Content Flashcards
What is the main functions of the kidney?
- Maintaining balance of salt, water and pH
- Endocrine functions: (secretion of hormones, vitamin D synthesis)
- Waste excretion
A - Acid / Base Balance W - water balance E - EPO T - Toxins B - BP control E - Electrolytes D - vitamin D activation
What percentage of cardiac output does renal blood flow take?
20%
What is the average renal blood flow and in turn renal plasma flow
- 1l/min
- Renal plasma flow- 600ml/min
What is the total urine flow?
-1ml/min
Explain the blood supply the the kidney
- Renal artery (branch of aorta at L1)
- Anterior and posterior divisions
- Interlobar arteries
- arcuate arteries
- Interlobular arteries
- Afferent arteriole
- Glomerular capillary
- Efferent arteriole
- Peritubular capillary
What are the two capillary beds of the nephron and how are they connected?
Glomerular capillary bed and the Peritubular capillaries connected by an efferent arteriole
What is the glomerular filtration?
Passage of fluid from the blood to the Bowmans space to form a filtrate?
What creates the filtration barrier?
- Capillary endothelium
- Basement membrane
- Single-celled epithelium of the Bowmans capsule
What is the benefit of the foot process of the podocytes being negatively charged?
- Albumin cannot pass through
- Smaller substances that are negatively charged that would ordinarily pass through are repelled
What are the 5 factors that determine the crossing of materials into the glomerular filtrate?
- Pressure
- Size of the molecule
- Charge of the molecule
- Rate of blood flow: determines how much fluid will pass into the urinary space per minute
- Binding to plasma proteins
What is the total SA of the Bowmans capsule?
1m squared
What molecules can freely pass through the filtration barrier?
Smaller molecules and ions up to 10kDa
What is the only protein secreted by the tubules found in the urine?
Tam Horsfall
What disease can be caused by damage to the filtration barrier and what can cause this damage?
- Nephronic syndrome
- Immune conditions, genetic abnormalities of proteins involved in podocytes/slit diaphragms, diabetes
What are the two pressure determining glomerular filtration rate?
- Hydrostatic pressure: usually at a constant, lower in bowmans space as fluid is always moving away.
- Oncotic pressure: zero in Bowmans space (no proteins), rising in the glomerular capillary due to removal of fluid)
What is the glomerular filtration rate and it’s equation?
- The filtration volume per unit time (minutes)
GFR = Kf (Pgc-Pbs) - (oncotic of glomerular capillary - oncotic of bowmans space)
K= filtration coefficient
What is the GFR of an average 70Kg person
125ml/min
How is glomerular filtration rate increased through pressure control?
1) constrict efferent arteriole- increase hydrostatic pressure- increase GFR
2) dilate afferent arteriole - increase blood flow - increase hydrostatic pressure - increase GFR
How is GFR decrease through controlling pressure?
1) constrict afferent arteriole- les blood flow - decreases hydrostatic pressure - decrease GFR
2) dilate efferent arteriole - reduce blood flow- decreased blood pressure - decrease GFR
What keeps renal blood flow, capillary pressure and GFR maintained at a constant?
- Autoregulation: constriction and dilation is an intrinsic property of vascular smooth muscles. It still occurs in Denervated kidneys and in isolated perfused kidneys (not dependent on blood supply or blood borne substances)
- Tubuloglomerular feedback
How does autoregulation prevent an increase in systemic arterial pressure?
Pressure within afferent arteriole rises - this stretches the vessel was - this triggers contraction of smooth muscle - arteriolar constriction
How is GFR measured and what kind of substance used?
- measuring the excretion of a marker substance (M)
- Freely filtered (all is filtered)
- Not secreted or absorbed in tubules
- not metabolised
What is typically used clinically to measure GFR?
Creatinine
What is the filtration fraction and how is it calculated ?
- The proportion of renal blood flow that gets filtered
- filtration fraction = GFR / renal plasma flow
What is renal clearance and the equation for it?
The volume of plasma from which a substance is completely removed per unit time (usually a minute)
Renal clearance = urine conc x urine vol / plasma conc
What epithelium surrounds the Bowmans capsule?
Parietal epithelium
Describe the flow of the glomerular filtrate
- Glomerular capsule
- PCT
- Loop of Henle
- DCT
- Collecting duct
- Papillary duct
- Minor calyx
- Major calyx
- Renal pelvis
- Ureter
- Bladder
- Urethra
What is ultra filtrate?
Filtrate that is cell free and contains virtually the non-protein substances in virtually the same concentration as in the plasma
What substances break the all non-protein substances have the same concentration as in the plasma rule?
Low molecular weight substances that are bound to plasma proteins
(E.g. half of plasma calcium and virtually all plasma fatty acids)
What is tubular reabsorption?
-Reabsorption of substance from the tubules to the Peritubular capillaries
What is tubular secretion?
Secretion of substances from the Peritubular capillaries to the tubular lumen
What 3 factors determine GFR?
- Net filtration pressure
- SA for filtration
- Permeability of corpuscular membrane
Why can’t the full length of the ureter be seen on an X-ray?
-Contraction of the ureter
At what level is the umbilicus?
-L4/ L5, where the aorta bifurcates
Why is the urethra narrower near the bladder?
-It is surrounded by the prostate
What can be found between the two medullary pyramid?
-Medullary column
Why do medullary pyramids appear striped?
-The collecting ducts and loops of henle run parallel, along with the blood vessels
What determines the differentiation of the different parts of the embryo?
-The chemical messages released from the notochord. The distance from the notochord determines the concentration of the chemical messengers.
What does the ectoderm become?
-CNS
What does the mesoderm become?
- Somites: develop into musculoskeletal system
- Intermediate mesoderm: develops into urogenital system (kidneys, bladder and genital system)
- Peritoneum on the body wall
- Peritoneum on the mesentery and around the bowel
What does the kidney develop from in the embryo?
-Intermediate mesoderm
What are the 3 systems of kidney development and where do they occur?
- pronephros: system in the neck
- Mesonephros: in the thoracic and lumbar region
- Metanephros: adult kidney
What do the individual glomeruli of the mesonephros drain into?
-Mesonephric duct
Where does the ureter grow out of?
-Mesonephric duct
What is the lowest part of the mesonephros?
-Metonephric blastema
What happens when the ureter reaches the metonephric blastema?
-Chemical messengers are released and this develops into the cortex of the kidney (glomeruli and tubules)
What will the mesenephric duct form in the male?
-Vas deferens
What are primordial germ cells and where do they migrate too?
- Produce sperm and eggs
- Genital ridge
What does the mesonephric duct end in?
-Cloaca
What forms from the cloaca?
-Bladder
What happens to cranial tubules as caudal tubules form?
-The cranial tubules start to degenerate whilst the caudal still form
What differs in the caudal tubules between males and females?
-In males, a few of the caudal tubules form efferent ducts of the testis. In females, they disappear.
What does the metanephric blastema form?
-Glomeruli and tubules
In the metanephros what does the uteric tube form?
-Collecting ducts and ureter
How many times does the uteric bud divide once it reaches the blastema?
-3 times
What is medullary sponge kidney?
-Where the glomeruli do not attach to the collecting ducts
What happens to the urine produced in utero?
-It is secreted into the amniotic fluid. Recycled back through the kidney of the foetus.
What does little amniotic fluid suggest?
-The kidneys are functioning efficiently
Where does the kidney develop and where does it shift too?
-It develops in the pelvis before shifting to a more cranial position in the abdomen.
How is shifting of the kidney achieved?
-Diminution of body curvature and growth of the lumbar and thoracic regions.
During fetal life, what is responsible for excretion of waste products?
-Placenta
When do glomerular capillaries start forming?
-10th week
When does the metanephros start functioning?
-12th
What is the allantois and what does it form?
-It is an anterior outgrowth of the cloaca and forms the bladder
What divides the cloaca between the 4th and 7th week and what does this form?
- It is separated by the urorectal septum
- This forms the urogenital sinus and the posterior anorectal canal
What are the 3 parts of the urogenital sinus?
- Upper part: largest and forms urinary bladder
- Middle (pelvic) part: gives rise to prostatic and membranous parts of the urethra.
- Phallic part: forms the penile urethra
Where do prostatic tubules grow out of and in too and at what month does the epithelium of the prostatic urethra begin to proliferate and form outgrowths?
- Prostate tubules grow out of the urethra and into the prostatic blastema
- Third month
In females, what does the urethral epithelium give rise too?
-Urethral and paraurethral glands
What is the cause of 3/4 kidneys?
-The uteric bud divides before it reaches the metanephric blastema
What issue arises from the uteric bud going straight through the bladder wall and not at an angel?
-When the bladder contracts, pressure increases and urine can pass back into the kidney.
What is the consequences of having two renal arteries?
- Can compress the ureter which leads to blockages
- Lengthy operation of used in a transplant.
What is horseshoe kidney?
-The metanephric blastema from the Right and left side fuse, when the kidney tries to migrate from the pelvis it gets stuck on the inferior mesenteric artery.
When does the pronephros develop and how long is it present
- Week 4
- One week
Where do urogenital organs derive from?
-Intermediate mesoderm
When do gonads acquire male/female characteristics and what sets off this differentiation?
- Week 7
- When germ cells pass into the genital ridge
Where do germ cells arise?
-Yolk sac
What do gonads appear as and where are they located?
-Genital ridges, medial to the mesonephros
What are the pairs of ducts that form on the gonads?
- Mesonephric duct (Wolffian duct)
- Paramesonephric duct (Mullerian duct)
What gene on the Y chromosome determines sexual dimorphism and what protein does this gene code for?
- SRY GENE: sex determining region on Y
- Testis determining factor
What happens to the primitive sex cords in males and females?
- Males: the cords continue to proliferate and penetrate deep into the medulla forming the cords of the testis. Towards the hilum, these cords break into a network to form the rete testis.
- Females: They eventually disappear
What happens to the mesonephric tubules as the glomerulus undergoes apoptosis and what does it become?
- They attach to the sex cords of the tubules
- The ductii efferentes
What causes the tunica albuginea in the male?
-It is a dense layer of fibrous connective tissue that develops under the surface of the epithelium of the genital ridge causing it to swell.
