SUGER Flashcards
Rare disease in Europe defined as…
Affecting 1/2000 or less
Kidney roles
Maintain balance of salt, water, pH
Excrete waste products
Endocrine function
Control BP
RBC production
Maintenance of bones
Removal of drugs from body
Components of nephron in cortex
Bowman’s Capsule
Proximal tubule
Distal Tubule
Components of nephron in medulla
Loop of Henle
Collecting Duct
Renal cardiac output
~5 L/min
Renal blood flow
~1 L/min
Renal blood pathway
Abdominal aorta
Renal artery
Interlobar artery
Arcuate artery
Interlobular artery
Afferent arteriole
(nephron) Glomerular capillary
Efferent arteriole
Peritubular capillaries
Vasa recta
Interlobular veins
Arcuate veins
Interlobar veins
Renal veins
IVC
Renal urine flow
1 ml/min
The Tubuloglomerular Feedback Loop
Increased arterial BP
= Increased blood flow and BP in glomerulus
=Increased GFR
= Increased delivery of NaCl to macula densa (this triggers afferent arteriolar constriction)
= Decreased blood flow and BP in glomerulus
Myogenic mechanism for kidney autoregulation
Increased BP
= Stretch in vessel walls
= Opens stretch-activated cation channels
= Membrane depolarisation
= Opens voltage-dependent Ca channels
= Increased intracellular Ca
= Smooth muscle contraction
= Increased vascular resistance
= Minimised change in GFR
(decreased BP does the opposite)
Autoregulation of the kidney comes with 2 mechanisms:
-Tubuloglomerular feedback
-Myogenic mechanism
Which maintain GFR and control water/waste excretion
3 components of kidney filtration barrier
Fenestrated capillary endothelium
Glomerular basement membrane
Podocytes (foot processes)
5 factors affecting glomerular filtration
Pressure
Molecule size
Charge of molecule
Rate of blood flow
Binding to plasma proteins
Small molecules and ions up to …. can pass freely through filtration barrier
10kDa (glucose, uric acid, K)
Why can’t negatively charged ions cross filtration barrier?
Fixed negative charge of glomerular BM repels negatively charged anions
GFR is…
Glomerular filtration rate (filtration volume per unit time)
Embryology of pancreas
At junction of foregut and midgut, 2 pancreatic buds (dorsal and ventral) are generated which fuse to form pancreas
When does exocrine function of the pancreas begin?
After birth
When does endocrine function of the pancreas begin?
Weeks 10-15
Size of pancreas
12-15cm
Anatomical position of pancreas
Retroperitoneal, posterior to greater curvature of stomach
Ejaculate is a mixture of…
Spermatozoa and Seminal Plasma
Anterior covering of testes
Saclike extension of peritoneum (tunica vaginalis)
Tunica albuginea
White fibrous capsule
Septa dividing the testis into compartments containing seminiferous tubules
Where in the testes are spermatozoa produced?
Seminiferous tubules (where meiosis occurs)
What are the Leydig cells?
Cluster of cells between the seminiferous tubules and source of testosterone
Blood-testis barrier
Formed by tight junctions between sertoli cells (separates sperm from immune system)
And basement membrane beneath sertoli cells
Sertoli cell role
Promote sperm development (through testosterone production)
What do the seminiferous tubules drain into?
Network called rete testis
Pendulous pouch holding the testes divided into 2 compartments by…
A median septum
Testicular thermoregulation is necessary because…
Sperm aren’t produced at core body temperature (about 34 degrees)
2 types of daughter cells produced by spermatogonia
Type A Spermatogonia - remain outside blood-testis barrier and produce more daughter cells until death
Type B - Differentiate into primary spermatocytes
In spermatogenesis, meiosis I produces…
2 secondary spermatocytes from 1 primary spermatocyte
In spermatogenesis meiosis II produces…
4 spermatids from 2 secondary spermatocytes
Spermiogenesis is…
Transformation of spermatids to spermatozoa (sprouts tail and discards cytoplasm to become lighter)
3 regions of tail of a spermatozoon
Midpiece - contains mitochondria around axoneme of flagellum
Principal piece - axoneme surrounded by fibres
End piece - axoneme only
Length of cycle of seminiferous epithelium (sperm from spermatogonia)
16 days
Seminal fluid produced together by…
Bulbourethral, prostate and seminal glands
Fluid expelled during orgasm
2-5mL fluid
60% seminal vesicle fluid
30% prostatic
10% sperm
Trace of bulbourethral fluid
Normal sperm count
50-120 million/mL
Menstruation cycle summary
Days 1-7: Menstruation (3-7 days)
Days 8-11: Lining of womb thickens in prep for egg
Day 14: Ovulation
Days 18-25: If fertilisation hasn’t taken place, corpus luteum fades away
Days 26-28: Uterine lining detaches leading to menstruation
2 things responsible for sperm movement in female reproductive tract
Sperm motility
Female reproductive tract movement
2 features of PCTs
Simple cuboidal brush border (cells as deep as hairs are long)
High mitochondrial density
PCT function
Bulk reabsorption of Na, Cl, H2O, glucose, amino acids, bicarbonate, lactate, phosphate
Secreting organic ions
Na+/K+ pump for Na reabsorption
