Endocrinology Flashcards
(120 cards)
1
Q
What is another name for the anterior pituitary
A
Adenohypophysis
2
Q
What is another name for the posterior pituitary
A
Neurohypophysis
3
Q
Describe the pathway of neurons from hypothalamus to anterior and posterior pituitary
A
Parvocellular neurons from hypothalamus to median eminence - release hypothalamic releasing/inhibitory factors into leaky capillaries which carry the factors to the anterior pituitary through portal circulation
Magnocellular neurons from hypothalamus travel directly to posterior pituitary
4
Q
Difference in structure and development of anterior and posterior pituitary
A
Anterior = adenohypophysis
- epithelial origin
- upward growth from oral ectoderm of primary oral cavity: Rathke’s Pouch
Posterior = neurohypophysis
- neural origin
- downward growth from diencephalon
5
Q
Which part of the pituitary gland is regulated by hypothalamic releasing and inhibiting factors
A
Anterior pituitary
6
Q
Explain the events that lead to the thyroid hormone being stimulated to release thyroxine
A
Hypothalamus releases TRH (thyrotrophin stimulating hormone) which travels via portal circulation and stimulates the thyrotrophes in the anterior pituitary to release TSH (thyroid stimulating hormone) / thyrotrophin
This travels via blood to the thyroid gland and stimulates it to release thyroxine
7
Q
What are the 5 types of endocrine cells found in the anterior pituitary and which hormones do they release and which hormones are their release regulated by
A
Somatotrophs - growth hormone (somatotrophin) - release is stimulated by “Growth hormone releasing hormone” and inhibited by “Somatostatin”
Lactotrophs - prolactin - release is reduced/inhibited by “dopamine” —> inhibitory control
Corticotrophs - corticotrophin and adrenocorticotrophic hormone (ACTH) - release is stimulated by “corticotrophin releasing hormone” and arginine vasopressin/ADH stimulates release of ACTH
Thyrotrophs - thyrotrophin (TSH) - release is stimulated by TRH (thyrotrophin releasing hormone”
Gonadotrophs - LH, FSH - release is stimulated by gonadotrophin releasing hormones
8
Q
What is the name of the bony dish that the pituitary gland sits in
A
Sella turcica
9
Q
How can a pituitary tumour affect your vision
A
Presses on optic chiasm
Causes bitemporal hemianopia
Compression of optic chiasm by tumour prevents transmission of sensory information from temporal/lateral visual fields to occciptal lobes
10
Q
2 mechanisms of action of the growth hormone
A
1) acts directly in the muscle
2) acts on liver, stimulating it to make insulin-like growth factor (IGF-1) which then acts in liver
11
Q
What is the difference between gigantism and acromegaly
A
Gigantism - pituitary tumour arises during puberty and secretes excess somatotrophin which causes person to become bigger and taller
Acromegaly - pituitary tumour arises after puberty and secrets excess somatotrophin,, person cannot grow taller as end plates of bones have fused so they can’t grow longer, but persons soft tissue grows eg hands nose etc
12
Q
Medical term for large jaw
A
Prognathism
13
Q
What are the posterior pituitary hormones
A
Arginine vasopressin (ADH - antidiuretic hormone)
Oxytocin
(They are produced in hypothalamus but stored in pituitary)
14
Q
How does AVP concentrate urine at a cellular level
A
It binds to the V2 receptor on membrane of collecting duct cell
This stimulates a cascade of intracellular signalling
These reactions cause aquaporin 2 to be inserted into the apical membrane of the cell
Water moves through aquaporin 2 down its conc gradient from urine in nephron of kidney into cell
Then water moves out of cell into plasma through aquaporin 3 on the other side of the cell
15
Q
What hormones could you measure to confirm diagnosis of acromegaly
A
Growth hormone (somatotrophin)
Growth hormone releasing hormone
Somatostatin
Insulin-like growth factor (IGF-1)
16
Q
Which two important structures lie close to thyroid gland and could be affected by thyroid surgery
A
Parathyroid glands - involved in Ca2+ metabolism
Recurrent laryngeal nerve - supplies vocal chords
17
Q
What is proximal myopathy
A
Weakness in muscle
18
Q
What is centripetal obesity
A
Obese in centre but thin arms and legs (lemon on stick)
Symptom of Cushing disease - excess cortisol
19
Q
4 causes of cushings disease
A
Taking steroid by mouth
Pituitary tumour (causes excess ACTH)
Adrenal adenoma or carcinoma (causes excess cortisol)
Ectopic (ie in wrong place) ACTH - due to lung cancer
20
Q
What makes the brain unique in terms of energy sources
A
It cannot utilise fatty acids as an energy store, only glucose or ketones
Skeletal muscles can use fatty acids
21
Q
Why do low insulin levels switch on lipolysis
A
Lipolysis results in the release of NEFA (non esterified fatty acids) which can be converted to ketones by the liver
Ketones are useful fuel for brain which cannot use fatty acids as an energy source
22
Q
Where are GLUT4 receptors usually found?
