Brainscape's Knowledge GenomeTM

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


See full index

Medicine Sem 1 > Case 4 > Flashcards

Case 4 Flashcards

1
Q

What hormones are involved in the growth of a human?

A
  • Growth hormone
  • Insulin-like growth factor-1
  • The thyroid hormones
  • Sex steroids – testosterone and oestrogen
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Describe the linked actions of GH and IGF-I, starting from the hypothalamus.

A
  • Produces growth hormone releasing hormone (GHRH)
  • GHRH acts on anterior pituitary (somatotrophs = cells in anterior pituitary) which have GHRH receptors
  • These cells produce growth hormone (GH)
  • GH travels in the blood stream to its target organs - affects bone, fat cells, muscle, liver (they all have the GH receptor)
  • Liver then produces IGF-I in response to growth hormone stimulation
  • Which acts on bone, adipocytes (fat cells) and muscle – the same tissues as GH affects
  • Growth hormone can also stimulate bone to produce IGF-I which then works in the bone (IGF-I therefore has endocrine actions but it also has paracrine actions)
  • GH has both direct and indirect effects
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Where is the gene for GH?what does the gene give rise to? and how and when is it secreted? and what issue does this cause?

A
  • Gene present on chromosome 17
  • Gene gives rise to 22 KDa (191 amino acids) and 20 KDa (deletion of residues 32-46) (kilodalton – an atomic mass unit – usually used to describe the molecular weight of large molecules such as proteins)
  • Secreted in pulses – particularly at night – makes it difficult to measure level
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Where is the gene for IGF-I? what does it give rise to? and how is it secreted?

A
  • gene on chromosome 12
  • 7.5 kDa (70 amino acids) – significant homology with insulin
  • Not produced in pulses – can take a one-off blood sample
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What are GH and IGF-I actions?

A
  • Promote growth in long bones, soft tissues and organs
    They can do this because they act on all major functions of the cell:
  • Effects on cellular proliferation, survival and differentiation and metabolism
  • In bone the hormones act on a particular region called the growth plate
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

How are GH and IGF-I involved in bone growth?

A
  • They stimulate the proliferation of the chondroblasts in the proliferative zone
  • They stimulate the maturation and differentiation of the chondrocytes in the maturation and hypertrophic zones
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

How is GH and IGF-I involved in metabolism?

A

GH stimulates lipolysis in adipocyte tissue = break down of fat -> increase in fatty acid level in plasma
GH stimulates uptake of amino acids in muscle and stimulates protein synthesis
GH also stimulates an increase an output of glucose from the liver – increase in glucose in circulation and it prevents peripheral tissues from taking up glucose
GH also stimulates liver to produce IGF-I which also has metabolic effects – it’s also anabolic so stimulates amino acid transport into muscle cells and conversion of those into protein – HOWEVER, for the other tissues IGF-I is much more like insulin and not like GH - it stimulates lipogenesis and reduces plasma glucose levels by reducing output of glucose by liver and stimulating uptake of glucose by peripheral tissues – i.e. like insulin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

How are thyroid hormones important in growth?

A

Important for chondrocyte hypertrophy

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

How are sex steroids important in growth?

A
  • Important for preventing any further growth
  • As oestrogen level rises it causes closure of the growth plate and therefore prevention of any more growth – thought that oestrogen stimulates progenitor cells in reserve zone to undergo apoptosis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Explain the regulation of thyroid hormones.

A
  1. Hypothalamus produces thyrotropin-releasing hormone (TRH)
  2. Stimulates anterior pituitary (thyrotrophs = cells in anterior pituitary) which produces thyroid stimulating hormone (TSH)
  3. Which travels to thyroid gland to stimulate production of T4 (thyroxine) and T3 (tri-iodothyronine)
  4. These two hormones can regulate their own production by having negative feedback at the anterior pituitary and hypothalamus level
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

How are thyroid hormones synthesised?

