SUGER Flashcards

(295 cards)

1
Q

Rare disease in Europe defined as…

A

Affecting 1/2000 or less

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2
Q

Kidney roles

A

Maintain balance of salt, water, pH
Excrete waste products
Endocrine function
Control BP
RBC production
Maintenance of bones
Removal of drugs from body

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3
Q

Components of nephron in cortex

A

Bowman’s Capsule
Proximal tubule
Distal Tubule

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4
Q

Components of nephron in medulla

A

Loop of Henle
Collecting Duct

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5
Q

Renal cardiac output

A

~5 L/min

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6
Q

Renal blood flow

A

~1 L/min

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7
Q

Renal blood pathway

A

Abdominal aorta
Renal artery
Interlobar artery
Arcuate artery
Interlobular artery
Afferent arteriole
(nephron) Glomerular capillary
Efferent arteriole
Peritubular capillaries
Vasa recta
Interlobular veins
Arcuate veins
Interlobar veins
Renal veins
IVC

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8
Q

Renal urine flow

A

1 ml/min

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9
Q

The Tubuloglomerular Feedback Loop

A

Increased arterial BP
= Increased blood flow and BP in glomerulus
=Increased GFR
= Increased delivery of NaCl to macula densa (this triggers afferent arteriolar constriction)
= Decreased blood flow and BP in glomerulus

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10
Q

Myogenic mechanism for kidney autoregulation

A

Increased BP
= Stretch in vessel walls
= Opens stretch-activated cation channels
= Membrane depolarisation
= Opens voltage-dependent Ca channels
= Increased intracellular Ca
= Smooth muscle contraction
= Increased vascular resistance
= Minimised change in GFR

(decreased BP does the opposite)

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11
Q

Autoregulation of the kidney comes with 2 mechanisms:

A

-Tubuloglomerular feedback
-Myogenic mechanism

Which maintain GFR and control water/waste excretion

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12
Q

3 components of kidney filtration barrier

A

Fenestrated capillary endothelium

Glomerular basement membrane

Podocytes (foot processes)

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13
Q

5 factors affecting glomerular filtration

A

Pressure
Molecule size
Charge of molecule
Rate of blood flow
Binding to plasma proteins

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14
Q

Small molecules and ions up to …. can pass freely through filtration barrier

A

10kDa (glucose, uric acid, K)

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15
Q

Why can’t negatively charged ions cross filtration barrier?

A

Fixed negative charge of glomerular BM repels negatively charged anions

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16
Q

GFR is…

A

Glomerular filtration rate (filtration volume per unit time)

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17
Q

Embryology of pancreas

A

At junction of foregut and midgut, 2 pancreatic buds (dorsal and ventral) are generated which fuse to form pancreas

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18
Q

When does exocrine function of the pancreas begin?

A

After birth

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19
Q

When does endocrine function of the pancreas begin?

A

Weeks 10-15

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20
Q

Size of pancreas

A

12-15cm

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21
Q

Anatomical position of pancreas

A

Retroperitoneal, posterior to greater curvature of stomach

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22
Q

Ejaculate is a mixture of…

A

Spermatozoa and Seminal Plasma

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23
Q

Anterior covering of testes

A

Saclike extension of peritoneum (tunica vaginalis)

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24
Q

Tunica albuginea

A

White fibrous capsule
Septa dividing the testis into compartments containing seminiferous tubules

