SUGER Flashcards
1
Q
Where is medelian genetics most important?
A
Rare diseases
2
Q
Where are complex trait genetics important?
A
Common diseases CVD VHD
3
Q
What is the importance of somatic genetics?
A
In cancer diseases
4
Q
How rare are rare diseases?
A
1 in 2000
5
Q
What is ADPKD?
A
Autosomal dominant polycystic kidney disease. Where the kidney is filled with cysts that stop it from functionning properly affect all ethnic groups
6
Q
What is a cyst?
A
A fluid filled growth that is lined with cells
7
Q
What does polycystic kidney disease affect?
A
it affects the kidneys and also lung endothelial problems, heart valve defects, intracranial aneurisms, cysts in other parts of the body
8
Q
How is PKD diagnosed?
A
The number of cysts in the kidney based on your age (cysts develop over time as natural ageing things)
9
Q
What is the link with genotype and prognosis?
A
the type of mutation can give you an idea of when you end up getting kidney problems
10
Q
What are the treatments for PKD?
A
dont understand causes. key molecules are cAMP and Ca2+ Vasopressin receptor -2 antagonist(blocker)
11
Q
What does sexual and reproductive health involve?
A
Respect safety and freedom from discrimination and violence, throughout whole life not just reproduction, supportive of all sexualities STDs, Fertility, abortion, sexual violence, mental health gender dysphoria
12
Q
Why is sexual health important?
A
it is in top 10 disease burdons
13
Q
What are some recent changes in sexual practices in the last 60 years?
A
Rising gap between sexual debut cohabitation and childbearing, fall in teenage pregnancy, older childbearing age, HIV/AIDS reduction in sexual prejudice, increasing expectations of sexual fulfilment at older ages
14
Q
What are the aims of sexual health policy?
A
Educate on consent, Condoms, HIV testing, Fall in unwanted pregnancies, educate young people, tackle inequalities
15
Q
How many organisms cause STI?
A
over 30
16
Q
What is a big problem with STI now?
A
Asymptomatic carriers and can increase risk of HIV contraction, antibiotic ressistance
17
Q
What is maternal mortality levels?
A
Very low in developed countries often in poorer countries
18
Q
What maternal inequalites are there?
A
Black african women are more likely to die than white people
19
Q
What can cause unwanted pregnancy?
A
Intoxication, availability of contraception, lack of ability to control contraception
20
Q
What is female genital mutilation?
A
when a surgical operation is done on the female which can cause pain and suffering. often done for religious or cultural reasons
21
Q
What are effects of FGM?
A
Scars, cysts formation, pain during sex, lack of pleasure, psychologiccal dammage
22
Q
What are some key challenges to Sexual and reproductive health?
A
Political gender sexuality hierachies
religious and moral beliefs of people
23
Q
Is obesity a disease?
A
some think it should but politics is behind
24
Q
What diseases are linked to obesity?
A
Cancers, heart disease, liver disease, stroke, depression and anxiety, sleep apnoea, diabetes, arthritis and asthem
25
What diseases are linked to obesity?
Cancers, heart disease, liver disease, stroke, depression and anxiety, sleep apnoea, diabetes, arthritis and asthem
26
What are global trends of obesity?
Increaseing in developing and less in developed
27
Why is obesity on the rise in developing countries?
Increased in ultra processed food, food of animal origin, sugar addes fast food, reduces fibre and fruit and vegetables
28
What is the effect of deprivation on childhood obesity?
More deprivation more obesity from lack of access to healthy foods
29
What are the key areas that can affect risk of obesity?
Food production, Biology, activity environment, individual activity, food consumption, social infulences, individual psychology
30
What is proven to work for obesity?
RCTs have been done on bariatric surgery, diet and physical behavioural intervention but cannot really measure most inerventions this way
31
What are the 4 levels of obesity intervention?
General population level education, multi-component/ lifestyle weight management eg weight watchers
specialist services in hospital and then surgical interventions
32
What is the fuction of the kidney?
Maintain salt water and pH balance, Endocrine funcitions, excrete waste products
33
What is the basic structure of the nephron?
Bowmans capsule, proximal convoluted tubule, loop of henle and distal convoluted tubule and collecting duct
34
How much blood flows through the kidney?
1L/min
35
What is the flow of urine
1ml/min/kg
36
What is the renal blood structure?
Renal artery interlobar artery arcuate artery, intdrlobular artery afferent arteriole then in the nephron glomerular capillaries
37
What is the afferent arteiole?
The arteriole that enters the glomerulus
38
What is the efferent arteriole?
The arteriole that exits the glomerulus containing filtered blood
39
Which part of the nephron is close to the glomerulus?
The distal convoluted tubule as part of juxtaglomerular aparatus. (macula densa)
40
What is surrounding the glomerulus?
The bowman's capsule.
41
What is the structure of the barrier of the glomerulus?
There is the endotheilia wall of the capillary, a thick basement membrane, foot processes of the podocytes
42
What is the aim of the barrier?
Only let small molecules through and stop negative ions/ molecules
43
What are the charges on the foot process?
They are negative to help stop albumin passing through the membrane
44
What determines crossing the filtration barrier?
Pressure size of molecule charge of molecule rate of blood flow and bindin to plasma protein
45
What can pass through the barrier?
Small molecules glucose uric acid creatinine
| negative charged things dont go through
46
Should protein be in the urine?
No albumin is negatively charged so cant pass through
47
Which way is the osmotic pressure in the capsule?
from the filtrate into the blood
48
What is the balance of hydro static pressure in the kidney?
from the blood into the capsule
49
What affects the glomerular filtrate rate?
difference in hydrostatic pressure minus difference inoncotic pressure
50
How can pressure in the caplilary?
Varying the size of the afferent and efferent arterioles
51
What is auto regulation of the kidneys?
The control of the blood pressure in the kidneys that is not related to innervation or blood substances this heps maintain the GFR
52
Describe autoregulation
Pressure within the afferent arteriol rises which increases strech and this contracts the smooth muscle
53
What is tubuloglomerular feedback?
When the cells in the macula densa measure the amount of NaCl in distal tubules
54
What is involved in the Justaglomerular apparatus?
the macula densa (cells of distal tubules) the granular cells outside and inside the glomerulus
55
What happens with low NaCl in the macula densa?
Decreases resistance to blood flow wich helps to raise glomerular hydrostatic pressure and GFR
it also increases renin relases form yxtaglomerular cells causing vasoconstiction of afferent arterioles
56
How can GFR be estimated?
Measure the amount of a substance in the urine over a period of time, the substance is freely filtered and is not metabolised or secreted through the kidney
57
What is the equation for GFR?
GFR=conc urine*urine flow / concentration in plasma
58
Where does the equation come from for GFR?
It comes from the amount in blood(conc*GFR) and amount in urine(conc*flow rate)
59
What is the normal GFR?
125ml/min
60
What is the substance used to clinically measure this?
Creatinine which is a muscle metabolite it does vary with muscle mass it is freely filtered but slightly secreted by tubules
61
What is the filtration fraction?
the GFR/renal plasma flow
62
What is the usual fitration fraction?
around 20%
63
What is renal clearance?
the volume of plasma from which a substance is completely removed by the kidney per unit of time
64
What does a clearance of less than the GFR mean?
The substance is reabsorbed/ not freely filtered
65
What does a clearance of greater than the GFR mean?
It means that the substance is actively secreted
66
What is the 12 rib a good marker for?
The kidneys
67
What lies posteriorly to the kidney?
The diaphragm
68
Where are glomeruli found?
in the cortex
69
Which area of the embryo becomes the urinary system?
The intermediate mesoderm
70
What are the three areas of the foetus that develop from the intermediate mesoderm?
Pronephros in cervical region, mesonephros, thoracic and lumbar, and the metanerphros which is the permanent kidney and develops in the pelovis
71
What are the nephral areas like?
they are blocks of tissue
72
What happens during the development of the nephros system?
One area develops and then dissapears as the next one develops, they do this all the way to the mesonephros
73
What is the name of the duct that carries urine early?
The mesonephric duct that moves as the older areas degenerate
74
Where does the lasting kidney develop?
In the lower portion of the foetus
75
what does the mesonephric duct do?
becomes the vas defferens in the male
76
What is metanephric balastema?
when the ureter grows towards the metanephros and makes contact causing it to develop into a kidney
77
What are primordial germ cells?
They are cells that migrade to the genital ridge where they can form sperm and eggs
78
Where does the mesonephric duct end up in the development?
In the cloaca where all holes are to begin with
79
What is the mesonephric duct's other name?
The wolffian duct
80
What develop into the gonads?
The genital ridge
81
What are the two functions of the mespnephric duct?
Sperm carrying in developed but also the early ureter
82
What is the metanerphros?
It develops after mesonephric. ureteric bud grows into the metanephric tissue
83
Hoe many major calycies are there usually?
3
84
How many minor calyxices are there?
8
85
What forms the medulla of the kidney?
The ureteric duct
86
How many collecting ducts are you born with?
2 million
87
Which part produces the collecting duct?
the metanephric duct
88
What can go wrong with formation of the nephron
Can go very wrong, and causes medukkary sphonge kidney
89
Where does the kidney move?