Other molecules taken up by secondary active transport, diffusion or osmosis
Water reabsorption in PCTs
By AQP1 channels
Water can also pass through the leaky tight junctions
Glucose reabsorption in PCTs
Early parts - SGLT2 - 1 Na+ and 1 glucose
Later parts - SGLT1 - 2 Na+ and 1 glucose
Sodium reabsorption in PCTs
Na+ actively transported out of PCTs via K+/Na+ (3Na+ out and 2K+ in)
This decreases Na conc in cell increasing gradient for Na+ to go lumen -> PCT cell
Na+ transported into cell either in exchange for H+ or co-transported
From cell, it’s pumped into the interstitium by Na/K ATPase or co-transported with bicarbonate
Amino acid reabsorption in PCTs
Co-transported with Na+
Chloride reabsorption in PCTs
Exchanged for formate in the NKCC2 channel
Formate then becomes formic acid (can diffuse across membrane and be reused)
Protein endocytosis and degradation in PCTs
Protein shouldn’t be in tubules but a mechanism is present for removing them
Microvilli have sensors which specifically bind any protein
Endocytosis occurs in endosomes and protein degradation by lysosomes producing amino acids
Bicarbonate reabsorption in PCTs
In lumen, H+ combines with HCO3- to form carbonic acid (requires carbonic anhydrase)
H2CO3 then -> H2O + CO2
CO2 diffuses through cell wall
H2O reabsorbed by osmosis
In cell, H2O + CO2 -> H2CO3 -> H+ + HCO3-
H+ recycled with transporting Na+
HCO3- co-transported with Na+ into interstitium (1Na+ with 3HCO3-)
Urachus
Remnant of channel between bladder and umbilicus
Renal plasma flow per minute
700ml/min
GFR
120ml/min
Renal blood flow
1250ml/min
How much bicarbonate water secretion does the pancreas produce per day?
1 litre per day
Role of pancreatic bicarbonate secretion
Protection of duodenal mucosa by neutralising stomach acid
Buffers duodenal content to optimise pH for enzyme digestion
Pancreatic proteases
(Protein digestion is initiated by pepsin in stomach and majority occurs in small intestine)
Trypsinogen and chymotrypsinogen which are transported in secretory vesicles containing a trypsin inhibitor (additional safeguard to prevent cell digestion)
Trypsinogen activated by enterokinase (secreted by small intestine epithelial cells)
Trypsin then activates chymotrypsinogen and additional trypsinogen
At this point the trypsin inhibitor is ineffective
Fat digestion due to 2 secretions
Pancreatic and hepatic secretions
Pancreatic amylase
Major source of amylase (salivary amylase has a small role)
Hydrolyses starch to more soluble sugars
Gastric secretion split into 2 stages
Cephalic stage - vagal innervation stimulates production of salivary amylase in mouth and gastrin in stomach (anticipation of a meal)
Intestinal stage - secretion of:
Cholecystokinin, secretin and gastrin
Cholecystokinin stimulus, produced in and action
Stimulus - HCl, protein, fats entering duodenum
Produced in - I cells of duodenum/jejunum
Action - Triggers pancreatic enzyme and HCO3- secretion, gallbladder contraction (releasing bile), inhibition of gastric secretion, delayed gastric emptying
Secretin stimulus, produced in and action
Stimulus - Low duodenal pH
Produced in - Upper small intestine
Action - Pancreatic water and bicarb secretion (flushing out into duodenum carrying enzymes)
Gastrin stimulus, produced in and action
Stimulus - Gastric distension/irritation
Produced in - G cells in stomach
Action - HCl secretion (parietal cells) enzyme release (acinar cells)
As proteins and fats are digested and absorbed, pH rises. What effect does this have on CCK and secretin secretion?
Stimuli for CCK and secretin disappear and pancreatic secretion reduces
Pancreatic endocrine function
Insulin and glucagon secretion
Difference in reabsorption between PCTs and DCTs
PCT - Bulk absorption, leaky
DCT - Fine tuning of filtrate, impermeable
Counter-Current Multiplication Mechanism in Loop of Henle
Generation of hyperosmotic interstitium to aid CT in water reabsorption by features of the thick ascending limb and thin descending limb
Role of thick ascending limb in developing a hyperosmotic interstitium
Driven by Na+/K+ ATPase pump on basolateral membranes of cells which keep intracellular Na low allowing ease of Na re-uptake
NKCC2 uses the gradient and pumps Na+ out lumen
K+ recycled on apical membrane back into lumen through ROMK channels
Cl- leaves cells through CLCK A channels (CLCK B in inner medulla) on basolateral membrane
Process promotes +ve charged lumen repelling Ca,Mg,Na ions which leave lumen
Creates a hyperosmotic interstitium
2 hormones secreted by posterior pituitary gland
Vasopressin (ADH) - controls water secretion into urine (primarily from supraoptic nuclei)
Oxytocin - expression of milk from glands of breasts to nipples, promote onset of labour (myometrium contraction) (primarily paraventricular nuclei). Stimulated by milk suckling.
Origin of posterior pituitary
Neuro tissue - large number of Glial-type cells
Max urine osmolality
1200mOsm/l
(In collecting tubules)
What inhibits ADH release?
Caffeine, alcohol
What stimulates ADH release?