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25
Where in the testes are spermatozoa produced?
Seminiferous tubules (where meiosis occurs)
26
What are the Leydig cells?
Cluster of cells between the seminiferous tubules and source of testosterone
27
Blood-testis barrier
Formed by tight junctions between sertoli cells (separates sperm from immune system) And basement membrane beneath sertoli cells
28
Sertoli cell role
Promote sperm development (through testosterone production)
29
What do the seminiferous tubules drain into?
Network called rete testis
30
Pendulous pouch holding the testes divided into 2 compartments by...
A median septum
31
Testicular thermoregulation is necessary because...
Sperm aren't produced at core body temperature (about 34 degrees)
32
2 types of daughter cells produced by spermatogonia
Type A Spermatogonia - remain outside blood-testis barrier and produce more daughter cells until death Type B - Differentiate into primary spermatocytes
33
In spermatogenesis, meiosis I produces...
2 secondary spermatocytes from 1 primary spermatocyte
34
In spermatogenesis meiosis II produces...
4 spermatids from 2 secondary spermatocytes
35
Spermiogenesis is...
Transformation of spermatids to spermatozoa (sprouts tail and discards cytoplasm to become lighter)
36
3 regions of tail of a spermatozoon
Midpiece - contains mitochondria around axoneme of flagellum Principal piece - axoneme surrounded by fibres End piece - axoneme only
37
Length of cycle of seminiferous epithelium (sperm from spermatogonia)
16 days
38
Seminal fluid produced together by...
Bulbourethral, prostate and seminal glands
39
Fluid expelled during orgasm
2-5mL fluid 60% seminal vesicle fluid 30% prostatic 10% sperm Trace of bulbourethral fluid
40
Normal sperm count
50-120 million/mL
41
Menstruation cycle summary
Days 1-7: Menstruation (3-7 days) Days 8-11: Lining of womb thickens in prep for egg Day 14: Ovulation Days 18-25: If fertilisation hasn't taken place, corpus luteum fades away Days 26-28: Uterine lining detaches leading to menstruation
42
2 things responsible for sperm movement in female reproductive tract
Sperm motility Female reproductive tract movement
43
2 features of PCTs
Simple cuboidal brush border (cells as deep as hairs are long) High mitochondrial density
44
PCT function
Bulk reabsorption of Na, Cl, H2O, glucose, amino acids, bicarbonate, lactate, phosphate Secreting organic ions Na+/K+ pump for Na reabsorption Other molecules taken up by secondary active transport, diffusion or osmosis
45
Water reabsorption in PCTs
By AQP1 channels Water can also pass through the leaky tight junctions
46
Glucose reabsorption in PCTs
Early parts - SGLT2 - 1 Na+ and 1 glucose Later parts - SGLT1 - 2 Na+ and 1 glucose
47
Sodium reabsorption in PCTs
Na+ actively transported out of PCTs via K+/Na+ (3Na+ out and 2K+ in) This decreases Na conc in cell increasing gradient for Na+ to go lumen -> PCT cell Na+ transported into cell either in exchange for H+ or co-transported From cell, it's pumped into the interstitium by Na/K ATPase or co-transported with bicarbonate
48
Amino acid reabsorption in PCTs
Co-transported with Na+
49
Chloride reabsorption in PCTs
Exchanged for formate in the NKCC2 channel Formate then becomes formic acid (can diffuse across membrane and be reused)
50
Protein endocytosis and degradation in PCTs
Protein shouldn't be in tubules but a mechanism is present for removing them Microvilli have sensors which specifically bind any protein Endocytosis occurs in endosomes and protein degradation by lysosomes producing amino acids
51
Bicarbonate reabsorption in PCTs
In lumen, H+ combines with HCO3- to form carbonic acid (requires carbonic anhydrase) H2CO3 then -> H2O + CO2 CO2 diffuses through cell wall H2O reabsorbed by osmosis In cell, H2O + CO2 -> H2CO3 -> H+ + HCO3- H+ recycled with transporting Na+ HCO3- co-transported with Na+ into interstitium (1Na+ with 3HCO3-)
52
Urachus
Remnant of channel between bladder and umbilicus
53
Renal plasma flow per minute
700ml/min
54
GFR
120ml/min
55
Renal blood flow
1250ml/min
56
How much bicarbonate water secretion does the pancreas produce per day?
1 litre per day
57
Role of pancreatic bicarbonate secretion
Protection of duodenal mucosa by neutralising stomach acid Buffers duodenal content to optimise pH for enzyme digestion
58
Pancreatic proteases
(Protein digestion is initiated by pepsin in stomach and majority occurs in small intestine) Trypsinogen and chymotrypsinogen which are transported in secretory vesicles containing a trypsin inhibitor (additional safeguard to prevent cell digestion) Trypsinogen activated by enterokinase (secreted by small intestine epithelial cells) Trypsin then activates chymotrypsinogen and additional trypsinogen At this point the trypsin inhibitor is ineffective
59
Fat digestion due to 2 secretions
Pancreatic and hepatic secretions
60
Pancreatic amylase
Major source of amylase (salivary amylase has a small role) Hydrolyses starch to more soluble sugars
61
Gastric secretion split into 2 stages
Cephalic stage - vagal innervation stimulates production of salivary amylase in mouth and gastrin in stomach (anticipation of a meal) Intestinal stage - secretion of: Cholecystokinin, secretin and gastrin
62
Cholecystokinin stimulus, produced in and action
Stimulus - HCl, protein, fats entering duodenum Produced in - I cells of duodenum/jejunum Action - Triggers pancreatic enzyme and HCO3- secretion, gallbladder contraction (releasing bile), inhibition of gastric secretion, delayed gastric emptying
63
Secretin stimulus, produced in and action
Stimulus - Low duodenal pH Produced in - Upper small intestine Action - Pancreatic water and bicarb secretion (flushing out into duodenum carrying enzymes)
64
Gastrin stimulus, produced in and action
Stimulus - Gastric distension/irritation Produced in - G cells in stomach Action - HCl secretion (parietal cells) enzyme release (acinar cells)