From the pelvis and other parts grow bellow it which leads to it being high in the abdomen
90
What happens to the mesonephric and ureter?
They both develop attached to each other. After a while they separate through growth so the attach to the baldder at diffeen points
91
What is the urogenital sinus?
The area where the urethra will develop
92
What are the three areas of the urogenital sinus?
The upper part that forms the bladder, low midddle pelvic part that gives rise to the prostatic and membranous parts of the urethra and the phalic part that forms the penile urethra
93
What forms the trigone?
The mesonephric duct moving inferior to the ureter but it passes over the ureter
94
When does the prostate develop?
In the end of the 3rd month
95
How does the prostate develop?
It develops from te prostatic urethra and is derived from the mesoderm
96
What does the urethral epithelium give rise to in the female?
The urethral and paraurethral glands
97
What can go wrong in GU embryology?
Ureteric bud can form multiple kidneys, wrongly positioned ureter that means reflux can happen, extra renal arteries, kedneys fuse to make a horseshoe kidney
98
What is s urachal cyst?
A part of bladder formed in the ligament between the umbilicus.
99
What is the pouch of douglas?
The area behind the uterus and in front of the rectum?
100
When does the indifferent gonad differentiate?
7th week
101
How do the gonads develop?
as a genital ridge on the anterior of the mesonephros
102
What stimulates the development of gonads?
The primordial germs cells that migrate from the yolk sac
103
Which ducts are improtant?
Paramesonephric duct(mullerian duct) and the mesonephric duct (wolffian duct)
104
Which duct is improtant in the female?
Paramesonephric duct mullerian
105
Where is the paramesonephric duct?
It develops anteriorly to the mesonephric duct
106
What is the first stage of development in the genital ridge?
The formation of primitive sex cords
107
What is the default system in the system?
Female need genes to turn on male genes
108
What do the primitive sex cords do in the male?
They compartmentalise the testicle and form the cords of the testicle
109
What happens to the primative sex cords in the female?
They disintegrate into irregular cell clusters and forms oogoniu and follicular cells
110
What does the wolffian duct do?
It joins to the open ends of the compartments of the testicle in the female it disintegrates
111
What does the mullerian duct do?
makes the Fallopian tubes uterus and most of the vagina. the two sides join together and produce the uterus
112
What cells do the testicles have?
sertoli cells and leydig cells that produce testosterone
113
what is the epididymis?
coils of wolfian duct where sperm cells can mature
114
Where does the testicle move?
It moves from the abdomen down through the inguinal canal into the scrotum
115
What does oestrogen do?
It prouces the development of unterin tubes, cervix, uterus, upper 2/3 vagina
116
What is the hymen made from?
Two cell layers, from the external part of the vagina and the uterus
117
What is the effect of testosterone on the male external genitalia?
The labia fuse up to the tip and the urethra moves upwards. They bring the cropra spongiousus and cavrnousis with it
118
What are some common problems with penile development?
Urethral outlet is at varying places along the penis. hypospadias, undescended testicle
119
What forms the scrotum?
The labia majorum
120
What are some of abnormalities with vaginas?
can have two uteruses, separate ones
121
What is an acidosis?
Disorder tending to make blood more acidic than normal
122
What is acidemia?
Low blood pH
123
What is alkalemia?
High blood pH
124
What is alkalosis?
Disorder tending to make blood more alkaline than normal
125
What is standard bicarbonate?
It is a measure of metabolic component of acid-base component. as absolute bicarbonate is affected by metabolic and respiratory components
126
What is base excess?
The quantity of acid required to return a pH to normal it is standardised to Hb of 50g/L
127
What does a negative base excess mean?
Acidosis
128
What does a postive base excess mean?
alkalosis
129
What is on a blood gas machine?
pH, pO2, pCO2, Std HCO3-, Std base exces, May inclue other measures
130
What are the two ways of approaching acid bases?
Stewards theory, henderson hasselbalach equation
131
What is the processes ivolved in acid base disorders?
CO2 dissociation into hydrogen ions and bicarbonate in the blood and HCO3 recycling and CO2 excretion lungs and kidneys
132
What changes CO2 levels?
Lungs or indirectly by kidney excretion
133
What is stewart's strong ion difference?
principle pH and HCO3 are dependant on pCO2, concentration of weak acids Phosphates albumin Proteins and strong ion difference Na K Mg Ca
134
How can acid base disorders be described?
Respiratory or metabolic
135
How should you look at a blood gas read out?
Look at pH acid or alkali
What is repiratory component?
What is Metabolic component?
Which links with the pH?
136
What cause metabolic acidosis?
Dilutional, failure of H+ secretion, renal failure hypoaldosteronism type 1 dubular renal acidosis
Excess H+ load lactic acidosis, ketoacidocis ingestion of acids
HCO3- loss diarrhoes, type 2 renal tubular acidosis
137
What are symptoms of metabolic acidosis
Increased respiratory rate and deep breathing
138
What is the anion gap?
looking at conc of ions wide anion gap is lactic acidosis ketoacidosis ingestion of acid or renal failure.
if its narrow sugests GI HCO3- loss and renal tubuler acidosis
139
What can cause metabolic alkalosis?
Alkali ingestion GI acid loss, Renal acid loss hyperaldosteronism, hypokalaemia.
140
What is the compensation form metabolic alkalosis?
Compensatory mechanism: hypoventilation but limited by hypoxi drive and renal bicarbonate excretion
141
What are the causes of respiratory acidosis?
CO2 retention from respiratory failure
142
When does renal compensation come in?
Over longer periods
143
When can respiratory alkalosis occur?
CO2 depletion due to hyperventilation in Type 1 resp failure
144
What is the renal urine flow?
1ml/kg/min
145
What is reabsorbed in the proximal tubule?
Glucose, amino acids, phosphate, bicarbonate multiple, sodium
146
What is renal glycosuria?
Sodium glucose transporter 2 is not functioning, failure of glucose reabsorption often incidental finding query diabetes
147
What is a type two diabetes treatment from kidney modification?
SGLT2 inhibitors for type two to make you week out sugar
148
What is aminoaciduria?
When you end up with amino acids in your urine
149
What is cystinuria?
defect of renal basic amino acid transporter, failure of cystine reabsorption causing stone formation
150
How can cystinuria be treated?
High fluid intake, alkaline urine will increase the solubility of cystine, chelation(bind to cystine) penicillamin and surgical intervention
151
What is hypophosphataemic rickets?
X linked hypophosphataemic rickets, dephect in PHEX zinc dependant metalloprotease affects FGF23, treatment is phosphate replacement
152
How is bicarbonate reabosorbed in the PCT
carbonate converted to CO2 to move into tubular cells, then convrted to bicarbonate where it crosses to blood with sodium. hydrogen moves out as sodium moves into tubular cells
153
What is type two renal acidosis?
When sodium hydrogan antiporter broken from bicarbnate reabsorption fails, causes acidosis way to treat is excess bicarbonate in diet
154
What happens in carbonic anhydrase defect?
Mixed renal tubule acidosis, from problems in proximal and distal tubule
155
What is the clinical use of carbonic anhydrase inhibitors?
Mild diuretica and can cause acidosis, used to treat altitude sickness allows for rapid compensation of respiratory alkalosis
156
What is faconi syndrome?
Genarlised PCT failure from sodium potassium pump, get many features usually genetic cancer leat poisioning cancer treatment
157
What is the function of the ascending limb in the nephron?
producing concentration gradient and sodium reabsorption
158
What balances the charge of salt moving into intersittial fluid?
Calcium and magnesium
159
What is barrter's syndrome?
Group of disorders in loop of henle low sodium potassium chloride cotransporters. get salt wasting hoypokalemic alkalosis and low BV. Antenatal features prematuritey delayed growith
160
What are some distal tubule and collecting duct disorders?
Gitelman's syndrome, Distal type 1 renal tubular axidosis, diorders resembling hyperaldosteronism, Type 4 renal tubular acidosis, nephrogenic diabetes insipidus
161
What its gitleman's sundrome?
Defect in thiazide sensitive chloride channel, failure of sodium chloride cotransport in distal tubule, hypokalaemic alkalosis impared magnesium absorption and increased calcium reabsorption
162
What is polydypisa?
Thirst
163
What happens in the distal tubule?
JGA look at BP and sodium levels fine absorption of nutrients
164
What is the action of aldosterone?
It acts on the distal tubule and collecting ducts. in the principal cells ENaC allows sodium in then on basolateral surface there is Na/K ATPase
in intercalated cell there is carbonic anhydrase which helps to halance this chatge with HCO3 and H+ leaving.
aldosterone reabsorbs sodium and lets H+ leave
165
What are principal cells?
They are main cells responsive to aldosterone in collecting ducts involved with sodium chloride
166
What is distal type 1 renal tubular acidosis?
Failure to excrete H+ by loss of fuction of enzymes
167
What is another reason for renal tubular acidosis?
Too much aldosterone which leasts to loss of potassium. could be from too much aldosterone production or renal artery stenosis
168
What is type 4 tubular acidosis?
low aldosterone levels. reduced generation of electrochemical gradient, resulting in failure of H+ and K+ excretion
169
What is nephrogenic diabetes insipidus?
Vasopressin receptor or aquaporing 2 channel problems. failure of water reabsorption in collecting duct so struggle with concentrating urine
170
What determines the sex of a child?