Increased osmolality
Decreased blood volume
Nausea, vomiting, stress, exercise
Osmolality
Concentration of particles per kilo of fluid
Vasopressin mechanism of action of collecting tubules
Vasopressin binds to receptor on collecting duct cell membrane
Receptor activate cAMP second messenger system
Cells into aquaporins into apical membrane
Water reabsorbed by osmosis into blood
Restoration of osmolality by 2 ways
Increased plasma osmolality =
-Increased thirst -> Increased fluid intake -> restored osmolality
- Increased ADH neurone firing -> release of ADH -> ADH at V2R -> Water reabsorption -> restored osmolality
Normal Osmolality
285-295 mOsmol/kg
3 skin layers
Epidermis
Dermis
Subcutis
Skin as a waterproof barrier
Tights junctions between cells in straum granulosum, epidermal lipids and keratin in straum corneum form both an inside-out and outside-in barrier to water
Epidermis functions
Waterproofing
Physical barrier
Immune function
Vit D synthesis (endocrine)
UV protection
Thermoregulation
Dermis functions
Thermoregulation
Vit D synthesis (endocrine)
Sensory organ
Subcutis
Thermoregulation
Energy reserve
Vit D storage
Endocrine organ
Shock absorber
Why does skin wrinkle when wet?
Skin on fingers and toes wrinkles if immersed for approx 5 mins
Mediated by sympathetic NS
Due to vasoconstriction in dermis
Improves grip
Skin as a physical barrier
Stratified epithelium helps resist abrasive forces
Fat in subcutis acts as shock absorber
Structure of skin helps resist trauma
Vitamin D synthesis in skin
7-dehydrocholesterol in plasma membranes of epidermal keratinocytes and dermal fibroblasts converted to previtamin D3 (cholecalciferol) by UV
15-25 min whole body exposure produces up to 10,000 IU Vit D
How is Vitamin D stored?
It’s lipid soluble so can be stored in subcutis adipocytes
Dietary Vitamin D intake
Vitamin D2 - Fish, meat Vitamin D3 - supplements
Skin as a site of hormone action
Androgens act on follicles and sebaceous glands
Thyroid hormones act of keratinocytes, follicles, dermal fibroblasts, sebaceous glands, endocrine glands
Skin as a site of hormone synthesis
Vit D unique site for cholecalciferol synthesis
17beta-hydroxysteroid dehydrogenase in sebocytes and 5alpha-reductase in dermal adipocytes convert dehydroepiandrosterone (DHEA) and androstenedione to 5alpha-dihydrotestosterone
Insulin-like growth factor (IGF) binding protein-3 (IGFBP-3) synthesised by dermal fibroblasts)
What rays is skin a barrier to?
UV-A and UV-B which damage skin (burns, photo-aging, DNA damage)
Skin colour depends on…
Melanin
Carotenoids
Oxy/deoxyhaemoglobin
Melanin synthesis and transport
Synthesised in melanosomes within melanocytes from tyrosine
Transported by dendrites to adjacent keratinocytes
Colour of melanin
Pheomelanin - red/yellow
Eumelanin - brown/black
The more eumelanin your skin contains…
The darker your skin (we all have the same number of melanocytes but different amount of melanin)
Which type of melanin do we have most of in the skin?
Eumelanin
Deleterious effects of melanin
Prone to photodegradation (may generate ROS)
Pheomelanin increases release of histamine
Lots of melanin = less able to utilize UV light to make Vit D
3 stages of response to sunlight
Immediate pigment darkening
Persistent pigment darkening (tanning)
Delayed tanning
Immediate pigment darkening in response to sunlight
Photooxidation of existing melanin
Redistribution of melanosomes
Occurs within minutes and lasts hours/days
Persistent pigment darkening
Oxidation of melanin
Occurs within hours lasting 3-5 days
Delayed tanning
Increased melanin synthesis
Occurs 2-3 days after UV exposure (maximal at 10-28 days)
Skin as a barrier to infection
Properties that render skin a barrier to water also help prevent infection
Range of peptides synthesised by granular layer keratinocytes have antimicrobial properties
Skin as a sensory organ
Merkle cells - basal epididymis (light touch)
Encapsulated mechanoreceptors in dermis
Myelinated and unmyelinated sensory nerve endings in dermis (pain, itch temperature)
What connects seminiferous tubule to epididymis?
Seminiferous tubules -> Straight tubules -> rete testis -> Epididymis
How many primordial follicles in ovary at birth?
400,000 (approx 400 will mature and ovulate)
Insulating role of skin
Insulation by subcutaneous fat
Cutaneous blood flow in heat loss
Deep vascular plexus (lower reticular dermis)
Superficial vascular plexus (upper reticular dermis)
Autonomic regulation of blood flow in dermal vascular plexuses
Sympathetic alpha-noradrenergic: vasoconstriction
Sympathetic cholinergic: vasodilation
(both in hairy skin, hairless skin only has adrenergic innervation)
Eccrine sweat glands
1.6-4 million in skin
1-3 L sweat per hour
Water availability major limiting factor
Piloerection (goosebumps)
Arrector pili muscles innervated by sympathetic alpha1-adrenergic fibres
Contraction raises cutaneous hairs
Epidermis immunity role
Keratinocytes secrete cytokines and chemokines to maintain leucocyte populations in skin
Langerhans cells are antigen-presenting cells and secrete cytokines
Immune cells in dermis
Regulatory T cells
Natural killer cells
Dendritic cells
Macrophages
Mast cells
98-99% of pancreatic cells are…
Glandular epithelial cells forming clusters called acini
What is pancreas exocrine function?
