SUGER Flashcards
1
Q
What sex chromosomes do males have?
A
XY
2
Q
What sex chromosomes do females have?
A
XX
3
Q
Why does the male partner determine foetal sex?
A
Because spermatozoon can be 23X or 23Y whereas the egg can only contribute X chromosome
4
Q
Which gene on the Y chromosome is important for the development of male gonads?
A
SRY gene
5
Q
Where are both the male and female gonads embryologically derived from?
A
Urogenital Ridge
6
Q
Primordial gonads remain undifferentiated until when?
A
up till 6th week of uterine life
7
Q
What are the components of the undifferentiated reproductive tract?
A
Wolffian Duct (mesonephric duct) Mullerian Duct (Paramesonephric duct) Common opening to outside for genital ducts
8
Q
Which duct regresses in male gonad embryological development and why?
A
Y chromosome present so SRY present so mullerian inhibiting substance produced which causes the mullerian duct to regress
9
Q
Which cells produce Mullerian inhibiting substance?
A
Sertoli cells
10
Q
What role does testosterone play in development of male genitalia?
A
Testosterone produced by Leydig cells causes the wolffian duct to differentiate in the epididymis, vas deferens, seminal vesicles and ejaculator ducts
11
Q
Which parts of the male genitalia is dihydrotestosterone responsible for?
A
Penis
Scrotum
Prostate
12
Q
Which duct regresses in the female and why?
A
Wolffian ducts regress because there’s no SRY gene so no MIF and no testes so no testosterone secretion
13
Q
What does the Mullerian system differentiate into in the female?
A
Uterus
Fallopian tubes
Inner vagina
14
Q
What is the first stage of gametogenesis of primordial germ cells?
A
Mitosis
15
Q
When does germ cell mitosis occur in the male?
A
Some mitosis occurs in embryonic testes to generate primary spermatocytes and the rest begins at puberty
16
Q
When does germ cell mitosis occur in the female?
A
Primarily during foetal development
17
Q
What does germ cell mitosis in the male produce
A
Primary spermatocytes
18
Q
What does germ cell mitosis produce in the female?
A
Primary oocytes
19
Q
What is the result of the first meiotic division in males
A
2 secondary spermatocytes are produced
20
Q
What is the result of the first meiotic division in females?
A
1 secondary oocyte and a polar body
21
Q
When does the second meiotic division occur in males
A
After puberty
22
Q
When does the second meiotic division occur in females?
A
After fertilisation
23
Q
What is the result of the second meiotic division in males
A
Production of 4 spermatids
24
Q
What is the result of the second meiotic division in females?
A
Zygote and a second polar body
25
The production of 2 identical daughter cells occurs in what process
Mitosis
26
Production of haploid (half the number of chromosomes) gametes occurs in what process
Meiosis
27
Where does meiosis occur in the male?
Seminferous tubules
28
Where does meiosis occur in the female?
Ovaries
29
What are the three erectile compartments of the penis?
Corpus cavernosum x2
| Corpus spongiosum
30
What is the peritoneal structure that covers the testis anteriorly?
Tunica vaginalis
31
What is the white fibrous capsule that covers each testicle?
Tunica Albuginea
32
At what point do the testes migrate from the abdomen to the scrotum?
7th month of pregnancy
33
Why do the testes need to descend from the abdomen to the scrotum?
Because sperm production requires a temperature 2 degrees lower than body temperature
34
How are the testes cooled to a temperature that enables spermatogenesis?
Pampiniform plexus venous blood carries heat away from the testes as it ascends
35
Where does spermatogenesis occur?
Seminiferous tubules
36
Which cells make up the blood testes barrier?
Sertoli cells
37
What do Leydig cells secrete?
Testosterone
38
Describe the passage of sperm to the epididymis
Seminiferous tubules to the straight tubules to the rate testes to the efferent ductus to the epididymis
39
What structure do the vas deferens pass through?
Inguinal canal
40
What are the 5 stages of sperm maturation
```
Spermatogonia
Primary Spermatocytes
Secondary Spermatocytes
Spermatids
Spermatozoa
```
41
Which part of the epididymis receives sperm from the efferent ductules?
Head of the epididymis
42
Where is spermatozoa primarily stored?
Tail of the epididymis
43
What is the name of the enlarged region of the ductus deferens prior to the seminal vesicle and prostate?
Ampulla
44
what are the 3 parts of the urethra?
Prostatic
Membranous
Spongy
45
What do secretions from the seminal gland contain?
High fructose conc
Prostaglandins to stimulate smooth muscle contraction
Fibrinogen to form fibrin clot
Alkaline to neutralise vaginal acid
46
Where do the bulbourethral glands enter the urethra?
Just after the urethra leaves the prostate
47
How much fluid is expelled during orgasm?
2-5ml
48
describe the composition of semen
60% seminal vesicle fluid
30% prostatic secretion
10% sperm
Trace of bulbourethral fluid
49
What does the prostatic secretion contain
Seminal plasmin which has antibiotic properties that help to prevent urinary tract infections in males
50
What does the bulbourethral fluid contain?
Lubricating thick alkaline mucus that neutralises urinary acids that remain in the urethra
51
What enzymes are found in the semen?
Protease to dissolve vaginal mucus
Seminal plasmin
Prostatic enzyme that coagulates semen through conversion of fibrinogen to fibrin
Fibrinolysin that coverts the semen clot to liquid after 15 mins
52
How long does spermatogenesis take?
64 days
53
What are the two types of daughter cell produced from the mitotic division of spermatogonia?
Type A - remain outside blood-testis barrier and produce more daughter cells
Type B - Differentiate in primary spermatocytes which pass through the blood-testis barrier through tight junctions of Sertoli cells
54
Define spermiogenesis
Transformation of spermatids to spermatozoa
| Grow tail and discard cytoplasm to become lighter
55
Describe the structure of spermatozoa
```
Pear shaped head
Nucleus with haploid chromosomes
Acrosome containing enzymes
Flagellum
Mitochondria
```
56
Where is gonadotrophin releasing hormone produced?
Hypothalamus
57
Describe the control of pituitary hormones on male reproduction
GnRH stimulates release of FSH and LH from anterior pituitary
FSH acts on Sertoli cells to initiate spermatogenesis
LH acts on leydig cells to produce testosterone
Testosterone diffuses into Sertoli cells and facilitates spermatogenesis
58
Describe the negative feedback mechanisms in the pituitary hormone control of males
High testosterone negatively feedbacks to decrease secretion of GnRH and also acts directly on anterior pituitary to decrease LH
Sertoli cells also secrete inhibin which acts on anterior pituitary to inhibit release of FSH
59
What are the functions of testosterone?
maintain sexual libido
Stimulate bone and muscle growth
Establish male secondary sex characteristics
Maintains organs and accessory glands
60
What two layers cover the ovaries
Outermost is visceral peritoneum
| Inner layer is tunica albuginea
61
What are the two divisions of the stroma (internal tissue) of the ovary?
