Year 1: Endocrinology Flashcards
1
Q
endocrine gland
A
group of cells which secrete messenger molecules directly into blood
2
Q
neurotransmitters
A
chemical signal which transmits informtation over a chemical synapse (from neuron to other target cell)
3
Q
List the three classification groups of hormones
A
Polypeptide/ Protein Hormones
Steroid Hormones
Miscellaneous Hormones (don´t fit into either category)
4
Q
Synthesis of Protein Hormones
A
Via Gene expression:
- pro hormone mRNA
- translation of rough ER
- transfered to Golgi for Processing
–> Packed into vesicles with enzyme to cleave pro-hormone (activation)
5
Q
Synthesis of Steroid Hormones
A
- all derive from cholesterol (stored in vesicles in cell)
- released by Esterase
- transport into Mitochondria (StAR - protein) (often rate-limiting step)
processing by enzymes in mitochondria
6
Q
Storage of Protein Hormones
A
Stored in Vesicles in Cells until secretion
7
Q
Storage of Steroid Hormones
A
- Stored in Blood
–> Bind to Plasma protein (e.g. Albumin (binds all steroid hormones) or specific plasma protein + some free hormones:
forms equilibrium: free hormones + free plasma protein = plasma bound protein
8
Q
Receptors /direct effect of protein Hormones
A
G-protein coupled receptors
- bind to receptors and all modify cell signaling
(e. g. cAMP production, drives cholesterol production)
9
Q
Receptos / direct effect of steroid hormones on cell
A
diffuse into cell (no membrane-boudn receptors required)
–> bind to intracellular target (receptor)
–> travel into nucleus with complex and regulate transcription
10
Q
Positive feedback
A
A increases which causes B to increase which causes A to increase ( exponential growth, rather unstable)
11
Q
Negative feedback
A
Negative feedback: secretion and production of hormone is controlled by released product (high concentration of product = low production /secretion of hormone)
–> controll of hormones (gives stability)
12
Q
Location of hypophysis
A
beneath hypothalamus
in sella turcica
13
Q
Hypothalmic nucleus
A
collection of neural cell bodies in hypothalamus
14
Q
List Five (Six) Hormones produced by Adenohypophysis
A
Somatotrophin
Prolactin
Thyroid stimmulating Hormone (TSH, THyrotrophin)
Luteinsing Hormone (LH), Follicle Stimmulating Hormone (FSH)
Adenocorticotrophic Hormone (ACTH, Corticotrophin)
15
Q
Somatrophin (cells, Hopothalamic Hormones, Effect)
A
Cells: Somotrophs
Hypothalamic Hormones: up: Growth Hormone / Somatrophin releasing Hormone (GHRH); down: Somatostatin
Effect:
growth: direct (on cells) indirect (on liver –> IGF 1)
– increased metabolism (protein synthesis, gluconeogenesis, fatty acid production, cartilage + somatic cell growth)
16
Q
Prolactin (cells, Hypothalamic Hormones, Effect)
A
Cells: Lactotrophs
Hypothalamic Hormones: down (constant) Dopamine
up: Thyrotropin-releasing hormone (TRH)
Effect:
Mild production (suppression of Dopamine)
17
Q
Control of Somatotrophin
A
Stimmuli on Hypothalamus: Sleep, oestrogen, stress, fasting, Gherline (from stomach))
Negative feedback:
IGF on Hypothalamus and Adenohyoophysis
Somatotrophin (GH) on Hypothalamus
18
Q
Control of Prolactine
A
Stimmulus: Suckling on Breast + TRH
Suppression of Dopamineproduction by Hypothalamus
–> Milk secretion
19
Q
Thyroid Stimmulating Hormone (cells, hypothalamic hormones, effect)
A
Cells: Thyrotrophs
Hormones: up: TRH (Thyrotrpin Releasing Hormone)
Effect:
On Thyroid
20
Q
LH and FSH (cells, hypothalamic hormones, effect)
A
Cells: Gonadotrophs
Hormones: Gonadotrophin releasing hormone (GnRH)
Effect:
Ovaries and Testicles
21
Q
Adenocorticotrphic hormone (ACTH) (cells, hypothalamic hormones, effect)
A
Cells: Corticotrophs
Hormones: UP: Cocticotrophin releasing hormone, Vasopressin
Effect:
Adrenal cortex
22
Q
Median eminence
A
Area which connects adenohypohysis with neurones,
Many blood vessels
23
Q