Which cells carry it out?
Secrete pancreatic juice (enzymes an fluid released into gut)
Performed by acinar cells
What is pancreas endocrine function?
Which cells carry it out?
Several peptide hormones (insulin, glucagon) released into portal vein
Performed by islet cells (Islets of Langerhans)
Delta cells of pancreas secrete…
Somatostatin (acts as an inhibitor across a lot of systems)
Alpha cells of pancreas secrete…
Glucagon
Beta cells of pancreas secrete…
Insulin
Insulin secretion from pancreas mechanism
GLUT2 glucose transporter (low affinity) on membrane of beta-cell brings glucose into cell where glucokinase phosphorylates it to glucose-6-phosphate which increasing rate of ADP->ATP
ATP closes K+ channel on membrane resulting in depolarisation of membrane
This opens a voltage-gate Ca channel causes influx of Ca2+ into cell
Triggering exocytosis of proinsulin (which is contained within vesicles)
Proinsulin then splits into C peptide and insulin
Biphasic insulin release
1st phase response - rapid release of stored product
2nd phase - slower release of newly synthesised hormone
Insulin action in muscle and fat cells
Insulin binds to receptor on membrane
This signals GLUT4 vesicles to travel to membrane and get incorporated into membrane
High Affinity GLUT4 receptor drags glucose into cell
(Insulin effectively provides more ‘doors’ for glucose to leave cell)
Glucose Homeostasis: short and long term response to high blood glucose
Short Term - Make glycogen
Long Term - Make triglyceride (lipogenesis)
Glucose Homeostasis: short and long term response to low blood glucose
Short Term - Split glycogen
Long Term - Gluconeogenesis from AAs, fats, etc.
Incretins (e.g - GLP-1)
Gut hormones that stimulate beta-cells to release insulin whilst dampening down effect of alpha-cells (which release glucagon)
They also delay gastric emptying (so feel full for longer)
What prevents hypoglycaemia caused by incretins?
DPP-IV cleaves GLP-1 (incretin) rendering it inactive so can’t stimulate beta-cells or slow down rate of gastric emptying
DPP-IV levels rise as GLP-1 levels rise
Factors affecting blood pH
Respiratory component: CO2 conc
Metabolic component:
Intrinsic acid (metabolised)
Extrinsic acid (diet)
Buffering capacity (bicarbonate
DCT role
Fine tuning of Na reabsorption, K and acid-base balance
Impermeable to passive movement of water and Na
Uses NCCT (Na/Cl) co-transporter to reabsorb last bit of Na
2 cell types in collecting ducts
Principal cells - Na, water reabsorption and K excretion
Intercalated cell (alpha or beta) - secrete H+ or HCO3- (pH balance)
Aldosterone effect on principal cells
Aldosterone binds to receptors on principal cells in CTs which increases number of open ENaC channels
ENaC channels are a Na transporter
GFR regulated by 2 things
Sympathetic NS
Hormones
Sympathetic NS effect on GFR
Afferent (and efferent but less so) arterioles receive sympathetic innervation
Strong symp stimulus = constricted afferent arteriole = reduced renal blood flow = reduced GFR
How to increase GFR through changing width of afferent and efferent arteriole?
To increase GFR either dilate afferent arteriole or constrict efferent arteriole (opposite to decrease GFR)
Stages of menstrual cycle
Follicular Stage - Days 1-13/14
Ovulation - Days 13/14
Luteal phase - Days 14-28
What difference does presence of Y chromosome make?
SRY gene triggers testicular development
Testis produce MIF preventing Mullerian duct development
Production of primary oocytes in utero
Rapid meiotic division from 12 weeks results in 5-10 million primary oocytes at 20 weeks
Rapid cell death leaves 1 million primary oocytes at birth
Primordial follicle is…
1 oocyte surrounded by granulosa cells
Secretes oestrogen, progesterone, inhibin
Primordial follicle becomes…
Primary follicle - oocyte grows and becomes separated from granulosa cells by zona pellucida (contains glycoproteins, binds sperm)
Primary follicle becomes…
Preantral follicle - granulosa cells differentiate into Theca cells (both function together for oestrogen synthesis)
Preantral follicle becomes…
Early antral follicle - Primary oocyte full size
Antrum forms full of fluid secreted from granulosa cells
Early antral follicle becomes…
The mature (Graafian) follicle after day 7 of each cycle
At beginning of each cycle, 10-15 pre/early antral follicles develop and grow
After 7 days, 1 follicle is dominant
Non-dominant follicles undergo atresia
Dominant follicle increases in size as does it’s antrum
Oocyte emerges from meiotic arrest due to LH surge
Completes its 1st division becoming a secondary oocyte
This increase in size ballooning out of ovary (ovulation)
Enzymatic digestion ruptures follicle and oocyte carried away by antral fluid
Where are cells in ovaries arrested before sexual maturity?