What forms in the 7th week and the 3rd month in the female?
- 7th week: surface epithelium of the ovary gives rise to a second generation of cords and these penetrate the underlying mesenchyme.
- 3rd month: the new cords surround each oogonium with a layer of epithelial cells called follicular cells.
Why is DNA more likely to break in an egg over the sperm?
- Sperm is continuously produced meaning the time between production to fertilisation is a few days.
- Females are born with the eggs they will have their while life and so time between production and fertilisation can be many years.
Once the genital ridge has developed into the testis, what 3 cells are found in the testis?
- Migrated primordial germ cells: these form spermatogonia.
- Sertoli cells: assist in the development of spermatogonia
- Leydig cells: Secrete testosterone
What is the role of Sertoli cells?
-Assist development of spermatogonia
What do leydig cells secrete?
-Testosterone
What happens when primordial cells arrive in the gonad?
-The mesoderm begins to thicken and starts to develop primitive sex cords.
Where do sperm mature?
-Epididymis
What is the advantage of having the testicle outside the body?
-Ensures optimal spermatogenesis: this process is at it’s optimum at temperatures lower than body temp.
How does the appendix testis become a problem?
-The narrow connection to the testicle can twist cutting off the blood supply. This can become painful.
What cells surround the Oocyte?
-Follicular cells
What happens to the mesonephric duct and the mesonephric excretory tubules in females?
-They degenerate
What does the para mesonephric duct form in the female?
-The bottoms fuse with the top ends ends forming the Fallopian tubes.
Why is it important that the Fallopian tubes are open to the peritoneal cavity?
-An egg is released into the peritoneal cavity during ovulation. This then needs to pass into the open ended Fallopian tubes.
What is oestrogen involved in the differentiation of the Müllerian ducts in to?
- Uterine tubes
- Uterus
- Cervix
- Upper 2/3 of the vagina
What does oestrogen stimulate the urogenital sinus to develop in to?
External genitalia:
- Lower 1/3 o the vagina
- Labia minora
- Labia majora
- Clitoris
What does the broad ligament divide the pelvic cavity in to?
- Urorectal pouch
- Uterovesical pouch
What are the properties of the skin on the urethral folds?
- Stratified squamous non keratinising
- No hair follicles / sweat glands
What does the absence of oestrogen and the presence of testosterone cause the labia minora to do and what does this form?
- They fuse
- Penile urethra
Fusing of the labia majora for a what?
-Scrotum
What are 2 common congenital abnormalities in males?
- Failure of testicle to migrate into the scrotum
- Incomplete fusing leading to an opening anywhere from between the testis to the tip of the penis
Explain the role of hormones in differentiation of male gonads
- Presence of the SRY gene on the Y chromosome
- Codes for the testis determining factor
- Testis form from the genital ridge
- Testis produce testosterone (leydig cells) cause development of external male genitalia from the mesonephric duct
- Sertoli cells secrete mullerian inhiniting factor leading to degenerating of the paramesonephric duct
Explain the role of hormones in the differentiation of female gonads
- Absence of the Y chromosome
- Absence of the SRY gene
- No testis and testosterone
- By default genital ridge develops into ovarian tissue
- The absence of testosterone means mesonephric duct degenerates
- Absence is mullerian inhibiting factor causes the paramesonephric ducts to develop
How many litres of filtrate do you produce a day?
-180L/day
Which tubules is permeable in the nephron?
-Proximal = bulk reabsorption
What is the function of the PCT?
- Bulk reabsorption of Na, CL, glucose, AA and bicarbonate
- Secretion of organic ions
What is the function of the loop of henle?
- More Na reabsorption
- Urinary dilution
- Generation of medullary hypertoxicity
What is the function of the DCT?
- Fine tuning
- Fine regulation of Na, K,Pi and Ca. And the separation of salt from water
- Dilution of urine by regulation of Na in water
What is the function of the collecting duct?
- Acid secretion
- Regulated water reabsorption concentrating the urine
- Regulated Na reabsorption and K secretion
What is the difference between a symporter and an anti porter?
- Symporter: simultaneously brings two positive substances in.
- Antiporter: Exchanges two positive substances
Explain how NaKATPase regulates reabsorption of glucose and phosphate in the PCT
- NaKATPase pumps 3Na+ ions out of the tubular epithelial cells and 2K+ in (primary active transport)
- This makes the intracellular conc of Na+ low compared to the tubular lumen.
- Na+ therefore moves into the cells while H+ moves out.
- As Na+ passes into the epithelial cells it contransports glucose and phosphate (secondary active transport)
Explain how glucose and phosphate reabsorption in the PCT contributes to osmosis
- As Na+ & other ions are reabsorbed water follows passively
- Also, the removal of solutes from the lumen decreases the osmolarity whilst the osmolarity of the interstitial fluid increases
- This difference in water concentration between the lumen and interstitial fluid results in net diffusion of water from the lumen across the cells plasma membrane and tight junctions into the interstitial fluid.
How is bicarbonate reabsorbed in the PCT?
- inside the epithelial cells, carbon dioxide and water combine to form H2CO3 (carbonic anhydrase)
- This rapidly dissociates to form H+ and HCO3-
- Bicarbonate moves via facilitated diffusion into the blood.
- H+ is secreted into the lumen via an Na+ / H+ cotransporter
- This H+ then combines with filtered bicarbonate in the lumen to generate H2CO3.
- Under the action of carbonic anydrase this is converted to carbon dioxide and water
- This then moves via diffusion into the epithelial cells.
What enzyme breaks H2CO3 into carbon dioxide and water?
-Carbonic anydrase
What is falcons syndrome?
-AA, glucose and bicarbonates leaking into the urine
What is the tubular maximum and what is it roughly for glucose?
- The amount of a material that can be transported per unit time. There is a limit due to saturation of proteins.
- Glucose: 375 mg/ min
What happens after the tubular maximum of glucose is reached?
-There is a sharp increase in excretion of glucose
What are features of proximal tubular damage?
-Aminaciduria, glycosuria and bicarbonate wasting
What is the result of the tight junctions between the cells in the PCT being leaky?
-Substances that don’t have specific transporters can pass through the membrane
What percentage of creatinine is secreted into the urine?
-15%
What is glomerulartubular balance ?
-More filtered load is matched by more proximal tubular reabsorption
What limb of the loop of henle is permeable to water?
-Descending
Where does solute reabsorption occur in the loop of henle and what channel does this involve?
-Thick ascending limb
Explain the countercurrent multiplication in the loop of henle
- Na+ and Cl- are reabsorbed along the length of the ascending limb. This involves NKCC2 pumps.
- This decreases the luminal osmolality whilst the medulla interstitial fluid becomes very hyperosmotic.
- Water passes out if the descending limb until the osmolalities are equal.
- This hyperosmotic medullary interstitium draws water out of the collecting ducts and concentrates the urine.
What is the action of the drug furosemide?
- Inhibits the NKCC2 pump on the ascending limb.
- Less Na+ and Cl- pass into the medullary interstitium
- The hyperosmolality is reduced and so less water passes out of the descending limb and collecting ducts.
- Less concentrated urine.
What is the cotransporter in the DCT and what drug inhibits it?
- NCC: transports Na-
- Thiazide
What are the 2 cells found in the collecting duct and what is their role?
- Principal cells: Na reabsorption
- Intercalated cells: Acid secretion (K is exchanged for acid).
What channels are found in principal cells?
-ENac: epithelial sodium channels
What is the action of aldosterone?
- Increases transcription of ENac and so increase apical Na influx.
- This charge movement facilitates K efflux.
What is the role of aldosterone in the ENac channels in the collecting duct
- Aldesterone binds to steroid receptors
- This cause vesicles containing the ENac channels to move to and bond to the membrane on the lumen always side.
- This increases the no. of channels in the membrane
- There is greater Na reabsorption
What is the action of amiloride?
-Blocks the ENac channel
What is the action of spirolactone?
-Blocks the steroid receptor that aldesterone would bind too.
What determines the limits of urine osmolarity?
-How dilute it can enter the distal segment and how hypertonic the medullary interstitium is.
When is the main osmolyte when urine enters the collecting duct?
-Urea
Where is ADH produced?
-Hypothalamus
What receptor does ADH bind to on the principal cells
- ADH binds to VR2 (andenyly cyclase vasopressin receptor) receptors on principal cells
- Kinase actions culminate the insertion of vesicles containing aquaporin 2 into the apical membrane
- This increases water permeability and thus water reabsorption = concentrated urine
What is the action of ADH once it has bound to the V2R receptor on the principal cells?
- Kinase actions culminate the insertion of vesicles containing aquaporin 2 into the apical membrane
- This increases water permeability and thus water reabsorption = concentrated urine
What do intercalated cells exchange for acid in its reaction?
-Potassium
What are tubulopathies?
-Mutations of apical sodium transporters
What sodium channel does Bartlers syndrome block?
-NKCC2: thick ascending limb
What sodium channel does Gitelmans syndrome block?
-NCC in DCT
What sodium channel does Liddle’s syndrome block?
-ENaC in collecting duct
What supplies the proximal and distal tubules with blood?
-Peritubular capillaries
What supplies the loop of henle with blood?
-Vasa recta
What are the two parts of the collecting duct?
- Cortical collecting duct
- Medullary collecting duct
What percentage of nephrons are juxtamedullary and what are these nephrons responsible for?
- 15%
- Generating hypertonic medullary interstitium
What percentage of nephrons are cortical and what are the loop of henle of these nephrons responsible for?
- 85%
- Reabsorption and secretion
Explain how the hairpin structure of the vasa recta minimises excessive loss of solute from the interstitium by diffusion
- As blood flows down the vessel loop, Na+ and Cl- do diffuse ou
- However, as the blood flows up the ascending loop this process is reversed
- Excessive loss of solute from the interstitium by diffusion is limited
What percentage of filtered urea is reabsorbed?
-50%
Who determines fetal sex?
The Male: provides the X or Y chromosome
Where is the yolk sac?
Hindgut
What movement allows migration of germ cells?
-amoeboid
How many oocytes are roughly left at birth?
-1 million
When does meiosis 1 occur in females?
-in month 3 of intrauterine life
When is metaphase 1 arrested in females?
-until after puberty
What triggers the resumption of meiosis 1 in the female and when does this occur?
-LH surge
When is meiosis II arrested and resumed in the female?
-Metaphase II and until fertilisation
What is gonadal dysgenesis?
-Defective development of gonads in the embryo.
Give a cause of gonadal dysgenesis
-Non-disjunction
Give 2 examples of gonadal dysgenesis
- Turners syndrome:45XO
- Kleinfelters syndrome: 47XXY
Give an example of a male disorder of sex differentiation
-Partial androgen insensitivity syndrome
Give an example of a female disorder of sex differentiation
-congenital adrenal hyperplasia
What is stage 1 of gametogenesis and how does it differ in males and females
- Mitosis
- In males some mitosis occurs in the embryonic testis but majority begins at puberty and continues throughout life
- In females, mitosis occurs primarily in fetal development
Where does meiosis occur in males and females?
Males: semiferois tubules
Females: ovaries
What is ejaculate a mixture of?
Sperm and seminal plasma
What are the 3 glands of the male reproductive system?
- Prostate
- Seminal vesicle
- Bulbourethral
What forms the blood-Testis barrier?
-The tight junctions between Sertoli cells
Where are the most mature cells found in the testis?
-Closer to the centre of the seminiferous tubules
Are leydig cells found inside or outside of the seminiferous tubules?
-Outside
What veins are responsible for lowering the temp of the testis for spermatogenesis?
-Panpiniform plexus
What do primary spermatocytes differentiate into after meiosis I?
-Secondary spermatocytes
What do secondary spermatocytes develop into after meiosis II?
-Spermatids
What is spermiogenesis?
-Transformation of spermatids into spermatozoa (sperm)
What 2 types of cell do spermatogonia produce after mitosis?
- Type A: remain outside the BTB
- Type B: differentiate into primary spermatocytes following mitosis
How much sperm is produced per gram of testis per second?
- 300- 600 sperm
What is the acrosome in the sperm cell?
-Compacted golgi: contains all the necessary enzymes to pass into the egg cell.
How long does it take to complete spermatogenesis?
-64 days
What does the head of the sperm contain?
-Acrosome
-Nucleus
Basal body
What are the 3 regions of the tail of the sperm?
- Mid-piece: contains mitochondria around the axoneme of the flagellum
- Principle piece: the axoneme surrounded by fibres.
- Endpiece: axoneme only, narrow tip of the flagellum
What are the 4 spermatic ducts?
- Efferent ducts: 12 ducts collecting sperm from rete testis to epididymis
- Epididymis : site of sperm maturation and storage
- Vas deferens
- Ejaculatory duct
How long does sperm remain fertile in the epididymis?
40-60 days
What are the 3 glands in the male reproductive system and what do they produce?
- Seminal vesicles, prostate and bulbourethral
- seminal plasma
What does semen contain?
-60% seminal vesicle fluid, 30% prostatic and 10% mixture of sperm and trace of bulbourethral fluid
Other components:
- Fructose : provide energy to increase sperm mobility
- Fibrinogen
- Clotting enzymes
- Prostoglandins : to stimulate female peristaltic contractions
- Buffers for protecting against acidic vaginal secretions and residual urine in the male urethra
What is the normal sperm count and what sperm count is associated with infertility?
50-120 million / ml
Infertility: <25 million / ml
What hormones are involved in spermatogenesis?
- FSH: influences Sertoli cells. Sertoli cells then produce inhibin which acts on the pituitary gland as negative feedback.
- LH : acts on the leydig cells. Testosterone produced by the leydig cells then acts on the pituitary gland as negative feedback.
Summary of the path of the sperm to outside
SREEVEN UP
S : seminiferous tubules R : rete testis E : efferent ducts E : epididymis V : vas deferens E : ejaculatory ducts N : nothing
U : urethra
P : Penile urethra
What does the BTB ensure?
- prevents movement of chemicals from the blood into the lumen of the seminiferous tubules and helps retain luminal fluid.
- Ensures proper conditions for germ cell development
- permits different stages of spermatogenesis to occur in different compartments and so different conditions
What are the two phases of the menstrual cycle and what are they separated by?
- Follicular phase
- Luteal phase
- Separated by ovulation
What days does the follicular phase of the menstrual cycle span between?
-Days 1-13
What do follicles within the ovaries begin as and what does this consist of?
- Primordial follicles
- A single primary oocyte surrounded by granulosa cells
What do granulosa cells produce?
- Oestrogen
- Small amounts of progesterone before ovulation
- Inhibin
What happens as a primordial follicle becomes a primary follicle?
- The oocyte increases in size
- The oocyte becomes separated from the inner layer of granulosa cells by the zona pellucida
What is the zona pellucida and what is it important for?
- A thick material secreted by the surrounding follicular cells that contains glycoproteins
- These glycoproteins are important for the binding of sperm to the surface of the egg after ovulation
After formation of the zona pellucida, how does the inner layer of granulosa cells remain in contact with the oocyte?
- Via cytoplasmic processes that transverse with the zona pellucida forming gap junctions
- The gap junctions are how chemical messengers and nutrients reach the oocyte
What occurs as a primary follicle develops in a preantral follicle?
- The follicle grows larger through mitosis of granulosa cells
- The theca forms
What is the theca?
-Where the connective tissue surrounding the granulosa cells differentiates and forms layers
What happens as the preantral follicle forms the early antra follicle?
- The primary oocyte reaches full size
- The antrum begins to form by fluid secreted by the granulosa cells
- The antrum is a fluid filled space
At what point does a single dominant follicle continue to develop and what determines a dominant follicle?
- After 1 week, a single dominant follicle is selected from a previous selection of 10-25 follicles that were allowed to develop into larger antral follicles
- It depends of oocyte condition and oestrogen production
What happens to the non-dominant follicles during the menstrual cycle?
-They undergo atresia
What causes a primary oocyte to emerge from its meiotic arrest?
-A surge in LH, this division leads to a secondary oocyte
What is ovulation and when does it occur in the menstrual cycle?
- Ovulation occurs at day 14
- It is where the secondary oocyte and surrounding cells are carried out of the ovary on to the ovary surface by antral fluid.
What causes ovulation?
-when the thin walls of the follicle and ovary rupture at the site where they are joined due to enzyme digestion
What is a mature follicle also known as?
-Graafian follicle
What causes formation of the corpus luteum and what does it secrete?
- After discharge of its antral fluid and egg, the follicle collapses and undergoes transformation - the granulosa cells enlarge and form this gland-like structure (corpus luteum)
- Oestrogen, progesterone and inhibin
If fertilisation does not occur, when does the corpus luteum reach maximum development?
-10 days, following this is undergoes apoptosis
What triggers menstruation and the beginning of a new cycle?
- Oestrogen, progesterone and inhibin levels are very low due to regression of the corpus luteum (this triggers menstruation)
- This prevents the negative feedback on the hypothalamus and anterior pituitary
- Plamsa concentration of FSH and LH therefore begins to increase
What hormones stimulate development of the follicle beyond the prenatal and early antral stage?
- FSH
- It stimulates the granulosa cells to multiply and secrete oestrogen
- Oestrogen further stimulates proliferation of granulosa cells, further increasing oestrogen
What causes levels of FSH to be higher at the start of the menstrual cycle?
-Low levels of oestrogen and progesterone
Why do theca cells aid granulosa cells in oestrogen production?
-Granulosa cells are deficient in the enzyme required to produce androgen precursors of oestrogen
What causes non-dominant follicles to undergo atresia at day 7?
-The levels of FSH begun to decrease at this point meaning there is not enough to prevent atresia
What stimulates LH receptors to develop on mature granulosa cells?
-The dominant follicle matures and develops LH receptors due to FSH
What causes a decrease in FSH and LH in the follicular phase and why is there a greater decrease in FSH?
- Increasing release of oestrogen.
- Oestrogen acts as negative feedback on the release of gonadotropins from the hypothalamus that leads to FSH and LH release.
- There’s a greater decrease in FSH, as granulosa cells also secrete inhibin which inhibits mainly FSH
What cells do LH act on in the first week?
-Theca cells
What do theca cells produce and how does this lead to oestrogen production ?
- LH stimulates theca cells to produce androgens
- These androgens diffuse into the granulosa cells where they are converted to oestrogen by aromatase
What causes the LH surge that leads to ovulation at day 14?
- very large concentrations of oestrogen (it increases sensitivity of LH releasing cells to GnRH
- LH acts on granulosa cells to induce ovulation
What causes the decline of the LH surge just as ovulation is occurring?
-The small amounts of progesterone secreted by the corpus luteum that acts as negative feedback on anterior pituitary and hypothalamus
Along with ovulation what does LH stimulate?
-Transformation of remaining granulosa and theca cells into the corpus luteum
What does the corpus luteum secrete large amounts of?
-progesterone
In the luteal phase, what does progesterone and oestrogen produced by the corpus luteum result in?
-negative feedback on the anterior pituitary and hypothalamus causing a decrease in gonadotropins and in turn FSH and LH
Why does the corpus luteum degrade after 14 days?
-No fertilisation
What does a decrease of progesterone and oestrogen towards the end of the cycle cause?
-Increase in FSH and LH as negative feedback is removed
What does the degradation of the corpus luteum cause a decrease in?
-Progesterone and oestrogen
What are the stages of follicle development?
- Primordial follicle
- Primary follicle
- Preantral follicle
- Early antral follicle
- Matue follicle
What days does the luteal phase occur between?
14-28
What are the uterine phases of the menstrual cycle?
- Menstrual
- Proliferative
- Secretory
When does the menstrual phase start and how long does it last?
- Begins on day 1 of the cycle, lasts 3-5 days
What occurs during the menstrual phase of the menstrual cycle?
- Endometrium (epithelial uterus lining) degenerates causing period
- Stimulated by withdrawal of progesterone
When does the proliferation phase of the menstrual cycle begin and how long does it last?
-Begins at cessation of menstruation until start of ovulation
What does the ovarian follicular face include?
- Menstrual phase
- Proliferative phase
What happens during the proliferative phase?
-Endometrium begins to thicken due to the influence of oestrogen
What influence does oestrogen have on the uterine lining during the proliferative phase?