Magnocellular neurones
A
terminate in neurohypohysis
(cell bodies both in paraventricular and supraoptic nuclei found)
24
Q
Parvocellular neurones
A
terminate in either median eminence or other part of brain
(cell bodies only found in paraventricular nuclei)
25
Supraoptic neurons
Go from Supraoptic nuclei to Neurohypophysis (Magnocellular neurons)
Store Hormones in Herring bodies
Either produce Vasopressin or Oxytocin
26
Paraventricular neurons
derive from **paraventricular neucleus** to neurohypohysis (**Magnocellula**r neurones, majority) or other parts + median eminence (parvocellular neurones)
Produce either **vasopressin** or **oxytocin**
27
Structural difference vasopressin, oxytocin
2AA differ
28
Synthesis of Vasopressin and Oxytocin
Pre-Prohormone (with Signaling peptide)
--\> Prohormone (cleavage for activation:
Vasopressin+Neurophysin+Glycopeptide
Oxytocin + Neurophysin (slightly different)
29
Compare differnet receptors for vasopressin
* V1: in atherial smooth muscle + adenohypophysis (ACTH production)
* linked to G-protein + phospholypase C (up: Ca2+, IP3, DAG in cell) --\> Vasoconstriction
1. V2: water reabsorbtion in duct cells (antidiuretic effect)
2. linked to G-Protein and cAMP production --\> induces travel of **Aquapoins (AQP2)** to lumen of kidney
30
Feddback control for Vasopressin
Stimmuli: Plasma osmolarity up (reabsorbtio of water required)
BP down ( vasoconstriction required, a bit less relevant)
31
Polydipsia
inceased thirst
32
Polyuria
increased volume of urine
33
Disregulatin of Vasopressin
Diabetis insipidus:
No reuptake /little reabsorbtion of water
--\> polydipsia + polyuria
Central/cranial = no VP produced
Nephrogenic = resistance to VP
34
Summarise the effects of Oxytocin on several organ systems
**On Uterus**
* contraction of myometrial cells in uterus --\> delivery of baby (+ encanced productio of prostoglandins which make cervix softer + dilate)
**On Mammary glands:**
* Contracti on of myoepithelial cells --\> Milk ejection (no milk production)
**CNS:** Tend and Befriend
**Other effects:** temporary vasodilaition, vasoconstriction of umbilicus, on kideny: Vasopressin -like effects
35
Regulatio of Oxytocin
36
Dysregulation of Oxytocin
No / too little milk ejection
induction of labout might be required
37
Which factors (Hormones) regulate Blood glucose level? (Feedback Loop)
It is controlled via blood glucose levels:
Down: Insulin
Up: Glucagon, Cortisol, Somatotrophin, Catecholamines
38
How gets glucose into cells?(and effect of insulin on it)
Via GLUT-4, Insulin enhanced Glucose transporter (7times higher with Insulin)
39
Islets of Langerhans
2% of pancreatic tissue
a,ß, delta cells
paracrine regulation
gap junctions allow small molecules to pass, tight junctions allow small intercellular spaces to form
40
a- pancreatic cells
secrete Glucagon
41
pancreatic ß cells
secrete insulin
42
pancreatic delta cells
secrete somatostatin
43
Synthesis of Insulin
Synthesis of pre-pro insulin
--\> cleaved: proInsulin + C-peptide (secreted 1:1 into blood)
posttranslational modification:
Insulin (two chains, connected through disulfide bonds)
44
When is insulin secreted?
What effects does insulin have?
45
When is Glucagon Secreted?
What are the effects?
+ Proteolysis
+ ketone body production
46
What is the Incretine effect? How is is achived?
More insulin is secreted after a meal compared to IV glucose
--\> Glucagon-Like-Peptide (GLP1)
--\> promotes insulin, supresses glucagon
47
DM type 1: patophysiology and clinical features
Diabetes Type 1:
Insulin deficiency because of autoimmune reaction to ß-cells
- proteolysis and weight loss
- Hyperglycaemia
- Polydipsia, Polyuria
- Ketouria
48
DM type 2: patophysiology and clinical features
Insuline resistance:
--\> no problem with receptors! --\> insulin as growth hormone still works, but no metabolic activity
60-80% OBESE.