Superficial cortex
| Deeper medulla
62
What are the 3 parts of the uterine tube
Infundibulum - closest to ovary and has fimbrae projections
Ampulla - middle region where smooth muscle thickens
Isthmus - Short segment connected to the uterus
63
What is the normal position of the uterus
Anteverted and ante flexed
64
Describe the anatomy of the uterus?
Main part is the body
Curvature of body above the entry point of uterine tubes I the fundus
Body ends at constriction point called isthmus
Cervix is inferior portion
Uterine cavity then internal Os then cervical cavity then external Os
65
What is the blood supply of the uterus?
Uterine artery (from internal iliac arteries) and vein which anastomose with the ovarian artery (from abdominal aorta) and vein
66
What are the 4 ligaments that hold the uterus in place?
Broad ligament
Uterosacral ligament - lateral uterus surface to anterior sacrum
Round ligament - lateral surface of uterus (inferior to uterine tubes) extend through the inguinal canal to external genitalia
Cardinal Ligaments - base of uterus and vagina to lateral pelvic wall
67
What are the three layers of the uterine wall?
Endometrium - innermost
Myometrium - thick muscle
Perimetrium - covers fundus, posterior uterine body and isthmus
68
What ligaments hold the ovaries in place?
broad ligament
Mesovarium
2 Supporting ligaments
69
What are the two supporting ligaments that hold the ovaries in place?
Ovarian ligament - extends from medial ovary to uterus near where uterine tubes attach
Suspensory ligament - extend from the lateral ovary to the pelvic wall
70
What structures are enclosed in the broad ligament?
Uterus
Uterine tubules
Ovaries
71
When does meiosis 1 in females becomes arrested
at metaphase I until puberty
72
When does meiosis 2 become arrested until?
Arrested at metaphase II until fertilisation
73
What are the 3 differences between spermatogenesis and oogenesis?
1 spermatocyte produces 4 spermatids whereas 1 oocyte produces 1 ovum
Both maturations for sperm occur in testis whereas one occurs in ovary and one in Fallopian tube for ovum
Spermatogenesis is continuous whereas oogenesis is discontinuous
74
What are the two phases of the ovarian cycle?
```
Follicular phase (day 1-13)
Luteal phase (day 14-28)
```
75
What does the primordial follicle contain?
primary oocyte surrounded by a single layer of granulosa cells
76
What do granulosa cells secrete?
Oestrogen
Small amounts of progesterone
Inhibin
77
What does the primordial follicle develop into?
Primary follicle
78
What separates the granulosa cells and the oocyte in a follicle?
Zona pellucida
79
Describe the development of the pre-antral follicle
Mitosis of granulosa cells of primary follicle causes follicle to grow and surrounding granulosa cells differentiate into theca cells
Theca cells and granulosa cells together secrete oestrogen
80
Describe the development of the early antral follicle
Primary oocyte reaches full size
| Granulosa cells secrete follicular fluid which creates the antrum
81
What happens to larger antral follicles that are not chosen to become the dominant follicle?
They undergo atresia
82
Describe the development of the mature (Graafian follicle)?
Dominant follicle enlarges as antrum increases in size
primary oocyte undergoes meiotic division to become secondary oocyte
Follicle becomes so large it balloons onto ovary surface and ovulation occurs releasing oocyte onto ovarian surface
83
What happens to the Graafian follicle following ovulation?
Following discharge of antral fluid and egg, the granulosa cells enlarge to form gland-like corpus luteum which remains for 10 days if there is no pregnancy before being broken down to the corpus albicans
84
How long is an oocyte viable for following ovulation?
24-48 hours
85
How long is sperm viable for in the vagina?
4-6 days
86
Describe the steps of follicle development in the follicular phase of the menstrual cycle
Mature (Graafian follicle) develops and so does the secondary oocyte
87
Describe the steps of follicle development in the luteal phase of the menstrual cycle
Begins at ovulation and ends with the death of the corpus luteum
88
Where is oestrogen synthesised in the follicular phase?
Granulosa cells
89
Where is oestrogen synthesised after ovulation?
by the corpus luteum
90
Where is progesterone synthesised before ovulation?
In small amounts by the granulosa and theca cells
91
Where is progesterone synthesised after ovulation?
By the corpus luteum
92
Describe the pituitary hormone control of female reproduction
GnRH pulses determine the release of FSH and LH from anterior pituitary
Release of FSH causes the development of follicle which in turn causes the release of oestrogen from granulosa cells
Increased oestrogen concentration as follicle develops has negativee feedback on hypothalamus release of GnRH
Inhibin is also released with causing further inhibition of FSH secretion
Increased oestrogen production from follicle causes change in GnRH pulse activity which causes surge of LH
LH binds and causes completion of meiosis I and ovulation of mature follicle
Following ovulation the corpus luteum forms which secretes progesterone and has a negative feedback on GnRH and lasts for 10 days before breaking down into the corpus albicans. When it degrades, oestrogen and progesterone drop and this removes negative feedback on FSH, LH and GnRH secretion causing the cycle to repeat
93
What do theca cells produce?
Androgens which are converted to oestrogen by the granulosa cell enzyme aromatase
94
What are the two effects of the LH surge?
Causes ovulation of the mature follicle and transforms remaining granulosa and theca cells into the corpus luteum
95
What are the three phases of the menstrual cycle?
Menses - day 1
Proliferative - day 6-13
Secretory - day 16-28
96
What happens in the menses phase of the menstrual cycle
Functional zone of endometrium degenerates due to constriction of spiral artery blood flow
This is due to removal of progesterone stimulus
97
What happens in the proliferative phase of menstrual cycle?
Between the cessation of menstruation and start of ovulation
Basilar zone and uterine glands of endometrium multiply
Oestrogen produced by the theca cells sustain the proliferation
By day 14, the functional zone is several mm thick
Increased oestrogen induces synthesis of progesterone receptors in endometrial cells
98
What happens in the secretory phase of the menstrual cycle?
Occurs between ovulation and onset of next menstruation
Uterine glands enlarge and accelerate secretion of glycogen rich mucus
Spiral arteries elongate through functional zone
Progesterone acts on oestrogen primed endothelium to convert it to an actively secreting tissue which makes the endometrium a more hospitable environment for implantation
99
What is the effect of ovarian hormones on the cervix
Progesterone and oestrogen effect the secretion of mucus in cervix
oestrogen causes mucus to be clear and water around the time of ovulation
Progesterone after ovulation causes mucus to become thick and sticky to form a plug to prevent bacteria entering the uterus
100
What effect do ovarian hormones have on the vagina?
High oestrogen causes columnar epithelium of vagina to become more mitotically active and show little keritanisation
101
Describe how an ovum is moved from the ovary to the site of fertilisation?
Extruded onto ovary surface then the fimbrae cilia beat waves towards the interior of the Fallopian tube, sweeping the egg inwards
Once in the Fallopian tube the eggs are moved by Fallopian tube cilia
102
How long does it take the egg to reach the uterus after release from the ovary?
4 days
103
Where do the sperm and the egg fuse together?
Ampulla of the Fallopian tube
104
What part of the ovum do sperm bind to?