The sperm can be X or Y
171
How is foetal sex determined?
It is determined by the Y chromasom with an area on the short arm SRY regionwhich switches on testicular development and prevents mullerian duct development
172
What are germ cells?
they are cells that in females produce the eggs and in males they produce the sperm producing cells
173
Where do genm cells come from?
in the yolk sac in the hindgut
174
When are eggs formed?
12 weeks up to 20 weeks when there are 5-10 million
175
When does the number of oocytes decrease?
at around 20 weeks
176
How many oocytes are females born with?
1- 2 million
177
What is the importance of meiosis?
It helps to form the sex sell
178
What is meiosis like in the female?
Meiosis 1 starts in utero before 12 weeks then they are arrested at metaphase 1 until after puberty when it is resumed by LH surge meiosis 2 finished at fertilisation
179
What significance does meiosis play in reproductive medicine?
Forms of chromosomal abnormalites from non-disjunction, polypoidy, and inheritaed traits and variation
180
When is sex difference evident in foetal development?
When the primordial germ cells enter the genital ridge and cause SRY to be expressed at 6 weeks
181
What is gonadal dysgenesis?
Caused by non-disjunction of the sex chromosomes
182
What 45 X/X0?
Turner's sydrome, absent/poor secondary sex characteristics normal intelect
183
What is 45XO/46XX mosaic?
Some cells have each genotype separately, they have streak gonads with premature ovarian failure
184
What is 47XXY?
Kleinfeiter's syndrome, tall feminine gynacomasstia infantile testes average intellect, wide hips, long arms and legs, fewer chest hairs narrow sholders
185
What is female appearance with 46XY ?
externally female, internally mixed this is androgen insensitivity syndrome can hae a mix it is x linkied
186
What is CAIS, PAIS, MAIS?
Complete has normal female external genitalia, partial has masculinised external genitalia and male androgen insensitive has normal male external genitalia
187
What is 46 XX female but can have ambiguous eternal genitalia?
congenital adrenal hyperplasia affects 21 hydroxylase it stops production of aldosterone and cortisol that leads to testosterone deficiency in adrenal gland pathway males are not really affeced only wiht large phallus and shorter stature it is recesslive
188
What are mullerian anomalies?
Structural disorders of the internal genitalia of females such as lateral and vertical fusion disorders
189
What system is involved with the onset of puberty?
Hypothalmic-pituitary-gonadal axis
190
What is the state of hormones before puberty?
Low pulsatility amplitude go Gonadotrophin releasing hormone. low levels of FSH LH and sex hormones
191
What happens at puberty to hormones?
Increased amplitude of GnRH and increasing levels of FSH and LH and sex sterioids also increased levels of GH
192
What is normal puberty like?
Centrally driven HPG axis can be affected by many things but is not understood what the trigger is
193
What is percocious puberty?
Early buberty
194
What is True precocious puberty?
Gonadotrophin dependand caused by brain problems or tumours releasing it or hypothyroidism.
195
How is precocious puberty treated?
Treat lesions or inhibit with GnRH analogues t avoid social problems of early sexual maturation and prevent early bone develpment
196
What are causes of delayed puberty?
General malabsorption chronic diseases, gonadal failure gonadotrphin deficiency
197
How can delayed puberty be treated?
Sex hormone treatment, growth hormone treatment pulsatile GnRH by pump and hMG
198
How can the urethra be immaged?
injecting contrast up the urethra using xrays.
| ultrasound also
199
Why is ultrasound used in reproductive immaging?
Widely available good for soft tissue, non ioisin
200
What is the use of doppler ultrasound?
It shows you the flow of blood
201
What will you look at with an ultrasound of the uterus?
The endometrium and myometrium
202
What is hystosalpinography?
Insertion of a contrast into the uterus to look at the fallopian tubes uses an x-ray
203
What is the problem with single sided uterus unicornuate?
Often early birth
204
What is likely to happen to a uterus that is split into two?
Can remove middle but otherwise early term pregnancy
205
What can cause tubular oclusions?
STI like chlamydia
206
What do pregnant women find out on scans?
12 week scan for progress and abnormality, 20 week anomaly scan for organs etc, additional dependant on clinical need
207
Why do we image in pregnancy?
give information, abnormality, for delivery, for future health of mother and baby
208
What are the two types of twins?
Monochorionic, dichorionic number of placentas di is more difficult
209
Why is it important to know about placental placement?
To know if a natural birth is safe
210
What is a foetal maternal scan?
More detailed when abnormalities have been detected
211
What is the use of an MRI scan for foetuses?
They need to look at some small details of stationary structures
212
Why might you do a post mortem image?
To see what went wrong for future babies and as an alterntative to an autopsy
213
What are the glands related to the male reproductive tract?
Bulbourethral, seminal vesicles and the prostate gland
214
What is the average size of the testicle?
4cm long 2.5cm diameter
215
What is the speta of the testicle?
They separate the organ into compartments containing seminiferous tubules where the sperm are produced
216
Whaere are the leydig cells?
They are clusters of cells between the seminiferous tubules and source of testosterone
217
Where are sertoli cells?
They are in the walls of thetubules of the testes
218
What is the purpose of the blood-testis barrier?
To stop immune cells from attaching them
219
What do the where do seminiferuse tubules lead? into?
to the rete testis
220
How does the testicle be cooler?
There is a countercurrent pampiniform plexus to allow the cooling of the testicle outside the body
221
What is the role of mitosis in spermatogeneis?
They produces identical daughter cells and is used for replicating the 2n spermatogonium
222
Where does mitosis happen in males?
In the seminiferous tubules
223
What happens to type b spermatogonia?
They cross the blood testis barrier to move toward the lumen and form a tight junction behind it. they differentiat into primary permatocytes
224
What are primary spermatocytes?
they are 2n cells
225
What turns primary spermatocytes into secondary spermatocytes?
meiosis 1
226
What are secondary spermatocytes?
n cells that will go on to form spermatids
227
What forms spermatids?
When secondary spermatocytes undergo meiosis 2 to form n cells
228
Which steps are spermiogeneis?
spermatids into spermatozoa by sprouting a tail and discards cytoplasm to become lighter
229
How many sperm are made per gram per second?
300 to 600 /g/s
230
What is the reason for high sperm production?
There are lots of defective sperm, with two heads two tails bent tails acrosome missing
231
What are sertoli cells?
There are sertoli cells which support the sperm and nourish them
232
What changes do the spermatids undergo?
More mitochondria, small condensed nucleus, acrosome, flagellum
233
How long does it take for the sperm to be generetaed?
64 days
234
HOW long is it in the seminiferous epithtlium cycle?
16days
235
How is permatogenesis stimulated?
hypothalamus releases, GnRH anterior pituitary produces FSH LH,
236
What does LH do for spermatogenisis?
This affects the Leydig cells to produce testosterone, which inhibits anterior pituitary and hypothalamus
237
What does FSH do?
It stimulates sertoli cells to produce sperm
238
What comes after the rete tetis?
The efferent ductules that lead to the epididymis
239
What is the epididymis?
6m long coiled duct adhering to the posterior testis site of sperm maturation and storage
240
What is the ductus(vas) deferens?
the muscular tube that is 45cm long passing up from the scrotum through the inguinal canal to posterior surface of the bladder and widens close to the prostate with the ampula
241
What is the ejaculatory duct?
2cm duct formed from ductus deferens and seminal vesicle passing though the prostate to empty into the urethra
242
What is semen made of?
seminal vesicle fluid, prostatic fluid, sperm and trace of bulbourethral fluid
243
What is the normal sperm count per ml?
50-120million/ml
244
What are the proposed roles of seminal fluid?
Contain fructoes for sperm motility, fibrinogen, clotting enzymes that convert fibrinogen to fibrin and then fibrinolysin to liquefy the semen, prostaglandins can stimulate femal peristaltic contractions is a base to spailise pH
245
What is the minimum urine pH?
4.5
246
Where is the acid load in the blood from?
CO2 in the blood, non-carbonic acids from proteins, buffers etc
247
Explain the bicarbonate buffer?
more co2 makes more H+ and bicarb the lungs can reduce CO2 kidney can remover HCO3
248
What role does the kidney play in the HCO3 CO2?
It reabsorbs or excretes HCO3 as needed. to excrete acid load phosphate and ammonium bufferes are needed
249
What is the need for urinary buffers?
Urine would be too acidic for our body and would end up with a lot of urine
250
How is bicarbonate reabsobed?
carbonic anhyrase concerts it to co2 to enter the cells. here it can go back to HCO3 by carbonic anhydrase. the H+ can go back into urineoposing sodium. cotransporter out of cell into capillary with sodium
251
Where is bicarbonate reabsorbed?
in the proximal convoluted tubule
252
Which types of pumps are used in bicarbonate ions?
Sodium potassium, Na HCO3 symport, Na H+ antiport into urine
253
What is the apical membrane?
The one with the urine space
254
What is the urinary phosphate buffer?
Alkaline phosphate HPO4 2- can accept H+ it is not able to pass through the apical membrane. most common urinary buffer
255
What is titratable acidity?
the abound of alkali needed to neutralise
256
How does the urinary phosphate buffer work?
sodium hydrogen antiport sodium into cell H+ into urine. Sodium and phosphate cotransport then sodium potassium
257
What is the urinary ammonia buffer?