65
As proteins and fats are digested and absorbed, pH rises. What effect does this have on CCK and secretin secretion?
Stimuli for CCK and secretin disappear and pancreatic secretion reduces
66
Pancreatic endocrine function
Insulin and glucagon secretion
67
Difference in reabsorption between PCTs and DCTs
PCT - Bulk absorption, leaky DCT - Fine tuning of filtrate, impermeable
68
Counter-Current Multiplication Mechanism in Loop of Henle
Generation of hyperosmotic interstitium to aid CT in water reabsorption by features of the thick ascending limb and thin descending limb
69
Role of thick ascending limb in developing a hyperosmotic interstitium
Driven by Na+/K+ ATPase pump on basolateral membranes of cells which keep intracellular Na low allowing ease of Na re-uptake NKCC2 uses the gradient and pumps Na+ out lumen K+ recycled on apical membrane back into lumen through ROMK channels Cl- leaves cells through CLCK A channels (CLCK B in inner medulla) on basolateral membrane Process promotes +ve charged lumen repelling Ca,Mg,Na ions which leave lumen Creates a hyperosmotic interstitium
70
2 hormones secreted by posterior pituitary gland
Vasopressin (ADH) - controls water secretion into urine (primarily from supraoptic nuclei) Oxytocin - expression of milk from glands of breasts to nipples, promote onset of labour (myometrium contraction) (primarily paraventricular nuclei). Stimulated by milk suckling.
71
Origin of posterior pituitary
Neuro tissue - large number of Glial-type cells
72
Max urine osmolality
1200mOsm/l (In collecting tubules)
73
What inhibits ADH release?
Caffeine, alcohol
74
What stimulates ADH release?
Increased osmolality Decreased blood volume Nausea, vomiting, stress, exercise
75
Osmolality
Concentration of particles per kilo of fluid
76
Vasopressin mechanism of action of collecting tubules
Vasopressin binds to receptor on collecting duct cell membrane Receptor activate cAMP second messenger system Cells into aquaporins into apical membrane Water reabsorbed by osmosis into blood
77
Restoration of osmolality by 2 ways
Increased plasma osmolality = -Increased thirst -> Increased fluid intake -> restored osmolality - Increased ADH neurone firing -> release of ADH -> ADH at V2R -> Water reabsorption -> restored osmolality
78
Normal Osmolality
285-295 mOsmol/kg
79
3 skin layers
Epidermis Dermis Subcutis
80
Skin as a waterproof barrier
Tights junctions between cells in straum granulosum, epidermal lipids and keratin in straum corneum form both an inside-out and outside-in barrier to water
81
Epidermis functions
Waterproofing Physical barrier Immune function Vit D synthesis (endocrine) UV protection Thermoregulation
82
Dermis functions
Thermoregulation Vit D synthesis (endocrine) Sensory organ
83
Subcutis
Thermoregulation Energy reserve Vit D storage Endocrine organ Shock absorber
84
Why does skin wrinkle when wet?
Skin on fingers and toes wrinkles if immersed for approx 5 mins Mediated by sympathetic NS Due to vasoconstriction in dermis Improves grip
85
Skin as a physical barrier
Stratified epithelium helps resist abrasive forces Fat in subcutis acts as shock absorber Structure of skin helps resist trauma
86
Vitamin D synthesis in skin
7-dehydrocholesterol in plasma membranes of epidermal keratinocytes and dermal fibroblasts converted to previtamin D3 (cholecalciferol) by UV 15-25 min whole body exposure produces up to 10,000 IU Vit D
87
How is Vitamin D stored?
It's lipid soluble so can be stored in subcutis adipocytes
88
Dietary Vitamin D intake
Vitamin D2 - Fish, meat Vitamin D3 - supplements
89
Skin as a site of hormone action
Androgens act on follicles and sebaceous glands Thyroid hormones act of keratinocytes, follicles, dermal fibroblasts, sebaceous glands, endocrine glands
90
Skin as a site of hormone synthesis
Vit D unique site for cholecalciferol synthesis 17beta-hydroxysteroid dehydrogenase in sebocytes and 5alpha-reductase in dermal adipocytes convert dehydroepiandrosterone (DHEA) and androstenedione to 5alpha-dihydrotestosterone Insulin-like growth factor (IGF) binding protein-3 (IGFBP-3) synthesised by dermal fibroblasts)
91
What rays is skin a barrier to?
UV-A and UV-B which damage skin (burns, photo-aging, DNA damage)
92
Skin colour depends on...
Melanin Carotenoids Oxy/deoxyhaemoglobin
93
Melanin synthesis and transport
Synthesised in melanosomes within melanocytes from tyrosine Transported by dendrites to adjacent keratinocytes
94
Colour of melanin
Pheomelanin - red/yellow Eumelanin - brown/black
95
The more eumelanin your skin contains...
The darker your skin (we all have the same number of melanocytes but different amount of melanin)
96
Which type of melanin do we have most of in the skin?
Eumelanin
97
Deleterious effects of melanin
Prone to photodegradation (may generate ROS) Pheomelanin increases release of histamine Lots of melanin = less able to utilize UV light to make Vit D
98
3 stages of response to sunlight
Immediate pigment darkening Persistent pigment darkening (tanning) Delayed tanning
99
Immediate pigment darkening in response to sunlight
Photooxidation of existing melanin Redistribution of melanosomes Occurs within minutes and lasts hours/days
100
Persistent pigment darkening
Oxidation of melanin Occurs within hours lasting 3-5 days
101
Delayed tanning
Increased melanin synthesis Occurs 2-3 days after UV exposure (maximal at 10-28 days)
102
Skin as a barrier to infection
Properties that render skin a barrier to water also help prevent infection Range of peptides synthesised by granular layer keratinocytes have antimicrobial properties
103
Skin as a sensory organ
Merkle cells - basal epididymis (light touch) Encapsulated mechanoreceptors in dermis Myelinated and unmyelinated sensory nerve endings in dermis (pain, itch temperature)
104