ZP3 glycoprotein of the zonal pellucida
105
Describe what happens in the acrosome reaction
Plasma membrane of sperm head is altered so acrosome enzymes are exposed to zona pellucida so enzymes can forge a path and fuse with the egg
106
What is the name of the mechanism that prevents polyspermy?
Cortical reaction
107
Describe what happens in the cortical reaction
Secretory vesicles release contents into space between the zona pellucida and egg plasma which inactivates the sperm binding proteins by hardening the entire zona pellucida
108
What happens 4-7 hours after gamete fusion?
Two haploid chromosome sets form the male and female pronuclei
109
Describe what happens in syngamy?
male and female pronuclei migrate to centre and haploid chromosomes pair and replicated DNA ready for first mitotic division
Pronuclear membrane breaks down and mitotic spindles form with 46 chromosomes aligned at spindle equator
110
Describe the process of cleavage on day 2 of fertilisation
Ooplasm divides into two equal halves with decondensation of pronuclei and movement into one of the two blastomeres
successive cleavages increase the cell number
111
When does the activation of the embryonic genome and embryonic gene transcription begin?
4-8 cell Embryo
112
What happens during compaction in day 4 of fertilisation?
Cells flatten to maximise their intracellular contents and tight junctions form
113
What happens during cavitation and differentiation in day 5 of fertilisation?
Tight junctions form between the outer cells and fluid filled cavity expands to form blastocyst
Blastocyst has outer layer of cells called trophoblast and inner cell mass and central fluid filled cavity
Trophoectoderm becomes the placenta
Inner cell mass forms the foetus
114
What happens In the expansion phase of day 5/6 of fertilisation?
Cavity expands with diameter increasing and zona pellucida thining to ensure blastocyst can break through
115
What happens during hatching on day 6+ of fertilisation?
Blastocyst expansion causes embryo to hatch from ZP
116
What is the genetic control of the early cleavage cells in fertilisation?
maternal
117
What is the genetic control of the blastocyst in fertilisation?
Embryonic
118
What is the metabolic activity of the early cleavage cells in fertilisation?
Low
119
What is the metabolic activity of the Blastocyst in fertilisation?
High
120
What is the biosynthetic activity of the early cleavage cells in fertilisation?
Low
121
What is the biosynthetic activity of the blastocyst in fertilisation?
High
122
What are the energy requirements of early cleavage cells in fertilisation?
Simple
| - low glucose and non essential amino acids
123
What are the energy requirements of blastocyst in fertilisation?
Complex
High glucose
Essential and non essential amino acids
Vitamins
124
What are the three phases of embryo implantation
Apposition
Attachment
Invasion
125
Describe the process of apposition?
Unstable adhesion between blastocyst and uterine lining
Synchronisation of embryo and endometrium
Hatched blastocyst orientates via embryonic pole
126
What happens in the process of attachment (adhesion)?
Apical surface of endometrial cells and trophoblastic cells express interns which leads to attachment
127
What happens in the process of invasion (Penetration)?
trophoblast protrusions penetrate the endometrium and change to syncyntiotrophoblast cells which erode the endometrial blood vessels
When syncyntiotrophoblast cells contact maternal blood and form chorionic villi it triggers the initiation of placenta formations
128
How is maternal recognition of the implanting embryo prevented?
Endometrial storm cells secrete interleukin 2 which prevents maternal recognition
129
Where is hCGa synthesised?
In the cytotrophoblastic cells
130
Where is hCGb synthesis
syncyntiotrophoblast
131
What is the role of hCG
Sustains early pregnancy
Ensures corpus luteum continues to produce progesterone
Immunosuppressive
132
What are the 7 stages of fertilisation in order
```
Fertilisation (Day 1)
Syngamy
Cleavage (Day 2-3)
Compaction (Day 4)
Cavitation and differentiation (Day 5/6)
Expansion (Day 6)
Hatching (Day 6+)
```
133
Describe the anatomical location of the kidneys
Retroperitoneal between T12 and L3 with the right kidney lower than the left due to the liver
134
Describe the anatomy of the kidney from outer to inner
Fibrous capsule - Cortex - medullary pyramids, minor calyx, major calyx - pelvis
135
At what level does the renal artery exit the abdominal aorta
L1
136
Describe the blood supply of the kidney
Abdominal aorta to the renal artery to segmental arteries to interLOBAR to arcuate arteries to interLOBULAR arteries to the afferent arterioles to glomerular capillaries to efferent arteriole
137
Describe the venous drainage of the kidney
peritubular capillaries/vasa recta to the interLOBULAR veins to arcuate veins to interLOBAR veins to segmental veins to renal vein
138
what are the components of the renal corpuscle
Glomerular tuft and Bowmans capsule
139
In histology, which stain is used to differentiate mesangial cells from glomerular capillaries and why?
Periodic Acid Shift because it stains the glycoproteins in the glomerulus
140
What are the 3 main functions of mesangial cells?
1. Structural support for capillary and production of extracellular matrix protein
2. Contraction of mesangial cells tightens capillaries and reduces GFR which is important in tubuloglomerular feedback
3. Involved in phagocytosis of GFR breakdown products
141
What are the two components of the juxtaglomerular apparatus
Afferent arteriole
| Distal convoluted tubule
142
Where are the granular cells located?
Afferent arteriole
143
What is the function of granular cells?
Detect blood pressure and secrete RENIN when BP reduces
144
Where are the macula densa cells located
expanded mass of the DCT close to the glomerulus and afferent arteriole
145
What is the function of macula densa cells?
Detect Na+ conc and adjust GFR accordingly by altering afferent arteriole resistance
146
What are the 3 cell types in the juxtaglomerular apparatus
Granular cells
macula densa cells
Lacis Cells
147
How is the PCT adapted for function?
Microvilli to increase surface area for absorption
| Many mitochondria to actively transport Na+ and K+
148
What is reabsorbed (and how much) at the PCT
```
Na+ (65%)
H2O (65%)
Glucose
AA
Lactate
K+
Mg2+
Cl-
HCO3-
Ca2+
```
149
The descending limb of the loop of Henle is impermeable to?
Ions
150
Descending limb of loop of Henle is permeable to?
Water
151
Ascending limb of loop of Henle is permeable to?
Ions (Na+, K+, 2Cl- via NKCC2) but also Mg2+ and Ca2+ via paracellular
152
What are the two cell types in the DCT and CD?
Principal
| Intercalated
153
What are the three major functions of the kidneys?
Endocrine function
Maintain balance of water, salt and pH
Excrete waste products
154
How much cardiac output does each kidney receive?
20%
155
What is the total renal blood flow for both kidneys per minute
1L/min
156
What is the purpose of the renal corpuscle?
To produce a filtrate that is free of proteins, cells and larger polypeptides
157
As blood flows through the glomerulus, what percentage of plasma filters into the Bowman's capsule?
20%
158
What are the three filtration barrier layers that separate the glomerulus from the Bowman's capsule?
1. Capillary endothelium
2. Basement membrane
3. Podocytes and their foot processes
159
What percentage of nephrons are juxtamedullary and what percentage are cortical?