Adaptive response NH3 synthesised form glutamine. Renal synthesis NH3 diffuses into lomen and NH4+ is formed and cant get back in
258
What are the pumps involved in urinary ammonia buffer?
Sodium H+ antiport, Na NH4+ antiporter Na HCO3 symport and Na KATPase
259
what is net acid excretion?
Titratable acidity+ammonium-HCO3-
260
What is the role of the kidney as an endocrine orga?
AngiotensinII through renin, erythropoetin and activation of vitamin D
261
What does erythropoetin do?
is a survival factor it is high in anaemia . it stimulates RBC maturation and bone marrow
262
What are the types of in urinary incontinence are there?
Stess inontinence- leakage on coughing straining due to weak sphincter
Urge incontincance leakage when urgency due to bladder overactivity
Retention with overflow- continuous drippling
Anatomical continuous dribbling with normal voids can be congenital or aquired
263
What is an ectopic ureter?
When the positionin of the ureter is not normal eg could be continuous with the urethra
264
Who does nocturnal uresis affect?
under fives, males and females equally then very low after 10
265
What is the function of the urinary tract?
To collect urine and store it an void it when appropriate
266
What are the key factors in normal bladder function?
Continence, sensation of bladder volume, receptive relaxation, voiding, volunaty initiation and complete emptying
267
what can some of the effects of urinary tract dysfuncition be?
Incontinence infections bladder stones, or pressure and stones in the kidney
268
What are the aims of bladder management?
Protect the kidneys reduce continence mannage it and promote independance, body image self esteem,
269
What does the upper urinary tract involve?
Prevention of reflux, competecy of ureter vesical valves and active perstalsis to protect kidney against bladder pressures.
270
What are the differnent sphincters?
bladder neck, distal urethral sphincter
271
When is the bladder neck sphincter active?
during ejaculation only
272
What is the rhabdosphincter?
intrinsic striated distal urethral sphincter striated muscle
273
What is Onuf's nucleus?
S234 at anterior horn which does the guarding reflex
274
What is the innervation of the bladder like?
Smooth muscle that is innervated intrinsicly it has tone and intrinsic characteristics
275
Where does sacral micturation centre have links to?
Parasympathetic sacral outflow s234 motor to bladder coordination of icromotions there are c fibre afferents that have the reflex bladder contractions
276
What do the sympathetics do?
Receptive relaxation, bladder neck in ejaculation, smooth muscle sphincter non relaxing sphincter obstruction
277
What does the pontine micturation centre do?
possible medial micturation and lateral storage centres motor centre for the autonomic control of urinary tract descending fibres presumed to be in the antero-lateral funiculus
278
What are the spinal reflexes based on urination?
Reflex bladder contraction, guarding reflex receptive relaxation probaly sympathetic
279
What happens when you are surpressing micturation?
periaqueductal gray gets signals you ned to urinate, looks to corticies for iut then pontine micturation centre doesnt send a signal?
280
what happens when micturation is allowed?
The pontine micturation centres sendssignals to surpres onuf's nucleus and this allows relaxation of the sphincters
281
What are the functions of the lower urinary system?
Low pressure insensible storage of urine, prevent leakage of the urine stored.
allow rapid lowpressure voiding at an appropriate time and place
282
What happens to stop voiding?
Urethra contracts, detrusor contraction switched off
283
What happens first during micturation?
Primary event is urethral relaxation, then bladder neck funnels, detrusor contraction begins
284
What drives detrusor contraction?
Parasympathetic pelvic splanchnic s234
285
What drives urethral contraction internal and external?
Internal - hypogastric plexus T10-L2
| External- Pudendal nerve conscious control S2-4
286
what happens normally when not voiding?
mid brain and higher centres stimulate micturation centres that stimulate sphincter muscles inhibit onufs nucleaus which stops the destrussor contracting
287
When do levels of FSH increase in the menstrual cycle?
In the first 4 days levels increase to begin the recruitment of follicles
288
What does LH do?
stimulates ovulation by causing the rupture of the follicle
289
When do oestrogen levels increase?
10-12 which supportes thickening of the uterine emdometrium
290
Which hormones are made in the ovary?
Oestrogen diol and progesterone
291
Which sex hormones are released by the anterior pituitary?
FSH and LH
292
What happens as the follicles are stimulated?
Oestrogen is produced by the follicles
293
what stimulates LH spike?
Oestrogen
294
What does the corpus luteum do?
Produces progesterone and lower levels of oestrogen
295
What happens to the corpus luteum if no fertilisation takes place?
it regresses to corpus Albucans, which doesn't produce as much oestrogen or progesterone
296
What is the function of GnRH (Gonadotrophin releasing hormone)
it stimulates the anterior pituitary to produce FSH
297
What does FSH do to the brain?
It inhibits pituitary to release GnRH and stimulates follicle growth
298
What does hCG (human chorionic gonadotrophin) do?
It maintains the corpus luteum until the placenta can take over production
299
What is the effect of progesterone on the brain?
it reduces production of FSH and LH
300
Where does fertilisation take place?
In the Fallopian tubes
301
What helps the sperm to reach the site of fertilisation?
Sperm motility and cilia in the fallopian tubes
302
What are the 3 parts of the Fallopian tubes?
the isthmus, ampula infundibulum.
303
How long can a sperm be live for in the female?
5 days
304
What is Capacitation?
final maturation stage of spermatozoa that takes place in the female genital tract before it can gain the ability to fertilise the oocyte
305
What does the sperm have to pass through to get to the egg?
The glycoprotein layer zona pellucida
306
What happens to the sperm when it attaches to the Zona pellucida?
the acosome helps break down the zona pellucida and there are proteins it can bind through
307
what is the role of ZP proteins?
They make proteins specific to species
308
what happens when the sperm has passed through the ZP?
It reaches the ollema membrane then the sperm binds to it then cortical granules cause a block of polyspermia by the changing of the proteins in the ZP
309
What happens to calcium levels in the egg?
When the sperm has entered then pulses happen which become longer gaps after a while
310
What is the final stage of maturation that the egg goes through and when?
The last meiosis to produce a polar body that is after te sperm has entered the egg
311
What is syngamy?
when the protonucleus of the sperm and the egg are joined
312
What is a morola?
When the zygote has doubled the cell numbers many times around 64 cells
313
What is the next stage after morola?
Blastocyst
314
What implants into the uterus?
The hatched blastocyt
315
What are the cells around the blastocyst and inside them?
The trophpblasts and inner cell mass
316
Where is sperm injected in IVF?
Under ZP and above ollema and now they put it into the egg cytoplasm iteself
317
What is the biggest factor in CHD?
Size at birth
318
What is the dutch famine birth cohort study?
Taken during famine at the end of the war that affected the birth weight of children
319
What is linked to large birth body size?
Cancer
320
What is linked to low body size?
Type 2 diabetes Osteoporosis, Scizophrenia depression and CHD
321
What is the Barker early origins hypothesis?
that nutritional state of the mother during pregnancy can affect the health of the child in the future.
322
What changes lead to CHD increased risk in foetal development?
Increased blood pressure throughout adult life smaller heart mass in females increased lung ACE activity and reduced capacity to dilate arterial vessels
323
What can contribute to Epigenetics?
DNA methylation, Histone modification
324
When and how is the epigenomic profile set?
before fertilisation
325
What is the relevance of the knowledge of epigenetics?
IVF changed the environment of fertilisatio greatly
326
What are some imprinting disorders?
Beckmans syndrome and anglemans syndrome
327
What is involved in activation of the egg?
Calcium release from a sperm protein phospholipase C zeta
328
What is the need for oocyte activation?
Transformation of the decondensed sperm nucleus into the pronuclueus
329
What is cleavage of the egg?
It is the first division of the embryo
330
What disorders can arise from bad cleavage?
diploid or triploid mosaics can occur
331
Where is the genetic control coming from in the embryonic development?
Prior to 4-8 cell storage the developmental control is normally from the RNA laid down in oogenesis in the mother. at blastula its is a mix, afterwards mainly zygotic
332
what type of cells are there in the cleavage stage?
Totipotent as each of the blastomeres are capable of forming an entire foetus
333
What is compaction?
When the cells flatten and maximise intracellular contacts to form tight junctions and polarisation of the outer cells takes place
334
What is cavitation?
tight juction cells form trophectoders and the fluid filled cell cavity expands and then the inner cell mass that is pluripiotent is formed
335
What is the expansion stage?
The cavity expands and the diameter increases the ZP thins
336
What comes after the expansion phase?
Hatching, blastocyst expansio and enzyes cause the embryo to hatch from the ZP this is needed for implantation
337
What are the early preimplatatio metabolic requirements of the embryo?
ATP turnover is low ATP/ADP ratio is high and the energy metabolism is characterised by consumption of pyruvate and glucose use is low
338
What are the blastocyst stage metabolic requirements of the embryo?
Metabolic activity rises sharply, ATP/ADP ratio falls reflecting increased demand for energy. Glucose in used heavily
339
What is the level of metabolic and bio synthetic activity like in blastocyst like in comparison to before?