A
  • Iodide – absorbed in gut
  • Makes way in circulation – plasma
  • Taken up by thyroid gland and oxidised to iodine (peroxidase enzyme) and then iodine is added onto tyrosine amino acid in a protein known as thyroglobulin
  • Either one molecule or two molecules get added onto thyroglobulin to form monoiodotyrosine or diiodotyrosine
  • Then two diiodotyrosine can combine to form T4
  • Or diiodotyrosine can combine with monoiodotyrosine to form T3
  • The T3 and T4 are cleaved off the thyroglobulin, released into the circulation, and then they travel bound to protein called thyroxine-binding globulin
  • In peripheral tissues, you can get T4 being converted into T3 (deiodinase) (T3 is the more active of the two thyroid hormones – it has a greater affinity for the thyroid hormone receptor)
  • TSH plays a role in this – it stimulates the uptake of iodide by thyroid gland from the circulation – it stimulates the production of MIT and DIT – stimulates the release of T3 and T4 from the thyroid gland
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Describe sex steroid synthesis.

A
  1. Hypothalamus – GnRH
  2. Anterior pituitary (gonadotrophs)
  3. Produces gonadotrophins (FSH and LH (males and females) which travel to the gonads

Female:
4. Thecal cells stimulated by LH to produce androgen/testosterone which is then converted in granulosa cells under influence of FSH to produce oestrogen
Male:
5. LH stimulates the Leydig cells to produce testosterone which is converted (aromatised) to oestrogen, stimulated by FSH

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Describe the normal pattern of growth from infancy through to puberty.

A
  1. Postnatal growth spurt occurs during their first two years of life, but with decelerating rate
  2. After age 2, growth continues at a slower rate until the beginning of adolescence (11 for girls; 13 for boys)
  3. Pubertal growth spurt occurs
  4. At the end of adolescence, which occurs in the late teens, growth stops and individuals attain their full adult stature
  5. Thereafter no further increase in height is possible (due to epiphyseal closure)

(faster rate in the pubertal growth spurt than in postnatal growth spurt)

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

Describe growth between birth and 2 years. What is the importance of it? and what are the causes of abnormal growth?

A
  • You’ve got rapid but decelerating growth
  • Nutrition dependent phase
  • Causes of abnormal growth: what you might be able to diagnose at this point:
  • chronic disease syndromes e.g. Turners
  • skeletal
  • psychosocial – can stop growth completely
  • SGA
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Describe growth in mid-childhood years. What are the causes of abnormal growth?

A
  • GH dependent phase
  • GV > 5cm/yr
  • Causes:
  • GHD – GH deficiency
  • endocrine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Describe growth during pubertal years. What are the causes of abnormal growth?

A
  • GH & sex steroid dependent phase
  • GV > 8cm/yr
  • Causes:
  • sex steroid deficiency
  • if GHD, then exclude SOL urgently
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What are the causes of poor growth?

A
  • Constitutional???
  • Genetic
  • Born small
  • Lack of food
  • Chronic illness – system disease
  • Psychosocial deprivation
  • Abnormal bones
  • skeletal dysplasia
  • metabolic disorders
  • Recognised conditions
  • chromosomal disorders – Turner syndrome 45X, DS
  • Hormone deficiencies (less common) e.g. GH, thyroid hormone, sex hormones
  • brain tumour
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What is CDGP? what are the causes?

A
  • growth slows down during puberty years – before that everything seems fine
  • however, they will catch up
  • not clear what is normal and what is pathology
  • many causes e.g. idiopathic hypogonadotrophic hypogonadism (IHH), Klinefelter syndrome (testes), Turner syndrome (ovaries)
  • you’re diagnosed it but it’s not pathological
  • commonest cause of delayed puberty in boys – both don’t forget other possibilities like a brain tumour
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What is Turners syndrome? what are the symptoms? how common? and what is treatment?

A
  • Webbing of neck
  • Shield chest
  • If a girl comes in worried about development – not worried if its CDGP but you do want to rule out turner syndrome first
  • Blood test – karyotype – 45X
  • Height function and ovaries malfunction – don’t always have no signs of puberty
  • 1:2500 – surprisingly common
  • Treatment – growth hormone, sex steroids, fertility
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

How does hypothyroidism cause short stature?

A
  • Thyroxin isn’t a puberty hormone or growth hormone
  • But if you don’t have enough thyroxin your other processes will stall
  • Treatment of hypothyroidism – weight slows down because gains weight if untreated
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What does hypopituitarism cause?

A

Growth hormone deficiency - can lead to short stature

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What’s Klinefelter syndrome? how common is it? and what is the treatment?

A
  • Very tall
  • 47 XXY
  • More common than turner syndrome – 1:1000
  • Treatment – sex steroids, fertility
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What are the causes of hypogonadotrophic hypogonadism?