Primordial follicles containing primary oocytes (FSH, LH secretion at sexual maturity)
What stimulate FSH and LH release from anterior pituitary on days 6-7 of menstrual cycle?
GnRH from hypothalamus
Mucus secretion in menstrual cycle
High oestrogen = abundant clear/watery mucus (good for sperm movement)
Progesterone and oestrogen = thick and sticky (stop entry of bacteria)
3 stages of uterine changes
Menstrual phase (days 1-5): withdrawal of progesterone = endometrial degeneration (trigger of menstrual flow)
Proliferative phase (days 5-14): oestrogen from granulosa and theca cells causes endometrium to thicken
Also stimulates myometrium contraction and progesterone receptor generation in endometrium
Secretory phase (days 15-28): Progesterone binds with its receptors on endometrium
Endometrium secretes glycogen from glandular epithelium (sperm and oocyte nutrition)
Progesterone overrides oestrogen to prevent myometirum contraction and prostaglandin secretion
Prostaglandins role in menstrual cycle
Dilate cervix aiding myometrium contraction
Oestrogen secretion in menstrual cycle
In follicular phase secreted by granulosa cells
In luteal phase secreted by corpus luteum
Progesterone secretion in menstrual cycle
In follicular phase made by granulosa and theca cells
In luteal phase made by corpus luteum (in much larger amount)
Inhibin role in menstrual cycle
Decreases FSH
Peaks for ovulation
Decreases as corpus luteum degenerates
LH secretion throughout menstrual cycle
Constant for most of follicular phase
LH surge - peaks about 18 hours before ovulation (generated by high oestrogen levels from maturing follicle)
Acts on hypothalamus and anterior pituitary to increase sensitivity to GnRH (+ve feedback)
LH surge allows oocyte to complete meiosis I
LH decrease - After ovulation, progesterone production = decrease in LH levels
LH action on Theca cells
Stimulates them to produce androgens which are converted to granulosa cells to produce oestrogen and antral fluid
Changes in FSH throughout menstrual cycle
Increases in early part of follicular phase
Slow decrease in levels throughout menstrual cycle
As 1 follicle beo mes dominant, more oestrogen = decreased FSH
Increase in FSH at day 10/11 triggering LH receptors to develop on Theca cells (presence of inhibin then actively inhibits FSH release)
Luteal Phase
Completion of meiosis I results in ovulation
Corpus luteum formed
Low LH maintains corpus luteum
Results in secretion of progesterone and oestrogen
-ve feedback - decreased GnRH and therefore decreased FSH and LH
After 14 days of no fertilisation, corpus luteum dies removing -ve feedback so LH and FSH rise (cycle repeats)
Meiotic arrests in females
Arrested in prophase I maturation during menstrual cycle
Arrested at metaphase II until ovulation
Meiosis completed after fertilisation
Spermatogenesis location, meiotic divisions and germ line epithelium involvement
Occurs entirely in testes
Equal division of cells
Germ line epithelium is involved in gamete production
Oogenesis location, meiotic divisions and germ line epithelium involvement
Occurs mostly in ovaries
Unequal division of cytoplasm
Germ line epithelium not involved in gamete production
Number and size of gametes produced in spermatogenesis
4 sperm that are smaller than spermatocytes
Number and size of gametes produced in oogenesis
1 ova (plus 2-3 polar bodies) larger than an oocyte
Spermatogenesis timing
Uninterrupted process
Begins at puberty
Continuous release
Lifelong (reduces with age)
Oogenesis timing
Arrested stages
Begins in foetus (pre-natal)
Monthly from puberty
Terminates with menopause
Constituents of semen
10% bulbourethral
30% prostate
60% seminal vesicles
How much semen secreted during orgasm?
2-5mL
Normal sperm count
50-120 million/mL
Sperm route
Seminiferous tubules
Rete testis
Efferent ducts
Epididymis
Vas deferens
Ejaculatory duct
Urethra
Penile urethra
Functions of semen
Buffers against acidic environment
Chemicals like fructose to increase motility
Prostaglandins present to stimulate female peristaltic contractions
Blood-Testis Barrier
Seminiferous tubules bound by a BM
Sertoli cells extend from BM into lumen
They’re joined to adjacent cells by tight junctions and form an unbroken ring inside seminiferous tubule
So sertoli cells form the B-T B preventing movement of chemicals
Length of spermatogenesis process
64 days
Spermatogonia divide mitotically at puberty into 2 types…
Type A - remain outside B-T B and produce more daughter cells
Type B - in basal compartment (primary spermatocytes)
Spermiogenesis
Spermatids -> Spermatozoa (grow tails and discard cytoplasm)
Release of sperm into lumen
Invaginations in sertoli cells retract releasing sperm
Spermatogonium undergoes a mitotic division to produce…
Primary spermatocyte
Primary spermatocyte undergoes meiosis I to produce…
2 secondary spermatocytes
2 secondary spermatocytes undergo meiosis II to produce…
4 early spermatids
What provide nourishment for developing spermatids?