What connects seminiferous tubule to epididymis?
Seminiferous tubules -> Straight tubules -> rete testis -> Epididymis
105
How many primordial follicles in ovary at birth?
400,000 (approx 400 will mature and ovulate)
106
Insulating role of skin
Insulation by subcutaneous fat
107
Cutaneous blood flow in heat loss
Deep vascular plexus (lower reticular dermis) Superficial vascular plexus (upper reticular dermis)
108
Autonomic regulation of blood flow in dermal vascular plexuses
Sympathetic alpha-noradrenergic: vasoconstriction Sympathetic cholinergic: vasodilation (both in hairy skin, hairless skin only has adrenergic innervation)
109
Eccrine sweat glands
1.6-4 million in skin 1-3 L sweat per hour Water availability major limiting factor
110
Piloerection (goosebumps)
Arrector pili muscles innervated by sympathetic alpha1-adrenergic fibres Contraction raises cutaneous hairs
111
Epidermis immunity role
Keratinocytes secrete cytokines and chemokines to maintain leucocyte populations in skin Langerhans cells are antigen-presenting cells and secrete cytokines
112
Immune cells in dermis
Regulatory T cells Natural killer cells Dendritic cells Macrophages Mast cells
113
98-99% of pancreatic cells are...
Glandular epithelial cells forming clusters called acini
114
What is pancreas exocrine function? Which cells carry it out?
Secrete pancreatic juice (enzymes an fluid released into gut) Performed by acinar cells
115
What is pancreas endocrine function? Which cells carry it out?
Several peptide hormones (insulin, glucagon) released into portal vein Performed by islet cells (Islets of Langerhans)
116
Delta cells of pancreas secrete...
Somatostatin (acts as an inhibitor across a lot of systems)
117
Alpha cells of pancreas secrete...
Glucagon
118
Beta cells of pancreas secrete...
Insulin
119
Insulin secretion from pancreas mechanism
GLUT2 glucose transporter (low affinity) on membrane of beta-cell brings glucose into cell where glucokinase phosphorylates it to glucose-6-phosphate which increasing rate of ADP->ATP ATP closes K+ channel on membrane resulting in depolarisation of membrane This opens a voltage-gate Ca channel causes influx of Ca2+ into cell Triggering exocytosis of proinsulin (which is contained within vesicles) Proinsulin then splits into C peptide and insulin
120
Biphasic insulin release
1st phase response - rapid release of stored product 2nd phase - slower release of newly synthesised hormone
121
Insulin action in muscle and fat cells
Insulin binds to receptor on membrane This signals GLUT4 vesicles to travel to membrane and get incorporated into membrane High Affinity GLUT4 receptor drags glucose into cell (Insulin effectively provides more 'doors' for glucose to leave cell)
122
Glucose Homeostasis: short and long term response to high blood glucose
Short Term - Make glycogen Long Term - Make triglyceride (lipogenesis)
123
Glucose Homeostasis: short and long term response to low blood glucose
Short Term - Split glycogen Long Term - Gluconeogenesis from AAs, fats, etc.
124
Incretins (e.g - GLP-1)
Gut hormones that stimulate beta-cells to release insulin whilst dampening down effect of alpha-cells (which release glucagon) They also delay gastric emptying (so feel full for longer)
125
What prevents hypoglycaemia caused by incretins?
DPP-IV cleaves GLP-1 (incretin) rendering it inactive so can't stimulate beta-cells or slow down rate of gastric emptying DPP-IV levels rise as GLP-1 levels rise
126
Factors affecting blood pH
Respiratory component: CO2 conc Metabolic component: Intrinsic acid (metabolised) Extrinsic acid (diet) Buffering capacity (bicarbonate
127
DCT role
Fine tuning of Na reabsorption, K and acid-base balance Impermeable to passive movement of water and Na Uses NCCT (Na/Cl) co-transporter to reabsorb last bit of Na
128
2 cell types in collecting ducts
Principal cells - Na, water reabsorption and K excretion Intercalated cell (alpha or beta) - secrete H+ or HCO3- (pH balance)
129
Aldosterone effect on principal cells
Aldosterone binds to receptors on principal cells in CTs which increases number of open ENaC channels ENaC channels are a Na transporter
130
GFR regulated by 2 things
Sympathetic NS Hormones
131
Sympathetic NS effect on GFR
Afferent (and efferent but less so) arterioles receive sympathetic innervation Strong symp stimulus = constricted afferent arteriole = reduced renal blood flow = reduced GFR
132
How to increase GFR through changing width of afferent and efferent arteriole?
To increase GFR either dilate afferent arteriole or constrict efferent arteriole (opposite to decrease GFR)
133
Stages of menstrual cycle
Follicular Stage - Days 1-13/14 Ovulation - Days 13/14 Luteal phase - Days 14-28
134
What difference does presence of Y chromosome make?
SRY gene triggers testicular development Testis produce MIF preventing Mullerian duct development
135
Production of primary oocytes in utero
Rapid meiotic division from 12 weeks results in 5-10 million primary oocytes at 20 weeks Rapid cell death leaves 1 million primary oocytes at birth
136
Primordial follicle is...
1 oocyte surrounded by granulosa cells Secretes oestrogen, progesterone, inhibin
137
Primordial follicle becomes...
Primary follicle - oocyte grows and becomes separated from granulosa cells by zona pellucida (contains glycoproteins, binds sperm)
138
Primary follicle becomes...
Preantral follicle - granulosa cells differentiate into Theca cells (both function together for oestrogen synthesis)
139
Preantral follicle becomes...
Early antral follicle - Primary oocyte full size Antrum forms full of fluid secreted from granulosa cells
140
Early antral follicle becomes...