- The oestrogen stimulates the growth of the endometrium and the myometrium (underlying uterine smooth muscle).
- Also synthesises receptors for progesterone in the endometrial cells
What phase of the menstrual cycle follows the proliferatory phase and how long does it last?
- Secretory phase
- Occurs between ovulation and the onset of the next menstruation
What occurs during the secretory phase of the menstrual cycle?
- Endometrium begins secreting glycogen in the glandular epithelium
- This is followed by glycoproteins
- This is followed by mucopolysaccharides
What is the action of progesterone during the secretory phase of the menstrual cycle?
- Converts endometrium to actively secreting tissue: essential for making endometrium hospitable for implantation and nourishment if embryo
- Also inhibits myometrial contraction: important for safe implantation of egg
What is the effect of oestrogen on the cervix?
- Makes mucus: abundant, clear and watery
- Allows sperm to be deposited in the vagina and move through the mucus more easily towards the uterus and Fallopian tubes
- Most pronounced are ovulation
What is the effect of progesterone on the cervix?
- Makes the mucus thick and sticky, present in large amounts after ovulation
- This allows mucus to form a plug and prevent bacteria entering the vagina - protects uterus and embryo following fertilisation
What is the site of fertilisation?
-Ampulla of the Fallopian tube
What is the cervical mucus penetration test?
- Is the sperm able to pass through the cervical mucus and reach the Fallopian tube
- It is a fertility test
What are the 3 parts of the Fallopian tubes, staring at the end closest to the uterus?
- Isthmus
- Ampulla
- Infundibulum
What part of the female reproductive system enables sperm storage and for how long?
- Epidermal cells of the Fallopian tube
- 4-6 days
Where does the final maturation stage of the sperm take place and what is this termed?
- Fallopian tube
- Capacitation: alters sperm plasma membrane enabling it to bind to the egg.
What is the window for fertilisation?
- 5 days before and one day after ovulation
- This is because sperm remains fertile for 4-6 days whilst the egg is viable for 24-48 hours.
How is the egg transported into the Fallopian tube following ovulation?
- During ovulation, the egg is extruded on to the ovary surface
- Smooth muscle of the fimbria cause the fimbria to pass over ovary whilst it’s cilia brush in males towards the interior of the Fallopian tube
- This cilia motion sweeps the egg into the Fallopian tube
Describe the passage of sperm following sex
- Vagina
- Cervical mucus
- Uterus
- A small number reach the Fallopian tubes
What enables sperm to pass through cervical mucus?
-oestrogen: makes the cervical mucus watery
Why is sperm mortality high during movement from the vagina to the Fallopian tube?
- Vaginal environment is acidic
- The length and energy requirements are very high
What are the six pre implantation stages necessary for implantation to occur?
- Fertilisation (Day 1)
- Cleavage (Day 2-3)
- Compaction (Day 4)
- Cavitation and differentiation (Day 5)
- Expansion (Day 5-6)
- Hatching (Day 6+)
During fertilisation, what do surface proteins in the sperm head bind to?
- ZP3 proteins on the zona pellucida
- Many sperm heads binding the many glycoproteins on the zona pellucida
Following binding of sperm to an egg, what reaction is triggered?
-Acrosome reaction
What is the acrosome reaction during fertilisation?
- The plasma membrane of the sperm head is altered meaning the underlying acrosomal enzymes are exposed to the zona pellucida
- The enzymes digest a path through the zona pellucida
- The first sperm to reach the egg plasma membrane fuses with the egg
What is a fertilised egg called?
-zygote
What occurs following fertilisation to prevent polyspermy
- A reaction is triggered that changes the egg membrane potential preventing further sperm binding
- Along with the cortical reaction
What is the cortical reaction ?
- Exocytosis of secretory vesicles into the space between the zona pellucida and the egg plasma membrane
- These vesicles contain enzymes that inactivate sperm binding receptors of the zona pellucida and cause hardening of the zona pellucida
How long after fertilisation does the egg complete meiosis 2?
4-7 hours
What are pronuclei ?
- The two sets of haploid chromosomes (23 from the egg and 23 from the sperm).
- They are each surrounded by a distinct membrane, are equal in size and contain nucleoli
What is cleavage?
- Mitotic cell divisions that occur 24 hours after fertilisation
- Does not result in cell growth, causes an increase in cell number.
- Provides sufficient cells for differentiation
- The cells are also totipotent: stem cells capable of differentiation into a whole individual
How do monozygotic twins develop?
- During cleavage, dividing cells may become completely separated.
- This results in two independently growing cell masses
Once formed, why does the zygote remain in the Fallopian tube for 3-4 days?
- oestrogen maintains contraction near where the Fallopian tube enters the uterus
- Once progesterone levels begin to rise, the muscle relaxes and the zygote can pass through the Fallopian tube.
What is compaction and what is it essential for?
- This is where cells flatten and maximise intracellular contacts.
- This results in the formation of tight junctions and polarisation of the outer cells.
- It is essential for quick differentiation of cells.
What is cavitation and differentiation?
- The fluid filled cavity of the zygote expands to form a blastocyst
- There are greater than 80 cells that have begun differentiation
What is a blastocyst?
- An outer layer of cells termed the trophoblast
- An inner call mass
- Central fluid filled cavity
What is expansion?
- The cavity expands further and the blastocyst increases in diameter
- Zona pellucida thins
What is hatching?
-Blastocyst expansion and enzymes result in hatching of the embryo from the zona pellucida
What are the implantation stages and when do they occur
- Aposition
- Attachment
- Differentiation of trophoblast
- Invasion
- Decidual reaction
- Maternal recognition
They occur on the 21st day of the cycle
What day does the embryo reach the uterus?
5/6
What is the aposition stage?
-The hatched blastocyst orientates via embryonic pole and synchronises with receptive endometrium
What occurs during the attachment implantation stage?
-Endometrial epithelial cells and trophoblastic cells express integrins which connect with one another
What do trophoblasts differentiate into during implantation?
- Cytotrophoblasts
- Syncitiotrophoblasts
What occurs during the invasion stage of implantation?
-Enzyme degradation of the basal lamina
What occurs during the decidual reaction of implantation?
-Differentiation of the stromal cells adjacent to the blastocyst
What occurs during maternal recognition of implantation?
- Secretion of interleukin-2
- This prevents antigen rejection of the embryo
What is syngamy?
Where male and female pronuclei migrate to the centre of the fertilised egg and are unified
What does FSH act on in men?
Sertoli cells
What does LH act on in men?
Interstitial / leydig cells
Stimulates them to secrete testosterone
What happens in the embryo after embryonic genome activation and before blastocyst formation?
Compaction
Which Genes confer self renewal and pluripotency in embryonic stem cells?
OCT4 and nanog
Explain the location of the suprarenal glands.
-Retroperitoneal and above the kidneys
Explain the arteries of the adrenal gland
Superior adrenal gland : comes from the inferior phrenic
Middle adrenal gland : comes from the abdominal aorta
Inferior Adrenal gland : comes from the renal artery
Explain the veins of the adrenal glands
- Right adrenal artery drains directly into the IVC
- Left adrenal artery drains into the left renal vein
What is the nerve supply of the adrenal gland?
-Splanchnic nerve
What are the 5 hormones secreted by the adrenal cortex?
-Aldosterone, cortisol corticosterone, dehydroepiandrosterone (DHEA) and androstenedione
Explain the 3 layers of the adrenal cortex and what they secrete
- zona glomerulosa: mineralocorticoids (e.g aldosterone)
- Zona fasiculata : glucocorticoids (e.g cortisol)
- Zona reticularis : sex hormones (Androgens)
GFR- make good sex
What control is the adrenal medulla under?
-Under sympathetic control, it is part of the autonomic nervous system
What hormones does the adrenal medulla secrete
- Adrenaline (80%)
- Noradrenaline (20%)
What does the adrenal medulla response to?
-Stress
What are mineralocorticoids and glucocorticoids classed as? And what is their precursor?
- corticosteroids
- Cholesterol
Why do problems with the pituitary or hypothalamus not affect aldosterone release?
-The release of renin from granular cells triggers aldosterone release
Explain the release of cortisol in response to stress
- Stress is detected an transmitted to the hypothalamus
- This stimulates secretion if CRH (corticotropin releasing hormone)
- CRH is carried to the anterior pituitary by hypothalami-hypophyseal portal vein
- Here CRH stimulates the release of ACTH (adrenocorticotropic hormone)
- ACTH travels in the blood to the adrenal cortex where it stimulates the release of cortisol
What percentage of cortisol is bio available?
5%
Explain the functions of cortisol in the absence of stress
- Permissive actions on the reactivity of smooth muscle to adrenaline and noradrenaline
- Maintain concentrations of certain enzymes that prevent glucose concs decreasing
- Inhibit production of leukotriene and prostaglandins
- Stabilises lysosomal membranes in damaged cells
- Reduces permeability of capillaries in injured areas
What is the developmental role of cortisol in fetal and neonatal life
- Responsible for differentiation of tissues and glands
- Essential for production of surfactant (reduces surface tension in lungs, making it easier for them to inflate)
Explain the stress functions of cortisol
Increases organic metabolism, increasing plasma concs of glucose, AA, glycerol and fatty acids
- AA for tissue repair
- Increases ability of vasoconstriction of smooth muscle in response to adrenaline
- Reduces inflammatory response to injury or infection
- Inhibits non-essential functions
What can chronic stress result in?
Severe decreases in bone density, immune function and reproductive fertility
-Caused by increased catabolism
What are the main androgens generated in the zona reticularis of the adrenal gland?
- Weak androgens are produced here
- DHEA (dehydroepiandrosterone) and androstenedione - this includes testosterone
DHEA and androstenedione play a greater role in the adult female that male with them having a less potent effect than testosterone
What regulates the production of androgens in the adrenal gland?
ACTH released in anterior pituitary
Where does the synthesis of catecholamines (adrenaline & noradrenaline) occur and what is the synthesis dependent on?
- Adrenal medulla
- It has specialised ganglia supplies by sympathetic preganglionic neurones
- Dependent on high local cortisol levels
What occurs during the fight or flight response ?
