Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

2nd Year - Systems 3 > Endo/Repro 1 > Flashcards

Endo/Repro 1 Flashcards

1
Q

Endocrine system

A
  • a system of hormone glands secreting substances into the bloodstream that influence remote tissues
    • also unexpected sources, eg heart -> ANP, adipose tissue -> leptin, skin -> vitamin D

Often in odd arrangement, layers inside and out

  • eg adrenal medulla in cortex
  • C cells inside thyroid
  • pancreatic islet cells inside exocrine pancreas
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Movement of bioregulators

A

INTERNAL

  • hormones + neurotransmitters
  • via haemolymph or blood stream

EXTERNAL

  • pheromones
  • via water (fish) or air
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Pheromonal signals

A

Origins of endocrine system

  • from unicellular organisms, move towards high pheromone concentration
  • become multicellular organisms

A chemical signal transmitted between individuals of the same species
- still present in complex multicellular organisms

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Uses of endocrine system

A 
Survival
- find optimal chemical and physical environment
- find sustenance
- optimise conditions for reproduction
- facilitate successful evolution
Competition
- steroids have antimicrobial effects
- host hormones can inhibit parasite growth
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Controls of the endocrine system

A

Circadian rhythm - internal clocks
Diurnal rhythm - external cues (driven mainly by vision, dark/light)
Ultradian rhythm - hour to hour fluctuations

Influenced by:

  • senses
  • autonomic input
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Underactive endocrine system causes

A
  • inherited metabolic fault, eg enzymes missing
  • destruction of glandular tissue, physical or autoimmune
  • abnormal hormone production
  • excessive binding protein
  • receptor not responding or absent
  • inappropriately high feedback
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Overactive endocrine system causes

A
  • autoimmune attack inducing overactivity
  • intrinsic receptor overactivity
  • reduced inhibition (eg tumour blocking feedback response)
  • neoplastic formation of a functional adenoma
  • persistent feedback stimulation leading to autonomy
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Anatomy of hypothalamus

A

Part of diencephalon
On either side of third ventricle below thalamus
Connected to pituitary by pituitary stalk (infundibulum) through dura mater layer

Nuclei arranged in three zones - periventricular, medial, lateral
Endocrine nuclei in periventricular and medial zones - contain neurosecretory cells to secrete hormones (transduce from neural to hormonal signal)
- pulsatile firing, so discrete package of hormone released, controlled by synaptic input

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Neural connections of hypothalamus

A

Descending to - hippocampus, amygdala, septal nuclei
Ascending from - locus ceruleus, dorsal vagal complex, midbrain raphe, midbrain ventral tegmentum
Extensive intrahypothalamic connections

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Circumventricular organs

A

Lie on midline, along 3rd and 4th ventricle
Leaky, reduced BBB - route for large molecules into brain
Release molecules to hypothalamus; for appetite (leptin), fever (cytokines), drinking (angiotensin)
(includes median eminence)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Embryological development of pituitary

A

At 4-5 weeks

Downgrowth from floor of diencephalon
= neural tissue

Upgrowth from roof of oral cavity
= glandular tissue
- stalk will regress, attaches to infundibulum process instead
- sphenoid bone develops around

  • > leaves pituitary gland in sella turcica, indent in bone - means if tumour can only grow up as bone below
  • > dura mater layer over top of pituitary, around stalk, diaphragm sella
  • > sharp processes on either side of stalk, in head injury can damage pituitary stalk
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Empty sella syndrome

A

Where there is no development of dura mater (diaphragm sella) over top of pituitary gland

  • > CSF gets into sella turcica, increase in pressure, flattens pituitary against walls (may appear absent)
  • > can be normal, or hypopituitarism - underproduction of one or more pituitary hormones
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Anatomy of pituitary gland

A

= hypophysis

Posterior pituitary
(from neural downgrowth)
- median eminence (top)
- infundibulum (stalk)
- posterior/neural lobe = pars nervosa

Anterior pituitary
(from glandular upgrowth)
- pars tuberalis (either side of infundibulum)
- anterior lobe = pars distalis
— intermediate lobe = pars intermedia — present only in foetus, poorly vascularised, direct hypothalamic innervation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Blood supply to pituitary gland

A

Very well vascularised
From internal carotid artery

Posterior pituitary

  • inferior hypophyseal artery into posterior lobe
  • efferent vein

Anterior pituitary

  • superior hypophyseal artery into primary portal plexus in median eminence
  • continues as long portal vessel down
  • into secondary plexus in anterior lobe

Veins drain to systemic blood via cavernous sinus, superior/inferior petrosal sinuses, jugular bulb and vein
- if need to take blood close to pituitary outflow, use inferior petrosal sinus, as close as you can get in humans

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Nerve supply to pituitary gland