Higher metabilic and biosynthetic activity in the blastocyst
340
Where is the nutrients for the embryo provided in the stages?
Cumulus cells, fallopian tube secretions, uterine secretions
341
What happens immediately after implantation?
The gastrolation and formation of the trilaminar disk
342
What does the trophectoderm do?
The chorionic ectoderm becomes chorian and placenta
343
What is the inner cell mass cella areas split into?
Embryonic ecto meso endo derm and the extra embryonic membrane meso and endoderm
344
What does the extra empryonic cells form?
Mainly Amnion and yolk sac also the placenta(extraembryonic mesoderm)
345
What regulates implantation?
Hormones, cell adhesion molecules, proteases, cytokines, growth factors, Genetic factors
346
What are the three phases of embryonic implantation?
Apposition, Attachment and invasion
347
What happens during apposition?
Unstable adhesion of the blastocyt to the uterine lining, synchronisation of embryo and endometrium it orientates its self so the ICM is close to the wall
348
What happens during Attachement(adhesion)?
Stronger attraction, penetrate with protrusions from the trophoblast cells, lots of receptor ligand reactions with the endometrium,
349
What happens during invasion/ penetration?
Tropoblast protrusionc continue to proliferate and cells change to syncytiotophoblasts this erodes the endometrial stroma, it is enxymatically mediated. it erodes blood vessels,when these cells come into contact with maternal blood it forms corionic villi and initiates the formation of the placenta
350
What is decidual reaction?
Progesterone primed endometrial stromal cells differentiate into dicidual cells that are secretory, these glands enlarge and become highly vascularised they also secrete frowht factors and other nutrients it is not a necessity as ectopic pregnancy doesnt take this stage
351
What is the role of progesterone in the implantation?
Modifides oestrogen receptor distribution, stimulates secretory activity, increases volume of blood vessels, primes decidual cells, could be immunosupressan
352
Why is maternal recognition required?
Embryo is antigenically different from the mother so at the same time a decidual reaction the leucocytes in the endometrial stromea secrete interlukin-2 which stops the mother recognising the foetus as a foreign body
353
What is the role of hGC?
Essential to sustain early prgnancy produced by the placenta, enusres corpus luteum continues throughout 1st trimester, interactes with the endometrium and is immunosuppressive
354
What is the doubling time for hCG?
Doubling time is 1.3 days for the first two weeks
355
What could a slow doubling time of hCG signify?
Early abortion, ectopic pregnancy, delayed implantation or inadequate trophoblast
356
What is the use of the knowledge of embryo metabolism?
To provide right culture for IVF
357
What can affect IVF embryos?
Exposure to light, high oxygen concentration, changes in pH or osmolarity, culture medium or volatile organic compounds
358
What is the biggest risk of fertility treatments?
Having twins
359
What is preimplantation genetic diagnosis?
When you test an embryo for specific genetic abnormalities
360
What are the main substances lost in the kidney?
Sodium for water, no sugar or amino acids and a small amount of bicarbonate
361
What is the main function of the proximal convoluted tubule?
Bulk absorption of fluid and sodium chlorine glucose amino acids HCO3 and organic ions
362
What is the main function of the distal convoluted tubule?
Selected reabsorption and secretion of Na K Ca Pi and separation of Na from H2O
363
What is the purpose of the loop of henle?
sodium reabsorption urinary dilution and generatior of medullary hypertonicity
364
What is the purpose of the collecting duct?
Acid secretion and fine modification urine concentration
365
What happens in the proximal tubule?
NaK ATPase drives sodium into capillary secondary active transport for re-uptake of glucose amino acids and lactate, t iss very efficient. Chloride follows the sodium and it has a high permeability to water
366
What does acute tubular necrosis mean?
Death of the cells of the tubule and change shape due to lack of oxygen
367
What happens to H+ in the PCT?
Antiported with sodium out into lumen of the tubule
368
How is bicarbonate reabsorbed in PCT?
Sodium potassium pump allowed bicarbonate to move out of cell into capillary with the sodium. there is the sodium proton antiporter on luminal side to balance pH. carbonic anhydrase has a big role in getting HCO3 moved
369
What is the tubular maximum?
The maximum amount of a substance that can be reabsorbed per minute
370
How are amino acid reabsorbed?
They are cotransported with sodium
371
What are symptoms of PCT problems?
Glucose in urine amino acids in urine and high bicaronate
372
How is chloride reabsorbed?
Through para-cellular mechanism through tight junctions
373
Which organic acids are removed from the blood?
creatinine, urate, bile salts
374
What does trimethroprim and cimetidine do?
Inhibit creatinine secretion
375
Where does solute re absorption occur in the loop of Henle?
In the thick ascending limb
376
How is the counter current multiplier set up?
The descending limb is impermeable to solutes. The ascending limb solute is released into the medulla. increasing its concentration. this change in concentration of the medulla allows water to leave in the descending limb. this eventually produces the gradient of the medulla
377
Other than sodium and chlorine what else contrinutes to the medullary hypertonicity?
backleak of urea out of the medullary collecting duct
378
Why doesnt blood flow wash out the osmotic gradient?
Vasa recta are long capillaries that extend in the medulla so they dont remove large quantities as they are permeable to solute and water
379
What is the walls of the ascending limbs like?
they have sodium potassium chloride transporters to reabsorb and potassium leaves to keep charge balance. chloride moves into blood and driven by basolateral sodium potassium pumps
380
What else i reabsorbed in the loop of henle and why?
Na Ca and Mg by paracellular dirven by charge
381
What happens in the distal convoluted tubule at the membrane?
Na K ATPase driven absorption of sodium and chlorine NCC and calcium reabsorbtion
382
What happens at the collecting duct wall?
Highly water imprmeable surounded by hypertonic medullary system regulated Na reabsorption and potassium secretion. Acid regulated water reabsorption
383
What are the two cell types on the collecting ducts?
Principal cell with sodium reabsorption and K release and intercalated cell acid secretion
384
What happens in the principal cells?
ENaC channels where sodium moves into cell from tubular fluid pushed by basolaeral NaK ATPase Aldosternone acts to increase ENaC expression
385
What acts on ENaC?
Amiloride it's potassium sparing which means that allows water loss but not at the expense of potassium loss
386
What does spirolactone do?
Blocks aldosterone receptor to stop ENaC channel
387
Where does ADH/Vasopressin act?
On the pricipal cells to allow adenylyl-cyclase coupless vasopressin receptor to allow insertion of aquaporins on the surface
388
How do the intercalated cells regulate acid secretion?
exchanged potassium for hydrogen ions. NaK ATPase pumps with chloride and HCO3 pumping on basolateral side ATPase H+ Potassium Hydrogen,
389
What is Bartter's syndrome?
Problem with NKCC2 in ascending loop of Henle, Hypo K alkalosis low ish BP
390
What is Gitelman's Syndrome?
NCC problems in Distal convoluted tubule HypoK HYpoMg lowish BP
391
What is Liddle's syndrome?
ENaC problems in collecting duct. lots of ENaC Hypertension Hypokalaemia
392
What allows the differentiation of the gonads?
Testis determining genes on Y chromosome and also maybe for females some sex testis rejecting genes
393
What hormones lead to testis development?
Testosteron dehydroxttestosteron and antimullerian hormone
394
Which organ differentiates from the same tissue as the indifferent gonad what is the clinical relevance?
the adrenal glands, this means people with sex problems could well be at risk of adrenal failure.
395
Which cells release antimullarian hormone?
The sertoli cells
396
Which cells release testosterone and dehydrotestosterone ?
the leydig cells
397
What is dihydrotestosterone responsiblle for?
The external genitalia
398
What are sex hormones derived from?
DHEA dehydroepiandrosterone
399
What can oestradiol be synthesised from?
Testosterone or oesterone by aromatase
400
How are hypospadias defined?
Their location Glanular Distal or Proximal
401
What is the significance of hypospadias?
They tell you when in the process the differentiation went wrong
402
What is the method used to describe disorders of sex development?
the karyotype and characteristics.
403
How common are disorders of sex development?
1 in 300-2500
404
Why is defining it important?
Some are at high risk of germ cell malignancies like intra-abdominal GD
405
What can often cause a sex development commonly?
Adrenal dysfunction
406
What are the three layers of the adrenal glands?
Zona glomerulosa, fasiculata, reticularis.
407
What does the zona glomerulosa produce?
Aldosterone mineralocorticoids
408
What does the zona fasiculata produce?
Cortisol glucocorticouds
409
What does the zona reticularis produce?
sex hormones
410
What leads to projuction of progesterone?
Cholesterol and pregenolone
411
What is a precursor to mineralocorticoids?
Progesterone
412
What is a precursor to glucocorticoids?
17OHP
413
What does cortisol bind to?
Mineralocorticoid and glucocorticoid receptors
414
What stimulates the adrenal glands?
ACTH adrenal corticotrophin hormone
415
What happens if the enzyme that produces cortisol is blocked 21 hydroxylase?
mineralocorticoid defficiency, glucocorticoid deficiency and sex hormone excess
416
What is 46, XX disordered sex development?
When there are ovaries but external genitalia can be somewhat male
417
What can lead to 46,XT DSD?