The mature (Graafian) follicle after day 7 of each cycle At beginning of each cycle, 10-15 pre/early antral follicles develop and grow After 7 days, 1 follicle is dominant Non-dominant follicles undergo atresia Dominant follicle increases in size as does it's antrum Oocyte emerges from meiotic arrest due to LH surge Completes its 1st division becoming a secondary oocyte This increase in size ballooning out of ovary (ovulation) Enzymatic digestion ruptures follicle and oocyte carried away by antral fluid
141
Where are cells in ovaries arrested before sexual maturity?
Primordial follicles containing primary oocytes (FSH, LH secretion at sexual maturity)
142
What stimulate FSH and LH release from anterior pituitary on days 6-7 of menstrual cycle?
GnRH from hypothalamus
143
Mucus secretion in menstrual cycle
High oestrogen = abundant clear/watery mucus (good for sperm movement) Progesterone and oestrogen = thick and sticky (stop entry of bacteria)
144
3 stages of uterine changes
Menstrual phase (days 1-5): withdrawal of progesterone = endometrial degeneration (trigger of menstrual flow) Proliferative phase (days 5-14): oestrogen from granulosa and theca cells causes endometrium to thicken Also stimulates myometrium contraction and progesterone receptor generation in endometrium Secretory phase (days 15-28): Progesterone binds with its receptors on endometrium Endometrium secretes glycogen from glandular epithelium (sperm and oocyte nutrition) Progesterone overrides oestrogen to prevent myometirum contraction and prostaglandin secretion
145
Prostaglandins role in menstrual cycle
Dilate cervix aiding myometrium contraction
146
Oestrogen secretion in menstrual cycle
In follicular phase secreted by granulosa cells In luteal phase secreted by corpus luteum
147
Progesterone secretion in menstrual cycle
In follicular phase made by granulosa and theca cells In luteal phase made by corpus luteum (in much larger amount)
148
Inhibin role in menstrual cycle
Decreases FSH Peaks for ovulation Decreases as corpus luteum degenerates
149
LH secretion throughout menstrual cycle
Constant for most of follicular phase LH surge - peaks about 18 hours before ovulation (generated by high oestrogen levels from maturing follicle) Acts on hypothalamus and anterior pituitary to increase sensitivity to GnRH (+ve feedback) LH surge allows oocyte to complete meiosis I LH decrease - After ovulation, progesterone production = decrease in LH levels
150
LH action on Theca cells
Stimulates them to produce androgens which are converted to granulosa cells to produce oestrogen and antral fluid
151
Changes in FSH throughout menstrual cycle
Increases in early part of follicular phase Slow decrease in levels throughout menstrual cycle As 1 follicle beo mes dominant, more oestrogen = decreased FSH Increase in FSH at day 10/11 triggering LH receptors to develop on Theca cells (presence of inhibin then actively inhibits FSH release)
152
Luteal Phase
Completion of meiosis I results in ovulation Corpus luteum formed Low LH maintains corpus luteum Results in secretion of progesterone and oestrogen -ve feedback - decreased GnRH and therefore decreased FSH and LH After 14 days of no fertilisation, corpus luteum dies removing -ve feedback so LH and FSH rise (cycle repeats)
153
Meiotic arrests in females
Arrested in prophase I maturation during menstrual cycle Arrested at metaphase II until ovulation Meiosis completed after fertilisation
154
Spermatogenesis location, meiotic divisions and germ line epithelium involvement
Occurs entirely in testes Equal division of cells Germ line epithelium is involved in gamete production
155
Oogenesis location, meiotic divisions and germ line epithelium involvement
Occurs mostly in ovaries Unequal division of cytoplasm Germ line epithelium not involved in gamete production
156
Number and size of gametes produced in spermatogenesis
4 sperm that are smaller than spermatocytes
157
Number and size of gametes produced in oogenesis
1 ova (plus 2-3 polar bodies) larger than an oocyte
158
Spermatogenesis timing
Uninterrupted process Begins at puberty Continuous release Lifelong (reduces with age)
159
Oogenesis timing
Arrested stages Begins in foetus (pre-natal) Monthly from puberty Terminates with menopause
160
Constituents of semen
10% bulbourethral 30% prostate 60% seminal vesicles
161
How much semen secreted during orgasm?
2-5mL
162
Normal sperm count
50-120 million/mL
163
Sperm route
Seminiferous tubules Rete testis Efferent ducts Epididymis Vas deferens Ejaculatory duct Urethra Penile urethra
164
Functions of semen
Buffers against acidic environment Chemicals like fructose to increase motility Prostaglandins present to stimulate female peristaltic contractions
165
Blood-Testis Barrier
Seminiferous tubules bound by a BM Sertoli cells extend from BM into lumen They're joined to adjacent cells by tight junctions and form an unbroken ring inside seminiferous tubule So sertoli cells form the B-T B preventing movement of chemicals
166
Length of spermatogenesis process
64 days
167
Spermatogonia divide mitotically at puberty into 2 types...
Type A - remain outside B-T B and produce more daughter cells Type B - in basal compartment (primary spermatocytes)
168
Spermiogenesis
Spermatids -> Spermatozoa (grow tails and discard cytoplasm)
169
Release of sperm into lumen
Invaginations in sertoli cells retract releasing sperm
170
Spermatogonium undergoes a mitotic division to produce...
Primary spermatocyte
171
Primary spermatocyte undergoes meiosis I to produce...
2 secondary spermatocytes
172
2 secondary spermatocytes undergo meiosis II to produce...
4 early spermatids
173
What provide nourishment for developing spermatids?
Sertoli cells
174
Timing for sperm to be introduced for fertilisation
5 day before to 1 day after ovulation As sperm can last 4-6 days, egg can only survive 1-2 days
175
What carries egg out of ovary
Antral fluid Smooth muscle and fimbriae Cilia in fallopian tube
176
Capacitation
Occurs in female reproductive tract Maturation of spermatozoon (tails becomes stronger, plasma membrane develops allowing for fusion with egg)