Sertoli cells
Timing for sperm to be introduced for fertilisation
5 day before to 1 day after ovulation
As sperm can last 4-6 days, egg can only survive 1-2 days
What carries egg out of ovary
Antral fluid
Smooth muscle and fimbriae
Cilia in fallopian tube
Capacitation
Occurs in female reproductive tract
Maturation of spermatozoon (tails becomes stronger, plasma membrane develops allowing for fusion with egg)
Summarise day 1 of fertilisation
Fusion of sperm and egg in ampulla
Glycoproteins on zona pellucida are receptors (ZP3) and sperm head contains binding proteins
Binding = acrosome reaction - enzymes exposed to zona pellucida cause it to be digested
Fusion can now occur with plasma membrane
Sperm head passes into cytosol = fertilisation
Fertilisation causes a reaction which changes the cell membrane potential preventing entry of other sperm
This is done by exocytosis of vesicles containing enzymes to inactivate ZP3 hardening zona pellucida
4-7 hours after gamete fusion, meiosis II completes
23 sperm and 23 egg chromosomes migrate to centre cell and the haploid chromosomes fuse
DNA replication occurs
Mitosis begins
Sections of fallopian tubes
Fimbriae -> Infundibulum -> Ampulla -> Isthmus
Summarise days 2-3 of fertilisation
Zygote remains in fallopian tube
Oestrogen maintains contractions within tubes
As progesterone increases, smooth muscle relaxes allowing zygote to pass through fallopian tube
Cleavage occurs and each cell is totipotent (can develop into an entire individual)
Summarise day 4 of fertilisation
Cells flatten
Tight junctions between cells
Polarisation of outer cells
These conditions allow for rapid differentiation
Summarise day 5 of fertilisation
Fluid filled cavity expands and forms blastocysts
>80 cells
Lost totipotency
Outer cell layer = trophoblast
Then you have inner cell mass and fluid filled cavity in middle
Summarise day 5-6 of fertilisation
Cavity expands further
Zona pellucida thins
Summarise day 6+ of fertilisation
Blastocyst expansion
Embryo out of zona pellucida
Summarise day 7-9 of fertilisation
Late-stage blastocyst hatches and implants in endometrium of uterus
Sperm can survive longer in the female reproductive tract with greater glucose availability which comes from..
Higher oestrogen levels
Placenta composition and development
Interlocking foetal and maternal tissues
Outer layer trophoblast (synctiotrophoblast cells invade endometrium)
4 placenta roles
Nutrition
Gas exchange
Waste removal
Endocrine and immune support
What is the chorion?
Outermost trophoblast cell layer that supplies embryonic portion of placenta
Extends chorionic villi into endometrium
Release digestive enzymes which break endometrial vessels
What forms between the inner cell mass and the chorion?
The amniotic cavity - lined by epithelial cells (amniotic sac) which eventually fuses with chorion so there’s only a single combined membrane around foetus
Role of fluid in amniotic cavity
Buffers mechanical disturbances and temperature changes
Human Chorionic Gonadotropin (hCG) production and effects
Produced by trophoblasts when they begin endometrial invasion
Maintains of corpus luteum, stimulates oestrogen and progesterone production preventing menstruation
Prolactin production and effects
Comes from anterior pituitary
Increases end of pregnancy when oestrogen and progesterone decrease
Involved in milk production and prevention of ovulation
Relaxin production and effects
Increases in early pregnancy
Produced by ovaries and placenta
Limits uterine activity, softens cervix
Oxytocin production and effects
Comes from posterior pituitary
Secreted throughout pregnancy and increases at end
Stimulates uterine contractions (+ve feedback)
Prostaglandins production and effects
Initiate labour
Produced by uterine tissue
Switch in oestrogen and progesterone production after 3 months of pregnancy
Corpus luteum regresses after 3 months
Trophoblast cells of placenta continue to produce oestrogen and progesterone
Cardiovascular maternal changes in pregnancy
Increased CO
Decreased systemic BP
Decreased total peripheral resistance
Increased uterine blood flow
Increase BV
Increased plasma and blood cell mass
Respiratory maternal change in pregnancy
Increased alveolar ventilation
GI maternal change in pregnancy
Increased acid reflux
Delayed gastric emptying - gastroparesis
(Foetus pressing on stomach)
Skin maternal change in pregnancy
Linea nigra - dark line around central abdomen
Striae gravidae - stretch marks on lower abdomen
Darkened areolar on breasts
Biochemical maternal change in pregnancy
Weight gain
Increased protein and lipid synthesis
Insulin resistance
Cervical ripening
Growth and remodelling of cervix
Stimulus oestrogen increases towards end of pregnancy
During pregnancy, uterus sealed by collagen fibres (maintained by progesterone)
Cervix becomes soft and flexible due to collagen breakdown (by oestrogen, progesterone and relaxin)
What stimulates oxytocin release pre-labour?
Increased prostaglandins
What occurs in labour?
Increased prostaglandin and oxytocin triggers contraction and pressure in cervix (+ve feedback from the pressure)
Amniotic sac ruptures
Contractions at 10-15 minute intervals moving from top to bottom
As frequency increases, cervix dilates
Stages:
Latent - little dilation (8 hours)
Active - organised contractions (5 hours) - dilation and full expansion
Post-partum - womb contracts and pushes placenta out of vagina
Do adrenal and gonad derive from same tissue?
