and arachnoid membranes extend to?
Sacrum- beyond the end of the cord at L1/2
Where is a lumbar puncture usually performed?
L2-5
What is the conus medullaris?
the terminal end of the spinal cord, which typically occurs at the L1 vertebrae
What is the name of the end of the spinal cord?
Conus medullaris
What is the filum terminale?
delicate filament, about 20 cm. in length, prolonged downward from the apex of the conus medullaris
What is the filum terminale made of?
Pia mater
Anatomy and function of denticulate ligaments?
bilateral triangular lateral extensions of pia mater that anchor the spinal cord to the dura mater
What are denticulate ligaments made of?
Pia mater
What limits the duration and frequency of action potentials?
Refractory periods
What does EPSP stand for?
Excitatory postsynaptic potential
What do EPSEs do?
Increase the firing of action potential on the postsynaptic membrane
What does IPSE stand for?
Inhibitory postsynaptic potential
What do IPSEs do?
Decreasede the firing of action potential on the postsynaptic membrane
What is a paroxysmal depolarising shift?
Abnormal fluctuations of the neuronal membrane voltage
A sustained depolarisation