A

MAGNOCELLULAR HYPOTHALAMIC NEUROSECRETORY NEURONES

  • large cell bodies, originating in paraventricular or supraoptic nuclei
  • directly innervate posterior pituitary
  • made, and released in same place directly into blood draining from pituitary

PARVOCELLULAR HYPOTHALAMIC NEUROSECRETORY NEURONES

  • small neurones in paraventricular nucleus
  • indirectly control anterior pituitary
  • originate in paraventricular, arcuate and periventricular nuclei
  • axons terminate in median eminence, blood to anterior pituitary and can affect pituitary function
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Cells in anterior lobe (pars distalis) of pituitary gland

A

(labile tissue, changes proportions of cell type easily eg in pregnancy, but makes it susceptible to tumour formation)

SOMATOTROPH -> growth hormone (GH)
LACTOTROPH -> prolactin (PRL)
GONADOTROPH -> leutinising hormone (LH), follicle-stimulating hormone (FSH)
THYROTROPH -> thyroid-stimulating hormone (TSH)
CORTICOTROPH -> adrenocorticotrophic hormone (ACTH)

+ in foetus, in pars intermedia, melanotrophs -> Melanocyte-stimulating hormone (MSH)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Corticotrophin-related peptide hormones

A

Made in anterior pituitary gland

  • single small peptides, derived from common precursor POMC (pro-opiomelanocortin)
  • can be cleaved at many points, specific enzymes to make products found in different regions
  • adrenocorticotrophic hormone (ACTH) - in corticotroph cells
  • alpha-melanocyte-stimulating hormone
  • beta-lipocortin
  • beta-endorphin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Glycoprotein hormones

A

Made in anterior pituitary gland

  • made of two peptides, alpha is always similar, beta differs for each hormone and confers specificity (binds to specific receptor)
  • hormones are glycosylated before being secreted, carbohydrate and sialic acid added (amount determines stability)
  • follicle-stimulating hormone (FSH)
  • leutinising hormone (LH)
  • thyrotrophin (TSH)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Somatomammotrophin hormones

A

Made in anterior pituitary
- single peptide chain, no carbohydrate, 2-3 disulphide bonds

  • prolactin (PRL)
  • growth hormone (GH)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Hypothalamic hormones - neuropophysial hormones

A
  • made in magnocellular neurosecretory cells
  • transported to and released from posterior pituitary

OXYTOCIN
-> milk ejection, expulsion of foetus
VASOPRESSIN
-> antidiuresis and ABP regulation

  • made in supraoptic and paraventricular nuclei of hypothalamus
  • 9 amino acid structure
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Hypothalamic hormones - hypophysiotrophic hormones

A
  • made in parvocellular neurosecretory cells
  • transported to median eminence, released into portal circulation (so control anterior pituitary function)
THYROTROPHIN-RELEASING HORMONE (TRH)
GONADOTROPHIN-RELEASING HORMONE (GnRH)
SOMATOSTATIN (SS)
GROWTH HORMONE RELEASING HORMONE (GHRH)
PROLACTIN-INHIBITING HORMONE (DOPAMINE)
CORTICOTROPHIN-RELEASING HORMONE (CRH)

All cause release or inhibition of anterior pituitary hormone release

  • pulsatile release, so makes pituitary pulsatile release
  • all have now been artificially synthesised
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Corticotrophin-releasing hormone

A

Hypophysiotrophic hormone
Synthesised in paraventricular nucleus
41 amino acids
Stimulates synthesis and release of ACTH from pituitary corticotroph cells
-> signals to adrenal glands, produce cortisol (negative feedback)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Thyrotrophin-releasing hormone

A

Hypophysiotrophic hormone
Synthesised in paraventricular nucleus
3 amino acids
Stimulates synthesis and release of TSH from pituitary thyrotroph cells
(in high levels, stimulates release of prolactin)
-> signals to thyroid gland, produce T3 and T4 (negative feedback)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Gonadotrophin-releasing hormone

A

Hypophysiotrophic hormone
Synthesised in arcuate nucleus
10 amino acids
Stimulates synthesis and release of LH and FSH from pituitary gonadotroph cells
-> signals to gonads (ovary/testes), release testosterone in males, progesterone/oestrogen in females (negative feedback)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Growth hormone releasing-hormone

A

Hypophysiotrophic hormone
Synthesised in arcuate nucleus
44 amino acids
Stimulates synthesis and release of GH from pituitary somatotroph cells
-> negative feedback back to release more GHRH

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Somatostatin

A

Hypophysiotrophic hormone
Synthesised in periventricular nucleus
14 amino acids, in cyclical structure
Inhibits synthesis and release of GH from pituitary somatotroph cells
-> signals to liver, and others. Release insulin-like growth factor 1 (IGF-1)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Prolactin-inhibiting hormone