17alpha-hydroxylase defficiencey where no testosterone cortisol or oestrogen is made
418
What is 46, XY DSD?
they have a a female external genitalia
419
What is testosterone carried by?
Sex hormone binding globulin.
420
What are the causes of complete androgen insensitivity and partial androgen insensitivity?
when the androgen receptors in the cell are not produced or functioning so the hormone cannot affect transcription
421
What is 5 alpha reductace type 2 deficiency?
46 XY can't turn DHT but have testosterone. female until puberty then male. They have ambiguous genitalia hypospadic phallus and a blind vaginal pouch they have normal wollfian ducts and no mullerian derivatives and normal testes
422
What are the characteristics of CAIS in XY individuals?
They get no mullarian ducts from AMH but end up with female phenotype as testosterone can't act
423
How can you assess geneder assignment?
Diagnosis, Likely gender identity, appearace of genitalia(less important now), options for surgery, hormone replacements fertility tumour risk
424
What are the ethical issues with assigning genders?
Minimising physical and psychosocial risk, preserving fertility, right to be involved with decision, leaving till later or not, support needs, cultural factors
425
When is the fastest growth levels?
In the womb not puberty
426
What determines growth in infancy?
Nutrition
427
What determines growth in childhood?
Hormone levels
428
What hormones are involved in growth during childhood?
Growth hormone and testosterone/ oestrogen causing the converstion of the growth plate.
429
What shows if you are growing at the right rate?
the growth per year chart
430
Describe normal growth rate throughout childhood?
Rapidly decreasing rate until 5yrs then slowing. A growth spurt at 12 years then rapid declie to around 15 or 16 years old
431
What are the sex differences in growth?
Girls peak growth rate is earlier and lower peak and men are average taller
432
What determines growth?
Parental phenotype and genotype, quality and duration of pregnancy, nutrition, specific system and organ integrity
psycho-social environment, growth Promoting hormones and factors
433
What is growth described as?
Chondrogenesis formation of cartilage to bone
434
What are factors regulating condrogenesis?
Inflammatory cytokines, Extracellular fluid acidosis, nutrition
435
What is achondroplasia?
Dwarfism, When chondrocytes are dysfunctional
436
What happens to stimulate growth hormone?
Growth hormone releasing hormone from the hypothalamus stimulates anterior pitiutary to realease Growth hormone, then the liver produces insulin like growth factor,
437
What can inhibit growth hormone release?
Somatostatin
438
What can regulate the hypothalamus releasing things?
Food, sleep, steroids neurotransmitters other hormones
439
What is the most abundant hormone?
Growth hormone
440
What is the secretion of growth hormone like?
At night and pulsatile
441
When should you take baseline growth hormone?
At night
442
What is the effect of growth hormone on metabilism?
Decreases glucose use and increases lipolysis, increases muscle mass
443
What stimulates growth hormone release?
Exercise Stress Hypoglycemia, Fasting, High protein meals, Perinatal developent Puberty
444
What suppresses growth hormone release?
Hypothyroidism, hyperglycemia, high carbohydrate meals, glucocorticoid excess again
445
What can cause inpaired final height?
Precocious puberty, Congenital hyperplasia, McAlbrights syndrome, Hyperthyroidism
446
What can lead to increased final height?
Androgen defficiency or resistance, GH excess Klinefelter syndrome Marfan syndrome
447
What is early puberty an indicator of?
In males could be brain tumors
448
What is the definitve signs of puberty?
Menarche in girls- first menstrual bleeding
| First ejactilation in boys
449
does pubertiy indicate fertiliy?
Pysiological morphological and behavoural changes but not fertility
450
What are the secondary sexual characteristics of puberty?
Females: ovarian oestrogen leading to breast and genitalia ovarian and adrenal androgens control pubic hair and axillary hair
In Males, testicular androgens cause development of the penis and enlargement of larynx and muscles and also pubic hair growth
451
Is puberty the same for everyone?
No african-american woment have earlier develepment
452
What is specific about puberty?
The order of the changes
453
What can be associated with early puberty and late puberty?
Late reduced peak bone mass and osteoporosis and early can lead to a short stature
454
What axis is involved with puberty?
The hypothalamus pituitary Gonadal axis
455
What does LH stimulate in the female?
The theca internal cells
456
What does FSH stimulate in the female?
Granulosa cells in the ovary
457
What does LH stimulate in the male?
the leydic cells
458
What does FSH stimulate in the male?
The Sertoli cells
459
What happens to hormone levels at puberty?
Lots of peaks of LH and FSH sleep- augmented secretetion pulse like, Later puberty LH daydime pulses
460
What generates the LH FSH peaks?
GnRH gonadotrophin releasing hormone. stimulated by glutamate and kisspeptie and decreased GABAergic systems
461
What is the role of nutrition in puberty?
Critical bodyweight needed for puberty to begin
462
What is true precocious puberty?
When whole system is activated early mostly happens in females
463
What are the causes of true precocious puberty?
In females mostly idiopathic, In males large chance of brain tumour
464
What is precocious pseudopubety?
Hormones lower in axis to be secreting to stimulate puberty, often from tumour
465
How can you differentiate true precocious puberyt and precocious pseudopuberty?
the levels of FSH and LH in pseudopuberty theyhave low levels since activation of gonads comes from lower down the system with stimulation
466
What is hypogonadism?
Under function of the gonad could be a problem wiht the gonad itself or higher up
467
What is primary hypogonadism?
Testis or ovary problem
468
With hypergonadotrophic hypogonadism what does it show?
problem with the gonads as there is a loss of the feedback
469
What is the menopause?
Cessation of mstruation
470
What is climacteric(perimenopause)?
the period around the menopause and at least te first year after it.
471
What is the age of onset of menoapuse in the UK?
51 average 48-52 range
472
What causes the onset of menopause?
Depletion of primordial follicles
473
What is the mechanism for the menopause?
Depleted of follicles, decline in oestrogen production, gradual decline with fluctuation over a few years, gradual rise of FSH and LH from reduction of negative feedback
474
What are the risks associated with premature menopause?
Increased risk of mortaity, cognitive difunction, heart disease, Mood and sexual disorders, bone density, autoimmune and thyroid issues
475
What are some symptoms of the menopause?
hot flushes night sweats palpitations headaches, irritability lethargy forgetfulness, vaginal dryness, dysparemuria (dryness), Dry skin brittle nails, osteoporosis, CHD
476
What is the treatment of menopause?
HRT(oestrogen replacemnet) and treat symptoms of it
477
What is HRT?
Oestrogen and also sometimes progesterone
478
List some endocrine glands
Hypothalamus pituitary, thyroid, parathyroid, Adrenals , pancreas ovaries testis, pineal gland (heart intestine skin fat kidney liver)
479
What are the three types of hormones?
Steroid hormones, Peptide hormones and thyroid hormones
480
What are some steroid hormones?
Aldosterone Cortisol, Oestrogen, Testosterone, Progesterone
481
What are catecholamines?
Synthesised from tyrosine amino acids DOPA dopamine pathways
482
What is the half life for peptide hormones?
minutes to hours
483
How long do chatecholamines last for?
seconds to minutes
484
What are the ways hormones can exert their effects?
Cell surface receptors an intracellular receptors
485
What is he active form of thyroid hormone?
T3
486
How does Thyroxin 3 act?
Thyroxine acts on gene transcription
487
What is the basic function of thyroxine?
Basal metabolic rate and growth
488
What is the basic action of cortisol?
Glucose regulation, inflamation potentiates catecholamines
489
How can hormone levels be tested?
Bioassays immunoassays, mass spectrometry
490
What is the role of the pituitary?
Small organ in the sella turcica, it is a key organ in the release of hormones
491
what does the anterior pituitary release?
ACTH (adrenocorticotrophic hormone), TSH (Thyroid stiumulating hormone, GH (Growth hormone), LH/ FSH ( Leutinising hormone/Follicle stimulating hormone) PRL(prolactin)
492
What doe the posterior pituitary release?
ADH (antidiuretic hormone), Oxytocin
493
What is theyrotoxicosis?
Overstimulation of thyroid, twitchy hot and very slim palpations
494
What is cushing's disease?
Cortisol from too much stimulation from anterior break down mscle to fat weak collagen and bruis easily high BP
495
What is acromegaly?
hands feet and face are responsive to growth hormones and can grow
496
Which part of the pituitary produces hormones?
The anterior. posterior just releases them
497
What is similar about thyroid stimulating hormone, luteinizing hormone and follicle stimulating hormone?
they are glycoprotein, have the same alpha unit and slightly different beta units
498
What is the role of the hypothalamus?
Regulating homeostasit inputs and outputs controls autonomic via brainstem
499
What is the blood supply to the anterior pituiitary?
It flows from the arterial capillaries into capillaries near the hypothalamus and then into portal in the anterior pituitary
500
How are the hormones stimulates to be released by the anterior pituitary gland?
The are stimulated by releasing hormones from the hypothalamus
501
What causes Thyroid stimulating hormone to be released?
thyrotropin releasing hormone
502
What causes adrenocorticotrophic hormone to be released?
Corticotropin releasing hormone
503
What causes FSH and LH release?
Gonadotrophin releasing hormone
504
What causes release of growth hormone?