177
Summarise day 1 of fertilisation
Fusion of sperm and egg in ampulla Glycoproteins on zona pellucida are receptors (ZP3) and sperm head contains binding proteins Binding = acrosome reaction - enzymes exposed to zona pellucida cause it to be digested Fusion can now occur with plasma membrane Sperm head passes into cytosol = fertilisation Fertilisation causes a reaction which changes the cell membrane potential preventing entry of other sperm This is done by exocytosis of vesicles containing enzymes to inactivate ZP3 hardening zona pellucida 4-7 hours after gamete fusion, meiosis II completes 23 sperm and 23 egg chromosomes migrate to centre cell and the haploid chromosomes fuse DNA replication occurs Mitosis begins
178
Sections of fallopian tubes
Fimbriae -> Infundibulum -> Ampulla -> Isthmus
179
Summarise days 2-3 of fertilisation
Zygote remains in fallopian tube Oestrogen maintains contractions within tubes As progesterone increases, smooth muscle relaxes allowing zygote to pass through fallopian tube Cleavage occurs and each cell is totipotent (can develop into an entire individual)
180
Summarise day 4 of fertilisation
Cells flatten Tight junctions between cells Polarisation of outer cells These conditions allow for rapid differentiation
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Summarise day 5 of fertilisation
Fluid filled cavity expands and forms blastocysts >80 cells Lost totipotency Outer cell layer = trophoblast Then you have inner cell mass and fluid filled cavity in middle
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Summarise day 5-6 of fertilisation
Cavity expands further Zona pellucida thins
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Summarise day 6+ of fertilisation
Blastocyst expansion Embryo out of zona pellucida
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Summarise day 7-9 of fertilisation
Late-stage blastocyst hatches and implants in endometrium of uterus
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Sperm can survive longer in the female reproductive tract with greater glucose availability which comes from..
Higher oestrogen levels
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Placenta composition and development
Interlocking foetal and maternal tissues Outer layer trophoblast (synctiotrophoblast cells invade endometrium)
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4 placenta roles
Nutrition Gas exchange Waste removal Endocrine and immune support
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What is the chorion?
Outermost trophoblast cell layer that supplies embryonic portion of placenta Extends chorionic villi into endometrium Release digestive enzymes which break endometrial vessels
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What forms between the inner cell mass and the chorion?
The amniotic cavity - lined by epithelial cells (amniotic sac) which eventually fuses with chorion so there's only a single combined membrane around foetus
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Role of fluid in amniotic cavity
Buffers mechanical disturbances and temperature changes
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Human Chorionic Gonadotropin (hCG) production and effects
Produced by trophoblasts when they begin endometrial invasion Maintains of corpus luteum, stimulates oestrogen and progesterone production preventing menstruation
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Prolactin production and effects
Comes from anterior pituitary Increases end of pregnancy when oestrogen and progesterone decrease Involved in milk production and prevention of ovulation
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Relaxin production and effects
Increases in early pregnancy Produced by ovaries and placenta Limits uterine activity, softens cervix
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Oxytocin production and effects
Comes from posterior pituitary Secreted throughout pregnancy and increases at end Stimulates uterine contractions (+ve feedback)
195
Prostaglandins production and effects
Initiate labour Produced by uterine tissue
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Switch in oestrogen and progesterone production after 3 months of pregnancy
Corpus luteum regresses after 3 months Trophoblast cells of placenta continue to produce oestrogen and progesterone
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Cardiovascular maternal changes in pregnancy
Increased CO Decreased systemic BP Decreased total peripheral resistance Increased uterine blood flow Increase BV Increased plasma and blood cell mass
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Respiratory maternal change in pregnancy
Increased alveolar ventilation
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GI maternal change in pregnancy
Increased acid reflux Delayed gastric emptying - gastroparesis (Foetus pressing on stomach)
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Skin maternal change in pregnancy
Linea nigra - dark line around central abdomen Striae gravidae - stretch marks on lower abdomen Darkened areolar on breasts
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Biochemical maternal change in pregnancy
Weight gain Increased protein and lipid synthesis Insulin resistance
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Cervical ripening
Growth and remodelling of cervix Stimulus oestrogen increases towards end of pregnancy During pregnancy, uterus sealed by collagen fibres (maintained by progesterone) Cervix becomes soft and flexible due to collagen breakdown (by oestrogen, progesterone and relaxin)
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What stimulates oxytocin release pre-labour?
Increased prostaglandins
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What occurs in labour?