A 
= dopamine
Hypophysiotrophic hormone
Synthesised in arcuate nucleus
1 amino acid
Inhbits synthesis and release of PRL from pituitary lactotroph cells
-> signals to mammary gland
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Signals stimulating HPA axis

A

CSF signals
Circumventricular organs
Neural inputs
Blood signals

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Causes of pituitary disorders

A

HYPERSECRETION

  • functioning tumours
  • drugs

HYPOSECRETION (=hypopituitarism)

  • craniopharyngeoma
  • non-functioning pituitary tumours (affects surrounding tissue)
  • radiotherapy
  • trauma
  • empty sella syndrome
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Hypopituitarism

A

GH deficient - growth retardation (children), tiredness, muscle weakness

FSH/LH deficient - hypogonadism: men - reduced body hair, low libido, impotence. women - amenorrhoea, dyspareunia, hot flushes

TSH deficient - weight gain, decreased energy, cold sensitivity, constipation, dry skin

ACTH deficient - pale, weight loss, low bp, dizziness, tiredness

ADH(AVP) deficient - thirst, polyuria

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Thyroid gland

A

Left and right lobes, connected by isthmus
Formed from floor of pharynx
20g weight
Rich blood supply
Produces thyroid hormone from follicles
TSH is principal regulator
Well vascularised - necessary to take up eg iodide, and to release hormone

In inactive state - wide colloid filled lumen, containing precursor to thyroid hormones. Follicle epithelial cells are flattened, inactive.

In active state - little colloid, as thyroid hormone is released as it is made. Taller, columnar epithelial cells.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

Thyroid hormone synthesis

A

1 - active transport of iodide in from blood stream - needs adequate iodine in diet, but efficiently absorbed from gut into extracellular pool, then thyroid or kidneys absorb here
2 - oxidised to iodine, released into colloid lumen
1 - amino acid uptake, conversion to thyroglobulin (hormone precursor)
2 - thyroglobulin release into colloid lumen
3 - thryoglobulin iodination
4 - reabsorption into cell
5 - digestion by lysosymes to form T3 and T4
6 - release

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

Thyroid hormones

A

98% is T4 (tetra-iodothyronine/thyroxine) - 2 DIT (dihydrotyrosine) joined
2% is T3 (tri-iodothyronine), but is 10x more potent - 1 DIT and 1 MIT (monoiodotyrosine) joined
Small amount reverse T3

T4 is prohormone, converted to T3 or rT3 by de-iodination before acting at a receptor

  • > increased calorigenesis (heat production)
  • > increased metabolism (energy expenditure)
  • > growth and maturation
  • > cardiovascular effects
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Disorders of thyroid gland

A

(Goitre is just enlarged thyroid, not indicative of hypo or hyper thyroid state)

  • hypothyroidism
  • hyperthyroidism
  • subclinical conditions

2% of females get, 0.2% males get (mainly hypo)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

Hypothyroidism symptoms

A

If present early in development:

  • neurological deficits
  • small stature, immature appearance
  • puffy hands and face
  • delayed puberty

If present in adulthood:

  • insidious onset
  • low BMR
  • cold sensitivity
  • bradycardia
  • slow, hoarse speech
  • lethargy, slow movements
  • weight gain
  • constipation
  • menstrual abnormalities, infertility
  • dry thickened skin (myxoedema)
  • slowing of mental function

(would have high TSH, low T3/4)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

Causes of hypothyroidism

A

Chronic autoimmune thyroiditis - antibody production against thyroglobulin/thyroid tissue = Hashimoto’s thyroiditis

Thyroid irradiation

Pituitary/hypothalamus defect

Iodide deficiency

  • need replacement therapy with T4 (dosage hard to optimise)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

Hyperthyroidism symptoms

A
  • nervousness, restlessness, tremors, anxiety
  • high metabolic rate, raised temperature
  • sweating, heat sensitivity
  • tachycardia and palpitations
  • increased appetite (but weight loss)
  • tiredness
  • more bowel movements
  • decreased menses (infrequent periods)

(would have low TSH, high T4)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

Causes of hyperthyroidism

A

Grave’s disease, diffuse toxic goitre (autoimmune disease) - identifiable by exopthalmos, bulging eyeball

Toxic multinodular goitre

Toxic adenoma in thyroid gland

Pituitary tumours (adenoma producing TSH)

  • treat with antithyroid drugs (thiocarbamides) or propanolol, radioactive iodine (thyroid irradiation), surgery (only really in malignancy
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

Growth hormone production and release

A

Synthesised in anterior pituitary somatotrophs (stable population, 50% of pituitary cells)

Signal to release from pulse of Growth hormone releasing-hormone (stimulatory), and a decrease in somatostatin (inhibitory)
Released in pulses, 5-8/day, lasting 2-3 hours