Growth hormone releasing hormone and somatostatin inhibits it
505
Which anterior pituitray hormone doesnt have negative feedback on the pituitary and hypothalamus?
Prolactin
506
What can affect the size of the adrenal gland?
the amount of stimulation it recieves
507
What does ACRH do?
Cortisol release, synthesis of cortiso.
508
What is the rhythm of the levels of ACTH?
early morning release peaking before lunch and lower over night
509
What is the importance of the diurnal rhythm of ACTH?
Need to take at midnight to see hif levels are low
510
What stimulates Growth hormone?
Low glucose exercise and sleep
511
What are the characteristics of GH?
Pulsatile and released throughout life
512
What does GH do?
Cartilage growth increase blood glucose and bone tissue growth. Linear growth in children, regulation of body composition, psychological and well-being
513
What is the order of loss of function to the pituitary?
Lose GH GNTH based on the quantity of the type of cells
514
What stimulates prolactin release?
Dopamine is negative TRH stimulates a bit linked to LH
515
What does prolactin do?
Essential for lactation breast feeding inhibits gonadal activity through supression og GnRH
516
What is the symptoms of high prolactin?
Less aparent in men, hypogonatism oestrogen diffifiecey, galactorrhoes
517
What can cales hyperprolctaemia?
post seizure greater in women, peak in sleep, stress
518
Where does the pituitary develop from?
Neural ectoderm is the posterior, anterio is from oral ectoderm and the rathke's pouch
519
What do pituitary tumours do?
pressure on chiasm itemporal hemianopia, hypopituitary, functioning tumour leading to high hormone levels
520
What is excess ACTH?
Cushing's disease
521
What is excess GH?
Acromegaly
522
What is ecess LH/FSH?
Gonadotrophinoma very rare
523
Where is the pancreas formed?
2 pancreatic buds dorsal and ventral and are at the junction of foregut and midgut
524
In the pancreas, what doe the acinar cells do?
They produce the digestive enzymes and form the exocrine pancreas
525
What do the islet cells of the pancreas do?
They form the endocrine pancreas and produces peptide hormones like insulin
526
What makes most of the pancreas?
The acinar cells 98-99%
527
What are the cell types in the islet of Langerhans?
alpha beta and delta cells
528
What is the structure of the islet?
There are alpha beta and delta cells around the islet is a good blood supply
529
What do delta cells secrete?
Somatostatin
530
What do the beta cells secrete?
Insulin
531
What do the alpha cells secret?
Glucagon
532
Why are alpha and beta cells close to eachother?
so that they can have paracrine cross talk beta tell alpha what to do
533
What is the structure of insulin?
Long polypeptide two chains joined by cystine bridges
534
What is glucagon like?
Short single chains
535
What does insulin do?
It decreases gluconeogenesis, and glycogenolysis and increases glucose uptake in muscle and fatty acid synthesis in fat it supresses lipolysis and breakdown of muscle
536
What does glucagon do?
increased glycogenolysis and gluconeogenesis reduces uptake of glucose and stimulates release of gluconeogenic precursors wiht lipolysis and muscle glycogen break down
537
What has a similar effect to glucagon?
Adrenaline cortisol and growth hormone
538
How do the beta cells work?
Glucose enters the cell by GLUT2 transporter low affinity meaning it flows easily, then glucokinate phosphorylates ADPP which means. then postassi channel closes with high ATP and this causes a voltage change and then voltage gated calcium channel opens then this causes secretion of insulin
539
What is released from the beta cells?
Proinsulin A and B chain joined by C peptide the c peptide shows it was produced in a cell. C peptide has no function itself
540
What is the biphasic insulin release?
Initially large peak of stored insulin, second phase of production of insulin as required get a second but lower peak
541
How does insulin cause an effect?
Insulin receptors cause GLUT4 transporters, to allow uptake of glucose
542
What is the effect of exercise on glucose uptake?
24-48 hours you get more GLUT4 and insulin receptors
543
What is a normal glucose?
around 5mmol/mol
544
What happens in the liver short and long term with high glucose?
Make glycogen in long term you get more triglyceride
545
What happens in the liver short and long term with low glucose?
Split glycogen to release glucose in long term you use muscle or fat
546
Where other than the pancreas are there cells that sense glucose levels?
In the medulla hypothalamus carotid bodies, and in walls of the gut
547
What is incretin?
Insulin response is greater from oral glucose than intravenous this is because the gut releases incretins that are similar effects to insulin
548
What are the two incretins?
GLP-1 glucose like peptide-1 and GIP glucode dependent insulinotrophic peptide
549
How can the GI tract help to reduce the levels of glucose in the blood?
Slowing gastric emptying
550
what is DPP4?
It cleaves GLP-1 to inactivate it
551
What is diabetes mellitus?
A disorder of carbohydrate metabolim characterised by hyperglycaemia
552
Where can the mutation be for diabetes?
In the potassium regulating cells,
553
How does diabetic ketoacidosis come about?
No insulin means you get very high glucose level. fat keeps getting broken down still then TCA cycle gets overloaded and end up with high ketones and weeing out glucose
554
What is a sing of thryroid problems?
Sweling of the thyroid, thyroid eye
555
Which arteries supply the thyroid?
Thyrocervical trunc off subclavian and the externa carotid
556
What are development problems related to the thyroid?
ectopic develpoment
557
What are some of the cell types in the thyroid?
C cell, Follicular cells, inside there is colloid
558
What do c cells do?
Produce calcitonin but not really needed
559
What does the thyroid do?
Energy generation and use control and growth control development role in brain development
560
What is the effect of T3?
It affects other all organs in metabolism, it also inhibits pituitary and hypothalamus
561
What is thyroid releasing hormone?
It is a chemical that causes the anterior pituitary to release thyroid stimulating hormone
562
How does thryroid stimulating hormone work?
It binds to thyroid stimulating hormone receptor and it is a g coupled receptor
563
How is thryroxine produced?
Once activated the cells activate Sodium iodine symporter (NIS) that brings iodine into the follicular cells then the thryroid peroxidase (TPO) which leads to storage and iodination of thryroglobulin in the colloud
564
What are the two hormones for thryroid?
T3 and T4 about number of iodine
565
What is the biologically active thryroid hormone?
T3
566
What is the most abundant form of thyroid hormone?
T4
567
What is the use of T4?
It is taken up in the tissues and converted to T3
568
What is the precursor to thryoid?
Tyrosine
569
How can T4 be carried in the blood?
Albumin transthyretin and thryroid binding globulin And dissolved in blood
570
How much Thyroid hormone is free?
0.03%
571
How does T3 act on cells?
It enters through a transporter, then binds to Thyroid hormone receptor and affects gene regulation
572
What are good to test to identify thyroid issues?
Serum TSH, Serum free T4, Serum free T3
573
What are the clinical signs of hyperthyroidism?
Decreased serum TSH increased T4 and T3
574
What are the clinical signs of Hypothyroidism?
Increased serum TSH decreased T4 T3
575
Who does thyroid conditions affect?
More women
576
What are the prevalence levels of thyroid problems?
2.7 % hyper 1.9% hypo
577
What can cause hyperthyroidism?
Graves' hyperthyroidism autoantibodies stimulate TSH receptors, toxic nodular goiter, thyroiditis, exogenous iodine, neonatal hyperthyroidism
578
What are the signs and symptoms of hyperthyroidism?
rapid heart rate, AF shortness of breath, loss of wight increased apetite, Tremor, Myopathy Anxiety, Sore gritty eyes Staring eyes, Puritus
579
What can cause hypothyroidism?
autoimmune Hashimoto's thyroiditis after treatment from hyperthyroidism, iodine deficiency
580
What are the symptoms of hypothyroidism?
Weight gain constipation, Depression Physcosis, Bradycardia Heart falure, Pericardial effusion skin problems
581
What do parathyroid do?
Regulate calcium and phosphate levels.
582
What does parathyroid hormone do?
It is increased in low calcium or high phosphate. It increases Ca reabsorption in the kidney distal tubule, it increase calcium absorption in the small intestine and it increases calcium release from bone and increases loss of phosphate
583
What is bone calcium used for?
Protecting organs support muscles and store calcium
584
What is blood calcium for?
Excitable tissue, muscle nerves cell adhestion
585
Which hormones affect extracellular calcium?
Parathyroid hormone Vitamin D Calcitonin FGF23
586
How is calcium transported?
In serum or with albumin half and half
587
what happens when calcium gets low?
PTH sereted from parathyroid glands in the kidney calcium phosphate reabsorption dist tubl is increased, and in intestine bone is released increased, 1,25D3 production in kidney
588
What is 1,25 vit D doing to PTH?
It inhibits mRNA prodiction
589
What is primary hyperparathyroidism?
Parathyroid tumour, causes hypercalcaemia or low phosphate. loss of negative feedbacl
590
What is secondary Hyperparathyroidism?
Renal disease increased phosphate and decreased activation of Vit D, treat with phosphate binders or Vit D analogues
591
Tertiary HPT what is is?
caused by long standing Secondary HPT leading to overgrowth
592
What does calcitonin do?
Releases in high calcium inhibits bone resorption
593
What doe ACTH do?
It causes the release of glucocorticoids and adrenal androgens.
594
What are the two areas of the adrenal gland?