Increased prostaglandin and oxytocin triggers contraction and pressure in cervix (+ve feedback from the pressure) Amniotic sac ruptures Contractions at 10-15 minute intervals moving from top to bottom As frequency increases, cervix dilates Stages: Latent - little dilation (8 hours) Active - organised contractions (5 hours) - dilation and full expansion Post-partum - womb contracts and pushes placenta out of vagina
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Do adrenal and gonad derive from same tissue?
Yes
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Testis present and Leydig cells making testosterone means Wolffian system develops into...
Epididymis Vas Deferens Seminal Vesicles Ejaculatory Ducts Sertoli cells also secrete AMH which leads to Mullerian system regression
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No testis or Leydig cells = no testosterone = Mullerian system develops into...
Fallopian tubes Uterus Upper 1/3 of vagina
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Common gential tubercle at 8 weeks becomes ... in male and .... in female
Glans Clitoris
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3 layers of adrenal gland
Zona Glomerulosa - Produces Aldosterone (salt) Zona Fasciculata - Cortisol (sugar) Zona Reticularis - DHEA (sex)
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Negative feedback for cortisol production in the adrenal glands
CRH secreted from hypothalamus stimulates ACTH release from hypothalamus which stimulates cortisol production in adrenal glands Cortisol inhibits release of both CRH and ACTH
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Sertoli cells secrete AMH resulting in...
Mullerian system regression
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3 phases of growth (infancy-childhood-puberty)
Infancy - rapid, decelerates after 2-3 years, determined by nutrition Childhood - switch from nutritional to hormonal dependence Puberty - growth spurt, height velocity increase due to GH and sex hormones (14-15 in girls, 16-17 in boys)
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What is chondrogenesis?
growth
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5 determinants of growth
Parental geno/phenotype Quality/duration pregnancy Nutrition Psycho-social environment Growth promoting hormones
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Where are GHs synthesised?
Somatotroph cells
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Action of GH
Decreases glucose use Increases lipolysis Increases muscle mass
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7 things that stimulate GH production
Exercise Stress Hypoglycaemia Fasting High protein meals Perinatal development Puberty
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5 things that suppress GH production
Hypothyroidism Hyperglycaemia High carb meals Glucocorticoid excess Agings
219
Factors influencing puberty
50-80% genetic Environmental (nutrition) Leptin production (for appetite)
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3 types of hormones
Steroids Peptides Thyroid hormones
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Role of somatostatin in hypothalamus
Inhibits release of GH and TSH
222
2 ways hormones exert their effect
Cell surface receptors Intracellular receptors
223
Time for action in peptides, steroids, thyroid hormones and catecholamines
Peptides - min-hour Steroids - hour-day Thyroid hormones - day Catecholamines - sec
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Thyroid hormones action
Basal metabolic rate, growth
225
Parathyroid hormones action
Ca2+ regulation
226
Cortisol action
Glucose regulation, inflammation
227
6 hormones released by anterior pituitary
ACTH, TSH, GH, LH, FSH, Prolactin
228
2 hormones released by posterior pituitary
ADH (vasopressin) Oxytocin
229
Pituitary releases hormones in response to signals from...
The hypothalamus
230
Pituitary weight
0.5g
231
Anterior pituitary has no arterial blood supply but receives blood through...
Portal venous system from hypothalamus
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What hormone type are TSH, FSH and LH?
Glycoprotein
233
What hormone type are ACTH, GH and Prolactin?
Polypeptide
234
Releasing hormone (hypothalamus) that stimulates release of TSH from pituitary
Thyrotorpin releasing hormone (TRH)
235
Releasing hormone (hypothalamus) that stimulates release of ACTH from pituitary
Corticotropin releasing hormone (CRH)
236
Releasing hormone (hypothalamus) that stimulates release of FSH and LH from pituitary
Gonadotropin releasing hormone
237
Releasing hormone (hypothalamus) that stimulates release of GH from pituitary
GH releasing hormone (GHRH)
238
Releasing hormone (hypothalamus) that inhibits release of GH from pituitary
Somatostatin
239
Releasing hormone (hypothalamus) that inhibits release of prolactin from pituitary
Dopamine
240
Actions of GH
Linear growth in children Acquisition of bone mass Stimulates: protein synthesis, lipolysis, glucose metabolism Regulation of body composition Psychological well-being
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Regulation of thyroid hormone levels
Hypothalamus releases TRH Stimulates pituitary to release TSH Stimulates thyroid to release thyroxine Thyroxine acts on tissue and has -ve feedback on pituitary and hypothalamus
242
Prolactin inhibition action
Inhibits gonadal activity through central suppression of GnRH (thus decreased LH/FSH)
243
Prolactin (PRL) is synthesised by...
Lactotrophs
244
Corticosteroid overview
Lipid soluble (for passing through membranes) Binds to specific intracellular receptors Alter gene transcription directly or indirectly
245
Where are glucocorticoids synthesised?
Zona fasciculata and reticularis of adrenal glands
246
Actions of glucocorticoids
Increase glucose mobilisation Maintain circulation (vascular tone, salt/water balance) Immunomodulation (dampen immune response)