- Gluconeogenesis in the liver
- Lipolysis in adipose Giuseppe
- Tachycardia and cardia contractility
- Redistribution of circulating volume
- More adrenaline release = vasoconstriction
- Less noradrenaline release = less vasodilation
What receptors have a high affinity for adrenaline and which for noradrenaline ?
- Alpha receptors = noradrenaline
- Beta receptors = adrenaline
What epithelium lines the renal pelvis, ureters, bladder and urethra?
Urothelium
What epithelium lines the PCT, DCT and collecting duct?
Cuboidal epithelium
What percentage of an adult males weight is water?
60%
Explain the breakdown of body fluid compartment
-2/3 intracellular
-1/3 extra cellular:
75% interstitial
25% plasma
Explain the breakdown of Na reabsorption in the nephron
PCT: 60%
Loop Of Henle: 25%
DCT: 19%
Collecting Duct: 4%
Explain how controlling GFR controls Na reabsorption
- when sodium is low, plasma volume is low and this results in decreased pressure. This is detected by baroreceptors and results in vasoconstriction of afferent arteriole and so reduced GFR.
- When sodium is high, plasma volume is high and so is pressure. This results in vasodilation so to increase GFR and so renal loss of sodium.
What 3 ways does the kidney maintain water balance?
1) regulation of osmolality - ADH
2) RAAS
3) Atrial natriuretic peptide ANP
Where is ADH synthesised and secreted
- Hypothalamus
- Posterior pituitary
-Explain the body’s response to low plasma volume
- Low plasma volume, so high osmolality and in turn low pressure is detected by baroreceptors and hypothalamic osmoreceptors.
- This causes an increase in ADH secretion
- ADH binds to VR2 receptors on principal cells of the collecting duct increasing the number of aquaproins
- water reabsorption increases to increase plasma volume
Explain the RAAS response to low blood volume
-Low blood volume causes low pressure detected by baroreceptors. These stimulate :
Hypothalamus to activate thirst response as well as ADH release.
Renin to be released by juxtaglomerular (granular) cells
What 3 factors result in renin release?
- low NaCl detected by macula densa cells
- Sympathetic stimulation
- Little arterial stretch (this is caused by low blood volume and so pressure)
Explain the actions of renin
- Renin cleaves angiotensinogen produced in the liver to angiotensin I (Done by removing a short AA chain.
- Angiotensin I is then converted to angiotensin II by ACE (ACE is produced in the lungs)
- Angiotensin II results In the release of aldosterone from the zona glomerulosa
What are the actions of aldosterone release ?
- Stimulates vasoconstriction of efferent arteriole to increase GFR
- Stimulates thirst
- Stimulates ADH release for water reabsorption
- Increased sympathetic activity
Explain the actions of ANP
- Synthesised In cardiac atria and released due to atrial wall stretching when the BP is too high
- They inhibit ENaC channels in collecting prevent sodium reabsorption
- Acts as a vasodilator on afferent arteriole to increase GFR and so Na release
- They also inhibit aldosterone release via renin inhibition
What are the two functions of the parathyroid hormone?
- Increases calcium reabsorption
- Stimulates activation of vitamin D
Explain the activation of vitamin D
- Vitamin D is hydrolysed in the liver by 25 hydroxylase to give 25- hydroxyvitamin D
- In the kidneys this hydrolysed to active vitamin D 1,25-dihydroxyvitamin D under the action 1-hydroxylase
- The parathyroid gland stimulates this hydrolysis
Explain the kidneys role in EPO (Erythropoietin)
- The produce EPO
- EPO is essential for maturation of erythrocytes from a reticulocyte in the bone marrow
- Too little = anaemia
- Too much = viscous blood (polycythemia)
Under what control is the detrusor muscle ?
It is under the control of the autonomic nervous system with some voluntary control
Give 4 causes of pre - Renal acute injury
- cellulitis
- Decompensated heart failure
- Decompensated liver failure
- Diarrhoea and vomiting
What is the overall effect of aldosterone ?
Lower blood pressure
What is blood flow to the kidneys per minute ?
1L/ min
Approx how many lire’s of filtrate passes through renal space per day?
280L
What is a normal healthy volume of urine production?
1ml / kg / hr
Give the 3 muscles of the bladder and the type of muscle
Detrusor- smooth
Internal urethral sphincter - smooth
External urethral sphincter - skeletal
What is the term for urination
Micturition
Explain the autonomic and voluntary components of the bladder
The detrusor muscle and internal sphincter are under autonomic control
The external sphincter is under voluntary somatic control
Explain the state of the bladder muscles during bladder filling
- There is minimal parasympathetic input to the detrusor muscle meaning it is relaxed. This relaxation cause closing of internal sphincter.
- In addition strong sympathetic input to internal and strong somatic input to external causes closing
Explain the reflex arc of the bladder stretch reflex
1) Bladder fills with urine causing stretching of bladder wall.
2) Afferent sensory nerves detect this stretching and transmit to spinal cord
3) Interneurones relay the signal via the parasympathetic pelvic splanchnic nerve
4) This causes contraction of detrusor muscle and stimulates urination.
Post childhood this reflex is non functional. However in injuries to the descending somatic pathway it can lead to in continence
Explain the nerve supply to the bladder during urination
1) Sympathetic input via the hypogastric nerve (T12-L2) causes relaxation of the detrusor.
2) Bladder fills with urine, pressure increases and bladder wall stretches
3) Afferent neurones from the receptors enter the spinal cord stimulating the parasympathetic pelvic splanchnic nerve (S2-S4), contacting detrusor
4) Contraction causes opening of internal sphincter. In addition, Afferent neurones stimulate sympathetic hypogastric nerve which opens internal.
5) Afferent neurones also inhibit somatic motor neurones via pudendal nerve (S2-S4)causing relaxation and opening of external
Afferent neurones in the bladder wall also communication with the brain to stimulate the need to urinate
What is urinary tract function
- Collect urine
- Store it under safe low pressure
- Store until socially acceptable to release urine
What are 2 key factors in the normal bladder?
1)Filling
-Continence
-Sensation of bladder volume
-Compliance: bladder stores urine at low pressure under receptive
relaxation
2) Voiding
- Voluntarily initiated
- Complete emptying
What are the 3 consequences of bladder dysfunction
- Incontinence
- Infection and bladder stones
- Upper urinary tract injury due to high pressure
What can the external urethral sphincter be known as?
Rhabdospincter
Where do encoring glands release directly into?
-The blood, they are ductless
What do endocrine glands allow?
- Rapid adaptive changes
- Integration of whole body physiology
- chronic maintenance of metabolic environment
- communication for multicellular organisms
When do thyroid glands begins producing thyroxine
18-20 weeks
What are the 2 hormones of the thyroid
T4 : Thyroxine
T3 : Triidothyronine
What protein rich material is at the centre of thyroid follicles
Colloid
Contains large amounts of thyroglobulin
Explain the synthesis of T1 and T2 hormones
- Iodide is cotranosported into follicular cells with Na+ (Iodide trapping)
- Na+ is pumped back out by Na+ / K+ ATPase
- Iodide then diffuses across follicular membrane into the colloid
- Iodide is then rapidly oxidised to iodine
- Iodine then binds to the thyrosine residue on the thyroglobulin molecules under the action of thyroid peroxidase
- If the thyrosine binds one iodine molecule = monoiodothyrosine (T1)
- If thyrosine binds two iodine molecules = diiodothyrosine (T2)
What is iodide trapping
When iodide is contransported with Na+ into follicular cells
Explain what happens to T1 and T2 hormones when the thyroid is stimulated
-The T1 and T2 molecules are cleaved from their thyrosine backbone but remain attached to thyroglobulin
and then join together
-T3 (T1 + T2)
-T4 (T2 +T2)
Explain how T3 and T3 is secreted into the blood
- Extensions of the colloid facing membranes of the follicular cells engulf portions of the colloid by endocytosis
- The iodated thyroglobulin is then brought into contact with the lysosomes of the cell interior
- Proteolysis of the thyroglobuin results in the release of T3 and T4 which then diffuses out of the follicular cells into the interstitial fluid and from there into the blood
What hormone stimulates all actions of the follicular epithelial cells ?
-Thyroid stimulating hormone (TSH)
Explain the control of thyroid function, starting with the hypothalamus
- The hypothalamus released thryroid releasing hormone (TRH).
- This stimulates the release of TSH from the anterior pituitary
- The plasma increase in TSH causes an increase in thyroid hormone (T3 and T4)
- A increase in plasma thyroid hormone acts as negative feedback on the anterior pituitary and to a lesser extent on the hypthalamus
What are the functions of TSH
- Stimulates production of T3 and T4
- Increases protein synthesis in follicular cells
- Increases DNA and cell division
- Increases the amount of rough ER and other cellular machinery required for protein synthesis by follicular cells
What can cause hypertrophy of thyroid glands ?
Exposure to greater amounts of TSH
It means it increases in size (goitre)
Why are the actions of T3 widespread?
Receptors for thyroid hormone are present on the nuclei of most cells in the body, this is different to most other hormones
What are the metabolic actions of T3?
- Increases metabolic rate, does so by stimulating carbohydrate absorption from the small intestine & fatty acid release from adipocytes
- This provides energy
- Most is used to support activity of Na+ / K+ ATPases
- Activity of these enzymes stimulated by T3 gives a by product of heat
- Another action of T3 is thus to produce heat for body homeostasis
What are the permissive actions of thyroid hormone ?
Up-regulates beta-andrenergic receptors for adrenaline
-Over active thyroid with excess T3 therefore has symptoms similar to that of excess adrenaline
What is the function of T3 in growth and development ?
- Production of growth hormone from anterior pituitary.
- Nervous system development in real life: formation of axon terminals, synapses, dendrites and dendritic extensions and myelin
- Proper nerve and muscle reflexes and normal cognition in adults
What is the hypothalamus stimulated to release by other areas of the CNS?
Hypophysiotropic hormones
What are the hypophysiotropic hormones released by the hypothalamus?
- Gonadotropin releasing hormone (GnRH) : stimulates release of FSH and LH.
- Growth hormone releasing hormone (GHRH) : stimulates release of GH
- somatostatin inhibits GNRH release - Dopamine : inhibits release of prolactin
- Corticotropin-releasing hormone : stimulates release of adrenocorticotropic hormone
- Thyrotropin releasing hormone : Stimulates release of thyroid stimulating hormone
How is blood delivered from the hypothalamus to the anterior pituitary?
- Ant. pituitary has no arterial supply
- There is a portal venous circulation from the hypothalamus termed the hypothalamo - hypophyseal portal vessel
- Blood is delivered by this directly from the hypothalamus to the cells of the ant. Pituitary
- The hormones therefore bypass general circulation
How many types of hormone producing cell does the ant. pituitary have ?
5
What is the benefit of the hypophysiotropic 3 hormone sequence?
- Allows hormonal feedback with negative feedback the most important
- Allows the amplification of a small number of hypothalamic neurones into a large peripheral hormonal sequence
What are the 6 hormones of the ant. Pituitary?
- F : FSH (produced in gonadotrophs)
- L : Lutenizing hormone (produced in gonadrotrophs)
- A : adrenocorticotropic hormone (produced in corticotrophs)
- T : thyroid stimulating hormones (produced in Thyrotrophs)
These are all basophilic cells = blue / purple
- P : prolactin (produced in lactotrophs)
- I : Ignore
- G : Growth hormones (produced in somatotrophs)
These are acidophilic cells = dark pink / red
What are the roles of the 6 ant. pituitary hormones?
- FSH and LH : Target gonads, stimulate release of hormones and stimulate germ cell development.
- Adrenocorticotropic hormone : stimulates adrenal cortex to secret cortisol
- TSH : Stimukates thyroid to release T3 and T4
- Prolactin : stimulates breast to produce milk and helps with breast development
- Growth hormone : Stimulates growth and protein synthesis
Explain the sequence of each of the 6 ant. pituitary hormones
- Thyrotropin- releasing hormone : thyroid stimulating hormones : increases release of T3 and T4 : this causes increased metabolism
- GnRH : LH and FH : target gonads increase oestrogen, progesterone and testosterone
- GHRH : GH : stimulates growth and protein synthesis
- Somatostatin : inhibits growth hormone : inhibits growth and proteinsynthesis
- CRH : ACTH : increases cortisol production in adrenal cortex from zona fasiculata
- Dopamine : inhibits prolactin : inhibits growth and milk production
What is loop loop negative feedback
The hormone secreted by the third endocrine gland has a negative feedback effect over the ant. pituitary and / or hypothalamus
Which of the 6 ant.pituitary hormones show loop loop negative feedback?
- ACTH
- FSH
- LH
- TSH
What kind of feedback does prolactin and GH exert and why is it not loop loop
- short loop negative feedback
- Loop loop negative feedback does not exist as the ant. Pituitary hormone does not have major control over another endocrine gland , there is nor 3 hormone sequence
- However prolactin does act on hypothalamus to secrete dopamine which inhibits prolactin = short loop negative feedback.
What do anterior pituitary tumours cause?
- Pressure on local structures : particularly optic nerves = bitemporal hemianopia
- Pressure in pituitary : this results in excess or inadequate pituitary hormone release (hyper / hypo- pituitarism)
What are the hormones of the posterior pituitary?
- ADH
- Oxytocin
Where are the 2 posterior pituitary hormones synthesised ?
- ADH (cell body of supraoptic nucleus)
- Oxytocin (cell body of paraventricular nucleus )
Both within hypothalamus
What are the 2 actions of ADH?
- Concentrates urine by increasing reabsorption in the collecting duct
- Causes contraction of smooth muscle around blood vessels (vasoconstriction). This acts to increase blood pressure
What is ADH released in response to?
- Decreased blood volume
- Decreased blood pressure
- Stress
- Trauma
- Increased osmotic pressure of the blood
- Increased blood CO2
- Decreased blood oxygen
What are the actions of oxytocin ?
- Promotes the onset of labour
- Stimulates contraction of uterine smooth muscles until the baby is born
- Stimulates contraction of breast tissue which results in milk ejection during lactation : occurs in response to stimulation of nippke
What type of receptors do all pituitary and hypothalamic hormones act on?
G-protein coupled receptors
What are 99% of the cells in the pancreas?
Acini
What function is performed by the acinar cells?
Exocrine function
What do acinar cells do?
- Manufacture and secrete pancreatic juice (digestive enzymes and fluid)
- This is released into the gut via the pancreatic duct which enters the small intestine at the duodenal papilla through the ampulla of vata.
What makes up 1-2% of the cells of the pancreas ?
Islets of langerhans
What does the islets of langerhans do?
Manufacture and release peptide hormones into the portal vein
What are the 3 cells of the islets of langerhans
Beta cells : insulin
Alpha cells : glucagon
Delta cells : somatostatin
What do beta cells of the pancreas secrete?
Insulin
What do alpha cells of the pancreas secrete?
Glucagon
What do delta cells of the pancreas secrete?
Somatostatin
What are the actions of insulin?
-Suppresses hepatic liver glucose output (decreases glycogenolysis & gluconeogenesis)
-Increases glucose uptake into insulin sensitive tissue:
Muscle: glycogen & protein synthesis
Fat : fatty acid synthesis
-Suppresses:
Lipolysis
Breakdown of muscle (decreased ketogenesis)
What are the general actions of glucagon?
-Increases hepatic liver output (increases glycogenolysis & gluconeogenesis)
-Reduces peripheral glucose uptakes
-Stimulates peripheral release of gluconeogenic precursors (glycerol and AA)
-Stimulates: lipolysis
Muscle glycogenolysis & breakdown (increased
ketogenesis
Explain the production of insulin from proinsulin
- Proinsulin has alpha and beta chains linked by a C peptide.
- Proinsulin is cleaved from its C peptide and then used to make insulin which is packaged into insulin secretory granules.
What is the difference between natural insulin and synthetic insulin?
- synthetic insulin does not contain C peptide.
- During natural insulin release, blood levels of C peptide rises.
- C peptide in the blood = natural insulin
Explain the secretion if insulin by the beta cells
- When glucose conc is high it binds to GLUT2 glucose transporters on beta cells
- Glucose enters beta cells
- Inside beta cells hexokinase converts glucose to glucose-6-phosphate using ATP
- The ADP is then converted back to ATP. This ATP then binds to the K+ATP on the beta cell membrane closing the channel.
- K+ can no longer leave, depolarising the membrane
- This depolarisation opens voltage-gates Ca2+ channels allowing Ca2+ to diffuse into the cell
- These Ca2+ ions bind to insulin secretory granules causing them to fuse with the membrane secreting insulin by exocytosis
Explain the effect of insulin on muscle and fat cells
- Insulin binds to insulin receptors in the cell membrane
- This causes an intracellular signalling cascade causing intracellular GLUT4 vesicles to fuse with the cell membrane.
- This fusion increases the number of glucose transporters in the membrane resulting in a greater rate of glucose diffusion into the cells by facilitated diffusion.
- This decreases blood glucose levels
What is meant by biphasic insulin release?
- Phase 1: rapid release of stored insulin
- The second phase is only initiated if glucose levels remain high. It involves synthesis of more insulin so takes longer.
What short term glucose homeostasis is carried out by the liver ?
- Liver glycogen is the short term glucose buffer
- HIGH blood glucose = glycogenesis. In the long term it makes triglycerides (lipogenesis)
- LOW blood glucose = glycogenolysis. In the long term gluconeogenesis (glucose from AA/lactate)
Where can glucose sensory cells be found?
- Primary ones are in the islets of langerhans.
- Medulla, hypothalamus and carotid bodies.
- Input from eyes, nose, taste buds and gut all involved in regulating food.
What are incretins and name 2 major ones
- Sensory cells in the gut that stimulate insulin release from the pancreas.
- They are secreted by endothelial cells in response to eating and act to amplify insulin’s response to glucose
- Glucagon-like peptide (GLP-1)
- Glucose-dependent insulinotropic peptide (GIP)
What are the main to mechanism for regulating glucose following feeding
- Rising plasma glucose stimulates pancreatic B-cells to secrete insulin
- Plasma glucose inhibits glucagon release by A-cells
How does the liver provide glucose during the fasting state ?
- Glycogenolysis (glycogen - glucose)
- Gluconeogenesis (uses lactate, alanine and glycerol to produce glucose)
- Glucose is delivered to insulin dependent tissues (brain & red blood cells)
- Muscles use fatty acids as fuel
How long after eating does blood glucose rise and what effect does this have on insulin and glucagon ?
5-10 mins
There is a 5-10 fold increase in glucose
Glucagon is suppressed
Explain the proportion of glucose to the liver and periphery
40% to liver
60% to periphery
What does ingested glucose help?
-replenish glycogen stores in liver and muscles
What happens to excess glucose?
It is stored as fat
What does hypoglycaemia cause?
- Stimulates release of glucagon
- Glucagon acts on the liver to convert glycogen to glucose and glucose from lactic acids and AA.
What does hyperglycaemia cause ?
-Inhibits release of glucagon and stimulates release of insulin
What are the actions of insulin on cells?
- Accelerate facilitated diffusion of glucose into cells
- Speeds up conversion of glucose to glycogen
- Increases uptake of AA and increases proteinsynthesis
- Speeds up synthesis of fatty acids
- Slows glycogenolysis
- Slows gluconeogenesis
What are the functions of the skin?
- Barrier to infection
- Thermoregulation
- Protection against trauma
- Protection against UV
- Vitamin D synthesis
- Regulates water loss
What are the 3 layers of the skin?
- Epidermis
- Dermis
- Subcutaneous tissue
What is the outermost layer of the epidermis of the skin and what is it’s role?
- Stratum corneum
- An efficient barrier to the penetration of irritants and allergens and to the loss of water
What makes up the stratum corneum of the epidermis ?
Corneocytes
These are made up of corneo-desmosomes and desmosomes
The condo-desmosomes keep corneocytes together
What disease sees increased numbers of corneo-desmosomes ?
Psoriasis : thickening of stratum corneum
What disease sees decreased numbers of corneo-desmosomes
Atopic eczema : thinning of stratum corneum, giving an increased risk of inflammation.
What produces natural moisturising factor (NMF) found in corneocytes?
-Filaggrin (derived from profilaggrin)
What is the role of NMF ?
Helps to maintain skins hydration by keeping water inside the skin
What is desquamation and why is it important?
Degradation of extracellular corneo-desmosomes under the action of protease.
Mature corneocytes are shed from the surface of the stratum corneum to balance induction of new cells in the basal layer.
Why is the pH of the skin 5.5?
Allows protease to remain on the skin and thus enable the balance of new cells from the basal layer of the epidermis (desquamation)
What is the role of the lipid lamellae?
- Keeps water inside the skin cells
- Irritants and allergens bounce off the surface
Why is vitamin D essential for skin ?
Producing anti-microbial peptides to defend the skin from bacteria and viruses
What is the effect of irritants on the skin?
They break down healthy skin
What is the effect of allergens on the skin?
Trigger skin flare ups by penetrating into the skin and causing the skin to react
How do allergens cause skin flare ups and inflammation ?
They penetrate the skin, where they met by lymphocytes which release chemicals that induce inflammation
Explain how allergens cause red, itchy and dry skin
- Red skin: dilation of blood vessels due to lymphocyte activity
- Itchy skin: stimulation of nerves
- Dry skin: skin cells leaking due to lymphocyte activity
What causes an increase in skin pH?
- No profilaggrin, means no filaggrin and therefore a lack of NMF. This means less water retention in the corneocytes
- Less water retention causes an increase in pH
What is the effect of an increased skin pH?
- Increased pH damages the corneodesmosomes
- This breaks down the skin barrier increasing the risk of infection
Explain the onset of acne
- Hypercornification causes adherent corneodesmosomes to block the entrance to hair follicles.
- This causes increased sebum production by sebaceous glands.
- Sebum becomes trapped in the narrowed hair follicle
- Sebum in the pit of the follicle becomes stagnant as there is no oxygen
- Anaerobic conditions allow propionic bacteria acnes (p.acnes) to multiply
- This bacteria breaks down triglycerides in the sebum into fatty acids causing irritation, inflammation and attraction of neutrophils
- Attraction of neutrophils causes pus and further inflammation
How can cosmetics and oily skin trigger acne?
They ‘plug’ the hair follicle and initiate the acne process
Explain how GnRH release stimulates FSH and LH release
- GnRH are released by the hypothalamus
- They travel to the ant pituitary via the hypothalami hypophyseal portal vessel
- This triggers the release of FSH and LH
Explain the effect of FSH on Sertoli cells
Stimulates the release of paracrine agents required fo initiate spermatogenesis
Explain the effect of LH on leydig cells
Stimulates them to secrete testosterone
Explain how testosterone inhibits LH by negative feedback
- Acts on hypothalamus to decrease GnRH production
- Acts on anterior pituitary to decrease LH response to GnRH
Explain the effects of testosterone
- Acts locally by diffusing from interstitial space into seminiferous tubules
- Enters sertoli cells to aid spermatogenesis
Explain how Sertoli cells inhibit FSH release
They secrete inhibin which inhibits FSH release from anterior pituitary
When does mitosis of oogonia occur?
Early fetal development, stops around the 7th month
What do all oogonia differentiate into?
Primary oocytes
When does meiosis I of primary oocytes begin ?
in-uteric before 12 weeks
When is meiosis I of a primary oocyte arrested and when is it completed ?
- Metaphase I
- Until puberty, completed just before ovulation
What does meiosis I of a primary oocyte produce ?
- Secondary oocyte (retains nearly all cytoplasm)
- small, non-functioning first polar body
When is meiosis II of a secondary oocyte arrested until ?
-Arrested at metaphase II until fertilisation in a Fallopian tube by a sperm
What does meiosis II of a secondary oocyte produce ?
- Ovum
- Second polar body
How many ovum can one primary oocyte produce?
1
What are the main differences between spermatogenesis and oogenesis
- 1 spermatocyte= 4 spermatozoa where as1 oocyte = 1 ovum
- Both maturations occur in testis where as one occurs in ovaries and one in Fallopian tube
- Continuous process where as disjointed process (days-years)
Explain the changes in GnRH and GHRH by the hypothalamus before and at puberty
Before : low levels of GnRH and GHRH secretion from the hypothaLamus
At puberty : Increase in levels of GnRH and GHRH
Explain the changes in FSH, LH, GH and sex steroids before and after puberty
Before : low levels of FSH, LH, GH and gonadal sex steroids
At puberty : Increase in FSH, LH, GH and sex steroids
In normal puberty, what it is driven by and dependent on?
- Centrally driven
- Dependent on an intact hypothalamic-pituitary gonadal axis
What is puberty influenced by?
- Nutrition
- Genetic factors
- Insulin
- Exercise
What are the physical changes in males at puberty?
- Starts age 9-14 yrs (average 12)
- 1st sign = testicular enlargement
- Pubic, axillary and facial hair growth
- Growth spurt
- Spermatogenesis begins
- Acne, body odour and mood changes
What are the physical changes in females at puberty?
- Starts 8-14 (average is 11)
- 1st sign breast development
- Pubic and axillary hair growth
- Growth spurt (not as large as males)
- Menarche (first menstruation, 2.5 yrs after puberty onset)
- Acne, body odour and mood changes
What is parturition ?
The birthing process- successful transition from intra-uterine life to extra-uterine life.
-The events that occur in the uterus and foetus in the last few weeks of pregnancy that culminate delivery
How many weeks are you pregnant
- 40 weeks (from first day of menstrual cycle)
- 38 weeks (counting from the day of ovulation and conception)
What maintains the relative disconnection of the smooth muscle cells of the myometrium during pregnancy?
Progesterone
What are donnexins and what stimulates their synthesis ?
- Proteins that form gap junctions between the cells which allow the myometrium to undergo coordinated contractions
- Stimulated by oestrogen in the last few weeks of pregnancy
What is cervical ripening ?
The growth and remodelling of the cervix prior to labour
What accelerates cervical ripening in the last 3 months of pregnancy ?
Oestrogen
Explain the change in the uterus in the last few weeks of pregnancy
- During pregnancy, uterus = sealed at its outlet by firm inflexible collagen fibres that constitutes the cervix (this is maintained by progesterone).
- In the last few weeks, the cervix becomes soft and flexible due to the enzymatically mediated breakdown of the fibres
What mediates the synthesis of enzymes to breakdown collagen fibres ready for birth ?
Oestrogen
Placental prostaglandins - PGE
Relaxin
What secrets relaxin and what is it’s role
Ovaries, placenta and uterus
Softens cartilaginous joints in the pelvis in prep for labour
What are the prelabour events
-Enhance prostaglandin production
-Initiation of labour : maternal signal - oxytocin
foetal signal - oxytocin, vasopressin
and cytokinins
PGF2a - enhances action of oxytocin
-Increased pressure on cervix - stimulates release of prostaglandins
-Contraction of actomyosin in the myometrium
What initiates labour?
- Increased PGF2a (prostaglandin)
- This enhances the action of oxytocin
- This results in myometrial contraction
- This exerts pressure on the cervix which promotes further contractions
What occurs at the onset of labour ?
Amniotic sac ruptures and the amniotic fluid flows through the vagina
When labour intensity increase what are the contraction intervals and where do they begin?
10-15 minutes
Upper portion of the uterus and sweeps downwards
What so increases intensity and frequency of contractions cause?
The cervix is forced open (dilation)
What is the maximum dilation of the cervix?
10cm
Explain the 3 stages of labour
- Latent: little cervical dilation - lasts around 8 hrs
- Active : organised uterine contraction and dilation- 5 hrs
1. Stronger, higher frequency contractions
2. Full dilation resulting in foetal expulsion
3. Placental expulsion - Post-partum phase
What happens or oestrogen and progesterone levels during pregnancy?
Continuously increase
What is the role of oestrogen in pregnancy ?
- Stimulates uterine muscle mass : contracts to deliver foetus
- Regulates progesterone levels
- Prepares breast for feeding
- Induces synthesis of receptors for oxytocin
What is the role of progesterone during pregnancy ?
- Inhibits uterine contractility to prevent early expulsion of the foetus
- Increases thickness of uterine lining to prevent miscarriage
What supplies almost all of the oestrogen and progesterone in the first 2 months of pregnancy ?
Corpus luteum (it remains for the first 3 months)
What causes the persistence of the corpus luteum in the first 3 months of pregnancy ?
Human chorionic gonadotropin (hCG) hormone
What produces the human chorionic gonadotropin hormone ?
Trophoblast cells when they begin the endometrial invasion at day 7-8 (onset of implantation)
What hormone is used as an indicator of pregnancy ?
hCG
What is the role of hCG?
- Stimulates secretion of oestrogen and progesterone by corpus luteum.
- Stimulates maternal ovaries fo secrete oestrogen and progesterone
When do hCG levels reach a peak?
60-80 days after last menstruation
What secreted necessary oestrogen and progesterone when hCG levels decrease?
Placenta
What is entirely responsible for the sharp increase in oestrogen and progesterone in the last 6 months of pregnancy?
Secretion by trophoblast cells of the placenta
Where does the placenta obtain the necessary androgen precursors for oestrogen ?
Maternal ovaries
Maternal adrenal medulla
Foetal adrenal medulla
What prevents secretion of GnRH, LH and FSH during pregnancy and this prevents menstruation during pregnancy ?
They are powerfully inhibited by Hugh concentrations of progesterone in the presence of oestrogen
Give a summary of prolactin during pregnancy
- Increases at end of pregnancy at oestrogen and progesterone decrease
- Produced in ant. Pituitary
- Role in milk production and prevention of ovulation
- Release controlled by sucking
- Prolactin stimulates milk production at birth as oestrogen and progesterone levels drop dramatically
Give a summary of relaxin during pregnancy
High in early pregnancy
Produced by the ovary and placenta
Helps to limit uterine activity, soften the cervix and involved in cervical ripening
Give a summary of oxytocin during pregnancy
Secreted throughout pregnancy, increases at the end Produced by post. Pituitary Stimulates uterine contractions Triggers caring reproductive behaviour Drug used to induce pregnancy
Give a summary of prostaglandins during pregnancy
PGF2a is the main one, PGE2 is 10x stronger
Produced by uterine tissues
Initiates labour
Give the cardiovascular changes during pregnancy
Increased cardiac output Reduced systemic blood pressure Reduced total peripheral resistance Increased uterine blood flow Increased blood volume Increased plasma and blood cell mass
Give the respiratory change during pregnancy
Increased alveolar ventilation
Give gastrointestinal changes during pregnancy
Increased acid reflux and gastroparesis (delayed emptying)
Give the skin changes during pregnancy
- Linea nigra :dark central line on the stomach
- Striae gravidarum : stretch marks in lumbar abdominal regions
- Darkened areolar of breast
What are the biochemical changes during pregnancy
- weight gain: more if carrying less weight prior to pregnancy
- Increased protein and lipid synthesis
- Insulin resistance
What are physiological changes during pregnancy ?
Placenta -oestrogen, progesterone, hCG secretion
Ant pituitary - increased prolactin, little LH and FAH
Adrenal cortex - increases aldosterone and cortisol
Post pituitary -increased vasopressin
Parathyroids - increased parathyroid
Breast- enlarge and develop glandular structure
What provides the embryo with nutrients in the first few weeks?
Simple nutritive system from the endometrial cells
When does the placenta begin to develop?
-At blastocyst implantation
What is the placenta?
Interlocking foetal and maternal tissues which serves as the organ of exchange between mother and foetus
What is the first stage of foetal development ?
Implantation - this is completed by the 11th day post ovulation
What occurs in the first stage of placenta development ?
- 8 cell morula arrives in the uterus and develops into a blastocyst
- The outer cell layer = TCM (primary trophoblastic cell mass)
- TCM invades the endometrium which degenerates and the trophoblast contacts stroma
What supplies the embryonic portion of the placenta ?
-Chorion = outermost layer of trophoblast cells?
Explain the development of placental sinus
- Chorion villa extend from the chorion to the endometrium
- Enzymes and paraffin molecules secreted from the cells of the invading villi alter the surrounding endometrium creating a placental sinus of maternal bloo
Explain maternal and placental blood flow?
Maternal : enters placental sinus through uterine artery, flows through sinus and leaves via the uterine veins.
Placental : blood flows into the capillaries of the chorion villi via umbilical artery and out via the umbilical vein.
Umbilical vessels are contained within the umbilical cord
What supplies the maternal portion of the placenta?
Decidua (uterine lining forming the maternal part of the placenta)
What does the placenta provide for the foetus ?
Nutrition
Gas exchange
Waste removal
Endocrine and immune support
What are the 3 main placental functions ?
Metabolism
Transport
Endocrine
What are the metabolism functions of the placenta ?
-Synthesis: Glycogen
Cholesterol
Fatty acids
-Provides nutrition and energy
What are the placental transport functions ?
- Gas and nutrition
- Water
- Glucose
- Vitamins
- AA
- Hormones (mainly steroid NOT protein)
- Electrolytes
- Maternal antibodies (IgG NOT IgM)
- Waste products
- Drugs and their metabolites
- Infectious agents
What are the physical barriers to transport?
- Fetal endothelial cells
- Fetal connective tissue
- Chorionic epithelial cells
- Endometrial epithelial cells
- Maternal connective tissue
- Maternal endothelial cells
Where does the amniotic cavity form?
-Between the inner cell mass and the chorion
What is the role of the amniotic fluid ?
Resembles foetal extracellular fluid and buffers mechanical disturbances and temp variations
How is the foetus attached to the placenta?
By the umbilical cord
When is pregnancy defined from?
-After implantation is complete , approx: one week after fertilisation
What is the concept behind oral contraception ?
Oestrogen and progesterone can inhibit anterior pituitary gonadotropin release, preventing ovulation
What is menopause and when does it usually occur?
Cessation of menstruation
48-52 yrs
Explain the mechanism behind menopause
- Primordial follicles deplete at around 40 yrs
- Decrease in follicular oestrogen production
- Gradual Increase in FSH and LH due to lack of negative feedback
- Decline of inhibin causing further FSH increase
- Increase in FSH causes rapid increase in oestrogen secretion from follicles
- This causes shorter menstrual cycles
- Fewer follicles remain, increase in FSH no longer stimulates oestrogen increase (6-12 months premenopausal)
- Decrease in oestrogen and lack of ova = menopause
What are the short term signs of menopause ?
Hot flushes,sweats, palpitation, headaches
Irritability, lethargy, panic attacks and depression
Shorter menstrual cycle
Altered blood loss
Skin dryness
What are the long term signs of menopause ?
Vaginal dryness = painful intercourse Decrease in libido Hair loss / thinning Dismissed urethral seal and loss in compliance General aches and pains
Why are women more likely to develop osteoporosis than men following menopause
The hormone changes that occur following menopause affect bone density
Oestrogen is essential for health bones, the drop after menopause causes a massive decrease in bone density
What is tubuloglomerular feedback?
- GFR of an individual nephron is measured by rate at which filtered fluid reach distal tube
- Macula densa detect NaCl arrival
- Reduction in NaCl leads to prostaglandin release by macula densa cells
- This acts on granular cells, triggering renin release activation renin-angiotensin system
What happens to the non-functioning X chromosome in a female?
Condenses into a nuclear mass called sex chromatin or Barr body = lyonisation
What is the pH calculation equation
pH = -log10 [H+]
What is the normal range of pH?
7.35-7.45
What is the base excess ?
Quantity of acid required the return plasma pH to normal
What is the standard base excess ?
Quantity of acid required to return extra cellular fluid back to normal [ICF]
What is acidosis ?
Blood more acid than normal
What is alkalosis ?
Blood more alkaline that normal
What is acidemia ?
Low blood pH
What is alkalemia?
High blood pH
What is the anion gap and how is it calculated ?
-The difference between measured anions and cations
Anion gap = [Na+] + [K+] - [Cl-] - [HCO3-]
What is the normal anion gap ?
10-16
What does a wide anion gap suggest?
Lactic acidosis, ketoacidosis, ingestion of aside, renal failure
What does a narrow anion gap (I.e. high CL) suggest?
GI HCO3- loss, renal tubular acidosis
What acts as a urinary buffer in the proximal tubule ?
Phosphate (HPO42-)
Explain how phosphate acts as a urinary buffer?
- Additional H+ that passes out of the epithelial cells into the tubular lumen (from the dissociation of H2CO3) combines with HPO42-.
- This forms H2PO4-
- This is then excreted in the urine
Why does the actions of phosphate urinary buffers alkalinize the blood plasma ?
- HCO3- from the dissociation of H2CO3 passes into the interstitial fluid, however no HCO3- is absorbed from the tubular lumen.
- This means there is net gain of HCO3- in the interstitial and thus plasma.
At what point does phosphate begin combining with excess H+?
After all filtered HCO3- has been reabsorbed
Explain how ammonium acts as a urinary buffer ?
- Glutamine is taken up from both the glomerular filtrate and peritubular plasma into the epithelial cells.
- Here it is metabolised to form ammonia (NH3) and bicarbonate
- NH3 reacts with H+ to form ammonium (The H+ comes from dissociation of H2CO3 or that absorbed along with Na+)
- Ammonium is secreted actively via Na+ / NH4+ countertransporter and excreted
- The bicarbonate moves into the capillaries causing a net gain of HCO3- thereby alkalising the blood plasma.
What is respiratory acidosis ?
Failure to get rid of Carbon dioxide causing a decrease in pH and a build up of CO2.
What causes respiratory acidosis ?
Hyperventilation
COPD
Any kind of respiratory failure (Pulmonary embolism : type 1, hypoventilation : type 2)
What causes respiratory alkalosis ?
CO2 depletion from hyperventilation
Hypoxia
Type 1 respiratory failure (e.g pulmonary embolism-decrease in oxygen, no change or decrease in carbon dioxide
What is respiratory alkalosis ?
Too much CO2 loss resulting in an increase in pH
What is the renal compensation for respiratory acidosis?
Kidneys increase H+ secretion (in the form of ammonium) and more bicarbonate is released into the plasma which will increase the pH
What is renal compensation for respiratory alkalosis ?
Decrease H+ secretion
The decrease in H+ secretion will also decrease bicarbonate reabsorption resulting in more bicarbonate excretion and thus a fall in HCO3- further helping to increase pH
What is metabolic acidosis ?
Excess acid production (intercalated cells release acid) resulting in a decrease in pH
What can cause metabolic acidosis ?
Renal failure
GI HCO3- loss
Dilution of blood (more water in blood, the more acidic it gets)
Failure of H+ secretion (I.e hypoaldosteronism where insufficient aldosterone is released so less Na+ reabsorbed meaning less H+ secreted)
Excess H+ (e.g. ketoacidosis)
What is the respiratory compensation for metabolic acidosis ?
The decrease in pH will stimulate chemoreceptors of the lung resulting in enhanced respiration resulting in a fall in CO2 resulting in an increase in pH
What is metabolic alkalosis ?
Excess bicarbonate, increasing pH
What can cause metabolic alkalosis ?
Vomiting (due to the loss of gastric secretions which are rich in HCl)
Volume depletion
Alkali ingestion
Hyperaldosteronism
Hyperkalaemia : resulting in increased aldosterone release
What is the respiratory compensation for metabolic alkalosis ?
The increase in pH inhibits the chemoreceptors of the lungs, reducing the respiratory rate thereby increasing CO2 causing a decrease in pH
What are the two endocrine organ functions of the kidney?
Vitamin D activation
Erythropoietin (EPO)
Where is EPO produced ?
-Peritubular cells in the interstitial space of the renal cortex
What does EPO stimulate ?
Stimulates bone marrow maturation of red blood cells (erythrocytes)
What does EPO increase in response too?
Anaemia, altitude and cardiopulmonary disorders
What does EPO decrease in response too?
Polcythaemia (abnormally increased haemoglobin in blood), renal failure
Explain the 2 step activation of vitamin D
In the liver : cholecalciferol is converted to 25-hydroxycholecaliferol (calcifedio)
In the kidney : 25-hydroxycholecalciferol is converted to 1,25-dihydroxycholecalciferol (calcitriol)
What is vitamin D essential for ?
Intestine: increases Ca and PO4 absorption
Increases Bon reabsorption
Increased kidney Ca PO4 reabsorption
Decreases parathyroid hormone (this inhibits the reabsorption in the bone)
