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1
Q

What is the main functions of the kidney?

A
  • 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
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2
Q

What percentage of cardiac output does renal blood flow take?

A

20%

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3
Q

What is the average renal blood flow and in turn renal plasma flow

A
  • 1l/min

- Renal plasma flow- 600ml/min

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4
Q

What is the total urine flow?

A

-1ml/min

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5
Q

Explain the blood supply the the kidney

A
  • 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
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6
Q

What are the two capillary beds of the nephron and how are they connected?

A

Glomerular capillary bed and the Peritubular capillaries connected by an efferent arteriole

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7
Q

What is the glomerular filtration?

A

Passage of fluid from the blood to the Bowmans space to form a filtrate?

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8
Q

What creates the filtration barrier?

A
  • Capillary endothelium
  • Basement membrane
  • Single-celled epithelium of the Bowmans capsule
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9
Q

What is the benefit of the foot process of the podocytes being negatively charged?

A
  • Albumin cannot pass through

- Smaller substances that are negatively charged that would ordinarily pass through are repelled

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10
Q

What are the 5 factors that determine the crossing of materials into the glomerular filtrate?

A
  • 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
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11
Q

What is the total SA of the Bowmans capsule?

A

1m squared

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12
Q

What molecules can freely pass through the filtration barrier?

A

Smaller molecules and ions up to 10kDa

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13
Q

What is the only protein secreted by the tubules found in the urine?

A

Tam Horsfall

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14
Q

What disease can be caused by damage to the filtration barrier and what can cause this damage?

A
  • Nephronic syndrome

- Immune conditions, genetic abnormalities of proteins involved in podocytes/slit diaphragms, diabetes

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15
Q

What are the two pressure determining glomerular filtration rate?

A
  • 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)
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16
Q

What is the glomerular filtration rate and it’s equation?

A
  • The filtration volume per unit time (minutes)
    GFR = Kf (Pgc-Pbs) - (oncotic of glomerular capillary - oncotic of bowmans space)

K= filtration coefficient

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17
Q

What is the GFR of an average 70Kg person

A

125ml/min

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18
Q

How is glomerular filtration rate increased through pressure control?

A

1) constrict efferent arteriole- increase hydrostatic pressure- increase GFR
2) dilate afferent arteriole - increase blood flow - increase hydrostatic pressure - increase GFR

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19
Q

How is GFR decrease through controlling pressure?

A

1) constrict afferent arteriole- les blood flow - decreases hydrostatic pressure - decrease GFR
2) dilate efferent arteriole - reduce blood flow- decreased blood pressure - decrease GFR

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20
Q

What keeps renal blood flow, capillary pressure and GFR maintained at a constant?

A
  • 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
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21
Q

How does autoregulation prevent an increase in systemic arterial pressure?

A

Pressure within afferent arteriole rises - this stretches the vessel was - this triggers contraction of smooth muscle - arteriolar constriction

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22
Q

How is GFR measured and what kind of substance used?

A
  • measuring the excretion of a marker substance (M)
  • Freely filtered (all is filtered)
  • Not secreted or absorbed in tubules
  • not metabolised
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23
Q

What is typically used clinically to measure GFR?

A

Creatinine

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24
Q

What is the filtration fraction and how is it calculated ?