A
  • Kallmann syndrome – genetic form - abnormal sense of smell
  • Idiopathic HH
  • Brain tumours
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What can GH and IGF-I deficiency cause? what causes the deficiency? and what’s the treatment?

A

(deficiency due to there being a problem in any point in the axis – due to either their production or signalling)

  • > short stature
  • > adiposity (increase in adipose tissue)
  • can get problem in the axis at any level – e.g. problem in the hypothalamus, problem with GHRH receptor, pituitary may not be able to produce GH, the liver might have a problem with GH receptor, might be a problem with the IGF-I gene

Treatment:

  • Depends on where in the axis the problem is
  • If its to do with hypothalamus or GHRH receptor then you would give GH
  • If there’s an issue with GH receptor or IGF-I hormone production then you should give them IGF-I in order to stimulate their growth
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What is the treatment for short stature for males and females?

A

NEED FOR PUBERTY INDUCTION
- to bring on physical features associated with growth and puberty – achieve peer similarity
- is it hypogonadotrophic hypogonadism (HH – idiopathic/acquired)?
- Bone mineral density? – improve sex steroid induced bone mineralisation
INDUCTION DOES OF TESTOSTERONE – boys
- Low dose testosterone esters (e.g. Sustanon) 50-100 mg once a month for 4 months
- Oral testosterone (e.g. Restandol) 40 mg once daily for 4 months
- Important to reassess – further courses? – longer duration of treatment?
INDUCTION DOSE OF OESTROGEN – girls
- Low dose ethinyl estradiol (2 mg) orally once daily for 4 months
- 17B estradiol (evorel) patches (50 mg) – ¼ patch twice a week for 4 months

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

What are the different parts of long bone?

A
  • Spongy
  • Diaphysis
  • Proximal epiphysis
  • Distal epiphysis
  • Periosteum – layer of dense connective tissue surrounding whole of the bone – protects the bone and provides muscle attachment sites
  • Metaphysis – between the head and the shaft – epiphysial (growth) plate inside
  • Compact – all over the outside of the bone
  • Endosteum – thin membrane lying inside the medullary cavity
  • Medullary cavity
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What does compact bone contain?

A

Haversian system (Osteon) – packed in compact bone
Contains:
- Central canal – blood vessels and nerves run inside
- Lamellae – bone layers – e.g. collagen and bone cells (e.g. osteocytes)
- Lacuna with osteocytes inside their space
- Canaliculi – channels for communication between osteocytes
Compact bone is FULL of osteons and that’s what makes it compact

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What does spongy bone contain?

A
  • Trabeculae – bone

- Adipose tissue – in between bone tissue – yellow bone marrow

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

What is bone?

A

Highly vascular mineralised connective tissue.

30
Q

What is the composition of bone?

A
  • Connective tissues are made up of cells and matrix
  • Cells (osteoprogenitor, osteoblasts, osteocytes, osteoclasts)
  • Matrix (collagen (95%), ground substance (ECF(extracellular fluid), proteoglycans(type of protein))
  • Mineralised – hydroxyapatite, calcium, phosphate – examples of minerals found in bone – they contribute to its hardness and toughness – they lie parallel to the collagen fibres that you find in the matrix
  • Remember – bones in our bodies are pliable and alive, not completely rigid like the ones we see in anatomy
31
Q

What are the different bone cells?

A
  1. Mesenchymal cells give rise to osteoprogenitor cells (sort of bone stem cells – flat, elongated nuclei) – differentiate into lots of different cell types e.g. osteoblasts, fibroblasts, adipocytes
  2. Osteoblasts are bone building cells (cuboidal with granular cytoplasm) – surrounded by matrix – secretes matrix to build bone
  3. Osteoblasts secretes lots of matrix and becomes surrounded by it and trapped in it and when that happens it becomes an osteocyte(circular)(surrounded by space called lacuna) – job is to maintain bone/mineral homeostasis
  4. Osteoclast are bone chewing cells – help in resorption of bone (look really different to the other cell types – they’re huge – got lots of nuclei within them – up to 50, ruffled collar – helps in their job as chewing cells (osteoclasts are linked like the other cell types are)
32
Q

What is cartilage? what does this mean in terms of repair? what is it made up of? and what are the different types?

A
  • It’s an avascular connective tissue
  • Hard for cartilage to repair itself because it doesn’t have a blood supply
  • Cells = chondrocytes
  • Matrix = water, collagens, proteoglycans
  • Types of cartilage = hyaline (most common), fibro (not at all elastic), elastic
  • articular cartilage (cartilage that covers bone surfaces) tends to be hyaline cartilage
33
Q

What is ossification? and what are the different types?

A

How bones grow.

Intramembranous – this is how flat bones grow
Endochondral – this is how long bones grow

34
Q

Describe the process of endochondral ossification.

A

Step 1
- Mesenchymal cells cluster together at the place where the future bone is going to be made – form template (these cells turn into cartilage)
- Cells differentiate into chondroblasts and then into chondrocytes, and hyaline cartilage starts to be lay down in the shape of the bone that you want to make
- Some cells in cartilage then differentiate into osteoblasts - bony collar formed by osteoblasts around diaphysis
(BMPs (bone morphogenic proteins) and growth factors initiate the development of the cartilage model)
Step 2
- Chondrocytes found in the diaphysis enlarge and become hypertrophic
- At the same time the matrix calcifies - due to enlarged chondrocytes secreting things like alkaline phosphatase
- Chondrocytes die because of lack of nutrients due to the calcification (in the bit that will be the cavity)
- Matrix breaks down, producing a cavity
(still have a cartilage model, and bone collar, but now also a cavity)
Step 3
- Artery enters the cavity, supplies the cavity with blood (brings with it mesenchymal cells)
- Mesenchymal cells introduced into cavity – differentiate into osteoprogenitor cells which differentiate into osteoblasts
- Osteoblasts lay down bone (in the cavity – the primary ossification centre)
- Primary ossification centre (because first place where bone is lay down) (bone is replacing the cavity)
Step 4
Primary ossification centre grows towards ends of bone (bone growing longer and wider all the time)
- Osteoclasts form medullary cavity
- Secondary ossification centres develop at birth, usually in proximal and distal epiphyses – almost have a complete bone with spongy and compact bone filled with lots of blood vessels
Step 5
- Almost complete – got the periosteum, spongy and compact bone
- All cartilage replaced except at epiphyseal plates in metaphysis
- Epiphyseal plate responsible for maintaining bone growth
- The plates will exist until well into puberty and then they become bone themselves

35
Q

What are the different zones in the bone from epiphysis to diaphysis? (on the epiphyseal plate)

A
  1. Reserve cartilage – couple of chondrocytes but not metabolically active – zone of resting cartilage
  2. Proliferation – chondrocytes are proliferating – producing lots of matrix – lining up in straight lines
  3. Hypertrophy (and maturation) – cells become really big and stop producing matrix in preparation for calcification
  4. Calcification – chondrocytes not doing anything – matrix around them in calcified and chondrocytes die
  5. Ossification – the calcified cartilage is replaced by bone - resorption – newly formed bone – lots of blood supply
36
Q

What is bone resorption?

A

Resorption of bone tissue, that is, the process by which osteoclasts break down the tissue in bones and release the minerals, resulting in a transfer of calcium from bone tissue to the blood

37
Q

What is bone remodelling and what are the benefits?

A
  • Continuous interplay between osteoblasts laying down matrix and osteoclasts resorbing it
  • Benefits:
    1. Bones thicken (in response to heavy loads) – more calcified
    2. Shape adjusts to stresses placed on bone
    3. Renews matrix
38
Q

What is the epiphyseal plate and what happens from adolescence to adulthood?

A

The epiphyseal plate is a hyaline cartilage plate in the metaphysis at each end of a long bone – it’s the part of a long bone where new bone growth takes place; this, the whole bone is alive, with maintenance remodelling throughout its existing bone tissue, but the growth plate is the place where the long bone grows longer. The plate is found in children and adolescents; in adults, who have stopped growing, the pate is replaced by an epiphyseal line – this replacement is known as epiphyseal closure

39
Q

What happens in each zone in the growth plate? and what is the importance of this plate?

A

Growth plate – reserve zone (contains progenitor cells which then feed cells into the proliferative zone), proliferative zone (contains chondroblast cells, which secrete matrix and undergo expansion and start to organise themselves into columns), maturation zone (cells from proliferative zone carry on secreting matrix, but they begin to mature into chondrocytes – they grow bigger and start moving into the hypertrophic zone), hypertrophic zone (here they differentiate into specialised hypertrophic chondrocytes and they begin to secrete type 10 collagen), invasion zone (eventually undergo apoptosis and they leave holes in the matrix known as lacuni, and they’re separated by septa of cartilaginous material, which become calcified and form the scaffold for laying down new bone – the osteoblasts come up from the bone marrow and they lay down the new bone over the scaffold that’s been produced by the chondrocytes)
–> This is how you get growth of long bones

40
Q

How are GH and IGF-I involved with the growth plate?

A
  • They stimulate the proliferation of the chondroblasts in the proliferative zone
  • They stimulate the maturation and differentiation of the chondrocytes in the maturation and hypertrophic zones
41
Q

What are other important hormones for the epiphyseal plate?

A

Thyroid hormones
- Important for chondrocyte hypertrophy
Sex steroids
- Important for preventing any further growth
- As oestrogen level rises it causes closure of the growth plate and therefore prevention of any more growth – thought that oestrogen stimulates progenitor cells in reserve zone to undergo apoptosis

42
Q

What factors affect bone growth?

A
  • Genetics (constitutional (inherent) and abnormalities)
  • Nutrition
  • Exercise – keeping bones strong and healthy
  • Hormones (growth hormone, thyroxine, glucocorticoids (class of corticosteroids)
43
Q

What is the biochemistry of bones? what are the hormones involved in maintaining calcium homeostasis?
What else is important for bone growth? (vitamins and hormones) and what do they do?

A
  • Parathyroid hormone – maintain calcium homeostasis – if calcium levels decrease, PTH is released (from parathyroid gland), and then osteoclast activity increases so calcium released
  • Calcitonin – maintain calcium homeostasis – if calcium levels increase, calcitonin released from thyroid, leading to decreased osteoclast activity
    (maintaining right calcium levels is vital)
  • Vitamins – A = increase osteoblast activity, C = collagen synthesis, D = increase calcium resorption from GIT promoting bone calcification
  • Growth hormone – stimulates cell growth
  • Thyroxine – increase osteoblast activity
  • Sex hormones – androgens increase osteoblast activity
44
Q

Describe the process of spermatogenesis.

A
  • At the base of the Sertoli cells, there are spermatogonial stem cells that colonise during fetal life, and they sit there until puberty when they start dividing
  • They divide asymmetrically at first, which gives rise to one cell that will stay at the base to maintain the population, but the other cell moves up and starts to divide – passes through stages of mitosis and then meiosis and after that at the top of the Sertoli cell, you start to see the features of the sperm cell that you would recognise
    Primordial germ cell -> (mitosis) x4 -> spermatogonia -> (growth) -> primary spermatocytes -> (meiosis I) -> secondary spermatocytes -> (meiosis II) -> spermatids -> (spermiogenesis - differentiating) -> spermatozoa
  • In the male (doesn’t happen in females), the two rounds of meiosis follow on mitotic divisions
  • Primordial germ cell is the one that colonises the testical region during fetal life
  • During puberty, the germ cell has 4 rounds of mitosis, producing 16 cells (diploid)
  • Each of those 16 cells are going to give rise to 4 spermatozoa as they undergoing 2 rounds of meiosis
  • Unlike in females when each ovarian follicle will produce one ovum and will lose a polar body
  • Cells remain diploid through meiosis I but become haploid during meiosis II
  • It’s only after the two rounds of meiosis that you start to see the morphological features of spermatozoa developing in the process called spermiogenesis (the final stage of spermatogenesis, which sees the maturation of spermatids into mature, motile spermatozoa)
  • The stem cells start at the basement membrane – the outer layer of the seminiferous tubule
  • They go through rounds of mitosis – first division is asymmetric!
  • The other daughter cell passes through rounds of mitosis and meiosis and then starts differentiating
  • The stage up to meiosis – the cells are linked together by junctions and they’re in a cohort
  • Sperm are released into the lumen of the tubule tail-first – tails stick out into the lumen
  • It takes around 64 days to progress from a spermatogonial stem cell to mature spermatozoan
45
Q

Describe the pathway from sperm being made to being ejaculated.

A
  • Sperm are made in the testis in the seminiferous tubules
  • They pass through the tubuli recti
  • They get concentrated through the ductus efferentes
  • And move through the rete testis
  • They move from the testis into the epididymis (and gain the ability to swim)
  • They proceed through the vas deferens
  • The pass by the three accessory glands where fluid is added to the concentrated spermatozoa
  • Then they move into the urethra, prior to ejaculation
46
Q

What happens to the hormones produced in the testes? and what do they do?

A

The hormones act WITHIN the testis to support spermatogenesis and are EXPORTED to other target sites such as male accessory glands (e.g. androgen made in the testis are important in the function of the epididymis and of the accessory glands)

47
Q

How does the sperm move until it gains the ability to swim in the epididymis?

A

All of the transport functions in the testis is a muscular activity than squeezes the spermatozoa along and into various compartments where they get concentrated – once they get into the epididymis, their tails start to move

48
Q

What are the different cells in the seminiferous tubules?

A
  • Sertoli cells – resident diploid somatic cells of the seminiferous tubules – found in the walls of the tubules – provides a nurturing environment for the spermatozoa
  • Myoid cells – muscle linage – thin layer of cells around the seminiferous tubules – allow the tubules to squeeze when spermatozoa reach the lumen
  • Leydig cells – bit between the seminiferous tubules – the site where hormones are made
49
Q

What is the epithelium of seminiferous tubules surrounded by?

A

Myoid cells

50
Q

What do the spaces between the tubules contain?

A

Connective tissue, blood and lymphatic vessels and interstitial cells (Leydig cells)

51
Q

What are Leydig cells? and what do they contain?

A

Leydig cells – large cells – large collection of vesicles – characteristic of steroid production as the vesicles store materials needed for steroid production

52
Q

Where are steroids produced and where do they move to?

A

Steroids move from the Leydig cells into the Sertoli cells, but they can also go out through the blood vessels

53
Q

Describe steroid synthesis in the testis. (how does it involve cell cooperation?)

A
  • In Leydig cell, cholesterol is converted into testosterone
  • In the Sertoli cell (nurse cell), dihydrotestosterone (DHT) is produced from the testosterone
  • DHT is a more potent androgen than testosterone and has the effect of activating the swimming action of the sperm in the epididymis
  • The two cells are cooperating, and this is driven by LH and FSH
  • FSH acts on receptors on the surface of the Sertoli cell (FSH = S) – drives conversion
  • LH acts on receptors on the surface of the Leydig cell (LH = L) – drives whole cycle of steroid production
  • Not all of testosterone is transported to the Sertoli cell – some of it is exported to blood and lymph – and has actions in the testis
54
Q

Describe the overall sex steroid synthesis pathways.

A
  • Acetate gives rise to cholesterol
  • Cholesterol is the biosynthetic precursor for all of the steroids (includes ones active in both male and female)
  • Cholesterol converted through pregnenolone to progesterone (is important in males)
  • Progesterone can be used to produce androstenedione but the following pathway is more important
  • Pregnenolone -> x -> DHEA -> androstenedione
  • Androstenedione and testosterone can both be converted to different oestrogens by aromatase enzyme – estrone and 17B-estradiol respectively
  • Testosterone -> DHT (only step that is specific to Sertoli cells – everything else in Leydig cells)
  • Leydig cells import cholesterol (so acetate to cholesterol doesn’t take place in them)
55
Q

What do all of the resident cells in the testes have receptors for? and what is dependent on these hormones?

A

All of the resident cells in the testes have receptors for androgens, primarily testosterone and DHT – spermatogenesis and swimming action of sperm dependent on them

56
Q

Explain how sperm become mobile and what makes them mobile.

A
  • The sperm tail (flagellum) contains microtubules (where the ATP is released) and dynein (an ATPase)
  • Hydrolysis of ATP generated in the adjacent mitochondria provides energy for motility
  • However, sperm are not motile in the seminiferous tubules of the testis
  • They mature and become motile in the epididymis as a result of the action of dihydrotestosterone (DHT) – released into lumen of epididymis and attaches to receptors, which produce substances which activate maturation of the sperm (don’t know what substances)
  • Further maturation occurs in the female tract (capacitation)
57
Q

What are the figures for sperm production? How many spermatozoa does each spermatogonia produce? How long does it take for them to be produced?

A
  • Each spermatogonium that differentiates gives rise to 16 primary spermatocytes
  • Each primary spermatocyte gives rise to 4 spermatids and finally 4 spermatozoa
  • So each of the 3x10^6 spermatogonia that begin the process each day gives rise to 64 spermatozoa
  • Of those, about half die, leaving about 1x10^8 (100 million) per day
  • Sperm formation takes around 70 days followed by around 14 days to reach the ejaculatory ducts
58
Q

What are the hormonal factors that stimulate spermatogenesis?

A

Testosterone
- Secreted by the Leydig cells located in interstitium of the testis, is essential for growth and division of the testicular germinal cells, which is the first stage in forming sperm
LH
- Secreted by the anterior pituitary gland, stimulates the Leydig cells to secrete testosterone
FSH
- Also secreted by the anterior pituitary gland, stimulates the Sertoli cells; without this stimulation, the conversion of the spermatids to sperm will not occur
Oestrogens
- Formed from testosterone by the Sertoli cells when they are stimulated by FSH, are probably also essential for spermiogenesis
GH (as well as most of the other body hormones)
- Necessary for controlling background metabolic functions of the testes
- GH specifically promotes early division of the spermatogonia themselves; in its absence as in pituitary dwarfs, spermatogenesis is severely deficient or absent, thus causing infertility

59
Q

What is used to measure growth in boys and girls? what are the first signs of puberty in terms of the measurements? and how do you know if puberty is delayed?

A 
TANNER STAGING – girls and boys 
1 = pre-pubertal, 5 = fully-developed 
-	Breasts change = girls 
-	Testicular change = boys 
1st sign of puberty:
-	B2 in girls 
-	Testicular volume 4 ml in boys – orchidometer = check volume of testes (1-25)
  • Puberty is delayed if testicular volume < 4 ml at age 14 yrs
  • Puberty is also delayed if no pubertal progress
60
Q

What are the pubertal changes in males? and what causes them?

A
  • Testosterone: secretion causes the penis, scrotum, and testes to enlarge
  • Testosterone causes the secondary sexual characteristics of the male to develop:
    1. Effect on hair: T stimulates the development of terminal hairs on the face, chest, axillae and the genitals
    2. Effect on the voice: T causes hypertrophy of the laryngeal mucosa and enlargement of the larynx – the effects cause the voice to ‘break’
    3. Increases thickness of the skin and can contribute to development of acne
    4. Protein formation and muscle development
    5. Increases bone matrix and causes calcium retention: after the great increase in circulating T that occurs at puberty, the bones grow considerably thicker and deposit considerably more calcium salts
    In males, testosterone stimulates the functional development of the accessory reproductive glands, such as the prostate gland and seminal vesicles, and helps promote spermatogenesis
61
Q

What are the pubertal changes in females? and what causes them?

A
  • Oestrogen stimulates the production of fine hairs on the face, chest, axillae and the genital region
  • Oestrogens cause development of breast tissue
  • Progesterone and prolactin cause the ultimate determinative growth and function of the breasts
  • Oestrogen accelerates bone deposition and skeletal growth and also rapidly promotes the closure f epiphyseal cartilage
  • Oestrogen promotes bone growth much faster than testosterone, therefore by the process of appositional growth the epiphyseal cartilage closes much faster – thus boys generally grow taller
62
Q

How do GH and IGF-I act? and what happens to cause the response?

A
  • They act at cell surface receptors
  • Protein hormones – hydrophilic – can’t cross cell-membrane
  • Hydrophilic signal molecule

Intracellular signalling: (once a hormone has binded to receptor it stimulates intracellular signalling)

  • Can be very fast or slow
  • E.g. taking up nutrients = fast, but slow if a signalling cascade leads to the production of a new protein (mins to hrs)

Enzyme-coupled receptors:
- On inside of cell, the receptor is coupled to an enzyme
GH
- GH receptor recruits enzyme when GH binds to it
IGF-I
- Enzyme is built in to receptor and enzyme activates when IGF-I binds
- Activation of enzyme leads to next stage in signalling cascade

GH and IGF-I activate kinase cascades/signalling cascades:

  • The kinase enzyme phosphorylates tyrosine residues on the next enzyme in the chain and therefore activating that enzyme/protein
  • Phosphatases can remove phosphates and switch off the signal from the hormone
63
Q

Describe what specifically happens with the GH receptor.