Yes
Testis present and Leydig cells making testosterone means Wolffian system develops into…
Epididymis
Vas Deferens
Seminal Vesicles
Ejaculatory Ducts
Sertoli cells also secrete AMH which leads to Mullerian system regression
No testis or Leydig cells = no testosterone = Mullerian system develops into…
Fallopian tubes
Uterus
Upper 1/3 of vagina
Common gential tubercle at 8 weeks becomes … in male and …. in female
Glans
Clitoris
3 layers of adrenal gland
Zona Glomerulosa - Produces Aldosterone (salt)
Zona Fasciculata - Cortisol (sugar)
Zona Reticularis - DHEA (sex)
Negative feedback for cortisol production in the adrenal glands
CRH secreted from hypothalamus stimulates ACTH release from hypothalamus which stimulates cortisol production in adrenal glands
Cortisol inhibits release of both CRH and ACTH
Sertoli cells secrete AMH resulting in…
Mullerian system regression
3 phases of growth (infancy-childhood-puberty)
Infancy - rapid, decelerates after 2-3 years, determined by nutrition
Childhood - switch from nutritional to hormonal dependence
Puberty - growth spurt, height velocity increase due to GH and sex hormones (14-15 in girls, 16-17 in boys)
What is chondrogenesis?
growth
5 determinants of growth
Parental geno/phenotype
Quality/duration pregnancy
Nutrition
Psycho-social environment
Growth promoting hormones
Where are GHs synthesised?
Somatotroph cells
Action of GH
Decreases glucose use
Increases lipolysis
Increases muscle mass
7 things that stimulate GH production
Exercise
Stress
Hypoglycaemia
Fasting
High protein meals
Perinatal development
Puberty
5 things that suppress GH production
Hypothyroidism
Hyperglycaemia
High carb meals
Glucocorticoid excess
Agings
Factors influencing puberty
50-80% genetic
Environmental (nutrition)
Leptin production (for appetite)
3 types of hormones
Steroids
Peptides
Thyroid hormones
Role of somatostatin in hypothalamus
Inhibits release of GH and TSH
2 ways hormones exert their effect
Cell surface receptors
Intracellular receptors
Time for action in peptides, steroids, thyroid hormones and catecholamines
Peptides - min-hour
Steroids - hour-day
Thyroid hormones - day
Catecholamines - sec
Thyroid hormones action
Basal metabolic rate, growth
Parathyroid hormones action
Ca2+ regulation
Cortisol action
Glucose regulation, inflammation
6 hormones released by anterior pituitary
ACTH, TSH, GH, LH, FSH, Prolactin
2 hormones released by posterior pituitary
ADH (vasopressin)
Oxytocin
Pituitary releases hormones in response to signals from…
The hypothalamus
Pituitary weight
0.5g
Anterior pituitary has no arterial blood supply but receives blood through…
Portal venous system from hypothalamus
What hormone type are TSH, FSH and LH?
Glycoprotein
What hormone type are ACTH, GH and Prolactin?
Polypeptide
Releasing hormone (hypothalamus) that stimulates release of TSH from pituitary
Thyrotorpin releasing hormone (TRH)
Releasing hormone (hypothalamus) that stimulates release of ACTH from pituitary
Corticotropin releasing hormone (CRH)
Releasing hormone (hypothalamus) that stimulates release of FSH and LH from pituitary
Gonadotropin releasing hormone
Releasing hormone (hypothalamus) that stimulates release of GH from pituitary
GH releasing hormone (GHRH)
Releasing hormone (hypothalamus) that inhibits release of GH from pituitary
Somatostatin
Releasing hormone (hypothalamus) that inhibits release of prolactin from pituitary
Dopamine
Actions of GH
Linear growth in children
Acquisition of bone mass
Stimulates: protein synthesis, lipolysis, glucose metabolism
Regulation of body composition
Psychological well-being
Regulation of thyroid hormone levels
Hypothalamus releases TRH
Stimulates pituitary to release TSH
Stimulates thyroid to release thyroxine
Thyroxine acts on tissue and has -ve feedback on pituitary and hypothalamus
Prolactin inhibition action
Inhibits gonadal activity through central suppression of GnRH (thus decreased LH/FSH)
Prolactin (PRL) is synthesised by…
Lactotrophs
Corticosteroid overview
Lipid soluble (for passing through membranes)
Binds to specific intracellular receptors
Alter gene transcription directly or indirectly
Where are glucocorticoids synthesised?
Zona fasciculata and reticularis of adrenal glands
Actions of glucocorticoids
Increase glucose mobilisation
Maintain circulation (vascular tone, salt/water balance)
Immunomodulation (dampen immune response)
Glucocorticoids in circulation
90% bound to Corticosteroid-Binding Globulin (CBG)
5% bound to albumin
5% free (only free is bioavailable)
Regulation of glucosteroid synthesis by…
ACTH
What is stress?
Sum of bodies response to adverse stimuli (infection, trauma, exercise, etc.)
Mineralocorticoids synthesised in…
Zona golmerulosa
Actions of mineralocorticoids
Effects of pancreas, sweat glands, salivary glands and colon
Sodium resorption, decreased sodium content
Adrenal androgens
Weak androgens generated in adrenal glands
Include oestrogen precursors in postmenopausal women
Production regulated by ACTH
Roles of adrenal medulla
Synthesises catecholamines
Main site of adrenaline synthesis
Relative production of catecholamines in adrenal medulla
80% adrenaline, 20% noradrenaline
Dopamine in small amounts
Adrenal cortex synthesises… (3)
Glucocorticoids
Mineralocorticoids
Androgens
Adrenal medulla synthesises…
Catecholamines
What are pituicytes?