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Glucocorticoids in circulation
90% bound to Corticosteroid-Binding Globulin (CBG) 5% bound to albumin 5% free (only free is bioavailable)
248
Regulation of glucosteroid synthesis by...
ACTH
249
What is stress?
Sum of bodies response to adverse stimuli (infection, trauma, exercise, etc.)
250
Mineralocorticoids synthesised in...
Zona golmerulosa
251
Actions of mineralocorticoids
Effects of pancreas, sweat glands, salivary glands and colon Sodium resorption, decreased sodium content
252
Adrenal androgens
Weak androgens generated in adrenal glands Include oestrogen precursors in postmenopausal women Production regulated by ACTH
253
Roles of adrenal medulla
Synthesises catecholamines Main site of adrenaline synthesis
254
Relative production of catecholamines in adrenal medulla
80% adrenaline, 20% noradrenaline Dopamine in small amounts
255
Adrenal cortex synthesises... (3)
Glucocorticoids Mineralocorticoids Androgens
256
Adrenal medulla synthesises...
Catecholamines
257
What are pituicytes?
Cells of POSTERIOR pituitary gland (cells of anterior named according to the hormone they produce)
258
Pineal gland secretes...
melanin
259
What makes a portal circulation?
Capillary bed at both ends
260
L and R lobes of thyroid gland unite via..
A narrow isthmus
261
Control of thyroid hormone secretion
Hypothalamus secretes TRH Stimulate pituitary to secrete TSH Stimulates Thyroid to release T3. And also T4 which targets tissue (target tissue releases T3) T3 and T4 have -ve feedback on hypothalamus and pituitary
262
Process converting T4->T3
Deiodination
263
Thyroid hormone action
T3 travels through transmembrane transporter (against conc gradient) Changes mRNA to alter the BMR of the cell
264
Enzyme responsible for production of thyroid hormone
Thyroid peroxidase
265
Parathyroid gland role
Regulate Ca and phosphate levels Secrete parathyroid hormone (PTH) in response to: low Ca or high phosphate
266
Actions of PTH
Increase Ca reabsorption in renal distal tubule Increase intestinal Ca absorption Increase calcium release from bone Decrease phosphate reabsorption
267
How many parathyroid glands?
Superior and inferior at back of thyroid on both lobes (4 total)
268
Normal adult range for PTH
1.6-6.9 pmol/L
269
Calcitonin production and action
Produced by thyroid c-cells Inhibits bone resorption (acting directly on osteoblasts)
270
What stimulates bone resorption?
PTH (acts directly on osteoblasts)
271
Female HPG axis in FSH and LH release
Hypothalamus releases GnRH Acts on gonadotrophs in anterior pituitary to release LH and FSH LH stimulates androgen production (oestrogen precursors) FSH stimulates granulosa cells to converts these oestrogen precursors to oestrogen
272
Male HPG axis in FSH and LH release
GnRH release from hypothalamus stimulates gonadotrophs in anterior pituitary to release FSH and LH LH stimulates Leydig cells to secrete testosterone (-ve feedback of LH and FSH) FSH stimulates sertoli cells to maintain spermatogenesis (produces inhibin -> -ve feedback of FSH)
273
Growth Hormone release axis
Somatostatin from hypothalamus inhibits GH release from anterior pituitary GHRH from hypothalamus stimulates release of GH from anterior pituitary GH acts directly to increase blood glucose and bone/tissue growth GH acts indirectly on liver to produce insulin-like growth factors which contribute to cartilage growth as well as the others in direct pathway
274
3 factors effecting GH release
Circadian rhythm Stress and cortisol Fasting (these factors alter GHRH/somatostatin release
275
3 methods of endocrine control of extracellular calcium homeostasis
Parathyroid hormone Vit D Calcitonin
276
Hypothalamic regulation of GnRH release
Kiss neuron releases Kisspeptin neurotransmitter which binds to GPR54 receptor on GnRH neuron triggers release of GnRH
277
HPA axis for cortisol release
Stress and Cytokines stimulate CRH release from Hypothalamus Stimulates ACTH from anterior pituitary Stimulates Cortisol from adrenal which acts on tissue (cortisol production has -ve feedback on pituitary and hypothalamus)
278
Relative 'free' calcium in the body
50% is 'free' 50% is bound to albumin (so can't diffuse into cells)
279
Regulation of plasma renin in RAAS
Renin produced in kidneys converts angiotensinogen (secreted by liver) to angiotensin I Angiotensin I -> Angiotensin II by ACE in lungs Angiotensin II stimulates aldosterone release from adrenal Aldosterone increases Na reabsorption and K secretion in kidneys
280
What stimulates renin release from kidneys? (3)
Decreases renal BP Prostaglandins Beta-adrenergic action
281
What suppresses renin release from kidney?
ANP Dopamin
282
What suppresses aldosterone release from adrenal glands?
Decreased extracellular [K+]
283
Zonation of adrenal
Outer capsule Cortex (zona glomerulosa -> zona fasciculata -> zona reticularis) Medulla
284
Where in the adrenal gland does corticosteroid synthesis occur?
Cortex
285
What is synthesised in the zona glomerulosa of the adrenal glands?
Mineralocorticoids - Aldosterone
286
What is synthesised in the zona fasciculata of the adrenal glands?
Glucocorticoids - Cortisol
287
What is synthesised in the zona reticularis of the adrenal glands?
Androgens - DHEA
288
What are synthesised in the medulla of the adrenal glands?
Catecholamines
289
Uric acid solubility
Poorly soluble in plasma Lower pH, less soluble it becomes
290
Uric acid comes from the breakdown of...
Purines (e.g - Adenine, Guanine)
291
3 sources of purines
Diet Breakdown of nucleotides in tissue Synthesis in body
292
Uric acid removal
Excreted in urine Broken down in gut
293
Dietary purines
Meat Offal Seafood Fish Fructose
294
Allopurinol prevents...
Conversion of purines to uric acid
295
Why does alcohol consumption increase uric acid levels?
Contains purines