The cortex and medulla
595
What are the three zones of the adrenal cortex?
Zona glomerulosa. Zona fasiculata and Zona reticularis
596
How can your remember the order of the adrenal cortex zones?
GFR out to in
597
What does the Adrenal cortex produce?
Corticosteroids
598
What is produced in the Zona glomerulosa?
Mineralocorticoids like Aldosterone
599
What is produced in the zona fasciculata?
Glucocorticoids like cortisol
600
What does the Zona reticularis produce?
Androgens like DHEA and androstenedione
601
What does the adrenal medulla produce?
Adrenaline and noradrenaline, catecholamines
602
What are most steroids made of?
Cholesterol
603
What receptors does aldosterone attach to?
Mineralocortiocid receptors
604
What does cortisol attach to?
Mineralocorticoids and glucocorticoids
605
What is the action of glucocorticoids (cortisol)?
it has many permissive actions on many tissues, important in homeostasis and stress response.
606
Why is it important that cortisol has a permissive action?
It is only apparent when it is not present.
607
What happens in glucocorticoid excess?
Depression psychosis, supresses endocrine axis, peptic ulcers, glycogen deposition insulin resistance, promotes obesity, salt and water retention. muscle atrophy decreased bone formation
608
What are the key areas of glucocorticoid action?
Immunodemodulation, Maintenance of circulation, Increase glucose mobilisation
609
How are glucocorticoids transported in the blood?
90% bound to cortocosteroid binding globulin, 5% bound to albumin and 5% free whihc is biologically active
610
What happens during inflamation t cortisol transport?
corticosteroid binding globulin levels decrease so free cortisol increases
611
What is the diyrnal rhythm of ACTH?
High in the mornings up to lunch lower at night
612
What triggers ACTH/ cortisol release?
Trauma stress infection
613
What happens after sugery to cortisol release?
It raises the levels and loses diurnal rhythm
614
What is the effect of mineralocorticoids (aldosterone)?
Water balance in body in kudney to resorb water
615
What percentage of hypertension is from ineralocorticoid problems?
20%
616
What is the effect of Aldosterone in the kidney?
It enter the cell and binds to a mineralocorticoid receptor that then affects expression of ENaC in distal convoluted tubules and collecting ducts leading to sodium re absorption and potassium secretion to get more water reabsorption
617
What regulates the mineralocorticoid release?
The justaglomerular apparatus cells at afferent glomerulus also the macula densa in the ascending loop of henle. this regulates renin release, which ends up with aldosterone release. also directly ECF loss of potassium switches it off
618
What happens to urine and plasma Na and K levels in the body with primary adrenal insufficiency?
The blood plasma has high potassium low sodium and uring has high sodium low potassium
619
How does renin cause aldosterone release?
Renin cleaves angiotensinogen into angiotensin 1 and then ACE from the lung turns it to angiotensin 2 then this causes release of aldosterone in the adrenal cortex
620
What is cortisone?
Inactive version of cortisol used as a way to stop too much mineralocorticoids
621
What is the most abundant androgen in the body?
DHEA dehydroepiandorsterone precursor to lots of hormones
622
What stimulates the adrenal medulla?
Innervation from sympathetic nerves ACh needs cortisol permissive effect
623
What is the preursor for adrenaline?
Tyrosine needs cortisol to do this
624
How are hormones released in the posterior pituitary?
Receive signals from paraventricular nucleus and supraoptic nucleus that cause release from neuroendocrine cells
625
What is the hypathalamic hyoophysial tract?
tract of neurones that release postrioro pituitary hormones
626
Which hormoens are secreted from the posterior pituitary?
Vasopressin and oxytocin
627
Where does Vasopressin act?
vasculature constriction, renal collecting tubules of aquaporins and pituitary can cause cortisol release
628
What happens when water is ingested?
Plasma osmolality goes down cells get more water so cause less thirst and vasopressin meaning it will lose water overall
629
What happens when water is lost?
plasma osmolality goes up, cellular hydration goes down increased thirst and vasopressin secretion and increases reabsorption of water and increase water intake
630
What diseases are associated with the posterior pituitary?
Lack of vasopressin from cranial diabetes
| resistance to vasopresin, too much vasporessin from syndrome of anti-diuretic hormone secretion
631
What is Oxytocin used for?
uterine contraction, love hormone stimulates milk production and release. activated by suckling
632
Which hormones are involved in pregnancy?
Progesterone oestrogen human chorionic gonadotrophin Prolactin, relaxin, oxytocin
633
What does human chronic gonadotrophin do?
Stimulates oestrogen and progesterone production by the ovary, diminishes once the placenta matures enough to take over oestrogen/progesterone production
634
What does oestrogen do throughout pregnancy?
Produced all the way through regulates progesterone levels prepares uterus for baby and breasts for lactation
635
What does progesterone do during pregnancy?
Prevents miscarriage builds the endometrium to support the placenta and prevents uterine contractions
636
What does prolactin do during pregnancy?
Produced by pituitary increases cells the produce milk and it stimulates milk production and helps to prevent ovulation
637
What does relaxin do?
In early pregnancy its high it inhibits uterine activity, it ripens the cervix to prepare it for delivery.
638
What does oxytocin do?
Causes contraction and can trigger reproductive behaviour, cause contractions felt when breast feeding
639
What doe prostaglandins do?
They cause initiation of labour sensitising to oxytocin
640
How heavy is the placenta and baby usually?
3.2-3.6 kg baby and 0.9kg placenta
641
Where other than placenta and ababy is weight gained during pregnancy?
The amneotic fluid, uterus, breast tissue, blood, fluid in maternal tissue, maternal fat stroes
642
How does the mother adapt to pregnancy?
Increased cardiac output reduced systemic blood pressure, reduced total peripheral resistance, increased uterine blood flow, increase in blood volume and RBC mass. Increased alveolar ventilation breast and nipples are bigger
643
What is a linea nigra and strae gravidarum?
Black line that grows down the centre of the abdomen and the stretch marks
644
What are some side effects of prenancy?
Acid reflux, lumbar lordosis, stretch marks
645
What happens when developmental issues happen early?
They are much more serious
646
What are landmarks of pregnance?
Conception linkes with missing a period, can see foetal heart beat on an ultrasound, quickening(when mother can feel baby moving), the size of the head or funds, show which is passage of mucous or blood stained mucus before giving birth
647
What is the decidua basalis?
The area beneath the placenta
648
What is the decidua capsularis?
Covers the conceptus
649
What is the decidua vera?
Inner surface of myometrium
650
What is the uterine cervix like?
It protects the foetus during development, it is mainly collagen and ground substance with glycosaminoglycans also collagen to increase strength
651
What are the partruitional phases of pregnancy?
Phase 0 myometrial repression Progesterone, Phase 1 myometrial activation in 2nd trimester CRH Cortisol Oestrogens, Phase 2 biochemical activation prostaglandings at the end of pregnancy Phase 3 at end permanent change
652
What are the sutures?
They are coronal fronta sagital and posterior frontanelle to allow flexibility
653
What is the type of contraction the myometrium?
Braxton-hicks contraction
654
What starts oxytocin release?
Head pushing against cervixs in positive feedback
655
Which way does the baby come out?
The head has to rotate as its passing through.
656
What are the phases of labour?
Latent and then active, can be very 10 hours
657
What are the stages of labour?
Active 1st stage is up to 10cm dilated, 2nd baby delivered, 3rd giving birth to the placenta
658
What can cause problems with labout?
Myometrium, pelvis baby
659
What can be wrong with the myometrium?
Too strong Too weak disorganised fibres cervix too rigid cervix weak post partum bleeding
660
What does the placenta do?
It delivers nutrition gas exchange waste removal and endocrine immune support
661
How big is the placenta?
20cm diabeter 3cm thick
662
What is the two parts of the placenta?
Embryonic villous chorion and maternal decidua basalis
663
What are the maternal arteries in the placenta?
Spiral arteries around the blobs from the foetal side
664
What is the structure of the umbilical cord?
It has a central umbillucal vein with smaller umbilival arteries on the outside.
665
What is placenta accreta?
Abnormal adherance with decidua basalis?
666
What is placenta percreta?
Villi penetrate the myometrium
667
What is placenta praevia?
Placenta overlies internal os of uterus, abnormal bleeding
668
What is a monochorionic placenta?
There are one placenta for both babies can end up with not enough
669
What are the areas of regenerative medicine?
Stem cell biology, Tissue engineering
670
What is a stem cell?
A primitive cell that is capable of self-renewal, make a range of cell types, convert to a different cell type
671
Where to cells turn over the most?
In small intestine and GI tract
672
Where is the slowest rate of repair?
Ocytes and lens in the eye
673
What are induced pluripotent stem cells?
They are cells that have been stimulated to get to a certain level
674
What are tissue-specific stem cells?
Present in adult tissue, can be derived from foetal tissue build and repare and are multipotent
675
What are stem cells used for?
Basic research, regenerative medicine, cancer growth, drug discovery
676
Why will regenerative medicine take quite a while to become usable?
Testing and certification
677
What are some prospective cases in regenreative medicine?
Macula degeneration, diabetes, heart attach, depression
678
What is requred to make a cell pluripotent?
Epigenetic factors such as methylation, removal of transcription factors