Then bound to GH binding protein in blood

Negative feedback via GH and IGF1 (to increase somatostatin output)
- and IGF1 acts at pituitary to reduce GHRH effects

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

GH secretagogues

A

GHRH - stimulates GH release
Somatostatin - inhibits GH release

Ghrelin

  • from specialised cells in submucosa of stomach
  • released before meals, decreases after meals
  • stimulates GH release, stimulates appetite
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

Factors affecting GH release

A

Age - increased in puberty, declines with age

Sleep wake cycle - surges in slow wave sleep

Gonadal steroids - stimulate release (men higher peaks)

Nutrition - increased during fasting/hypoglycaemia, increased following high protein meal, reduced by elevated free fatty acids (so low in obesity)

Stress increases

Exercise increases

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

GH actions

A

Indirect effects - via IGFs

  • increases height in children (not required in utero)
  • stimulates limb growth

Direct effects (mainly metabolic)

  • increases muscle mass - sarcomere hyperplasia, increased protein synthesis - but NO effect on strength
  • increases internal organ size
  • promotes gluconeogenesis
  • promotes lipolysis
  • stimulates immune system
43
Q

GH therapy in adulthood

A

No effect on strength, despite increasing muscle and decreasing fat
May lessen fatigue
Increases risk of bowel cancer
Increases death rate on ITU, despite catabolic state and low endogenous GH
(drug of abuse in athletes)

44
Q

Insulin-like growth factors

A

IGFs, IGF1 most important
Plasma IGF1 is GH dependent, so levels are parallel
Produced in liver, and many other tissues
Transported with binding proteins, eg IGFBP3

45
Q

GH deficiency in adults

A

Long general list of symptoms including low mood, low confidence, tiredness, struggle to concentrate, poor memory
If more than 11 of these, give IV bolus of GHRH and measure GH levels

In old age, spontaneous GH secretion falls despite normal pituitary reserves of GH

  • > functional GH insufficiency
  • won’t benefit from supplements, as get increased muscle mass and decreased fat, but no change in strength (and get side effects)
46
Q

Acromegaly symptoms

A

Where there is excess growth hormone after full development reached

  • coarsening of features
  • growth of extremities (growth at cartilage end plates, so most apparent where many bones eg hands and feet)
  • soft tissue growth - lip and nose
  • snoring, obstructive apnoea
  • headaches
  • carpal tunnel syndrome
  • arthralgia, arthritis
  • spacing of teeth
  • sweating
47
Q

Anatomy of adrenal glands

A

Capsule
Cortex - yellowish, 90% (full of lipid, making steroids)
Medulla - reddish, 10%

Circumferential blood supply:

  • aorta supplies via renal artery (below) and inferior phrenic artery (above)
  • arteries then pierce capsule and into cortical sinusoids
  • blood runs through cortex and medulla, drains into adrenal vein
48
Q

Zones of adrenal glands

A

Zona glomerulosa - mineralcorticoids eg aldosterone

Zona fasiculata - glucocorticoids eg cortisol (and some androgens)

Zona reticularis - androgens eg dehydroepiandrosterone (DHEA) (and some glucocorticoids)

Medulla - catecholamines eg adrenaline, noradrenaline

49
Q

Chromaffin cells

A

Modified post-ganglionic neurones
In adrenal medulla
- receive sympathetic innervation via splanchnic nerves to coeliac ganglion to chromaffin cell
- discharge hormones in packets to blood
- 80% adrenaline, 20% noradrenaline
- neurohormones, so circulate and have effect on whole body

Rapid release, as ANS has direct control over chromaffin cells

50
Q

Adrenaline vs Noradrenaline

A

Adrenomedullary catecholamines in circulation

ADRENALINE
- 50% bound to albumin
- shorter half life (10 mins)
- 20-50 ng/ml
- all from adrenal medullary chromaffin cells
- stronger agonist
(phaeochromocytoma is tumour of adrenal medulla, extreme increase in A levels)

NORADRENALINE

  • 50% bound to albumin
  • longer half life (15 mins)
  • 100-350 ng/ml
  • mostly from postganglionic sympathetic neurones

Released in response to stress - hypoglycaemia, haemorrhage, hypoxia, pain, psychological stress

51
Q

Adrenocortical steroids

A

Mineralcorticoids
eg aldosterone
- for sodium (water) retention and potassium excretion
- from zona glomerulosa

Glucocorticoids
eg cortisol
- for metabolic control, stress, actions on immune system
- from zona fasiculata, and some from zona reticularis

Androgens
eg dehydroepiandrosterone (DHEA)
- for libido in females
- from zona reticularis, and some from zona fasiculata