A
  • GH receptor is a homodimer
  • GH bind to receptor via a two-step mechanism
    1. First binds to a high affinity site on one receptor
    2. Then to a lower affinity site on the second hormone receptor – forming a dimer
  • GH binding induces conformational change in the receptor
  • The receptor is activated when shape changed
  • That is when it recruits its enzyme – JAK2 (type of kinase)
  • JAK2 then phosphorylates the GH receptor
  • This means there’s binding sites available for a transcription factor (known as stat5)
  • Transcription factor is phosphorylated and then moves into nucleus and binds to DNA that has the appropriate recognition sequence and causes a change in the transcription of DNA
64
Q

Describe the insulin-like growth factor (IGF-I) axis.

A
  • The enzyme is built into receptor so when IGF-I binds to receptor, the intracellular domain becomes phosphorylated on tyrosine residue
    Two cascades:
    1. PI-3 kinase pathways – signalling cascade using phosphorylation – this pathway stimulates cell survival and metabolism
    2. MAP kinase pathway – signalling cascade using phosphorylation – this pathway important for the proliferative response
65
Q

What are IGF binding proteins? what do they do? and which is the most important one?

A
  • IGFBP
  • 6 have been discovered
  • Bind to IGF with very high affinity
  • Thought to be important with transporting IGF around in the circulation and therefore prolong IGF half-life as they stop it being degraded
  • They’re thought to also modify IGF action – because they have such high affinity for IGF, they prevent IGF from binding to the receptor and so in order to get IGF to bind to the receptor you need to get rid of the binding protein, so there are proteases at the cell surface which cleans the binding protein into fragments so it can no longer hold onto the IGF and the IGF can bind to receptor (??why modify)
    IGFBP-3 = most important binding protein – that’s the one that holds most the IGF in the circulation – acts as a storage mechanism by storing it in the circulation
66
Q

How do sex steroids and thyroid hormones work? what is their mechanism?

A
  • Able to cross cell-membrane to receptors are inside cell
  • Hormones diffuse across cell-membrane
  • Bind to receptor which is in the cytoplasm
  • Normally the receptor is kept in check by an inhibitory molecule, but when the receptor binds, the inhibitory molecule/protein moves away
  • The hormone and receptor as a complex move into the nucleus where they bind to elements of DNA and affect the transcription of that DNA (sex steroids and thyroid hormones are part of the nuclear hormone receptor family) – they can activate and repress transcription
67
Q

What is the basic structure of all intracellular receptors?

A
  • Always a ligand-binding domain / hormone-binding domain
  • Always a DNA-binding domain – binds to regulatory elements of the DNA
  • Always a transcription-activating domain – allows to activate or repress genes
68
Q

Growth is an increase in body size that results from an increase in what?

A

Growth is an increase in body size that results from an increase in the:

  1. Size of existing cells (hypertrophy)
  2. Number of cells (hyperplasia)
    - In addition, a tissue can sometimes grow in size because the material between cells increases
    - As well as growth of soft-tissues there is growth of the bones – lengthening and thickening
    - GH plays a role in cell growth (hypertrophy) and cell proliferation (hyperplasia) as well as many other things
69
Q

What is the difference between hyperplasia and hypertrophy?

A
  • Hypertrophy occurs in permanent cells while hyperplasia occurs in labile or stable cells. Hypertrophy is due to increased demand while mostly hyperplasia is due to excessive cell stimulation.
  • Both hypertrophy and hyperplasia can occur together as a result of increased demand.
  • Hypertrophy features enlargement of stromal and cellular components by increasing their size without multiplying while hyperplasia increases tissue size by cell division.
70
Q

How is adolescence characterised psycho-socially?

A

Teenagers will be experiencing an identity crisis (as you may well remember from your own high school experience). They will be unsure of themselves, unsure of their future and unsure of how they want to proceed. This is also a time when teenagers are seeking independence and autonomy. They will want to make their own decisions and use their own morality scale. Friendships and intimacy are important to adolescents and this will be a major priority. Peers have a great influence on behaviors and attitudes, particularly in early adolescence (Stang 6). Lastly, they will be concerned about what the future holds and will need guidance.

Erikson’s Theory of Development:
13-21 years = identity vs. role confusion (psycho-social crisis)

Medicine Sem 1 (8 decks)

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