Cells of POSTERIOR pituitary gland (cells of anterior named according to the hormone they produce)
Pineal gland secretes…
melanin
What makes a portal circulation?
Capillary bed at both ends
L and R lobes of thyroid gland unite via..
A narrow isthmus
Control of thyroid hormone secretion
Hypothalamus secretes TRH
Stimulate pituitary to secrete TSH
Stimulates Thyroid to release T3. And also T4 which targets tissue (target tissue releases T3)
T3 and T4 have -ve feedback on hypothalamus and pituitary
Process converting T4->T3
Deiodination
Thyroid hormone action
T3 travels through transmembrane transporter (against conc gradient)
Changes mRNA to alter the BMR of the cell
Enzyme responsible for production of thyroid hormone
Thyroid peroxidase
Parathyroid gland role
Regulate Ca and phosphate levels
Secrete parathyroid hormone (PTH) in response to: low Ca or high phosphate
Actions of PTH
Increase Ca reabsorption in renal distal tubule
Increase intestinal Ca absorption
Increase calcium release from bone
Decrease phosphate reabsorption
How many parathyroid glands?
Superior and inferior at back of thyroid on both lobes (4 total)
Normal adult range for PTH
1.6-6.9 pmol/L
Calcitonin production and action
Produced by thyroid c-cells
Inhibits bone resorption (acting directly on osteoblasts)
What stimulates bone resorption?
PTH (acts directly on osteoblasts)
Female HPG axis in FSH and LH release
Hypothalamus releases GnRH
Acts on gonadotrophs in anterior pituitary to release LH and FSH
LH stimulates androgen production (oestrogen precursors)
FSH stimulates granulosa cells to converts these oestrogen precursors to oestrogen
Male HPG axis in FSH and LH release
GnRH release from hypothalamus stimulates gonadotrophs in anterior pituitary to release FSH and LH
LH stimulates Leydig cells to secrete testosterone (-ve feedback of LH and FSH)
FSH stimulates sertoli cells to maintain spermatogenesis (produces inhibin -> -ve feedback of FSH)
Growth Hormone release axis
Somatostatin from hypothalamus inhibits GH release from anterior pituitary
GHRH from hypothalamus stimulates release of GH from anterior pituitary
GH acts directly to increase blood glucose and bone/tissue growth
GH acts indirectly on liver to produce insulin-like growth factors which contribute to cartilage growth as well as the others in direct pathway
3 factors effecting GH release
Circadian rhythm
Stress and cortisol
Fasting
(these factors alter GHRH/somatostatin release
3 methods of endocrine control of extracellular calcium homeostasis
Parathyroid hormone
Vit D
Calcitonin
Hypothalamic regulation of GnRH release
Kiss neuron releases Kisspeptin neurotransmitter which binds to GPR54 receptor on GnRH neuron triggers release of GnRH
HPA axis for cortisol release
Stress and Cytokines stimulate CRH release from Hypothalamus
Stimulates ACTH from anterior pituitary
Stimulates Cortisol from adrenal which acts on tissue
(cortisol production has -ve feedback on pituitary and hypothalamus)
Relative ‘free’ calcium in the body
50% is ‘free’
50% is bound to albumin (so can’t diffuse into cells)
Regulation of plasma renin in RAAS
Renin produced in kidneys converts angiotensinogen (secreted by liver) to angiotensin I
Angiotensin I -> Angiotensin II by ACE in lungs
Angiotensin II stimulates aldosterone release from adrenal
Aldosterone increases Na reabsorption and K secretion in kidneys
What stimulates renin release from kidneys? (3)
Decreases renal BP
Prostaglandins
Beta-adrenergic action
What suppresses renin release from kidney?
ANP
Dopamin
What suppresses aldosterone release from adrenal glands?
Decreased extracellular [K+]
Zonation of adrenal
Outer capsule
Cortex (zona glomerulosa -> zona fasciculata -> zona reticularis)
Medulla
Where in the adrenal gland does corticosteroid synthesis occur?
Cortex
What is synthesised in the zona glomerulosa of the adrenal glands?
Mineralocorticoids - Aldosterone
What is synthesised in the zona fasciculata of the adrenal glands?
Glucocorticoids - Cortisol
What is synthesised in the zona reticularis of the adrenal glands?
Androgens - DHEA
What are synthesised in the medulla of the adrenal glands?
Catecholamines
Uric acid solubility
Poorly soluble in plasma
Lower pH, less soluble it becomes
Uric acid comes from the breakdown of…
Purines (e.g - Adenine, Guanine)
3 sources of purines
Diet
Breakdown of nucleotides in tissue
Synthesis in body
Uric acid removal
Excreted in urine
Broken down in gut
Dietary purines
Meat
Offal
Seafood
Fish
Fructose
Allopurinol prevents…
Conversion of purines to uric acid
Why does alcohol consumption increase uric acid levels?
Contains purines