52
Q

Hypothalamo-pituitary-adrenal axis

A 
Stress (+ diurnal rhythm)
-> hypothalamus
-> release corticotrophin-releasing hormone and antidiuretic hormone
-> anterior pituitary
-> release adrenocorticotrophic hormone
-> adrenal cortex
-> cortisol
(negative feedback to anterior pituitary and hypothalamus)
53
Q

Functions of glucocorticoids

A

Metabolic - mainly catabolic - cause muscle weakness, skin + connective tissue breakdown, lipolysis, to release proteins for gluconeogenesis and fuel generation

Cardiovascular
Immunologic (anti-inflammatory)
Homeostatic
Musculoskeletal (breakdown)
Arousal and mood

All permissive, indirect actions

54
Q

Cushings’ syndrome symptoms

A

Chronic glucocorticoid excess

  • truncal obesity
  • reddened moon face
  • hypertension
  • low mood
  • easy bruising
  • abdominal striae
  • hirsuitism (hair)
  • muscle wasting
  • increased appetite
  • osteoporosis
  • thinning of skin
55
Q

Causes of Cushings’ syndrome

A

Exogenous steroid use (most common) - suppresses HPA axis, atrophy of adrenal cortex

Pituitary tumour (= Cushings' disease)
Ectopic ACTH/CRH

Adrenal adenoma/carcinoma/adrenal disease

56
Q

Adrenocortical deficiency causes

A

Deficient production of glucocorticoids or mineralcorticoids

1 - destruction/deficiency of adrenal cortex (primary)

  • Addison’s disease (autoimmune) or adrenal haemorrhage
  • both glucocorticoids and mineralcorticoids low

2 - deficient pituitary ACTH (secondary)

  • withdrawal from prolonged glucocorticoid therapy
  • glucocorticoids low, mineralcorticoids normal
57
Q

Addison’s disease symptoms

A
  • weakness, fatigue
  • anorexia, weight loss
  • hyperpigmentation
  • hypotension
  • GI disturbances
  • salt craving
  • amenorrhea (loss of axillary and pubic hair)
58
Q

Therapeutic uses of glucocorticoids

A
  • replacement therapy in Addison’s disease
  • acute inflammatory disease
  • chronic inflammatory disease
  • neoplastic disease
  • immunosuppression
  • emergency medicine

MANY MANY SIDE EFFECTS

59
Q

Requirements for fertility treatment

A 
Couple trying for 2 years
Both aged under 40
Both BMI under 30
Both non-smoking
No previous children together
No prior sterilisation

-> postcode lottery
NICE recommend offer 3 rounds on the NHS (stop if reach aged 40 in this time)
DON’T offer ovarian stimulants if cause of infertility unknown

60
Q

Techniques for fertility promotion

A

Ovarian induction
Induce spermatogenesis

IVF - stimulate ovaries to make many eggs, collect (aspirate follicles), fertilise by mixing, assess womb with ultrasound daily until correct environment, implant embryo

GIFT - put unfertilised gametes straight into fallopian tube (may be allowed in some religious groups)

ICSI - as with IVF, but inject single sperm into egg - concerns about allowing genetic conditions to perpetuate, selecting one sperm

Epididymal sperm extraction + ICSI

Testicular sperm extraction + ICSI

Surrogacy

Egg donation

61
Q

Improving techniques for fertility promotion

A

Genetic screening

Sperm collection

Better incubation, so embryos can grow more, select best one to implant (if get to blastocyst stage, success rate doubles)

Womb transplants now possible?

Egg freshening - remove ooplasm and replace with donor’s (removes mitochondrial disease)

62
Q

Roles of calcium

A 
Mineral component of skeleton and teeth
Muscular contraction
Blood coagulation
Enzyme activity
Neuronal excitability
Hormone secretion
Cell adhesion

-> so if very deficient, death

63
Q

Where is calcium in the body?

A

99% - bone, inorganic, mineralised matrix

  1. 9% - intracellular, in endoplasmic reticulum
  2. 1% - extracellular fluid
  3. 000002% - free in cytosol

Of that which is free in the cytosol:
50% ionised - biologically active, available for above functions
5% complexed (calcium salts)
45% protein bound
- proportions change depending on pH, dissociates from proteins at pH decreases, free amount increases

64
Q

Calcium as a second messenger/regulatory ion

A

10,000 fold increase in calcium extracellularly vs intracellularly free in cytosol

  • so when calcium channels open, calcium floods into cell
  • can now act as signalling ion to activate intracellular processes (neurotransmitter release/contraction/secretion)
65
Q

Calcium homeostasis

A

Gained from diet
Exchange between bone remodelling
Lost to urine, faeces, lactation

Balance controlled by parathyroid hormone (calcium too low), calcitonin (calcium too high), active vitamin D (calcium too low)