\* Dyslipidaemia (abnormal fat content in blood)
\* Later insulin deficiency (exhaustion of beta cells).
\* Hyperglycaemia.
\* Fewer osmotic symptoms.
\* T2DM presents with complications whereas T1DM hardly ever presents with complications.
--\> resides in liver, muscle and adipose tissue
49
Explain relationship between dyslipidemia, hypertension and insulin resistance
dyslipidemia: hypertension in LDL which is associated with Ischaemic heart disease and atherosclerosis --\> hypertension
No insulin= no uptake of triglycerides into cell but only release --\> free fatty acids (mainly LDL)
50
Metabolic effects of insulin resistance
increase in NEFA (non-essential fatty acids), tryglycerides, LDL cholesterol
- decrease in: HDL, lipoprotein lipase activity, VLDL clearance
--\> enough insulin present to suppress proteolysis and ketone production --\> no ketones in urine and no weight loss
51
Explaint the Anatomy of thyroid gland and a thyroid follicle
52
Basal metabolic rate
Grundumsatz
53
Explain the Synthesis of thyroid hormones
54
Explain Mechanism of action of thyroid hormones
T4 gets into T3
--\> stimulation of Protein synthesis via binding toTHR (Thyroid hormone receptor) in nucleus
+ less important: T3 non-nuclear actions on ion-channels
+ metabolic stimulation of cell
55
Actions/Effect of Thyroid hormones
fetal growth and development
- increases basal metabolic rate --\> carbohydrate, fat and protein metabolism
- potential increase of catecholamines --\> adrenaline, dopamine etc. --\> increases heart rate, lipolysis etc.
- also effects on GI, CNS and reproductive symptoms
56
Control of TH production
57
Wolff-Chaikoff- Effect
Iodine inhibits release of Thyroid horomones (for about 17 days)
58
Where does the thyroid gland originates from?
back of tounge (thyro glossal dot) (average ca. 20g)
59
What is the foramen caecum of the tounge?
Little dot at apex of tounge due to thyroid development (disappearing thyroid duct)
60
Anatomy of the thyroid
Weight: 20g
61
Three possible problems with thyroid
Agenisis (no formation)
Incomplete descent (e.g. Lingual thyroid)
Thyroglossal cyst
62
Effects of Agenesis of thyroid (or total lack of thyroxin)
Cretin:
- irreversible brain damage bc of lack of thyroxin
Treatment/ prevention: Life-long replacement
63
Simple thyroxin sinthesis diagram
64
Compare thyroglobulin and thyroxin binding globulin
Thyroglobulin: protein in colloid of follicular cell , storage of thyroxin
Thyroxin binding globulin TBG: protein in blood that binds to Thyroxine in blood ( 75% bind, 1% free)
65
Pimary hypothyroism (cause, effects, symptoms)
-Primary thyroid failure (myxoedema)
damage = autoimmune
Up: TSH, down: T3+T4
_Symptoms_
* fatigue,
* cold intolerance
* depression
* weight gain
* less appetite
* bradycardia
* costipation (verstopfung) --\> a lot because of decrease of basal metabolic rate + no help in catecholamides
--\> eventually
myxoedemal coma
66
Hyperthyroidism symptoms + reason
Autoimmune --\> antibodies stimmulate TSH receptors on thyroid
- inceased basal metablic rate:
* raised temperature,
* increased appetide,
* weight loss,
* tachycardia,
* myopathy,
* mood swings,
* tiredness,
* diarrhea,
* tremor of hands
67
Graves Disease
Autoimmune disease
Symptomps of hyperthyroidism
+ Sore + swollen eyes --\> 2nd antibodies on eye
non-pitiing ptetibial myxoedema --\> growth of soft tissue in ankle region (3rd. antibodies)
68
Anatomy of Adrenals
Medulla =produces catecholamines (e.g.adrenaline)
Cortex --\> produces cortecosteroids (e.g. aldosterone, cortisol\* sex steroids)
69
Which Zones in Adrenals produce which hormones?