A
  • The proportion of renal blood flow that gets filtered

- filtration fraction = GFR / renal plasma flow

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25
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
26
What epithelium surrounds the Bowmans capsule?
Parietal epithelium
27
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
28
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
29
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)
30
What is tubular reabsorption?
-Reabsorption of substance from the tubules to the Peritubular capillaries
31
What is tubular secretion?
Secretion of substances from the Peritubular capillaries to the tubular lumen
32
What 3 factors determine GFR?
- Net filtration pressure - SA for filtration - Permeability of corpuscular membrane
33
Why can’t the full length of the ureter be seen on an X-ray?
-Contraction of the ureter
34
At what level is the umbilicus?
-L4/ L5, where the aorta bifurcates
35
Why is the urethra narrower near the bladder?
-It is surrounded by the prostate
36
What can be found between the two medullary pyramid?
-Medullary column
37
Why do medullary pyramids appear striped?
-The collecting ducts and loops of henle run parallel, along with the blood vessels
38
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.
39
What does the ectoderm become?
-CNS
40
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
41
What does the kidney develop from in the embryo?
-Intermediate mesoderm
42
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
43
What do the individual glomeruli of the mesonephros drain into?
-Mesonephric duct
44
Where does the ureter grow out of?
-Mesonephric duct
45
What is the lowest part of the mesonephros?
-Metonephric blastema
46
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)
47
What will the mesenephric duct form in the male?
-Vas deferens
48
What are primordial germ cells and where do they migrate too?
- Produce sperm and eggs | - Genital ridge
49
What does the mesonephric duct end in?
-Cloaca
50
What forms from the cloaca?
-Bladder
51
What happens to cranial tubules as caudal tubules form?
-The cranial tubules start to degenerate whilst the caudal still form
52
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.
53
What does the metanephric blastema form?
-Glomeruli and tubules
54
In the metanephros what does the uteric tube form?
-Collecting ducts and ureter
55
How many times does the uteric bud divide once it reaches the blastema?
-3 times
56
What is medullary sponge kidney?
-Where the glomeruli do not attach to the collecting ducts
57
What happens to the urine produced in utero?
-It is secreted into the amniotic fluid. Recycled back through the kidney of the foetus.
58
What does little amniotic fluid suggest?
-The kidneys are functioning efficiently
59
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.
60
How is shifting of the kidney achieved?
-Diminution of body curvature and growth of the lumbar and thoracic regions.
61
During fetal life, what is responsible for excretion of waste products?
-Placenta
62
When do glomerular capillaries start forming?
-10th week
63
When does the metanephros start functioning?
-12th
64
What is the allantois and what does it form?
-It is an anterior outgrowth of the cloaca and forms the bladder
65
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
66
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
67
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
68
In females, what does the urethral epithelium give rise too?
-Urethral and paraurethral glands
69
What is the cause of 3/4 kidneys?
-The uteric bud divides before it reaches the metanephric blastema
70
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.
71
What is the consequences of having two renal arteries?
- Can compress the ureter which leads to blockages | - Lengthy operation of used in a transplant.
72
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.
73
When does the pronephros develop and how long is it present
- Week 4 | - One week
74
Where do urogenital organs derive from?
-Intermediate mesoderm
75
When do gonads acquire male/female characteristics and what sets off this differentiation?
- Week 7 | - When germ cells pass into the genital ridge
76
Where do germ cells arise?
-Yolk sac
77
What do gonads appear as and where are they located?
-Genital ridges, medial to the mesonephros
78
What are the pairs of ducts that form on the gonads?
- Mesonephric duct (Wolffian duct) | - Paramesonephric duct (Mullerian duct)
79
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
80
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
81
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
82
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.
83
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.
84
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.
85
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
86
What is the role of Sertoli cells?
-Assist development of spermatogonia
87
What do leydig cells secrete?
-Testosterone
88
What happens when primordial cells arrive in the gonad?
-The mesoderm begins to thicken and starts to develop primitive sex cords.
89
Where do sperm mature?
-Epididymis
90
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.
91
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.
92
What cells surround the Oocyte?
-Follicular cells
93
What happens to the mesonephric duct and the mesonephric excretory tubules in females?
-They degenerate
94
What does the para mesonephric duct form in the female?
-The bottoms fuse with the top ends ends forming the Fallopian tubes.
95
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.
96
What is oestrogen involved in the differentiation of the Müllerian ducts in to?
- Uterine tubes - Uterus - Cervix - Upper 2/3 of the vagina
97
What does oestrogen stimulate the urogenital sinus to develop in to?
External genitalia: - Lower 1/3 o the vagina - Labia minora - Labia majora - Clitoris
98
What does the broad ligament divide the pelvic cavity in to?
- Urorectal pouch | - Uterovesical pouch
99
What are the properties of the skin on the urethral folds?
- Stratified squamous non keratinising | - No hair follicles / sweat glands
100
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
101
Fusing of the labia majora for a what?
-Scrotum
102
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
103
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
104
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
105
How many litres of filtrate do you produce a day?
-180L/day
106
Which tubules is permeable in the nephron?
-Proximal = bulk reabsorption
107
What is the function of the PCT?
- Bulk reabsorption of Na, CL, glucose, AA and bicarbonate | - Secretion of organic ions
108
What is the function of the loop of henle?
- More Na reabsorption - Urinary dilution - Generation of medullary hypertoxicity
109
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
110
What is the function of the collecting duct?
- Acid secretion - Regulated water reabsorption concentrating the urine - Regulated Na reabsorption and K secretion
111
What is the difference between a symporter and an anti porter?
- Symporter: simultaneously brings two positive substances in. - Antiporter: Exchanges two positive substances
112
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)
113
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.
114
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.
115
What enzyme breaks H2CO3 into carbon dioxide and water?
-Carbonic anydrase
116
What is falcons syndrome?
-AA, glucose and bicarbonates leaking into the urine
117
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
118
What happens after the tubular maximum of glucose is reached?
-There is a sharp increase in excretion of glucose
119
What are features of proximal tubular damage?
-Aminaciduria, glycosuria and bicarbonate wasting
120
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
121
What percentage of creatinine is secreted into the urine?
-15%
122
What is glomerulartubular balance ?
-More filtered load is matched by more proximal tubular reabsorption
123
What limb of the loop of henle is permeable to water?
-Descending
124
Where does solute reabsorption occur in the loop of henle and what channel does this involve?
-Thick ascending limb
125
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.
126
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.
127
What is the cotransporter in the DCT and what drug inhibits it?
- NCC: transports Na- | - Thiazide
128
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).
129
What channels are found in principal cells?
-ENac: epithelial sodium channels
130
What is the action of aldosterone?
- Increases transcription of ENac and so increase apical Na influx. - This charge movement facilitates K efflux.
131
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
132
What is the action of amiloride?
-Blocks the ENac channel
133
What is the action of spirolactone?
-Blocks the steroid receptor that aldesterone would bind too.
134
What determines the limits of urine osmolarity?
-How dilute it can enter the distal segment and how hypertonic the medullary interstitium is.
135
When is the main osmolyte when urine enters the collecting duct?
-Urea
136
Where is ADH produced?
-Hypothalamus
137
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
138
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
139
What do intercalated cells exchange for acid in its reaction?
-Potassium
140
What are tubulopathies?
-Mutations of apical sodium transporters
141
What sodium channel does Bartlers syndrome block?
-NKCC2: thick ascending limb
142
What sodium channel does Gitelmans syndrome block?
-NCC in DCT
143
What sodium channel does Liddle’s syndrome block?
-ENaC in collecting duct
144
What supplies the proximal and distal tubules with blood?
-Peritubular capillaries
145
What supplies the loop of henle with blood?
-Vasa recta
146
What are the two parts of the collecting duct?
- Cortical collecting duct | - Medullary collecting duct
147
What percentage of nephrons are juxtamedullary and what are these nephrons responsible for?
- 15% | - Generating hypertonic medullary interstitium
148
What percentage of nephrons are cortical and what are the loop of henle of these nephrons responsible for?
- 85% | - Reabsorption and secretion
149
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
150
What percentage of filtered urea is reabsorbed?
-50%
151
Who determines fetal sex?
The Male: provides the X or Y chromosome
152
Where is the yolk sac?
Hindgut
153
What movement allows migration of germ cells?
-amoeboid
154
How many oocytes are roughly left at birth?
-1 million
155
When does meiosis 1 occur in females?
-in month 3 of intrauterine life
156
When is metaphase 1 arrested in females?
-until after puberty
157
What triggers the resumption of meiosis 1 in the female and when does this occur?
-LH surge
158
When is meiosis II arrested and resumed in the female?
-Metaphase II and until fertilisation
159
What is gonadal dysgenesis?
-Defective development of gonads in the embryo.
160
Give a cause of gonadal dysgenesis
-Non-disjunction
161
Give 2 examples of gonadal dysgenesis
- Turners syndrome:45XO | - Kleinfelters syndrome: 47XXY
162
Give an example of a male disorder of sex differentiation
-Partial androgen insensitivity syndrome
163
Give an example of a female disorder of sex differentiation
-congenital adrenal hyperplasia
164
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
165
Where does meiosis occur in males and females?
Males: semiferois tubules Females: ovaries
166
What is ejaculate a mixture of?
Sperm and seminal plasma
167
What are the 3 glands of the male reproductive system?
- Prostate - Seminal vesicle - Bulbourethral
168
What forms the blood-Testis barrier?
-The tight junctions between Sertoli cells
169
Where are the most mature cells found in the testis?
-Closer to the centre of the seminiferous tubules
170
Are leydig cells found inside or outside of the seminiferous tubules?
-Outside
171
What veins are responsible for lowering the temp of the testis for spermatogenesis?
-Panpiniform plexus
172
What do primary spermatocytes differentiate into after meiosis I?
-Secondary spermatocytes
173
What do secondary spermatocytes develop into after meiosis II?
-Spermatids
174
What is spermiogenesis?
-Transformation of spermatids into spermatozoa (sperm)
175
What 2 types of cell do spermatogonia produce after mitosis?
- Type A: remain outside the BTB | - Type B: differentiate into primary spermatocytes following mitosis
176
How much sperm is produced per gram of testis per second?
- 300- 600 sperm
177
What is the acrosome in the sperm cell?
-Compacted golgi: contains all the necessary enzymes to pass into the egg cell.
178
How long does it take to complete spermatogenesis?
-64 days
179
What does the head of the sperm contain?
-Acrosome -Nucleus Basal body
180
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
181
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
182
How long does sperm remain fertile in the epididymis?
40-60 days
183
What are the 3 glands in the male reproductive system and what do they produce?
- Seminal vesicles, prostate and bulbourethral | - seminal plasma
184
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
185
What is the normal sperm count and what sperm count is associated with infertility?
50-120 million / ml | Infertility: <25 million / ml
186
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.
187
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
188
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
189
What are the two phases of the menstrual cycle and what are they separated by?
- Follicular phase - Luteal phase - Separated by ovulation
190
What days does the follicular phase of the menstrual cycle span between?
-Days 1-13
191
What do follicles within the ovaries begin as and what does this consist of?
- Primordial follicles | - A single primary oocyte surrounded by granulosa cells
192
What do granulosa cells produce?
- Oestrogen - Small amounts of progesterone before ovulation - Inhibin
193
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
194
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
195
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
196
What occurs as a primary follicle develops in a preantral follicle?
- The follicle grows larger through mitosis of granulosa cells - The theca forms
197
What is the theca?
-Where the connective tissue surrounding the granulosa cells differentiates and forms layers
198
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
199
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
200
What happens to the non-dominant follicles during the menstrual cycle?
-They undergo atresia
201
What causes a primary oocyte to emerge from its meiotic arrest?
-A surge in LH, this division leads to a secondary oocyte
202
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.
203
What causes ovulation?
-when the thin walls of the follicle and ovary rupture at the site where they are joined due to enzyme digestion
204
What is a mature follicle also known as?
-Graafian follicle
205
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
206
If fertilisation does not occur, when does the corpus luteum reach maximum development?
-10 days, following this is undergoes apoptosis
207
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
208
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
209
What causes levels of FSH to be higher at the start of the menstrual cycle?
-Low levels of oestrogen and progesterone
210
Why do theca cells aid granulosa cells in oestrogen production?
-Granulosa cells are deficient in the enzyme required to produce androgen precursors of oestrogen
211
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
212
What stimulates LH receptors to develop on mature granulosa cells?
-The dominant follicle matures and develops LH receptors due to FSH
213
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
214
What cells do LH act on in the first week?
-Theca cells
215
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
216
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
217
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
217
Along with ovulation what does LH stimulate?
-Transformation of remaining granulosa and theca cells into the corpus luteum
218
What does the corpus luteum secrete large amounts of?
-progesterone
219
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
220
Why does the corpus luteum degrade after 14 days?
-No fertilisation
221
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
222
What does the degradation of the corpus luteum cause a decrease in?
-Progesterone and oestrogen
223
What are the stages of follicle development?
- Primordial follicle - Primary follicle - Preantral follicle - Early antral follicle - Matue follicle
224
What days does the luteal phase occur between?
14-28
225
What are the uterine phases of the menstrual cycle?
- Menstrual - Proliferative - Secretory
226
When does the menstrual phase start and how long does it last?
- Begins on day 1 of the cycle, lasts 3-5 days
227
What occurs during the menstrual phase of the menstrual cycle?
- Endometrium (epithelial uterus lining) degenerates causing period - Stimulated by withdrawal of progesterone
228
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
229
What does the ovarian follicular face include?
- Menstrual phase | - Proliferative phase
230
What happens during the proliferative phase?
-Endometrium begins to thicken due to the influence of oestrogen
231
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
232
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
233
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
234
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
235
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
236
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
237
What is the site of fertilisation?
-Ampulla of the Fallopian tube
238
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
239
What are the 3 parts of the Fallopian tubes, staring at the end closest to the uterus?
- Isthmus - Ampulla - Infundibulum
240
What part of the female reproductive system enables sperm storage and for how long?
- Epidermal cells of the Fallopian tube | - 4-6 days
241
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.
242
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.
243
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
244
Describe the passage of sperm following sex
- Vagina - Cervical mucus - Uterus - A small number reach the Fallopian tubes
245
What enables sperm to pass through cervical mucus?
-oestrogen: makes the cervical mucus watery
246
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
247
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+)
248
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
249
Following binding of sperm to an egg, what reaction is triggered?
-Acrosome reaction
250
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
251
What is a fertilised egg called?
-zygote
252
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
253
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
254
How long after fertilisation does the egg complete meiosis 2?
4-7 hours
255
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
256
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
257
How do monozygotic twins develop?
- During cleavage, dividing cells may become completely separated. - This results in two independently growing cell masses
258
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.
259
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.
260
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
261
What is a blastocyst?
- An outer layer of cells termed the trophoblast - An inner call mass - Central fluid filled cavity
262
What is expansion?
- The cavity expands further and the blastocyst increases in diameter - Zona pellucida thins
263
What is hatching?
-Blastocyst expansion and enzymes result in hatching of the embryo from the zona pellucida
264
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
265
What day does the embryo reach the uterus?
5/6
266
What is the aposition stage?
-The hatched blastocyst orientates via embryonic pole and synchronises with receptive endometrium
267
What occurs during the attachment implantation stage?
-Endometrial epithelial cells and trophoblastic cells express integrins which connect with one another
268
What do trophoblasts differentiate into during implantation?
- Cytotrophoblasts | - Syncitiotrophoblasts
269
What occurs during the invasion stage of implantation?
-Enzyme degradation of the basal lamina
270
What occurs during the decidual reaction of implantation?
-Differentiation of the stromal cells adjacent to the blastocyst
271
What occurs during maternal recognition of implantation?
- Secretion of interleukin-2 | - This prevents antigen rejection of the embryo
272
What is syngamy?
Where male and female pronuclei migrate to the centre of the fertilised egg and are unified
273
What does FSH act on in men?
Sertoli cells
274
What does LH act on in men?
Interstitial / leydig cells Stimulates them to secrete testosterone
275
What happens in the embryo after embryonic genome activation and before blastocyst formation?
Compaction
276
Which Genes confer self renewal and pluripotency in embryonic stem cells?
OCT4 and nanog
277
Explain the location of the suprarenal glands.
-Retroperitoneal and above the kidneys
278
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
279
Explain the veins of the adrenal glands
- Right adrenal artery drains directly into the IVC | - Left adrenal artery drains into the left renal vein
280
What is the nerve supply of the adrenal gland?
-Splanchnic nerve
281
What are the 5 hormones secreted by the adrenal cortex?
-Aldosterone, cortisol corticosterone, dehydroepiandrosterone (DHEA) and androstenedione
282
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
283
What control is the adrenal medulla under?
-Under sympathetic control, it is part of the autonomic nervous system
284
What hormones does the adrenal medulla secrete
- Adrenaline (80%) | - Noradrenaline (20%)
285
What does the adrenal medulla response to?
-Stress
286
What are mineralocorticoids and glucocorticoids classed as? And what is their precursor?
- corticosteroids | - Cholesterol
287
Why do problems with the pituitary or hypothalamus not affect aldosterone release?
-The release of renin from granular cells triggers aldosterone release
288
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
289
What percentage of cortisol is bio available?
5%
290
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
291
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)
292
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
293
What can chronic stress result in?
Severe decreases in bone density, immune function and reproductive fertility -Caused by increased catabolism
294
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
295
What regulates the production of androgens in the adrenal gland?
ACTH released in anterior pituitary
296
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
297
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
298
What receptors have a high affinity for adrenaline and which for noradrenaline ?
- Alpha receptors = noradrenaline | - Beta receptors = adrenaline
299
What epithelium lines the renal pelvis, ureters, bladder and urethra?
Urothelium
300
What epithelium lines the PCT, DCT and collecting duct?
Cuboidal epithelium
301
What percentage of an adult males weight is water?
60%
302
Explain the breakdown of body fluid compartment
-2/3 intracellular -1/3 extra cellular: 75% interstitial 25% plasma
303
Explain the breakdown of Na reabsorption in the nephron
PCT: 60% Loop Of Henle: 25% DCT: 19% Collecting Duct: 4%
304
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.
305
What 3 ways does the kidney maintain water balance?
1) regulation of osmolality - ADH 2) RAAS 3) Atrial natriuretic peptide ANP
306
Where is ADH synthesised and secreted
- Hypothalamus | - Posterior pituitary
307
-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
308
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
309
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)
310
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
311
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
312
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
313
What are the two functions of the parathyroid hormone?
- Increases calcium reabsorption | - Stimulates activation of vitamin D
314
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
315
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)