66
Q

Parathyroid hormone

A

Peptide hormone
Released in response to falling levels of circulating calcium

From parathyroid glands (embedded in thyroid gland)

  • PTH protein stored in secretory granules of chief cells
  • high calcium inhibits secretion, low calcium allows

For minute to minute, fine regulation

BONE EFFECTS
- release from calcium salts in bone extracellular fluid - osteoblasts - immediate
- breakdown hydroxyapatite crystals - osteoclasts - long term - only indirect, via ligands released from osteoblasts
(efflux of calcium from bone)

KIDNEY EFFECTS
- increase tubular reabsorption of calcium
(decreased loss of calcium in urine)
- release of vitamin D, promotes formation of active vitamin D
(enhanced absorption of calcium from intestine)

-> increased concentration of calcium in the blood

67
Q

Calcitonin

A

Peptide hormone
Released in response to high blood calcium
An emergency hormone (not minute to minute like PTH)

Secreted by C cells in thyroid gland (not follicular cells, between them)

  • > reduce blood calcium levels
  • > prevent hypercalcaemia

BONE
- inhibit bone reabsorption
KIDNEY
- reduce calcium reabsorption

68
Q

Active vitamin D

A

Steroid, produced from cholesterol
… or percursor from diet (dairy, fortified cereals)
Produced in response to falling blood calcium, via PTH

Cholesterol

  • – UV light —
  • > cholecalciferol
  • – liver —
  • > 25-hydroxycholecalciferol
  • – kidney, with PTH present —
  • > active vitamin D

For longer term regulation of calcium
Increases absorption of calcium from intestine
-> protect bone

69
Q

Vitamin D deficiency

A

Rickets in children, osteomalacia in adults

  • diet deficient in vitamin D, lack of sunlight
  • renal 1alpha hydroxylase (genetic cause)
Low active vitamin D
Decreased calcium uptake in gut
Increased PTH
Increased calcium resorbed from bone
(cartilage not properly mineralised, weak malformed bones)
70
Q

Hyperparathyroidism

A

Excessive PTH secretion

PRIMARY
Unregulated parathyroid glands (eg adenomas of chief cells)
Increased PTH
-> Increased calcium resorption from bone, decreased bone density and multiple fractures
-> Increased calcium uptake in kidney

SECONDARY
Chronic renal failure -> excess PTH secretion
Reduced kidney function
-> Low calcitriol production, low Ca absorption in gut
-> Low Ca retention in kidney
–> Hypercalcaemia, increased PTH, bone deformation and fractures

71
Q

Hypoparathyroidism

A

Inadequate PTH secretion
(eg from accidental removal of parathyroid glands during thyroid surgery)

Low PTH

  • > Reduced calcitriol production, reduced Ca absorption in gut
  • > Reduced bone resorption
  • > Reduced Ca retention in kidney
  • -> Hypocalcaemia, increased neuromuscular excitability (lowered threshold), paresthesia and tetany, abnormalities in enamel formation
72
Q

Obesity

A

Obese phenotype is from exposing individuals with a predisposing genotype to an inappropriate environment.
(interplay between genes (poly or monogenic) and environment)
- exponential rise in risk of type II diabetes and cardiovascular disease mortality as BMI increases

73
Q

Ob / Db mice experiments

A

ObOb mouse - no Ob gene for blood bourne hormone (leptin)
- so loses weight when parabiosis to healthy mouse

DbDb mouse - no Db gene for hormone receptor
(leptin receptor)
- so stays overweight when parabiosis to healthy mouse

74
Q

Leptin

A

= Ob
Polypeptide hormone
Plasma concs decrease in fasting, increase in feeding (is reporter of fed state)
- secreted by adipose tissue
- signals to hypothalamus
- decreased feeding, increased thermogenesis

(rarely works in human treatment, unusual to be deficient in leptin)

75
Q

Hypothalamic hormones regulated by leptin

A

OREXIGENIC (hunger inducing)
- neuropeptide Y (NPY)
- agouti-related peptide (AgRP)
Leptin reduces expression

ANOREXIGENIC (decreases appetite)
- melanocyte stimulating hormone (alpha MSH) - endogenous, made from POMC, ACTH
- cocaine and amphetamine-related transcript (CART)
Leptin increases expression

76
Q

Male reproductive tract

A

Tract activity regulated by androgen

Testis covered by fibrous capsule - tunica albuginea
Sperm made in seminiferous tubules
Tubules converge to drain in rete testis
Into efferent ductules
Into duct of epididymis
Into vas deferens

(need to go through epididymis in order to be fertile and motile, most fluid absorbed and head so by the time sperm is at tail, very concentrated)
Sperm first appear in the testis at puberty, as regulated by androgen