A
Myocytes and adipocytes
23
Q
Will ketone bodies be high or low in fasting state
A
High
24
Q
Tests for diabetes Mellitus
A
Fasting glucose
Random glucose
Oral glucose tolerance test
HbA1C
25
Symptoms of type 1 diabetes mellitus
Weight loss
Hyperglycaemia
Glycosuria (polyuria, nocturia, polydipsia)
Ketones in blood and urine
26
Diagnostic tests for type 1 diabetes mellitus
Presence of Ketones
Antibody test - GAD or IA2
Low C peptide
27
What is impaired awareness of hyperglycaemia
Reduced ability to recognise symptoms of hyperglycaemia due to the counter regulatory response to hyperglycaemia - involves release of adrenaline which masks symptoms of hyperglycaemia
So get recurrent hyperglycaemia
28
How is type 2 diabetes managed
```
Oral medication (metformin)
Education about changes to diet and exercise
May need insulin later if do not comply to changes to diet and exercise (administering high dose of insulin can overcome the resistance)
```
29
How does PTH increase plasma ca2+ levels?
1) acts on kidney to increase calcium reabsorption into the blood from urine, and to increase phosphate excretion into the urine
2) acts in kidney to increase 1 alpha hydroxylase activity which increases 1,25(OH)2 cholecalciferol synthesis. This acts on the gut to increase calcium and phosphate absorption from food into blood
3) acts on bones to increase bone resorption. PTH binds to receptors on osteoblasts, causing osteoclast activating factors to be released. This causes the osteoblast to change into an osteoclast. The osteoclast ‘consumes’ the bone, releasing calcium into blood
30
How is PTH secretion regulated
G protein coupled calcium sensing receptors on the chief cells in the parathyroid gland sense the levels of calcium in the circulation.
The chief cells secrete pre-pro-PTH which is then cleaved to form PTH.
The secretion is inversely proportional to the level serum calcium. (Negative feedback at the level of the parathyroid)
31
Describe the formation of calcitriol
- 2 sources of Vitamin D3 to the blood, one is vitamin D2 from diet which is converted to D3, the second is 7-dehydrocholesterol which is converted by UVB to previtamin D3 which is converted to vitamin D3
- the vitamin D3 in the blood is converted to 25(OH)cholecalciferol by 25-hydroxylase in the liver
- 25(OH)cholecalciferol is converted by 1alpha hydroxylase to 1,25(OH)2 cholecalciferol aka calcitriol
32
Describe the action of calcitriol on the bone
- When there is low serum calcium, the calcitriol increases the calcium resorption - osteoclast activity - so bones are consumed and calcium is released into ciculation (calcitriol binds to calcitriol receptor on osteoblast, releasing osteoclast activating factors which change it to an osteoclast)
- when there is normal serum calcium, the calcitriol works to increase bine formation - osteoblast activity
33
How does the removal of the thryoid gland affect serum calcium
It doesnt
34
How is calcitonin released
Calcitonin is released from parafollicular cells in the thryoid gland, the parafollicular cells detect the increase in plasma Ca2+ and release calcitonin
35
How does Fibroblast Growth factor 23 (FGF23) regulate serum phosphate?
- Inhibits the sodium/phosphate cotransporter so less phospahte is absorbed from the urine into the blood
- inhibits calcitriol so less phosphate is absorbed from the gut (decreases intestinal phosphate reabsoprtion)
36
Does hypercalcaemia result in more or less membrane excitability
Less - the large number of calcium ions block Na+ ions from entering through their channels into the cell and depolarising the membrane
37
Name 2 signs of neuromuscular irritability due to hypocalcaemia
Chvostek’s sign - tap the facial nerve just below the zygomatic arch and the facial muscles will begin to twitch
Trousseau’s sign - you get an inflation of the blood pressure cuff for several minutes, inducing carpopedal spasm (frequent and involuntary muscle contractions of the hands and feet) —> tetany: muscle contracts but cant relax
38
What are the causes of hypocalcaemia
- vitamin D deficiency:
malabsorption/dietary insufficiency, inadequate sun exposure, renal disease, liver disease, vitamin D receptor defects
- low PTH levels: hypoparathyroidism
Surgical (neck surgery), autoimmune, magnesium deficiency (need magnesium for PTH), congenital
39
What are the physiological manifestations of vitamin D deficiency
Loss of bone density - soft bones
In children: rickets
In adults: osteomalacia
40
What are the symotoms of hypercalcaemia
“Stones, abdominal moans and psychic groans”
Stones = renal effects: nephrocalcinosis, kidney stones, renal colic
Abdmoninal moans = GI effects: anorexia, nausea, dyspepsia, constipation, pancreatitisb
Psychic groans = CNS effects: fatigue, depression, impaired concentration, altered mentation, coma
41
Causes of hypercalcaemia
- primary hyperparathryoidism: too much PTH often due to parathryoid gland adenoma, no negtaive feedback
- malignancy: bony metastases peoduce local factors to activate osteoclasts, increasing calcium resorption
- vitamin D excess: rare
42
Describe the circualtion of the adrenal glands
1) both right and left adrenal glands have many arteries but only one vein each
- right/left adrenal arteries (top)
- right/left middle adrenal arteries
- right/left inferior adrenal arteries
- right adrenal vein
- left adrenal vein
2) right adrenal vein drains into the inferior vena cava directly, whilst the left adrenal vein drains into the renal vein
43
Describe the microanatomy of the adrenal cortex and what hormones each part produces
Adrenal cortex:
Produces corticosteroids
(From outside going in)
zona glomerulosa - produces mineralcorticoids (aldosterone)
zona fasciculata, zona reticularis - produce glucocorticoids (cortisol) and sex steroids (androgens and oestrogens)
Adrenal medulla:
Produces catecholamines - adrenaline/epinephrine and noradrenaline/norepinephrine
44
What is the precursor for steroids
Cholesterol
| All steroids come from cholesterol
45
What is the common precursor/pathway for the formations of aldosterone and cortisol?
Cholesterol — (side chain cleavage) —> pregnonolone — (3 Beta hydroxy steroid dehydrogenase) —> progesterone
46
Describe the formation of aldosterone from cholesterol
```
Cholesterol
(Side chain cleavage)
Pregnenolone
(3 beta hydroxy steroid de hydrogenase)
Progesterone
(21 hydroxylase)
11 deoxycorticosterone
(11 hydroxylase)
Corticosterone
(18 hydroxylase)
Aldosterone
```
47
Describe the formation of cortisol from cholesterol
```
Cholesterol
(Side chain cleavage)
Pregnenolone
(3 beta hydroxy steroid de hydrogenase)
Progesterone
(17 hydroxylase)
17 hydroxy progesterone
(21 hydroxylase)
11 deoxy cortisol
(11 hydroxylase)
Cortisol
```
48
What is the mechanism of action of aldosterone
Stimulates Na+ reabsorption from urine into blood in convoluted tubule and cortical collecting duct in kidney —> due to osmosis, the increased Na+ reabsorption increases water absorption, raising blood volume
Stimulates K+ and H+ secretion into urine in convoluted tubule and cortical collecting duct
49
How is aldosterone regulated?
There are macula densa cells in the distal convoluted tubule of the kidney
Blood vessels run close to this and the cells detect blood pressure/remal perfusion
Decreased renal perfusion pressure (due to decreased arterial BP) causes renin to be released into the juxtaglomerular apparatus (space between macula densa and blood vessels)
The renin acts on angiotensin produced by the liver, converting it to angiotensin I
ACE acts on the angiotensin I converting it to angiotensin II
Angiotensin II binds to receptors on the sona glomerulosa of the kidney to increase aldosterone production (by increasing the activation if the enzymes needed to convert cholesterol into aldosterone - side chain cleavage, 3 beta hydroxysteroid dehydrogenase, 21 hydroxyalse, 11 hydroxylase, 18 hydroxylase)
(ACTH, decreased Na+, increased K+ all also stimulate adrenal gland to produce more aldosterone)
Aldosterone acts on kidney, increasing Na+ reabsorption into blood and therefore increasing blood pressure, and increasing movement of K+ and H+ into urine
50
Describe the negative feedback system of cortisol
HPA - hypothalamo pituitary adrenal - axis:
```
Reduces production of ACTH at anterior pituitary level
And CRH (corticotrophin releasing hormone) at hypothalamus level
```
51
What is the variation of cortisol levels throughout the day
Diurnal rhythm
Highest levels in the morning
Lowest levels at midnight
52
What is addisons disease and what are the 2 main causes
Primary adrenal failure - get cortisol amd aldosterone deficiency
2 main causes:
Autoimmune - immune system destroys teh adrenal cortex
Tuberculosis of the adrenal glands
53
Why do patients with addisons disease have a tan
Pituitary starts secreting more ACTH due to the negative feedback system (adrenal gland isnt producing cortisol, so no cortisol is inhbiting ACTH production in anterior pituitary)
POMC (pro opio melanocortin) is precursor for ACTH, and it is cleaved to form ACTH and MSH (melanocyte stimulating hormone)
so when ACTH is oriduced, so is MCH
54
If you do a blood test for someone with addisons disease, what will you find
Low Na+
High K+
Low cortisol and aldosterone
(Also will have low blood pressure)
55
Treatment of addisonian crisis
Rehydrate with saline
Give dextrose to prevent hypoglycaemia which could be as a result of glucocorticoid deficiency
Give hydrocortisone or another glucocorticoid
56
What is cushings disease
Excess cortisol or another glucocorticoid
57
Clinical signs of cushings syndrome
```
Thin skin
Proximal myopathy
Striae
Centripetal obesity
Moon face
Immunosuppression - eg reactivation of TB of had it before
Diabetes
Hypertension
Osteoperosis
```
58
Symotoms of addisons disease
```
Hyperpigmentation of skin
Low blood pressure
Weakness
Weight loss
Nausea
Diarrhea
Vomiting
Constipation
Abdominal pain
Vitiligo
```
59
Symotoms of adrenal/addisonian crisis
```
Fever
Syncope ie fainting
Convulsions
Hypoglycaemia
Hypnotremia ie v low blood conc of sodium
Severe vomiting and diarrhea
```
60
What is the spermatic cord, where is it formed, and what does it consist of?
```
Tubular structure that susoends in the testes and epididymis in the scrotum of the abdominal cavity
Formed at the deep inguinal ring
Contains several structures including:
- testicular artery
- pampiniform plexus (of veins)
- autonomic and genitofemoral nerves (gf nerves arise in abdomen and supply sensation to thigh and part of genitals)
-lymph vessels
-vas/ductus deferens
```
61
What does the seminal fluid consist of?
```
Fructose
Citric acid
Bicarbonate
Fibrinogen
Fibrinolytic enzymes
```
62
What are the muscles that make up the penis
2 x Corpora Cavernosa
| 1 x Corpora Spongiosum
63
What type of stimulation of the muscles of the penis is needed for erection, and for ejection?
Erection —> Parasympathetic stimulation
Ejaculation —> Sympathetic stimulation
(Point and Shoot)
64
Name the 3 accessory glands that help with the secretion of seminal fluid
Prostate gland
Bulbourethral glands
Seminal vesicles
65
What is the lymphatic drainage of the testes
Para aortic lymoh nodes
66
Where in the fallopian tube does fertilisation occur
Widest part - “ampulla”
67
What are the connective tissue kayers surrounding the testes
(Outermost to innermost):
- tunica vaginalis
- tunica albuginea
- tunica vasculosa
68
Describe the structure and drainage of the testes
- Joined to vas deferens and surrounding by epididymis
- has 3 layers of connective tissue - tunica vaginalis/albuginea/vasculosa
- contains 300 lobules separated from each other by septa, and each containing 1-4 seminiferous tubules
- seminiferous tubules drain into the “rete testes” and subsequently drain into the epididymis
- vas deferns at the end of the epipdidymis delivers sperm out of testes, via the spermatic duct
69
All areas suoerior to the cervix are sterile, so the vagina is non sterile. How is it protected from infection?
Contains lactobacillus vaginalis whihc secrete lactic acid to lower the pH
70
How does the structure of the fallopian tubes help to move the ovum along?
Fallopian tube contains cilia (“beating” movement) and spiral muscles’ contractions in peristaltic waves
71
What is the lymphatic drainage if the ovaries, uterus and vagina?
Ovaries: para aortic lymph nodes
| Uterus/vagina: iliac, sacral, aortic and inguinal lymph nodes
72
How can someone taking antibiotics increase their chance of vaginal infection?
Antibiotics can work systemically so could kill the lactobacillus vaginalis
So no lactic acid is secreted
So there is a rise in pH of vagina
So bacteria are not killed if they enter vagina
Increases chance of infection
73
What are the 3 layers of the uterus
(From outermost to innermost)
Perimetrium
Myometrium
Endometrium
74
Where does spermatogenesis occur
The intratubullar compartment of the seminiferous tubules
75
Decscribe the process of spermatogenesis
2n (germ cell) —> 2n (spermatogonium) — “mitosis” —> 2 x 2n (primary spermatocytes) —“first meiotic division” —> 4 x n (secondary spermatocytes) HAPLOID —“second meiotic division” —> 8 x n (spermatids) —“differentiation” —> 8 x spermatozoa
76
What is each seminiferous tubule surrounded by?
Tunica propria
77
Decsribe the structure of the seminiferous tubules in the testes
- Surrounded by tunica propria
- spermatogonium cells lie against the tunica propriaand mature as they move inwards into the centre of the circular seminiferous tubule
- so you see primary spermatocytes (secondary are rarely seen) and then spermatids as go inwards
- Leydig cells are found on the outside of the tubule (between them) and sertoli cells are within the tubule
78
What receptors do sertoli cells have and what is their function
FSH receptors
Sertoli cells
- support developing germ cells
- hormone synthesis: produce inhibin (-ve effect on FSH) and activin (+ve effect on FSH)
79
What receptors do leydig cells have and what is their function
LH receptors
Leydig cells:
- hormone synthesis: secrete androgens on LH stimulation (testosterone, androstenedione, dihydrotestosterone/DHEA)
These can be aromatised to form oestrogens
80
What is the process of the sperm penetrating the zona pellucida and fertilising the egg called
Acrosome
81
At which stage is meiosis halted at before birth in females
Prophase 1
82
Why can body temperature be a useful indicator for ovulation
Body temp increases by about 0.5 degrees celcius during ovulation
83
What is oligomenorrhea
A long menstrual cycle lasting over 35 days
84
Describe the process of oogenesis
2n Germ cell —> 2n oogonium —“mitosis”—> 2 x 2n primary oocyte —“first meiotic division”—> n first polar body (dies) and n secondary oocyte —“secondary oocyte is arrested in metaphase II until ovulated, then undergoes second meiotic division if fertilised ”—> n second polar body (dies) and 2n
85
2 main causes of hypocalcaemia
Low PTH —> hypoparathyroidism
| Vitamin D deficiency
86
Signs and symptoms of hypocalcaemia
```
CATS Go Numb
Convulsions
Arrythmias
Tetanu
Parasthesia
```
87
Where is calcitonin produced
In the parafollicular cells of the thyroid gland
88
Effects of thryoidectomy on calcium levels
Unaffected - calcitonin is oriduced by parafollicular cells in thyroid gland but isnt a main regulator of calcium, PTH and vit D are main regulators
89
A 29 yr old man presents to his GP with numbness in his hands and feet. He also reports experiencing recurrent seizures and repeated muscle spasms. The GP decides ro perform an examination of his face, tapping just below the zygomatic arch. The mains facial muscles on the side of his face twitch. What is the most probable differential diagnosis?
Hypocalcaemia (positive for Chvosteks sign)
90
What is the most important step that activates vitamin D
The 2nd hydroxylation
| 25(OH)cholecalcifriol to 1,25(OH)2cholecalcifriol aka calcitriol aka active vitamin D
91
Effects of calcitriol on bone? Gut? Kidney?
Bone - increase calcium reabsorption
Gut - increase calcium absorption, increase phosphate absorption
Kidney - increases calcium reabsorption, increases phosphate reabsorption
92
When serum calcium levels are low, which bone cell type is activated more than the other by the action of calcitriol?
Osteoclasts
93
Difference between effects of PTH and calcitriol on the kidney
Calcitriol increases calcium and phosphate absorption
| PTH increases calcium reabsorption and phosphate secretion and 1-alpha hydroxylase activity which increases calcitriol
94
Which hormone stimulates follicle maturation
FSH
95
What do parafollicular cells release
Calcitonin
96
Which thyroid hormone is more active
T3
97
What is the major hormone product of the thryoid gland
T4
98
When is T4 deiodianted into reverse T3 and why
Under circumstances requiring reduced metabolism (starvation)
Reverse T3 is the biologically inactive form of T3 (deiodinated in the wrong position)
99
What are the hakf lives of T3 and T4
T3 - 2 days
| T4 - 7 to 9 days
100
What are some complications if combined thyroid hormone replacement therapy (T3 and T4)
Symptoms of toxicity - palpitations, tremor, anxiety (combination treatment often supresses TSH)
101
Causes of hyperthryoidism
Graves disease (autoimmune condition)
Toxic multinodular goitre
Solitary toxic nodule
102
What is the adrenal medulla derived from
Ectodermal neural crest
103
What is the precursor for adrenaline and noradrenaline
Tyrosine
104
Are catecholamines stored before release
Yes unlike corticodteroids (because catecholamines are peptide hormones)
105
How is adrenaline formed from its amino acid precursor
Tyrosine hyrdoxylated to form dopa
Dopa decarboxylated to form dopamine
Dopamine hydroxylated to form noradrenaline
Noradrenaline methylated to form adrenaline
106
What 2 hepatic enzymes can catecholamines be degraded by
Monoamine oxidase
| Catechol-O-methyltranserase
107
What is the recommded calcium intake for adults
About 1000 mg/day
108
How can you diagnose premature ovarian insufficiency
(Early menopause)
| High FSH levels of above 25 iU/L on 2 occasions at least 4 weeks apart
109
What is aromatase and which factors cause increased aromatase activity
```
Enzyme that converts
testosterone into 17 beta oestradiol
And
androstenedione into oestrone
- alcohol
-age
-obesity
-gonadotrophins
-insulin
```
110
What is anostrazole and what can it treat
An aromatase inhibitor
| Can treat breast cancer
111
What is finasteride and what can it treat
A 5 alpha reductase inhibitor
| Can treat prostate cancer
112
What is the difference between testosterone and dihydrotestosterone
Testosterone: erectile function, libido, fertility
DHT: prostate and make pattern baldness, facial and pubic hair growth
DHT is a more potent ligand for the androgen receptor
113
What is AMH, when does it peak, what secretes it and what is it a good marker for
Ant Mullerian hormone
Peaks during early adult life
Granulosa cells secrete it
Good marker of ovarian reserve
114
How to treat menopause
Oestrogen hormone replacement therapy - to stimulate growth of endometrium
If endometrium is intact, combine this oestrogen with progesterone, progesterone will prevent endometrial hyperplasia which can cause cancer
115
What is classed as delayed ouberty and is it more common in boys or girls
Puberty onset after 14 yrs
| Boys
116
What is precocious puberty and is it more common in boys or girls
Early puberty - before 8 yrs
| Girls
117
What does non pulsatile administration of GnRH cause
Reduced LH and FSH secretion therefore reduced oestradial and testosterone
118
What hormones can u measure when diagnosing acromegaly
Growth hormone aka somatotrophin
Growth hormone releasing hormone
Somatostatin
Insulin like growth factor 1
119
Treatments for aacromegaly
Radiotherapy / chemotherapy / surgery to remove tumour
| Somatostatin analogues
120
Origins of hypothalamic magnocellular neurones which supply oxytocin and AVP to neurohypophysis
Supraoptic hypothalamic nucleus - AVP
| Paraventricular hypothalamic nucleus - oxytocin