316
Under what control is the detrusor muscle ?
It is under the control of the autonomic nervous system with some voluntary control
317
Give 4 causes of pre - Renal acute injury
- cellulitis - Decompensated heart failure - Decompensated liver failure - Diarrhoea and vomiting
318
What is the overall effect of aldosterone ?
Lower blood pressure
319
What is blood flow to the kidneys per minute ?
1L/ min
320
Approx how many lire’s of filtrate passes through renal space per day?
280L
321
What is a normal healthy volume of urine production?
1ml / kg / hr
322
Give the 3 muscles of the bladder and the type of muscle
Detrusor- smooth Internal urethral sphincter - smooth External urethral sphincter - skeletal
323
What is the term for urination
Micturition
324
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
325
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
326
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
327
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
328
What is urinary tract function
- Collect urine - Store it under safe low pressure - Store until socially acceptable to release urine
329
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
330
What are the 3 consequences of bladder dysfunction
- Incontinence - Infection and bladder stones - Upper urinary tract injury due to high pressure
331
What can the external urethral sphincter be known as?
Rhabdospincter
332
Where do encoring glands release directly into?
-The blood, they are ductless
333
What do endocrine glands allow?
- Rapid adaptive changes - Integration of whole body physiology - chronic maintenance of metabolic environment - communication for multicellular organisms
334
When do thyroid glands begins producing thyroxine
18-20 weeks
335
What are the 2 hormones of the thyroid
T4 : Thyroxine | T3 : Triidothyronine
336
What protein rich material is at the centre of thyroid follicles
Colloid | Contains large amounts of thyroglobulin
337
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)
338
What is iodide trapping
When iodide is contransported with Na+ into follicular cells
339
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)
340
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
341
What hormone stimulates all actions of the follicular epithelial cells ?
-Thyroid stimulating hormone (TSH)
342
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
343
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
344
What can cause hypertrophy of thyroid glands ?
Exposure to greater amounts of TSH | It means it increases in size (goitre)
345
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
346
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
347
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
348
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
349
What is the hypothalamus stimulated to release by other areas of the CNS?
Hypophysiotropic hormones
350
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
351
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
352
How many types of hormone producing cell does the ant. pituitary have ?
5
353
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
354
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
355
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
356
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
357
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
358
Which of the 6 ant.pituitary hormones show loop loop negative feedback?
- ACTH - FSH - LH - TSH
359
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.
360
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)
361
What are the hormones of the posterior pituitary?
- ADH | - Oxytocin
362
Where are the 2 posterior pituitary hormones synthesised ?
- ADH (cell body of supraoptic nucleus) - Oxytocin (cell body of paraventricular nucleus ) Both within hypothalamus
363
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
364
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
365
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
366
What type of receptors do all pituitary and hypothalamic hormones act on?
G-protein coupled receptors
367
What are 99% of the cells in the pancreas?
Acini
368
What function is performed by the acinar cells?
Exocrine function
369
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.
370
What makes up 1-2% of the cells of the pancreas ?
Islets of langerhans
371
What does the islets of langerhans do?
Manufacture and release peptide hormones into the portal vein
372
What are the 3 cells of the islets of langerhans
Beta cells : insulin Alpha cells : glucagon Delta cells : somatostatin
373
What do beta cells of the pancreas secrete?
Insulin
374
What do alpha cells of the pancreas secrete?
Glucagon
375
What do delta cells of the pancreas secrete?
Somatostatin
376
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)
377
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
378
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.
379
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
380
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
381
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
382
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.
383
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)
384
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.
385
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)
386
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
387
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
388
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
389
Explain the proportion of glucose to the liver and periphery
40% to liver | 60% to periphery
390
What does ingested glucose help?
-replenish glycogen stores in liver and muscles
391
What happens to excess glucose?
It is stored as fat
392
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.
393
What does hyperglycaemia cause ?
-Inhibits release of glucagon and stimulates release of insulin
394
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
395
What are the functions of the skin?
- Barrier to infection - Thermoregulation - Protection against trauma - Protection against UV - Vitamin D synthesis - Regulates water loss
396
What are the 3 layers of the skin?
- Epidermis - Dermis - Subcutaneous tissue
397
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
398
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
399
What disease sees increased numbers of corneo-desmosomes ?
Psoriasis : thickening of stratum corneum
400
What disease sees decreased numbers of corneo-desmosomes
Atopic eczema : thinning of stratum corneum, giving an increased risk of inflammation.
401
What produces natural moisturising factor (NMF) found in corneocytes?
-Filaggrin (derived from profilaggrin)
402
What is the role of NMF ?
Helps to maintain skins hydration by keeping water inside the skin
403
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.
404
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)
405
What is the role of the lipid lamellae?
- Keeps water inside the skin cells | - Irritants and allergens bounce off the surface
406
Why is vitamin D essential for skin ?
Producing anti-microbial peptides to defend the skin from bacteria and viruses
407
What is the effect of irritants on the skin?
They break down healthy skin
408
What is the effect of allergens on the skin?
Trigger skin flare ups by penetrating into the skin and causing the skin to react
409
How do allergens cause skin flare ups and inflammation ?
They penetrate the skin, where they met by lymphocytes which release chemicals that induce inflammation
410
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
411
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
412
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
413
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
414
How can cosmetics and oily skin trigger acne?
They ‘plug’ the hair follicle and initiate the acne process
415
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
416
Explain the effect of FSH on Sertoli cells
Stimulates the release of paracrine agents required fo initiate spermatogenesis
417
Explain the effect of LH on leydig cells
Stimulates them to secrete testosterone
418
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
419
Explain the effects of testosterone
- Acts locally by diffusing from interstitial space into seminiferous tubules - Enters sertoli cells to aid spermatogenesis
420
Explain how Sertoli cells inhibit FSH release
They secrete inhibin which inhibits FSH release from anterior pituitary
421
When does mitosis of oogonia occur?
Early fetal development, stops around the 7th month
422
What do all oogonia differentiate into?
Primary oocytes
423
When does meiosis I of primary oocytes begin ?
in-uteric before 12 weeks
424
When is meiosis I of a primary oocyte arrested and when is it completed ?
- Metaphase I | - Until puberty, completed just before ovulation
425
What does meiosis I of a primary oocyte produce ?
- Secondary oocyte (retains nearly all cytoplasm) | - small, non-functioning first polar body
426
When is meiosis II of a secondary oocyte arrested until ?
-Arrested at metaphase II until fertilisation in a Fallopian tube by a sperm
427
What does meiosis II of a secondary oocyte produce ?
- Ovum | - Second polar body
428
How many ovum can one primary oocyte produce?
1
429
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)
430
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
431
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
432
In normal puberty, what it is driven by and dependent on?
- Centrally driven | - Dependent on an intact hypothalamic-pituitary gonadal axis
433
What is puberty influenced by?
- Nutrition - Genetic factors - Insulin - Exercise
434
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
435
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
436
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
437
How many weeks are you pregnant
- 40 weeks (from first day of menstrual cycle) | - 38 weeks (counting from the day of ovulation and conception)
438
What maintains the relative disconnection of the smooth muscle cells of the myometrium during pregnancy?
Progesterone
439
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
440
What is cervical ripening ?
The growth and remodelling of the cervix prior to labour
441
What accelerates cervical ripening in the last 3 months of pregnancy ?
Oestrogen
442
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
443
What mediates the synthesis of enzymes to breakdown collagen fibres ready for birth ?
Oestrogen Placental prostaglandins - PGE Relaxin
444
What secrets relaxin and what is it’s role
Ovaries, placenta and uterus | Softens cartilaginous joints in the pelvis in prep for labour
445
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
446
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
447
What occurs at the onset of labour ?
Amniotic sac ruptures and the amniotic fluid flows through the vagina
448
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
449
What so increases intensity and frequency of contractions cause?
The cervix is forced open (dilation)
450
What is the maximum dilation of the cervix?
10cm
451
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
452
What happens or oestrogen and progesterone levels during pregnancy?
Continuously increase
453
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
454
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
455
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)
456
What causes the persistence of the corpus luteum in the first 3 months of pregnancy ?
Human chorionic gonadotropin (hCG) hormone
457
What produces the human chorionic gonadotropin hormone ?
Trophoblast cells when they begin the endometrial invasion at day 7-8 (onset of implantation)
458
What hormone is used as an indicator of pregnancy ?
hCG
459
What is the role of hCG?
- Stimulates secretion of oestrogen and progesterone by corpus luteum. - Stimulates maternal ovaries fo secrete oestrogen and progesterone
460
When do hCG levels reach a peak?
60-80 days after last menstruation
461
What secreted necessary oestrogen and progesterone when hCG levels decrease?
Placenta
462
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
463
Where does the placenta obtain the necessary androgen precursors for oestrogen ?
Maternal ovaries Maternal adrenal medulla Foetal adrenal medulla
464
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
465
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
466
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
467
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 ```
468
Give a summary of prostaglandins during pregnancy
PGF2a is the main one, PGE2 is 10x stronger Produced by uterine tissues Initiates labour
469
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 ```
470
Give the respiratory change during pregnancy
Increased alveolar ventilation
471
Give gastrointestinal changes during pregnancy
Increased acid reflux and gastroparesis (delayed emptying)
472
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
473
What are the biochemical changes during pregnancy
- weight gain: more if carrying less weight prior to pregnancy - Increased protein and lipid synthesis - Insulin resistance
474
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
475
What provides the embryo with nutrients in the first few weeks?
Simple nutritive system from the endometrial cells
476
When does the placenta begin to develop?
-At blastocyst implantation
477
What is the placenta?
Interlocking foetal and maternal tissues which serves as the organ of exchange between mother and foetus
478
What is the first stage of foetal development ?
Implantation - this is completed by the 11th day post ovulation
479
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
480
What supplies the embryonic portion of the placenta ?
-Chorion = outermost layer of trophoblast cells?
481
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
482
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
483
What supplies the maternal portion of the placenta?
Decidua (uterine lining forming the maternal part of the placenta)
484
What does the placenta provide for the foetus ?
Nutrition Gas exchange Waste removal Endocrine and immune support
485
What are the 3 main placental functions ?
Metabolism Transport Endocrine
486
What are the metabolism functions of the placenta ?
-Synthesis: Glycogen Cholesterol Fatty acids -Provides nutrition and energy
487
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
488
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
489
Where does the amniotic cavity form?
-Between the inner cell mass and the chorion
490
What is the role of the amniotic fluid ?
Resembles foetal extracellular fluid and buffers mechanical disturbances and temp variations
491
How is the foetus attached to the placenta?
By the umbilical cord
492
When is pregnancy defined from?
-After implantation is complete , approx: one week after fertilisation
493
What is the concept behind oral contraception ?
Oestrogen and progesterone can inhibit anterior pituitary gonadotropin release, preventing ovulation
494
What is menopause and when does it usually occur?
Cessation of menstruation | 48-52 yrs
495
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
496
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
497
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 ```
498
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
499
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
500
What happens to the non-functioning X chromosome in a female?
Condenses into a nuclear mass called sex chromatin or Barr body = lyonisation
501
What is the pH calculation equation
pH = -log10 [H+]
502
What is the normal range of pH?
7.35-7.45
503
What is the base excess ?
Quantity of acid required the return plasma pH to normal
504
What is the standard base excess ?
Quantity of acid required to return extra cellular fluid back to normal [ICF]
505
What is acidosis ?
Blood more acid than normal
506
What is alkalosis ?
Blood more alkaline that normal
507
What is acidemia ?
Low blood pH
508
What is alkalemia?
High blood pH
509
What is the anion gap and how is it calculated ?
-The difference between measured anions and cations Anion gap = [Na+] + [K+] - [Cl-] - [HCO3-]
510
What is the normal anion gap ?
10-16
511
What does a wide anion gap suggest?
Lactic acidosis, ketoacidosis, ingestion of aside, renal failure
512
What does a narrow anion gap (I.e. high CL) suggest?
GI HCO3- loss, renal tubular acidosis
513
What acts as a urinary buffer in the proximal tubule ?
Phosphate (HPO42-)
514
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
515
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.
516
At what point does phosphate begin combining with excess H+?
After all filtered HCO3- has been reabsorbed
517
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.
518
What is respiratory acidosis ?
Failure to get rid of Carbon dioxide causing a decrease in pH and a build up of CO2.
519
What causes respiratory acidosis ?
Hyperventilation COPD Any kind of respiratory failure (Pulmonary embolism : type 1, hypoventilation : type 2)
520
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
521
What is respiratory alkalosis ?
Too much CO2 loss resulting in an increase in pH
522
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
523
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
524
What is metabolic acidosis ?
Excess acid production (intercalated cells release acid) resulting in a decrease in pH
525
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)
526
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
527
What is metabolic alkalosis ?
Excess bicarbonate, increasing pH
528
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
529
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
530
What are the two endocrine organ functions of the kidney?
Vitamin D activation | Erythropoietin (EPO)
531
Where is EPO produced ?
-Peritubular cells in the interstitial space of the renal cortex
532
What does EPO stimulate ?
Stimulates bone marrow maturation of red blood cells (erythrocytes)
533
What does EPO increase in response too?
Anaemia, altitude and cardiopulmonary disorders
534
What does EPO decrease in response too?
Polcythaemia (abnormally increased haemoglobin in blood), renal failure
535
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)
536
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)

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