77
Q

Seminiferous tubule cells

A

Sertoli cells - somatic cells, controlled by FSH to support germ cell development - extend full length of epithelia, bridges to support engulfed germ cells, and secrete fluid for sperm

Germ cells - start at base of epithelia, then mature and detach at lumen as sperm

Encircled by myoid cells

-> spermatogenesis
(basal and adluminal compartments, above and below the level of the blood-testis barrier)

78
Q

Interstitial area cells

A

Leydig cells - controlled by LH to make testosterone

Lymph vessels

Macrophages

79
Q

Purpose the blood-testis barrier

A
  • maintain differences in fluid composition between fluid within and outside tubule
    (tubular fluid is environment for developing germ cells and vehicle for sperm transport)
  • protect developing sperm from auto-immune attack from blood-bourne antibodies
    (otherwise ant-sperm antibodies would attack sperm, have haploid gamete)
80
Q

Steroid production by testis

A 
STEROIDS
Prostagens
Androgens
Oestrogens
(all sex steroids - women make all the same but in different proportions)
\+ Corticosteroids
81
Q

Testicular androgen synthesis

A

5-7 mg/day testosterone - 50% potency
2 mg/day androstendione - 8% potency
70 μg/day DHT (5alpha dihydrotestosterone) - 100% potency

Testosterone is prohormone, converts to more active DHT metabolite

82
Q

Testicular testosterone/DHT synthesis

A

LH causes conversion of cholesterol to testosterone in Leydig cell via delta 5 pathway

  • testosterone then released to blood and lymph to regulate epithelial lining of reproductive duct
  • mainly testosterone into Sertoli cell, converted to DHT via 5alpha reductase. DHT then released to tubular fluid
83
Q

Testicular oestrogen synthesis

A

LH causes conversion of cholesterol to testosterone in Leydig cell via delta 5 pathway

  • testosterone converted to oestradiol 17beta
  • oestradiol 17beta released to blood and lymph to regulate brain, bone, vascular system
  • testosterone converted to oestradiol 17beta in Sertoli cell, via aromatase. Oestradiol 17beta released to blood and lymph for fluid reabsorption, increasing concentration of sperm (NECESSARY)
84
Q

Oestrogens in men

A

Oestradiol via aromatase enzyme in testis

+ most oestradiol from peripheral conversion of testosterone and androstenedione (in fat, breast, testes, muscle)

85
Q

Functions of testosterone

A

PUBERTY

  • induce growth and development of male reproductive tract
  • induce secondary sex characteristics (DHT maintains)
  • growth and fusion of long bones

ADULTS

  • spermatogenesis
  • libido, sex behaviour, aggression, mood
  • maintain muscle mass and bone
  • maintain accessory sex glands
  • regulate secretion of gonadotrophins
86
Q

Causes of male infertility

A
  • obstructive azoospermia (eg following inflammation from STD)
  • varicocele (swelling of veins in testicles, compresses)
  • endocrine (HPT axis failure
  • disorders of seminal plasma (eg poor liquefaction)
  • presence of antibodies to sperm
  • pathological damage of seminiferous epithelium (eg mumps, radiation)
  • ejaculatory malfunction
  • high scrotal temperatures
  • chromosomal abnormalities
  • cryptorchidism (undescended testes)
  • poor diet (deficient in vitamins A/B/D)
  • drugs, especially cannabis
87
Q

Hypothalamo-pituitary-testicular axis

A

Pituitary -> FSH -> sertoli cells
Pituitary -> LH -> leydig cells
Controlled by GnRH (gonadotrophic neurone releasing hormones)

88
Q

Intersex disorders of development of male reproductive tract

A

NO alpha reductase

  • so no conversion from testosterone to DHT
  • > internal male genitalia (seminal vesicles, epididymis, vas deferens), female appearing external genitalia (no penis, scrotum, prostate)

ANDROGEN INSENSITIVITY SYNDROME
= testicular feminisation syndrome
- lack of androgen receptors (partial or complete)
- XY with testes
- no internal tract, but has female genitalia and secondary sex characteristics

89
Q

Semen quality

A

30 million sperm per ml ejaculate, 2-5ml per ejaculation usually
Seminal plasma needed: transport vehicle, buffering, nutrient supply

Infertility problems

  • low sperm count - oligospermia
  • low sperm motility - asthenospermia
  • abnormal sperm morphology - teratospermia
  • low semen volume - hypospermia

(need 4% of sperm to be normal to be considered fertile)

90
Q

Spermatogenesis

A 
MITOSIS
Type A dark spermatogonia
Type A light spermatogonia
Type B spermatogonia
Primary spermatocyte

MEIOSIS
Secondary spermatocyte
Spermatid

SPERMIOGENESIS
Spermatozooa
- here acquire acrosome (cap-like head), flagellum, midpiece, lose excess cytoplasm)