```
15% = juxtamedullary
85% = Cortical
```
160
Define a juxtamedullary nephron
Renal corpuscle lies in the part of the Cortex closest to the cortical-medullary junction
Loop of Henle of these nephrons plunge deep into the medulla and are responsible for generating a an osmotic gradient in the medulla for water absorption
161
Define a cortical nephron
Renal corpuscle lies in the outer cortex and their loop of Henle does not penetrate deep into the medulla
162
Define tubular reabsorption
Movement from the tubular lumen to the peritubular capillary plasma
163
Define tubular secretion
Movement of fluid from the peritubular capillary plasma to the tubular lumen
164
What is the size of molecules that can freely pass through the filtration barrier of the glomerulus?
10kDa
165
What charge does the glomerular basement have and why is it useful?
Negative charge which repels negatively charged anions such as the plasma protein albumin
166
What is the only protein found in the ultra-filtrate?
Tamm Horsfall protein that is produced by the thick ascending limb of the loop of Henle
167
What is the only protein found in the ultra-filtrate?
Tamm Horsfall protein that is produced by the thick ascending limb of the loop of Henle
168
What are the pressures determining glomerular filtration?
Glomerular Capillary hydrostatic pressure (45mmHg)
Bowmans space hydrostatic pressure (10mmHg)
Glomerular capillary oncotic pressure (25mmHg and rising)
Bowmans space oncotic pressure (0mmHg)
169
Why is oncotic pressure in the Bowmans space 0?
Because there are no proteins in the bowmans space to generate an oncotic pressure
170
Why does the glomerular capillary oncotic pressure increase along the capillary?
Because fluid reabsorption means the proteins that remain in the capillary become more and more concentrated
171
What factors affect the rate of filtration at the glomerulus
Size of the molecule
Charge of the molecule (Negative molecules are repelled)
Rate of blood flow
Binding to plasma proteins
172
Define GFR
Volume fluid filtered from the glomeruli into the Bowmans space per unit of time (Minutes)
173
Which forces favour filtration at the glomerulus?
Glomerular capillary hydrostatic pressure (60mmHg)
174
What forces oppose filtration at the glomerulus and what are their values?
Bowmans space hydrostatic pressure (15mmHg)
| Bowmans space oncotic pressure (29mmHg)
175
Write an equation for GFR
GFR = Kf (Pglomcap - Pbowsp-ocot press glom cap)
176
What factors determine the the filtration coefficient KF?
Permeability of the filtration barrier
| Surface area available for filtration
177
What is the average GFR of a 70Kg male?
125ml/min
178
What is the effect on GFR of constricting the afferent arteriole?
Decreases the hydrostatic pressure in the glomerular capillaries which leads to decrease in GFR
179
What is the effect on GFR of constricting the efferent arteriole?
Increases hydrostatic pressure in the glomerular capillaries because constriction of the efferent arteriole which lies beyond the glomerulus causes blood to 'dam back' into the glomerular capillaries thus raising hydrostatic pressure and increasing GFR
180
What is the effect on GFR of dilating the afferent arteriole?
Increases the glomerular capillaries hydrostatic pressure leading to an increase in GFR
181
What is the effect on GFR of dilating the efferent arteriole?
Decreases the glomerular capillary hydrostatic pressure which decreases GFR
182
How is GFR measured?
Measuring the excretion of a marker substance that is freely filtered, not absorbed or secreted in the tubules and not metabolised
183
Define filtration fraction
GFR/renal plasma flow
| therefore if renal plasma flow = 600ml/min and GFR is approx 120ml/min then 120/600= 0.2%
184
Define renal clearance
The volume of plasma from which a substance is completely removed by the kidney per unit time
185
Write an equation for renal clearance
Clearance = urine conc x urine vol / plasma conc
186
What are the two intrinsic auto regulation processes of the kidney
Myogenic reflex
| Tubuloglomerular reflex
187
What is the extrinsic autoregulation process of the kidney?
Sympathetic stimulation
188
Describe the myogenic response of the kidney to high blood pressure
mechanoreceptors in the smooth muscle surrounding the afferent arteriole detect stretch. Normally Na+ channels are closed by when stretched these cells open causing Na+ influx which causes threshold to be reached. Depolarisation causes release of Ca2+ from sarcoplasm which binds calmodulin and causes contraction = Vasoconstriction of afferent arteriole which decreases blood pressure, decreases glom cap hydrostatic pressure and decreases GFR
189
Describe the myogenic response of the kidney to low blood pressure
Low Bp doesn't stretch the smooth muscle cells surrounding the afferent arteriole so no Na+ influx so no Ca2+ release so not contraction so muscle cells relaxes = vasodilation which causes increased blood flow, increased glom cap hydrostatic pressure and increased GFR
190
Describe the tubuloglomerular feedback response to increased GFR
Increased GFR means more NaCl in tubular fluid but only a set amount can be reabsorbed in the PCT so some reaches the macula densa cells of the DCT where it is reabsorbed by NaCl symporter. Causes Na+ accumulation which causes a positive voltage formation which causes ATP release into extracellular space
ATP converted to adenosine which acts on mesangial cells to produce Ca2+.
Ca2+ enters granular cells via connexins which causes renin release.
Ca2+ also enters SM cells around afferent arteriole causing vasoconstriction
191
How does the tubuloglomerular feedback respond to decreased GFR
decreased GFR = decreased Nacl which means less reabsorbed in DCT so no depolarisation and ATP production so no adenosine release which means no calcium enters the SM cells around the afferent arteriole so it vasodilator which increases BF which increases glom cap hydrostatic pressure which increases GFR
192
Describe the extrinsic mechanism of the kidney in response to reduced blood pressure
Baroreceptors in the aortic arch and carotid sinus detect low Bp and send signals via vagus and glossopharyngeal nerves respectively to the vast-motor region of medulla which activates the granular cells of juxtaglomerular apparatus to release renin and also causes direct vasoconstriction of afferent arteriole. Renin causes the conversion of angiotensinogen from the liver into angiotensin I which is then converted by ACE from the lungs to angiotensin II which has a number of effects
193
What are the 6 ways in which angiotensin II increases blood pressure?
1. ANG II binds supraoptic nucleus in hypothalamus causing ADH release which stimulates water reabsorb in the CD which increases blood volume and blood pressure
2. ANG II stimulates Zona glomerulosa of adrenal cortex to produce steroid hormone aldosterone which acts on principal cells of DCT to put more Enac channels to increases Na+ reabsorption into blood, Na+ is followed into blood by H2O when ADH is present which increases blood volume and blood pressure
3. ANG II binds receptors on pre-capillary sphincter causing vasoconstriction which increases resistance which increases BP
4. ANG II binds receptors directly on mesangial cells causing contraction and increase in GFR
5. ANG II binds PCT which increases reabsorption of Na+, Cl- and H20. Water follows which increases blood volume and blood pressure
6. ANG II causes constriction of efferent arteriole which causes blood to flow back to the glomerulus which increases GFR
194
What transporter is the main driver of bulk reabsorption in the Proximal convoluted tubule?
Na+/K+ ATPase
195
What is the primary type of transport In the PCT?
Secondary active transport
196
Describe the process of bulk reabsorption of Na+ and water in the proximal convoluted tubule
On the basolateral membrane of PCT cells is an Na+/K+ ATPase which creates a low Na+ gradient in the cell. Na+ therefore diffuses down conc gradient from the tubular lumen into the cell via symporters with glucose, lactate, phosphate and Amino acids which use Na+ gradient (Secondary active transport) to be absorbed. Water will follow the reabsorption of Na+ passively by osmosis
197
Describe the process of bicarbonate reabsorption in the PCT
high Co2 from bloodstream diffuses across basolateral membrane of PCT cells where it combines with H2O under influence of CA to form H2CO3. This dissociates to form H+ and HCO3-. HCO3- is reabsorbed across basolateral membrane into blood stream down its conc gradient by facilitated diffusion. H+ is pumped into tubular lumen in exchange for Na+ via Na+/H+ anti porter. H+ in tubular fluid then recombines with some filtered bicarbonate to form H2Co3 which then dissociates to H2O and CO2.
198
How much of the filtered sodium is absorbed by the PCT?
65%
199
How much water is reabsorbed by the PCT?
65%
200
How are calcium, magnesium and potassium reabsorbed in the PCT?
Paracellularly due to weak tight junctions between PCT cells
201
What is the name of the syndrome given when a patient presents with amino acuduria, glycosuria and bicarbonate wasting?
Falcon Syndrome
202
Describe the principle of transport maximum
Many of the resorptive pathways in the kidney have to limit the amount of a substance they can transport per unit of time as the binding sites of the membrane transport proteins become saturated when the concentration of a substance is raised beyond a certain level
203
What is the osmolality of the fluid in the PCT?
300mOsm
204
Define osmolality
concentration of a solution expressed as the number of solute particles per Kg.
205
Describe hypertonic
When there is an increased concentration of solutes and a decreased concentration of water
206
Describe hypotonic
When there is a decreased concentration of solutes and an increased concentration of water
207
Describe isotonic
When the concentration of solutes is equal to the concentration of water
208
What process occurs at the loop of Henle
Counter current multiplication
209
Where does solute reabsorption occur in the loop of Henle?
in the thick ascending limb
210
What transporter is responsible for the reabsorption of solute (Na+/K+/2Cl-) in the loop of Henle?
NKCC2 transporter
211
Describe the properties of the tubular fluid at the base of the loop of Henle in comparison to the plasma osmolality
Fluid will be hypertonic compared to the plasma
212
Describe the properties of the tubular fluid at the end of the ascending limb of the loop of hence in comparison to the plasma osmolarity
Fluid will be hypotonic compared to the plasma
213
How much H2O is reabsorbed in the loop of Henle?
15%
214
How much Na+ is reabsorbed in the loop of Henle?
25%
215
What happens to the medullary interstitium the further down the loop of henle you go and why?
Becomes more and more hypertonic (300 at start, 1200mOsm at base) because as salt is actively reabsorbed in the ascending limb which is also impermeable to water making the medullary interstitium hypertonic which helps to draw water out of the collecting duct in order to achieve maximum water retention
216
What happens in the descending loop of Henle?
Permeable to water and does not reabsorb Na+ or Cl- so there is net diffusion of water out of the descending limb into the medullary interstitial
217
What is the purpose of the vasa recta
Counter current exchanger
| Prevent the elimination of the medullary interstitial gradient and prevents rapid removal of NaCl
218
Describe how the vasa recta work
run in hairpin loops parallel to the loops of Henle.
Blood enters and as passes down loop deeper into the medulla, NaCl is reabsorbed into the vasa recta and water passes out. However, after the bend, the process reverses and NaCl moves out the vasa recta and H2O moves in then minimising the excessive loss of solute from the interstitium by diffusion
219
How much of the filtered water from the glomerulus enters the DCT?
20%
220
How much of the filtered sodium from the glomerulus enters the DCT?
10%
221
Describe the reabsorption of sodium in the early distal convoluted tubule?
Na+/K+ ATPase on basolateral membrane creates a low sodium conc inside the cell which creates gradient for sodium to enter alongside Cl- via NCC co- transporter
222
Which drug inhibits the reabsorption of Na+ and Cl- by blocking the NCC transporter in the DCT?
Thiazide
223
Describe the reabsorption of Ca2+ in the Early DCT
Ca2+ reabsorb dependent on needs of body - if Ca2+ is low then parathyroid glands release parathryoid hormone which binds receptor on Early DCT cells and causes PKA production which stimulates insertion of Ca2+ modulatory channels and influx of Ca2+. However Ca2_ is lower conc in cell then in blood so uses secondary active transport using Na+/Ca2+ co-transporter or H+/Ca2+ counter transporter
224
What 3 stimuli cause the adrenal glands to release aldosterone
Angiotensin II
Hyponatraemia
Hyperkalaemia
225
Describe the action of aldosterone on the cells of the late distal convoluted tubule
Aldosterone is a steroid hormone so passes through the membrane to the nucleus
Aldosterone causes gene transcription resulting in insertion of Na+/K+ ATPase on basolateral membrane and ENAC and K+ channels on the apical membrane. Na+/K+ ATPase creates gradient for Na+ reabsorption. If ADH is present and acting on the collecting duct, AQP2 channels will be inserted on apical membrane enabling water to follow the sodium reabsorption
226
What are the two cell types found in the collecting duct and what are their main functions?
Intercalated cells type A and B = Acid base balance
Principal Cells = mineral balance
227
Describe the function of intercalated A cells during acidosis
Acidosis = decreased pH which means Co2 in the blood is high. CO2 diffuses from blood in A cell and combines with H2O (CA) to form H2Co3. this dissociates into HCO3- and H+. HCO3- is absorbed across the basolateral membrane into the blood in exchange for Cl-. H+ is secreted into the lumen in exchange for K+ that has been excreted from the DCT cells. H+ now in the tubulars fluid combines with NH3 which has diffused from the blood to form the weak acid ammonium (NH4) which can be excreted.
228
Describe the function of intercalated B cells during Alkalosis
Alkalosis = increased pH
H2CO3 dissociates in intercalated B cells into HCO3- and H+. HCO3- is secreted into the tubular fluid in exchange for chloride ions which then diffuse into the blood. The H+ is absorbed across the basolateral membrane in exchange for K+ via the H+/K+ ATPase
229
Describe the production and action of ADH on the principal cells of the collecting duct
Supraoptic nucleus in hypothalamus projects to posterior pituitary to cause ADH to be released.
ADH binds the V2 receptor on principal cells activates Gs G-protein which causes adenylate cyclase to convert ATP to cAMP which activates PKA to phosphorylate AQP2 vesicle to insert onto luminal membrane. Water enters the principal cells and moves into the bloodstream via AQP3 and 4 transporters
230
What is ADH released in response to?
Angiotensin II
| High plasma osmolality detected by hypothalamic osmoreceptors
231
Describe the purpose of urea reabsorption
Urea reabsorbed in late collecting duct which then enters and concentrates the medullary interstitium making the urine more concentrated
232
Describe the ADH response to excess water consumption
Low plasma osmolality detected by the hypothalamic osmoreceptors which causes decreased secretion of ADH from the posterior pituitary which decreases the permeability of the collecting duct resulting in decreased water reabsorption and increased water excretion
233
Do baroreceptors increase or decrease their firing in response to low blood pressure?
Decrease their firing
234
Which reflex is less sensitive to change in cardiovascular pressure, osmoreceptor reflex or baroreceptor reflex
Baroreceptor reflex is less sensitive than the osmoreceptor reflex
235
What three steps initiate the release of renin from juxtaglomerular cells in order to cause sodium reabsorption?
Macula densa cells detect low NaCl in DCT
Sympathetic stimulation
Little or no arteriolear stretch due to low blood volume as a result of a lack of Na+
236
Describe the action of Atrial Natriuretic peptide
1. INHIBITS NA+ REABSORPTION by blocking ENAC in collecting duct
2. Vasodilates the afferent arteriole which increases GFR and Na+ excretion
3. Inhibits aldosterone which leads to Na+ excretion
237
Where is ANP synthesised and secreted?
Cardiac atria
238
Why is ANP released?
When there is too much Na+ in the body there will also be excess water in the vessels which increases blood volume meaning the atria become stretched with stimulates ANP secretion
239
Where does the majority of K+ reabsorption take place?
Proximal tubule (90%)
240
What is normal blood pH
7.35-7.45
241
What do bases do?
Accept protons
242
What do acids do?
Accept protons
243
Define base excess
The quantity of acid required to return plasma pH to normal
244
Define anion gap and write an equation
Difference between the measure anions (negative) and cations (positive)
Anion gap = Na+ + K+ - Cl- - HCO3-
245
What is the normal anion gap range?
10-16
246
What conditions does a wide anion gap indicate?
Lactic acidosis
Keto acidosis
Ingestion of acid
Renal failure
247
What does a narrow anion gap indicate?
GI HCO3- loss
| renal tubular acidosis
248
What is the primary urinary buffer
Alkaline phosphate (H2PO4)2-
249
Describe the levels of GnRH and GHRH before puberty
Levels of secretion of both hormones are low
250
Describe the levels of anterior pituitary hormones (FSH,LH,GH)1
Low levels of secretion
251
What happens to the levels of GnRH, GHRH and anterior pituitary hormones at puberty?
They increase
252
What are the 4 factors affecting puberty
Nutrition
Insulin
Genetic factors
Exercise
253
What are the common physical changes seen in the male at puberty?
```
Starts at 9-14 years
1st sign is testicular development
Pubic, axilla and facial hair growth
Growth spurt
Spermatogenesis begins
Acne, body odour and mood change
enlargement of larynx and laryngeal muscles = voice deepening
```
254
What are the common physical changes seen In females at puberty?
```
Starts at 8-14 years
1st sign is breast development
pubic and axilla hair growth
Growth spurt
Menarche (2.5 years after puberty onset)
Acne, body odour and mood changes
```
255
Describe the infancy component of the infancy childhood puberty model
rapid but decelerating growth in first 2-3 years
| determined by nutrition
256
Describe the childhood component of the infancy childhood puberty model
Switch from nutritional to hormonal dependence
| High velocity slows 2-3 years to puberty
257
Describe the puberty component of the infancy childhood puberty model
Growth spurt
Increase in heigh velocity due to GH
Growth ends with the fusion of the epiphyses
258
What are the determinants of growth
```
Parental phenotype and genotype
Quality and duration of pregnancy
Nutrition
Specific system and organ integrity
Psycho-social environment
```
259
Describe the regulation of growth hormone secretion
GHRH bodies in the arcuate nucleus of hypothalamus release GHRH which acts on anterior pituitary to release GH. Somatostatin is released from hypothalamus to negatively feedback on the pituitary prevent GH release. GH either acts directly on bone or acts on the liver to release insulin like growth factor 1 which acts on bone
260
Where is growth hormone synthesised?
Somatotroph cells of the anterior pituitary
261
What are the 3 main effects of GH and insulin like growth factor 1?
Decrease glucose use
Increase lipolysis
Increase muscle mass
262
What factors increase GH release
```
Exercise
Stress
Hypoglycaemia
Fasting
High protein meals
Perinatal development
Puberty
```
263
What factors decrease GH release
```
Hypothyroidism
Hyperglycaemia
High carbohydrate meals
Glucocorticoid excess
Aging
```
264
Define Puberty
Physiological, morphological and behavioural changes as gonads switch from infantile to adult forms
265
Describe precocious puberty
Onset of secondary sexual characteristics before 8yrs in girls and 9yrs in boys
266
Describe delayed puberty
Absence of secondary sexual characteristics by 14yrs (girl) and 16yrs (boy)
267
Describe Turner's Syndrome
45, XO girls
Oedema of back of hands, feet, loose skin folds at nape of neck, low posterior hairline , small mandible, prominent ears
Cardiovascular malformations
Short stature
268
Describe Klinefelters syndrome
```
47, XX
Primary hypogonadism
Azoosermia and gynaemastia
Reduced secondary sexual hair
Osteoporosis
Tall stature
Reduced IQ by 40%
```
269
What hormone is required for the development of male external genitalia
5a-dihydrotestosterone
270
Male sex development is completed after...
9-10 weeks
271
Due to testosterone production from leydig cells, Wolffian duct develops into
Epididymis
vas deferens
Seminal vesicles
Ejaculatory duct
272
What does the mullerian duct develop into
Fallopian tubes
Uterus
Upper third of vagina
273
What does the genital tubercle become in the male
glans of the penis
274
What does the genital tubercle become in the female
Clitoris
275
What does the lateral urethral folds form in the male
Corpus spongiosum
276
What does the lateral urethral fold form in the female
labia minora
277
What do the labiascrotal folds form in the male?
Scrotum or ventral penis
278
What do the labiascrotal folds form in the female
labia majora
279
What does the zona glomerulosa of the adrenal gland produce
Aldosterone
280
What does the zona fasciculata of the adrenal gland produce
Cortisol
281
What does the zona reticular of the adrenal gland produce
DHEA
282
What acid are carbohydrates and fats metabolised too?
Carbonic acid
283
What acid are proteins metabolised too?
Non-carbonic acids
284
What is required to secrete an acid load?
Urinary buffers such as phosphate and ammonium
285
Describe how phosphate ions act as a urinary buffer
When H+ is secreted into the tubular lumen in exchange for Na+ ions, it binds with phosphate ions to form acid phosphate
286
Define titratable acidity
Quantity of a base to bring pH back to 7.4
287
What are the consequences of acidosis?
Cardiovascular (Arrhythmia, myocardial depression, vasodilation and circulatory collapse)
Hyperkalaemia
Neurological (Coma and lethargy)
Bone (Growth disorder and fractures)
288
What are the causes of a respiratory acidosis
Hypoventilation and COPD, respiratory failure
289
What are the causes of a respiratory alkalosis
Hyperventilation and hypoxia and type 1 respiratory failure
290
What are the causes of a metabolic acidosis
Failure of H+ excretion (Renal failure, hypoaldosteronism, T1 renal tubular acidosis)
GI HCO3- loss (Diarrhoea, T2 renal tubular acidosis)
Excess acid production (Lactic acidosis, ketoacidosis, ingestion of acids (Salicylate, ethylene glycol)
Dilution of the blood
291
What are the causes of a metabolic alkalosis
GI Acid Loss (Vomiting)
Volume depletion
Alkali Ingestion
Renal Acid Loss (Hyperaldosteronism, hypokalaemia)
292
What happens during compensation
pH will be normalised but HCO3- and PCO2 will remain disturbed
293
What happens during correction
pH, HCO3- and pCO2 are all normalised
294
Describe the renal compensation process for a respiratory acidosis
H+ secretion into the urine will increase, acid will be secreted as ammonium
HCO3- reabsorption will increase further
pH will return to normal but this takes days
295
Describe the renal compensation process for respiratory alkalosis
H+ secretion will decrease meaning more H+ is retained
Insufficient H+ secretion for HCO3- reabsorption
HCO3- excreted
296
What is the respiratory compensation for metabolic Acidosis
Decrease in pH is detected by chemoreceptors which stimulate an increased respiratory rate and drive pCO2 down
297
What is the respiratory compensation for metabolic alkalosis?
Increase in pH causes chemoreceptors to become inhibited reducing the respiratory rate and increasing pCO2
298
What conditions increase EPO synthesis
Altitude
Anaemia
Cardiopulmonary disorders
299
What conditions decrease EPO synthesis
Polycythaemia
| Renal failure
300
Where in the nephron does Bartter's Syndrome affect what molecule does it affect
Loop of Henle
| NKCC2, ROMK or basolateral K/Cl efflux
301
What is the blood supply of the superior adrenal gland?
Inferior phrenic
302
What is the blood supply of the middle adrenal gland?
abdominal aorta
303
What is the blood supply of the inferior adrenal gland?
Renal artery
304
Where does the vein of the left adrenal gland drain?
into the left renal vein
305
Where does the vein of the right adrenal gland drain?
Directly into the IVC
306
What is the nerve supply of the adrenal glands?
Splanchnic nerves
307
What are the 5 main hormones secreted by the adrenal glands?
```
Aldosterone
Cortisol
Corticosterone
Dehydroepiandrosterone
Androstenedione
```
308
What are the three layers of the adrenal gland from outermost to innermost?
Zona glomerulosa
Zona fasciculata
Zona reticularis
309
What does the zone glomerulosa secrete?
Mineralocorticoids including aldosterone
310
What does the zona fasciculata secrete?
glucocorticoids such as cortisol
311
What does the zona reticularis secrete?
Androgens
312
What hormones does the adrenal medulla secrete?
Catecholamines (Adrenaline and noradrenaline)
313
Which molecule is the precursor for all corticosteroids?
Cholesterol
314
Outline the properties of corticosteroids
Lipid soluble so pass through membranes and bind to specific intracellular receptors where they alter gene expression directly or indirectly
315
Which hormone released by the zona fascicularis and is important in the bodies stress response and immune system regulation?
Cortisol
316
Describe the process of cortisol secretion
1. Stress transmitted to hypothalamus with stimulates the release of corticotrophin releasing hormone from hypothalamus
2. CRH is carried by the hypothalami-hypophyseal portal vessels to the anterior pituitary
3. This stimulates the release of adrenocorticotropic hormone
4. ACTH travels in the blood to the adrenal glands where it stimulates cortisol release
317
What are the effects of cortisol on the body
Increase glucose mobilisation
- Gluconeogenesis
- Amino Acid generation
- Increased lipolysis
Maintenance of circulation
- Vascular tone
- Salt and water balance
Immunomodulation
- Dampen immune response
318
Describe the transport of glucocorticoids
90% bound to corticosteroid binding gobulin (CBG)
5% bound to albumin
5% free (Bioavailable)
319
Production of androgens is regulated by which anterior pituitary hormone?
ACTH
320
Describe the nerve supply of the adrenal medulla
Sympathetic preganglionic neurones
321
What are the relative proportions of adrenaline and noradrenaline produced in the adrenal medulla?
Adrenaline (80%)
Noradrenaline (20%)
322
What are the effects of catecholamines in a fight or flight response?
Gluconeogenesis
Lipolysis
Tachycardia
Redistribution of circulation volume
More adrenaline release - serves to vasoconstriction
Less noradrenaline release to vasoldilate to increase blood supply to skeletal muscles
323
What is the name of the smooth muscle in the bladder wall?
Detrusor muscle
324
What is the innervation of the detrusor muscle?
Parasympathetic which is inhibited during filling and stimulated during micturition
325
What is the innervation of the internal urethral sphincter (Smooth muscle)
Sympathetic which is stimulated during filing and inhibited during micturition
326
What is the innervation of the external urethral sphincter (Skeletal muscle)?
Somatic motor which is stimulated during filing and inhibited during micturition
327
Describe the process of micturition
1. As the bladder fills with urine, the pressure within increases which stimulates stretch receptors in bladder wall
2. Afferent neurones from these receptors enter spinal cord and stimulate parasympa neurones to cause detrusor muscle to contract
3. Contraction of the detrusor muscle causes bladder shape change which pulls the internal urethral sphincter open
4. Simultaneously the afferent input from stretch receptors inhibits sympathetic neurones to further open the internal spinchter
5. Afferent input also inhibits somatic motor neurones to external urethral sphincter causing it to relax
6. Opening of both sphincters produces urination
328
What is the parasympathetic nervous supply to the bladder
Pelvic splanchnic nerve S2-S4
329
What is the sympathetic nervous supply to the internal urethral sphincter
Hypogastric nerve (T1-L2)
330
What is the somatic motor nervous supply to the external urethral sphincter?
Pudendal nerve (S2-S4)
331
What is the blood supply of the thyroid gland?
Superior and inferior thyroid arteries
332
Where does the superior thyroid artery branch from
External carotid artery
333
Where does the inferior thyroid artery branch from
Subclavian artery
334
What are the two main molecules produced by the thyroid gland
Thyroxine (T4)
| Triiodothyronine (T3)
335
Which enzyme is responsible for converting T4 into T3
Deiodinase
336
what is the major thyroid hormone?
T3, T4 acts as a T3 reservoir
337
Describe the process of thyroid hormone secretion
1. Hypothalamus secreted thyroid releasing hormone
2. increased plasma TRH in hypothalamus-pituitary portal vessels causes anterior pit to release TSH
3. TSH acts on thyroidd gland to release T3 and T4
4. T4 Is converted in the target tissue to T3
338
What are the three main roles of thyroid hormones?
Control metabolism
Regulation of growth
Brain development in first 2-3 years
339
Describe the process of thyroid hormone synthesis
1. TSH binds to the TSH receptor on follicular cells
2. Iodide cotransported into follicular cell with Na+ = iodide trapping
3. in the colloid, iodide is oxidised to iodine which bind to tyrosine residues on thyroglobulin molecules under action of thyroid peroxidase
4. tyrosine with one iodine = monoiodotyrosine
tyrosine with two iodine = di-iodotyrosine
5. When thyroid stimulated, T1 and T2 are cleaved from tyrosine backbone and combine to form T3 and T4
6. Thyroglobulin undergoes proteolysis to release T3 and T4
340
Describe the mechanism of T3
Steroid hormone so acts by inducing gene transcription and protein synthesis
341
What are the parathyroid glands responsible for regulating?
Calcium and phosphate
342
What is parathyroid hormone released in response to?
Low calcium
| High phosphate
343
What are the actions of PTH?
Increase Ca reabsorption in renal distal tubule
Increase intestinal Ca absorption (Via Vit D)
Increases Ca release from bone (Osteoclast activity)
Decrease phosphate reasbrotpion
344
Describe the bodies response to hypocalcaemia
Parathyroid glands release PTH which causes bone resorption, increases urinary phosphate, decreases urinary calcium, increases 1,25D3 production, increases intestinal Ca absorption and increases intestinal phosphate absorption
345
Where is calcitonin producted?
By the C-cells of the thyroid
346
When is calcitonin released and what is its function?
During hypercalcaemia, acts directly on the bone to inhibit bone resorption
347
Define a hormone
A substance that is secreted directly into the blood by specialised cells and have actions away from their sites of production
348
Catecholamines are derived from which precursor molecule?
Tyrosine
349
Which part of the pituitary gets stimulated by hormones from the hypothalamus?
Anterior pituitary
350
Which part of the pituitary stores hormones made by the hypothalamus
Posterior pituitary
351
Which hormones are produced by the anterior pituitary?
```
ACTH
TSH
GH
LH/FSH
PRL
```
352
Which hormones are produced by the posterior pituitary?
ADH
| Oxytocin
353
An overproduction of ACTH results in what disease?
Cushing's Disease
354
An overproduction of GH results in what disease?
Acromegaly
355
Where does the pituitary gland lie?
in the sella turcica in the sphenoid bone
356
What structure connects the pituitary to the hypothalamus?
Infundibulum
357
Why can tumours of the pituitary gland cause issues with vision?
Because the tumour causes the pituitary to grow out the sella turcica and compress the optic chiasm
358
Name 6 hypophysiotropic hormones which are carried via the hypothalami-hypophyseal portal vessels to the anterior pituitary
```
CRH
TRH
GHRH
GRH
Dopamine (Inhibits prolactin release)
Somatostatin (Inhibits GHRH release)
```
359
Blood is delivered from the hypothalamus to the anterior pituitary by which structure?
hypothalamus-hypophyseal portal vessels
360
What are the two nuclei in the hypothalamus?
Paraventricular
| Supra-optic
361
How can a tumour of the pituitary gland present?
Pressure on optic chiasm producing bitemporal hemianopia
Pressure on normal pituitary - hypopituitarism
Functioning tumour
- prolactinoma
- Acromegaly
- CUshings disease
362
Which part of the pituitary gland is an extension of the hypothalamus?
Posterior pituitary
363
Where is ADH synthesised
Cell body of the supra optic nuclei
364
Where is oxytocin synthesised
Cell body of the paraventricular nuclei
365
What is the function of oxytocin?
Stimulates contraction of smooth muscle of breasts to cause milk ejection
Stimulates contraction of uterine smooth muscle until baby is born
Promotes onset of labour
366
Which cells of the pancreas perform its exocrine function?
Acinar cells
367
What is the function of acinar cells?
Manufacture and secrete digestive enzymes (Lipase, trypsin and chymotrypsin)
368
What are the three cell types found in the islets of langerhans?
```
Delta cells (5%)
Alpha cells (20%)
Beta cells (60-75%)
```
369
What do delta cells secrete
Somatostatin
370
What does beta cells secrete?
Insulin
371
What do alpha cells secrete
Glucagon
372
What are the effects of insulin?
Suppresses hepatic glucose output (decreases glycogenolysis and gluconeogenesis)
Increased glucose uptake
- Glycogen and protein synth
- Fatty acid synthesis
Suppresses Lipolysis and muscle breakdown
373
What are the effects of glucagon?
Increase hepatic glucose output (Increased glycogenolysis and gluconeogenesis)
Reduce peripheral tissue uptake
Stimulate peripheral release of gluconeogenic precursors (Glycerol and AA)
Increases lipolysis and muscle breakdown
374
Describe the process of insulin secretion from Beta cells
1. High glucose in bloodstream will equilibriate across plasma membrane of B-cells via GLUT-2
2. Glucose then phosphorylated by glucokinase to glucose-6-phosphate
3. This increases glycolysis rate leading to production of ATP
4. Presence of ATP causes KATP channel to close which prevents a K+ efflux leading to membrane depolarisation
5. Depolarisation causes voltage gated Ca2+ channels to open enabling rapid Ca2+ influx into the cell
6. Triggers the exocytosis of primed insulin secretory granules
375
Describe the structure of pro-insulin
Contains A and B insulin chains joined by a C-peptide
A and B chains are lined by disulphide bridges and as soon as insulin is secreted the C-peptide is removed
376
Describe the biphasic release of insulin
First phase is rapid releasee of stored insulin
Second phase Is slower as it relies on newly synthesised hormone
377
Describe the effect of insulin on muscle and fat cells
Insulin binds insulin receptors on muscle and fat cells which triggers an intracellular signalling cascade resulting in mobilisation of GLUT4 vesicles to cell membrane. GLUT4 becomes inserted at plasma membrane enabling diffusion of glucose into cells thus decreasing blood glucose levels
378
What is the short-term response to increased blood glucose?
Glycogenesis - make glycogen
379
What is the longer term response to increased blood glucose?
Make triglyceride (Lipogenesis)
380
What is the short term response to low blood glucose?
Glycogenolysis
381
What is the long term response to low blood glucose?
Make glucose - gluconeogenesis from AA and Lactate
382
Where are the main glucose sensors?
primarily in the islets of langerhans but also in medulla, hypothalamus and carotid Bodies
383
What are incretins?
Sensory cells in the gut wall that stimulate insulin release
384
Which cells secrete incretins in response to eating
GIT endothelial cells
385
What are the two major incretins?
Glucagon like peptide 1 (GLP-1)
Glucose dependent insulinotropic peptide (GIP)
386
Describe carbohydrate metabolism in the fasting state
All glucose comes from the liver
- glycogen breakdown
- Gluconeogenesis (Using lactate, alanine and glycerol)
Insulin levels are low in the fasting state so muscles use FFA for fuel
387
Describe carbohydrate metabolism in the post prandial state
Rising glucose levels stimulate insulin secretion and suppress glucagon with glucose replenishing glycogen stores in the liver and muscle
Excess glucose is converted to fats
high insulin suppresses lipolysis