Binding of the two hormones in blood
Glucocorticoid + mineralcorticoid
+ Medulla = catecholamides
Glucocorticoid: colesterole (only 10 % free)
Mineralcorticoid: Aldosterone (45% free)
70
To which receptors do Aldosterone and Cortisol bind?
Aldosterone: Bind to Mineralcorticoid receptors
Cortisol Bind to Glucocorticoid receptors + **Mineralcorticoid receptors**
--\> some tissues are prodected from cortisol by 11bhsd2 so aldosterone has a task to do (Kidney + Placenta)
71
When is aldosterone secreted?
Angiotensinogin ---Renin---\> Angiotensin 1
(Renin : low BP, low Na2+, sympathetic renal activity)
Angiotensin 1 ---ACE---\> Angiotensin 2
**Angiotensin 2** --\> stimulates Aldosterone secretion (can be also stimulated by low Na+ and high K+ but to a lesser extent)
72
Effects of Aldosterone + Mechanism of action
Effect on Kidney (collecting duct)
-\> reabsorbtion of Na2+ (Transcrtiption of proteins: sodium chanel formation + Na2+/K+ ATPase active pump of Na2+ into blood --\> loss of potassium)
73
Feedback control of cortisol
74
Mechanism of Action of Cortisol + effects
highly binds to MR, Partly binds to GR
**Metabolic actions**: central glucose availability and storage
up: gluconeogenesis, glycogenesis
down: peripheral glucose storages, uptake of fatty acids in skeletal muscleand fat tissue, reduction of blood flow in these tissues)
**Memory:** pro memory (up: serotonin receptors) (down for supraphysological effects)
**Immune:** Anti-inflammatory and immunosupressive
75
Addisons disease (cause, clinical features, management)
Primary adrenal failure --\> lack of cortisol
**Causes**
1. autoimmune desease damages adrenal cortex
2. TB of adrenal gonads
**Features**
* Tanning (A lot of ACTH released --\> hypothalamus wants to make more Cortisol --\> POMC is cleaved into ACTH and MSH (Melanocyte stimulating hormone)
* Salt loss (low sodium, high potassium levels)
* Hypotonic
* weight loss, decreased appetite
* fatigue
**Management**
* IV saline for rehydration and sodium intake
* IV glucose
* oral steroid hormone replacements
76
Cushing`s syndrome (causes + features)
High cholesterol levels
**Causes**
* Oral replacement /intake of steroid hormones
* Pituitary adenoma(Cushing`s disease)
* Adrenal adenoma/carcinoma
* Ectopic ACTH (lung cancer)
**Clinical features**
* diabetes (long times of high blood glucose levels)
* weight gain (redistribution: central weight, thin legs and arms, excessive nuchal fat, moon face)
* Skin (acne, facial hair, thin, easy bruise, striae (stretch marks))
* proximal myopathy --\> reduction of protein and muscle + osteoporosis
* depression
* hypertension
* immunosupression (poor wound healing, reactivation of TB)
77
Conn's syndrome
Cause:Aldosterone Adenoma
Features:
Hypertension
Oedema
high Na+, Low K+
78
Primary + secondary amenorrhoea
Primary amenorrhoea:
never had period
Secondary amenorrhoea:
have had normal periods, but don't have it anymore
79
Oogenesis
gametogenesis in females
oogonia "freezed" untill puberty
80
Spermatogenesis
begins at puberty
81
Hypothalamo-Pituitary-Testicle Axis
FSH: gametogenesis
LH: hormone production
82
Describe the main Main structures in testis from spermatogenesis to urethra
**1. Coiles seminiferous tubules** (spermatogenesis)
* -\> formes tubules --\> Seitoli cells (Spermatogenesis; FSH sensitive)
2. Rete testis and Vasa efferentia --\> connect coiles siminiferous and vas dererens
3. Epididymis (storage of sperms)
4. Vas deferens (to urethra)
Next to it: Leydig cells --\> produce and secrete hormones, LH sensitive
83
Andrgoens physical actions (fetus + adults)
Main active component: Dihydroxitestosterone (reduction)
Fetus: development of genital organs in men, growth of fetus
Adults: spermatogenesis, anabolism of bone + muscle, development of prim, 2nd. sex characteristics, growth in puberty, sexual behavioral (conversion into oestrogen in brain)
84
Oestrogens definition + physical actions
Definition:Everything that induces proliferation of endometrium Mainly: 17ß-oestradiol
- triggers LH---\> ovulation, breast growth, skin, vaginal secretion, behavioral, osteoblast stimmulation, metabolic actions
85
Definiton and physical actions Progestrogens
Anything that changes secretory activity of endometrium
Mainly: Progesterone
stimmulates secretion of endometrium and cervix
increases basal body temperature, growth of alveolar in breasts etc.
86
What are the Main Structure in Ovaries?
87
Hypothalao-ovarian axis
**Changes within menstrual cycle (feedback) + production**
88
Definiton and reason for infertitliy
Definiton: no pregnancy after 12 month of unprotected sex
pituitary failure, prolactinoma (prolactin inhibits LH/FSH), Testicular failure, ovarian failure, polycystic ovarian syndrome
89
Main phases and hormone levels in menstrual cycle (better overview in notes)
1. Early follicular phase (follicles in ovaries develop FSH) follicles slowly produce E2
2. Early-mid-follicular phase (one follicle gets bigger than others, production of oestrogen, + feedback loop oestrogen, granulosa cells)
3. Mid-follicular phase (low FSH kills smaller follicles, development of Graafian follicle produces E2)
4. Late-follicular phase: extremelx high E2, +feedback on LH FSH, high levels of E2 stimmulate ovulation
5. Luteral phase (corupus luteum (rest of follicle) produces high amounts of progesterone) preperation for implantation
--\> no fertilization:stron neg. feedback --\> low levels --\> menstruation
90
Physiological functions of calcium
* Neuromuscular excitability
* Muscle contraction
* Strength in bones
* Intracellular second messenger
* Intracellular co-enzyme
* Hormone/neurotransmitter stimulus-secretion coupling
* Blood coagulation (factor IV)
91
What are the action of PTH
Parathyroid horomne (synthesized there)
--\> up calcium
92
PTH regulation Feedback
93
DIHYDROXY-CHOLECALCIFEROL actions
gegenspieler gegen knochenabbau und PO43- ausscheidung
--\> preserves bone
94
Action and regulation of Calcitonin
Synthesized in parafollicular cells of thyroid
95
Phosphate control
More reabsorbtion:
1,25 (OH)2 D3 in kidney and small intestine
Release by PTH when breaking down bones --\> thats why excreted by PTH
Excretion:
Directly PTH + Calcitonin
Fibroblst Growth Factor 23 (FGF 23) --\> Kidney excretion (high levels of phosphate and VitD3) --\> protection from too much phosphate
96
Sings and causes for hypocalcaemia
Signs :easy exitable cells : Hand and cheek contraction
1. Hypoparathyroidism (ideopathic, low magnesium)
2. Pseudo-hypoparathyroidism (resistance to PTH)
3. Vit D deficiency (sign: bone matrix too thin (bowing, fractures)
97
Hypercalcaemia (reasons, differentiation between primary, secondary and tertiary hyperparathyroidism)
Resons:
1. Primary hyperparathyroidism --\> adenoma (no negative feedback)
(2. Secondary hyperparathyroidism (no hypercalcaemia)--\>chronic low Ca2+--\> kidney disease (no reabsorbtion possbile, no synthesis of 1,25 (OH)2 D3))
3. Tertiary Hyperparathyroidism ---\> reason for secondary is cured --\> but parathyroids went autonomous, dont respod to feedback anymore
4. Too much Vitamin D3
98
What is the effect of Somatotrophin on the body?
99
How does the V1a receptor of Vasopressin woirk? (intracellular mechanism)
phospholipase C
1. PIP2 into inositol triphosphate IP3(and diacyl glycerol, DAG)
2. which increase cytoplasmic [Ca2+] and other intracellular mediators (PKC)
3. which produce a cellular response
100
How does the V2 receptor of vasopressin work? (cellular mechanism)
linked via G proteins to **adenylcyclase**
which acts on ATP to form **cyclic AMP**
which activates **protein kinase A**
which in turn activates other intracellular mediators
which produce cellular response **(aquaporins, AQP2)**
101
What may be the clinical use of oxytocin?
**Induction of Labour at term**
* controlled i.v.infusion
**Prevention+ treatment of post-partum** **hemorrhage**
* Slow i.v.injection/infusion
* Local pressor action in uterus suppresses bleeding
**•FACILITATION OF MILK LET-DOWN**
* Intranasal spray
**•AUTISM – SOCIAL RESPONSIVENESS??**
* Intranasal spray
102
What is Acromegaly?
What are its symptoms?
It is an excess of growth hormones --\> overproduction of Somatrophin
* organs enlarge
* body continues to grow
103
What is a normal glucose level? (mMol)
4-5mmol
104
What are the effects of insulin secretion
Decreases **Blood glucose**
* Increased glycogenesis
* Increased glycolysis
* increased uptake of glucose via GLUT-4 transporters
Increased **Protein synthesis** and Amino-acid transport
Increased **lipogenesis****,** decreased lipolysis
105
When is insulin secreted?
Mainly: low blood golucose
But also
* certain AA
* Glucagon
* GI hormones
* PNS
106
Which effect does somatostatin have on insulin and glucagon secretion?
It inhibits both, insulin and glucagon secretion
107
What are the effects of Glucagon secretion?
Increased blood glucose
Increased heptic glcogenolysis
Increased gluconeogenesis
* AA transport into liver
* Lypolysis
108
Which effect does Glucokinase have on insulin secretion?
How?
Glucokinase (Hexokinase IV) transforms Glucose into Glucose-6-phosphate --\>
sets off intercellular pathways that trigger insulin release
1. ATP generation
2. Blockage of ATP-sensitive K+ channel
3. allows Ca2+ influx
4. Triggers insulin secretion
109
Which molecule is also referred to the Insulin Glucose sensing molecule?
Glucokinase
110
Through which receptor does glucose enter a pancreatic ß-cell?
Through the **GLUT-2**
111
Compare insulin storage in healthy individuals and individuals with DMT2
In healthy individuals: Stored insulin is present
In DMT2 --\> they don't have stored insulin resulting in steeper increase in blood glucose
112
What is thyroxine?
T4 (thyroid hormone)
113
How are thyroid hormones transported in the blood?
1. 70-80% thyroid-binding globulin
2. albumin (10-15%)
3. prealbumin
•Only 0.05% T4 and 0.5% T3 unbound (bioactive components)
114
What is the main hormone product of the thyroid?
T4 is mainly produced (though T3 is the bioactive form)
115
Which nerve runs close to the thymus? What does it supply?
the left recurrent laryngeal nerve is close (supplie the vocal cords)
116
what is the function of the colloid of the thyroid?
It stores thyroglobulin and Thyroxine (also iodinisation + formation of T3/T4 happens here)
117
What is myxoedema?
It is primary hypothyroidism
118
How would blood levels for Thyroxine and TSH be in primary hypothyroidism?
It would be a low Thyroxine (can't be produced) and high TSH (doesn't receive negative feedback)
119
How are the effects of untreated hypothyroidism and how is it treated
Patients will die untreated--\> high cholesterol leading to stokes and heart attacks
Treatment: Just replacement of T3/4 (monitor until TSH is normal)
120
Which factor in the adrenals determines, which hormone is produced (e.g. aldosterone and not cortisol)
It is the different content/concentration of the enzymes in different zones (e.g. aldosterone/cortisol only 2 enzymes differ)
low level for reproductive hormone enzymes
121
How is aldosterone transported in the blood?
* 40% free
* 15% bound to CBG =corticosteroid binding globulin
* 45% Albumin
--\> A lot is free
122
How is Cortisol transported in Blood?
Only 10% free
80% bound to CBG (Corticosteriod binding globulin)
10% Albumin
123
Why do we have aldosterone, if cortisol can bind to both (MR and GR) receptors?
Some tissues are "protected" from cortisol (e.g. placenta, kidney)
## Footnote
**11b-hydroxysteroid dehydrogenase 2** breaks down Cortisol into **Cortisone** (inactive)
124
Why get people with primary adrenal failure get tanned?
Becaue of an increased production of ACTH
--\> ACTH is a cleaving product of POMC, other product is MSH
MSH (melanocyte stimmulating hormone)
125
Explain symptoms of primary adrenal failure (Addison's disease)
no cortisol or aldosterone, so low blood pressure
* Cortisol deficiency
* Salt loss --\> no Aldosterone
* Low blood pressure --\> No aldosterone
* Eventual death
126
How do you treat Addison's disease?
Urgent treatment
* Rehydrate with normal saline
* •Give dextrose to prevent hypoglycaemiawhich could be due to the glucocorticoid deficiency
* •give hydrocortisone or another glucocorticoid
--\> Replacement of hormones
127
What is the difference between Cushing's syndrome and Cushing's disease?
Syndrome= can be any cause of too much cortisol
Disease= Pituitary dependant (e.g. pituitary adenoma)
128
Name four reasons for Cushing's syndrome
* Taking steroids by mouth (common)
* pituitary-dependent Cushing’s disease (pituitary adenoma)
* Ectopic ACTH (lung cancer)
* adrenal adenoma or carcinoma
129
How would a patient with Cushing's syndrome present?
**Hypercortisolism**
Lemon on stick appearance
* central weight gain
* stretch marks
* proximal myopathy
* moon face
* Diabetes --\> long exposure to high glucose
* thin skin, extra hair growth
* hypertension
immunosuppression --\> e.g. reactivation of TB?
130
What are the side effects of (non-medical) use of steroids?
* Hypertension
* Diabetes
* Osteoporosis
* reactivation of infection (immunosuppression)
* easy bruising
* poor wound healing, thin skin
131
How is the disease with an aldosterone-producing adenoma is called? What are its effects?
It is the Conn's disease
* hypertension
* oedema
* high Na+, low K+
132
Explain the structure of a semeniferous tubule
Overall structure:
1. Lumen with Spermatozoa
2. Cell layer of Sertoli cells (Spermatogenesis, FSH sensitive)
3. Zone with Spermatogonia
4. Leydig cells associated with it (produce and secrete hormones, LH sensitive)
133
What is the function of the Seretorli cells?
Which stimmulus do they respond to?
Are located at the cell layer in a seminiferous tubule
* Spermatogenesis
* FSH sensitive
* Produce Inhibin in response to FSH
134
Explain the location, control and function of the Leydig cells (in male)
Are outside Seminiferous tubule
produce androgens in response to LH (mainly testosterone)
135
Explain the structure of a Graafian Follicle
From Outside to inside
* Thecal cells (LH sensitive)
* Granulosa cells (FSH)
* Follicular Fluid
* Ovum
136
In which phase of the ovarian cycle is oestrogen produced?
Which effect does this have on the endometrium?
It is produced in the follicular phase of the ovarian cycle and promotes proliferation of the endometrium
137
In which phase of the ovarian cycle is oestrogen and progesterone produced?
Which effect does it have on the endometrium?
It is produced in the Luteal phase and causes the secretory phase of the endometrium (preparation for arrival of the Egg)
138
Explain the Levels of FSH and LH in the menstrual cycle and how they change
Both: about baseline til Follicular phase
139
What is the first part of the menstrual cycle?
What happens during this phase?
1. Early follicular face
**FSH dependant development of the follicles** in the ovaries
Follicles produce **Progesterone and Oestradiol** which has a negative feedback on Hypothalamus/Pituitary ---\> Levels fall
140
What happens in the early-mid-follicular phase of the menstrual cycle?
Ho do levels of LH, FSH, Oestrodiol and Progesterone change?
The follicle most sensitive to FSH gets bigger --\> induced **autocrine feedback loop of E2**
* (more granulosa cells, produce more E2 (oestrogen), more oestrogen produce more granulosa cells
**FSH and LH** stay the same or fall slightly (because of feedback)
**Progesterone** does not change
**Oestrogen** increases
141
What is the Graafian Follicle?
What happens to the other follicles?
What does it produce?
The **largest follicle no longer requires FSH** to develop and proliferate
A **fall of FSH kills** other follicles that can't develop FSH independently
It keeps **growing a**nd **producing** large amounts of **E2**
142
What happens during the mid-follicular phase?
Graafian follicle develops (produces E2)
## Footnote
other follicles get killed by fall of FSH
--\> increase of oestradiol + inhibin
-ve feedback on FSH reduces levels,
No change in levels of LH/Progesterone
143
What happens during late follicular phase of ovulation?
Extremly high levels of E2 (produced by Graafian Follicle) induce +ve feedback on GnRH and LH
## Footnote
High E2 levels of E2 and LH/GnRH trigger ovulation
144
What happens during the Luteal phase of the menstrual cycle?
2nd phase of cycle
## Footnote
high levels of progesterone produced by Corpus Luteum
--\> prepares for implantation
If no fertilisation: -ve feedback of inhibin, E2 and Progesterone on GnRH/ LH+FSH
145
What is the bioactive form of Testosterone?
How is testosterone transported in blood and seminiferous fluid
Active form: DHT
--\> Dihydrotestosterone
Transport:
* 60% bound to Sex hormone binding globulin (SHBG, blood) or Androgen binding globulin (seminiferous fluid)
* Albumin 38%
* 2% free ( = bioactive)
146
How is the bioactive form of Oestrogen?
E2= 17ß- Estradiol
147
What kind of receptors does the Parathyroid hormone bind to?
What is its mechansim of action in the cell?
It binds to a G-protein coupled receptor--\>
## Footnote
•Activation of adenyl cyclase, but also probably PLC as second messenger systems
148
What do osteoblasts/osteoclast do?
What is their function in calcium metabolism?
Osteoblast:
* Built bone (need Ca2+)
* inhibited with Parathyroid hormone
Osteoclasts
* break down bone (release Ca2+)
* inhibited by Calcitonin/ stimulated by Parathyroid hormone
149
What is the activated form of Vitamin D3? What are its Names?
1,25(OH)2 Vit D3, Calcitriol, dihydroxi-cholecalciferol
150
WHat is the effect of Fibroblast-Growth factor 23?
It is a factor that influences Phosphate
* is stimmulated by a combination of hight levels of Phospate and VitD3
* Drives Phosphate secretion
* Negative feedback on Calcitriol
151
Which effect does insulin have on the GLUT-4 receptors?
Where are these receptors most abundant?
Insulin recruits the GLUT-4 receptor vesicles to the membrane when binding to the insulin receptors
They are most abundant in **muscle and adipose tissue**
152
Through which receptor is Glucose taken up into muscle and adipose tissue?
Via the GLUT-4 receptor
153
Which effects does Insulin have on proteins and muscle cells?
* Insulin I**NHIBITS proteolysis**, Cortisol STIMULATES it.
* Insulin **INHIBITS oxidation of** **amino-acids** in the cell.
* Insulin **STIMULATES re-synthesis of proteins** from amino-acids.
* --\> This means **less** **amino-acids leave the cell** to go to the liver to be used to produce glucose.
154
Which hormones stimulate gluconeogenesis?
Glucagon
Somatotrophin
Cortisol
Catecholamines
155
What is Hepatic glucose output? Which two processes normally contribute to this?
it is the amount of **synthesized glucose that leaves the liver**
There are two mechanisms:
1. **Gluconeogenesis**
2. **Glycolysis**
156
Which effect does insulin have on the liver?
It stimmulates
* protein synthesis
* glycogen formation
It inhibits
* Gluconeogenesis
* Ketone-body production
* Glycolysis
157
Which effect does insulin have on adipose tissue?
**It stimulates**
* Fat entering the cell (via activation of lipoprotein lipase)
* Formation of triglycerides
**It inhibits:**
* Lipolysis
158
Which effect does cortisol have on the uptake of glucose into the cell?
It tends to inhibit uptake
159
In which tissues is insulin resistance found?
What is the part that does not work properly?
Insulin resistance resides in the
* LIVER
* MUSCLE
* ADIPOSE TISSUE
but note that the receptors for insulin are normally functioning, the **post-receptor effect is faulty.**
160
Which substances are normally increased or decreased as a result of Type 2 diabetes?
Insulin resistance causes
An increase in
* Non-esterified fatty acids
* Triglyceride
* LDL cholesterol
A decrease in
* HDL
* VLDL clearance (decrease in lipoprotein lipase)