91
Q

Stages of germ cell development

A

Distinct cell-cell associations
Each batch of epithelia initiate new wave of spermatogenisis every 16 days
So allows continuous production of sperm, not synchronised

92
Q

Functions of epididymis

A

Storage of sperm in tail, very concentrated
Maturation - loss of cytoplasmic drop, stabilisation of cell membrane, increased energy reserve

  • sperm movement through here is passive (and through testis)
  • sperm can survive here about 10 days
  • non-ejaculated sperm are resorbed (or lost in urine)
93
Q

Accessory sex glands

A 
Seminal vesicles (60%)
Prostate gland (40%)
Bulbourethral glands = Cowper's glands (pre-ejaculate to flush tract)

For producing secretions (constituents of seminal plasma)

  • fructose - fuel for sperm motility
  • ascorbic acid, spermine, citric acid - protection of DNA of sperm
  • cholesterol, phospholipids
  • prostaglandins - contraction of female reproductive tract to propel sperm up
  • phosphate buffers, bicarbonate buffers - against acidity of female tract
94
Q

Prostate disorders

A

Prostatitis
- inflammation of prostate gland

Benign prostatic hyperplasia (BPH)
- uniform, smooth, normal enlargement with ageing

Prostatic cancer
- craggy appearance
(most common male cancer)

95
Q

Phases of ejaculation

A

Seminal emission phase

  • contractions of epididymis and vas deferens
  • sends sperm to ampulla
  • contractions of prostate, ampulla and seminal vesicles
  • send semen to upper urethra

Ejaculation phase
- contractions of smooth and striated muscle associated with urethra

96
Q

Causes of erectile dysfunction

A

Failure to initiate
Failure to fill
Failure to store blood volume

Caused by:
In older men - diabetes, atherosclerosis, drugs
- psychogenic factors
- alcoholism
- endocrine factors
- trauma/pelvic injury
- spinal lesions/MS

Treat with intracorpal injection or Viagra

97
Q

Monogenic disorders of human obesity

A

No leptin secreted, as with ObOb mice (also infertile)
No leptin receptor, as with DbDb mice
MC4R (melanocortin 4 receptor), so alpha MSF (anorexigenic hypothalamic hormone) can’t stimulate
Prohormone convertase-1 absent, so can’t make alpha MSH

All VERY rare, far more common to be polygenic (99%)

98
Q

Polygenic causes of obesity

A

13 loci identified so far, possibly up to 100

  • MC4R variants
  • FTO gene

Each locus may account for ~0.1 BMI units

Also possible epigenetic changes

99
Q

Anti-obesity therapies

A

CURRENT: behaviour, physical activity, surgery

  • Orlistat/Xenical - gut and pancreatic lipase inhibitor, so reduced digestion of fats, weight loss (but steatorrhoea). Available over the counter if BMI>28
  • Reductil, Acomplia both withdrawn

FUTURE:

  • MC4R agonists - selectivity a problem.
  • Mitochondrial uncoupling protein activators (so thermogenesis, but no ATP made)
100
Q

Satiety-inducing peptides

A

Produced endogenously by L cells in small intestine in response to nutrient intake
- supress appetite

Glucagon-like peptide
PYY
Cholecystokinin (CCK)

101
Q

Hunger-inducing peptides

A

Ghrelin
Orexins A and B

(major pharmacological targets, but levels reduce after bariatric surgery)

102
Q

Fasting vs fed state hormones

A

FASTING

  • high ghrelin release from stomach
  • low leptin release from fat cells
  • > so high AgrP, high NYP, low POMC
  • > increased appetite

FED

  • low ghrelin release from stomach
  • high leptin release from fat cells
  • > low AgrP, low NYP, high POMC
  • > reduced appetite
103
Q

Bypass surgery types

A

Roux-en-Y gastric bypass

  • join top of stomach to the ileum, so bypass most of stomach, duodenum and jejunum
  • reduced ghrelin expression as stomach not stimulated
  • increased GLP-1 and PYY
  • if BMI>40, aged over 18

Sleeve gastrectomy

  • majority of stomach removed, nutrients pass straight through remaining stomach into GI tract
  • reduced ghrelin expression
  • increased GLP-1 and PYY

Gastric band to restrict stomach

-> reduced appetite, weight loss, improved glucose tolerance
(unsure of long term consequences for eg cardiovascular disease)

104
Q

Treatment of hyperthyroidism

A 
Drugs inhibiting T3/4 secretion
High dose iodide
Thyroidectomy
Beta blockers
Radio iodine (concentrates in and destroys follicle cells)
  • amiodorone (anti-arrhythmic), lithium and interferons all also interfere with iodination

2nd Year - Systems 3 (10 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions