Endocrine refined Flashcards
1
Q
Endocrine glands
- Function
- Vascularity
A
- Function: secrete hormones directly into the bloodstream upon stimulation
- Vascularity: highly vascularised
2
Q
The three arrangements of endocrine tissue
A
1- Endocrine organ
2- Distinct clusters of cells within an organ
3- Individual cells scattered throughout an organ
3
Q
Major hormone products of the hypothalamus
- RH and IF
- Examples
A
- Releasing hormones and inhibiting factors
- E.g. CRF, GnRH, GHRH, TRH, dopamine
4
Q
Major products of the posterior pituitary (2)
A
- Anti-diuretic hormone (ADH)
- Oxytocin
5
Q
Major hormone products of the anterior pituitary (6)
- ACTH
- GH
- P
- FSH
- LH
- TSH
A
- Adrenocorticotrophic hormone (ACTH)
- Growth hormone
- Prolactin
- Follicle stimulating hormone (FSH)
- Luteinising hormone (LH)
- Thyroid stimulating hormone
6
Q
Major hormone products of the thyroid gland (3)
A
- Thyroxine (T4)
- Tri-iodothyronine (T3)
- Calcitonin
7
Q
Major hormone product of the parathyroid gland
A
- Parathyroid hormone
8
Q
Major hormone products of the adrenal gland (2)
A
- Adrenaline
- Cortisol
9
Q
Major hormone products of the pancreas (2)
A
- Glucagon
- Insulin
10
Q
Major hormone products of the gonads (3)
A
- Progesterone
- Oestrogen
- Testosterone
11
Q
Modes of hormone action
- Autocrine and Paracrine
- Endocrine and Neuroendocrine
A
- Autocrine and Paracrine: Local diffusion
- Endocrine and neuroendocrine: Circulation
12
Q
Chemical nature of hormones is related to …. (5)
- How they are….
- Nature of the H….
- Ability to b…..
- degradation
A
- How they are synthesised
- Nature of the hormone receptor they bind to
- Ability to bind to other proteins (e.g. transport proteins)
- How they partition in tissues
- How they are degraded
13
Q
Steroid hormone examples:
- Prog…
- Gluco…
- Mineral…
- And….
- Oest…..
A
- Progestagens
- Glucocorticoids
- Mineralocorticoids
- Androgens
- Oestrogens
14
Q
Non-steroid hormones
- Poly…
- Glyco…
- Eico….
- Pep….
- Ami….
A
- Polypeptides
- Glycoproteins
- Eicosanoids
- Peptides
- Amines
15
Q
Hypothalamus-pituitary axis:
A
- Interface between central nervous system and endocrine system
16
Q
Hypothalamus-pituitary axis controls homeostatic regulation of (7)
- S and I F
- R
- G and D
- W/E B
- E B/A C
- T
- S/W
A
- Stress and immune function
- Reproduction
- Growth and development
- Water/electrolyte balance
- Energy balance/appetite control
- Thermoregulation
- Sleep/wakefulness
17
Q
Hypothalamus, anatomical boundaries:
- Anterior: OC
- Posterior: MB
- Superior: T
- Inferior: ME
A
- Anterior: Optic chiasm
- Posterior: Mammillary bodies
- Superior: Thalamus
- Inferior: Median eminence
18
Q
Hypothalamus structure: (2)
A
- Divided into anatomical nuclei
- Contains hypothalamic neurosecretory cells
19
Q
Action of the hypothalamus: (2)
- HNC R P F AT A to C
- I NI F BS, LS a HA, W R A
A
- Hypothalamic neurosecretory cells release peptides from axon terminals adjacent to capillaries
- Integrates neural inputs from brainstem, limbic system and hypothalamic areas, which regulate activity
20
Q
Pituitary (hypophysis): two gland in one
A
- Posterior lobe: under DIRECT control
- Anterior lobe: under INDIRECT control
21
Q
Tissue of the posterior lobe:
A
- Neural tissue: axons and nerve terminal endings of neurosecretory cells
22
Q
Tissue of the anterior lobe:
A
- Glandular tissue: cells controlled by releasing hormones, delivered via hypophyseal portal system
23
Q
Vascular supply of the pituitary gland:
- Anterior
- Posterior
- Drainage: CSS/IPS
A
- Anterior lobe: primary portal plexus transports releasing hormones to the secondary plexus
- Posterior lobe: a single plexus
- Drainage: cavernous sinus superior / inferior petrosal sinus
24
Q
Anterior pituitary lobe: hormones secreted (6)
A
Hormones with trophic action
- Follicle stimulating hormone (FSH)
- Luteinising hormone (LH)
- Adrenocorticotrophic hormone (ACTH)
- Thyroid stimulating hormone (TSH)
- Growth hormone (GH)
- Prolactin
25
Hormones with trophic action:
- They go on to regulate a third hormone
26
"Tripartite" neuroendocrine system:
- The idea that 3 separate hormones are involved in a system
1. Releasing hormone
2. Tropic hormone
3. Hormone (hits target cells)
27
Tripartite neuroendocrine system is prominent in control of major glands e.g. (3)
- Thyroid gland
- Adrenal gland
- gonads (ovary/testis)
28
What controls biorhythms?:
- The hypothalamic suprachiasmatic nucleus (SCN), the body's master clock
29
Role of the hypothalamic SCN: (2)
| - Partial control on …. Of …. Release from rhythm generators in the SCN
- Partial control on pulsatile patterns of hormone release from rhythm generators in the SCN
- E.g. paraventricular nucleus receives circadian input from SCN, regulating hypothalamus-pituitary-adrenal (HPA) axis activity and cortisol release
30
Polyuria:
Polydipsia:
- Excessive production and passing of urine
| - Excessive thirst
31
What causes polyuria:
- In uncontrolled diabetes mellitus, osmotic diuresis (glucosuria) causes increased passive water loss
32
Principles of metabolic regulation:
- The flow of metabolites through pathways must be regulated to maintain homeostasis
- Homeostasis occurs when metabolite concentrations are at a steady state
33
Reasons why the levels of required metabolites may vary: (3)
Hint:exercise
- To increase the rate of glycolysis during exercise
- To reduce the rate of glycolysis after exercise
- To increase the rate of gluconeogenesis after exercise
34
What is the Km of a reaction:
- Rates are more sensitive to concentration near or below their Km
35
Km variation in glucose transporters:
- Different tissues have different glucose transport proteins present.
- The Km for each GLUT type varies due to its tissues function
36
GLUT1:
- Tissue/organ:
- Km
- Red blood cells
| - 3 mM
37
GLUT 2:
- Tissue/organ
- Km
- Liver, pancreas
| - 17 mM
38
GLUT3:
- Tissue/organ
- Km
- Brain
| - 1.4 mM
39
GLUT4:
- Tissue/organ
- Km
- Muscle, adipose tissue
| - 5 mM
40
Contact-dependant signalling:
- A cell-surface-bound signal molecule binds to a receptor protein on an adjacent cell, no molecules are released
41
Paracrine signalling:
- Paracrine signals are released by cells into the EF, acting as a local mediator
42
Cell surface receptors:
- Most signalling molecules....
- instead, they bind to .....
- Most signalling molecules are large and hydrophilic, they can't cross the plasma membrane.
- Instead, they bind to cell-surface receptors which generate intracellular second messenger signalling molecules
43
Intracellular receptors:
- Some small hydrophobic.... pass through the target cells plasma membrane binding to ….
- That regulate, for example.....
- Some small hydrophobic extracellular signalling molecules pass through the target cells plasma membrane, binding to intracellular receptors.
- That regulate, for example, gene transcription
44
Apoptosis:
- A form of cell suicide that occurs when a cell does not receive the necessary signals to survive
45
Timescales of a cell's response
- Fast
- Slow
- Fast: processes that rely on altered protein function; movement, secretion and metabolism
- Slow: processes that rely on altered protein synthesis; differentiation, growth and division
46
Ion-channel-coupled receptors:
- Signal molecules.....
- Causing a change in......
- Thus, a chemical change.....
- Signal molecules (acetylcholine) cause the receptors to open in response to binding,
- causing a change in the electrical potential across the membrane
- Thus, a chemical signal is transducer into an electrical signal
47
G-Protein coupled receptors are transmembrane proteins:
- Extracellular
- Intracellular
- Extracellular portion of a GPCr binds to signalling molecules
- The cytoplasmic portion binds to a G-protein
48
The two most common enzyme targets of G-proteins are:
- Adenyl cyclase action:
- Phospholipase C action:
- Adenyl cyclase catalyses the formation of the second messenger cyclic AMP (cAMP)
- Phospholipase C produces the second messengers inositol triphosphate (IP3) and diacylglycerol (DAG). IP3 promotes the accumulation of cytosolic Ca2+, another 2nd messenger
49
The effect of adrenaline on skeletal muscle:
- Adrenaline indicates a .....
- Adrenaline activates a .....
- The increase in cAMP activates.....
- Phosphorylase kinase activates......
- Adrenaline indicates a requirement for glucose in muscle
- Adrenaline activates a GPCR, activating a G-protein which activates cAMP
- The increase in cAMP activates protein kinase A (PKA), which phosphorylates, activating phosphorylase kinase
- Phosphorylase kinase activates glycogen phosphorylase, the enzyme that breaks down glycogen
50
GPCRs and cholera:
- Cholera toxin affects cells of the intestinal epithelium
- Modifies a G protein, preventing it from deactivating, so it continually activates adenylyl cyclase
- Causes continuous outflow of Cl- and H2O
- Causing diarrhoea, dehydration and death
51
Growth hormone:
- Location
- Effect
- Action
- Anterior pituitary
- Causes growth in most tissues and promotes differentiation in some cell types
- Binds to GH receptor in target tissues
52
Effect of somatostatin on GH secretion:
- Somatostatin inhibits GH secretion
53
Effect of GRH dopamine on GH secretion:
- GRH dopamine increases GH release
54
GH secretion frequency:
- Periodic secretion, affected by sleep
55
Feedback control of GH:
- SS
- GH
- GH stimulates somatostatin (SS), SS inhibits GH release
| - GH also inhibits GHRH release and GH release
56
GH action: acute
- Protein
- Lipid
- Carbs
- Key effect
- Protein: Increased amino acid uptake and usage, increased protein synthesis.
Decreased protein catabolism
- Lipids: decrease in lipogenesis
increase in lipolysis
- Carbohydrates: decrease in glucose uptake and oxidation
Increase in blood glucose
-KEY EFFECT: PROTECTS PROETIN
57
Regulation of bone growth: IGF-1
- PM
- R of P C
- M of D S
- Pro-mitogenic
- Recruitment of precursor cells
- Maintenance of differentiated state
58
Regulation of bone growth: Glucocorticoids
- P
- Chronic effect
- Permissive: presence required for normal processes
| - In chronic high doses leads to bone loss and catabolism
59
Regulation of bon growth: Androgens
| - T S
- Testosterone surge during puberty accelerates closure of growth plates
60
Effects of an abnormal increased GH secretion:
1. Gigantism (before epiphyseal growth plate has sealed)
| 2. Acromegaly (after growth plate closure)
61
Adrenal cortex zones: (3)
- g
- f
- r
- Zona glomerulosa
- Zona fasiculata
- Zona reticularis
62
Hormone produced in the zone glomerulosa:
- Aldosterone
63
Hormone produced by zona fasiculata:
- Cortisol (and androgens)
64
Hormone produced by zona reticularis:
- Androgens (and cortisol)
65
Hormones produced by the adrenal medulla
- Adrenaline
| - Noradrenaline
66
Synthesis of adrenocortical steroids
- All based on cholesterol, synthesised as required
| - Expression of key enzymes regulated
67
Cortisol (glucocorticoid):
- secretion:
- regulation:
- Secreted by zona fasiculata
- Release controlled by CRH/ACTH
CRH: Cortisol releasing hormone
ACTH: adrenocorticotrophic hormone
68
Circadian rhythm for Cortisol:
- Synchronisation
- Effect of stress
- CRH secretion synchronised with sleep cycle.
| - Stress-induced CRH secretion increases glucocorticoid secretion approx. 20 fold
69
Cortisol actions:
- Metabolic effects
- Cardiovascular effects
- Other
- ME: Stimulates gluconeogenesis and glycogenolysis (provides fuel)
- CE: Maintains blood volume (protects CVS)
- OE: Anti-inflammatory, immunosuppressive
70
Cortisol action on CVS:
- Increases contractility
- Increases peripheral resistance
Amplifying the effects of noradrenaline and adrenaline
71
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Cortisol effect on inflammatory/immune response:
-INHIBITS
. S of C
. H R
. P of I C
. S of A
```
```
- Inhibits:
. Secretion of cytokines
. Histamine release
. Proliferation of immune cells
. synthesis of antibodies
```
72
Regulation of cortisol release: tripartite
1.
2.
3.
1. Hypothalamus: releases CRH
2. Anterior pituitary: releases ACTH
3. Adrenal cortex: cortisol
CRH: corticotropin releasing hormone
ACTH: adrenocorticotropic hormone
73
Feedback control of cortisol
- Positive
- Negative
- Positive: stressors (physical/emotional)
| - Negative: Pituitary, hypothalamus
74
Aldosterone:
- Secretion
- Half-life
- Zona glomerulosa
| - 30 mins
75
What stimulates the release of cortisol?:
- Angiotensin 2
| - Low Na stimulates renin release in kidney, renin cleaves angiotensin into Ang1
76
What does aldosterone stimulate?:
- Answer
- Effect
- aldosterone stimulates Na-K ATPase in renal collecting ducts
- Na reabsorbed in filtrate, K secreted into filtrate, Water retention
77
Corticosteroid receptors:
| - two cytosolic receptors
- Glucocorticoid receptor (GR)
. Cortisol - higher affinity at GR
. Most cells have GR
- Mineralocorticoid receptor (MR)
. Aldosterone - higher affinity at MR
. MR mainly in kidney and gut
78
Termination of action (adrenocorticoid):
- Half-life:
- Liver
- Kidney
- Half-life:
. Cortisol: 60 mins
. Aldosterone: 15 mins
- Liver: cortisol and aldosterone inactivated
- Kidney: inactivated forms excreted in urine
79
Dysregulation of glucocorticoid release (2)
- Addison's: too little cortisol
| - Cushing disease: too much cortisol
80
Paths to dysregulation:
1. Primary
2. Secondary
3. Tertiary
1. Primary: failure of adrenal cortex to secrete cortisol
2. secondary: failure of pituitary to secrete ACTH
3. tertiary: failure of hypothalamus to secrete CRH
81
Addison syndrome: too little cortisol
| -Symptoms(6)
Symptoms:
- Hypotension
- Hypoglycemia
- Hyponatremia
- Hypovolumia
- Hyperpigmentation
- Hyperkalemia
82
Addison's disease :
- Main cause
- Other cause
- Main cause: autoimmune destruction of adrenal cortical cells (primary adrenocortical insufficiency)
- Other causes:
. Chronic glucocorticoid treatment
. Infection
83
Cushing's SYNDROME:
- ACTH???
- Causes????
- ACTH low
- Adrenal neoplasm or hyperplasia
- Chronic glucocorticoid treament
84
Cushing's disease:
- ACTH high
| - Excessive and unregulated pituitary ACTH secretion
85
Glucocorticoid treatment:
- wanted effects
- unwanted effects
- Wanted effects:
- reduces inflammation and suppresses immune system
- Unwanted effects:
- Atrophy of the zona fasicula (cortex)
86
Cushing's treatment:
- Remove or destroy source of ACTH or cortisol
87
Cushing's treatment:
- Remove or destroy source of ACTH or cortisol
88
General thyroid and parathyroid anatomy:
- TG
- PTG
- Thyroid gland has lateral lobes connected by isthmus
| - Parathyroid glands are located behind the lateral lobes of the thyroid
89
T4 and T3 synthesis:
-Location
1. Active uptake of..... I
2. Production of ..... Thy
3. Iodination of ...... tyr
4. Reabsorption of..... thy
5. Digestion by .....
- Occurs in the thyroid follicles
5 steps
1. Active uptake of iodide I-
2. Production of thyroglobulin
3. Iodination of tyrosine on thyroglobulin (in colloid)
4. Reabsorption of thyroglobulin
5. Digestion by lysosomal enzymes causes secretion of T4 and T3
90
Dietary iodide facts:
- Daily requirement:
- AVG. daily intake
- Efficiently absorbed
- Absorbed into....
- Removed from EP by ....
- Kidneys...
- Thyroid contains.....
- Daily requirement: >75 micro grams
- Avg. daily intake: 500 micro g
- Efficiently absorbed: only 15 micro g lost from gut in bile
- Absorbed into extracellular pool: 150 micro g.
- Removed from EP by thyroid or kidneys
- Kidneys excrete 485 micro gram/day
- Thyroid contains huge iodide store in colloid (8000 micro g)
91
Actions of thyroid hormones:
- TBG
- Method of action
- Target genes
- Target cells
- >99% is reversibly bound to proteins - thyroid binding globulin (TBG)
- T4 and T3 operate through nuclear receptors regulating gene transcription (latency of several days)
- Genes regulating cell differentiation and metabolism
- Affects most tissues
92
Hypothyroidism: in early development
- Definition
- Symptoms (4)
- Cretinism: complete absence of thyroid hormone during development
- symptoms: Neurological deficits (retardation)
- Small stature and immature appearance
- Puffy hands and face
- Delayed puberty
93
Hypothyroidism in adulthood: symptoms (9)
- L BMR and C S
- B
- S S
- L
- W G
- C
- M A
- D T S
- S M F
- Low BMR and cold sensitivity
- Bradycardia (abnormally low resting HR)
- Slow speech
- Lethargy
- Weight gain
- Constipation
- Menstrual abnormalities
- Dry thickened skin
- Slow mental function
94
Hyperthyroidism symptoms:
- Nervousness
- High BMR, raised temp
- Tachycardia (abnormally high resting HR)
- Increased appetite/ weight loss
- Tiredness
95
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Physiological role of calcium: (6)
- B S
- B C
_ N E
- M I T
- E R
- C
```
- Bone strength
- Blood coagulation
- Neuromusclular excitability
- Membrane ion transport
- Enzyme regulation
- Contraction
96
3 hormones of Ca regulation:
- PTH
- Calcitonin
- Vitamin D
97
Normal plasma calcium range:
- 2.2 to 2.6 mmol/L
98
Low Plasma Ca2+ response:
- Parathyroid glands (chief cells) secrete PTH, increasing plasma Ca2+
99
High plasma Ca2+ response:
- Thyroid parafollicular C cells secrete calcitonin, lowering plasma Ca2+
100
Hypocalcaemia:
- Cause
- Symptoms
- Increased N E
- T, M C, T
- C and D (severe)
- Caused by hypoparathyroidism, caused by accidental damage to parathyroid glands during thyroid surgery
- Symptoms:
- Increased neuromusclular excitability
- Twitching, muscle cramps, tetany
- Carpodeal spasm
- Coma and death (severe)
101
Hypercalcaemia:
- Cause
- Symptoms
- Associated with primary hyperparathyroidism and malignancy
- Symptoms of stones bones and groans
102
Insulin:
- Role:
- Secreted:
- Role: signals the fed state, lowers blood glucose levels
| - Secreted by beta-cells in the pancreas
103
Insulin synthesis:
1. Starts as preproinsulin, signal sequence....
2. A and B peptides linked by ....
3. Mature insulin leaves .....
1. Starts as preproinsulin, signal sequence directs it into the endoplasmic reticulum
2. A and B peptides linked by disulfide bonds, proinsulin cleaved twice by a protease, removing C peptide
3. Mature insulin leaves Golgi network and enters a secretory vesicle
104
Insulin action:
- Insulin binds to ......... .......... ......... on the surface of muscle and adipose cells
- ...... is activated, auto phosphorylating ..........
- Phosphorylated receptor binds to .....
allowing ..... to be converted to .......
- ........ activated ....... which activates Akt
- Activated Akt increases cell glucose uptake
- Insulin binds to enzyme-coupled receptors on the surface of muscle and adipose cells
- RTK is activated, auto phosphorylating tyrosines
- Phosphorylated receptor bind to IRS-1 allowing PIP2 to be converted to PIP3
- PIP3 activates PDK1, which activates Akt
- Akt ac
105
Effect of activated Akt on GLUT4 transporters:
- Activated Akt causes GLUT4 transporter vesicles to fuse to the cell surface membrane, increasing glucose uptake 15x
106
Glucose regulates insulin secretion from beta-cells:
- Glucose enters.....
- Glycolysis causes an.....
- ATP binds to .....
- Membrane depolarisation causes.....
- Causing more ....
- Triggering insulin release via .....
- Glucose enters the beta-cell via GLUT2
- Glycolysis causes an increase in ATP
- ATP binds to ATP-gated K+ channels, closing them
- Membrane depolarisation causes opening of Ca2+ channels
- Causes more Ca2+ to be released by the ER
- Triggering insulin release via exocytosis
107
Sulfonylurea drugs in treating diabetes:
- Binds to SUR1 subunit, closing K+ channel, causing insulin release
108
Insulin main aim:
- Stimulate the uptake of glucose into cells, lowers plasma blood sugar levels
109
Glucagon main aim:
- Glycogen breakdown, raises plasma blood sugar levels
110
Diabetes symptoms:
- Mutual (2)
- Type 1 specific: ketoacidocis
- Elevated blood sugar
- Excessive urination and thirst
In type 1:
- Accelerated fat break down, increase in ketone bodies, some of which are ketoacids, raising [H+], causing ketoacidosis
111
Long-term effects of raised blood sugar:
- Hemoglobin becomes glycated, compromising O2 deliveries (especially to extremities)
112
Luteinizing hormone (LH) role:
- Stimulation of testosterone secretion
113
Follicle-stimulating hormone role: (2)
- Spermatogenesis
| - Oestrogen synthesis
114
DHEA (Dehydroepiandrosterone) role:
- Weaker androgens, no effect in males
115
Testosterone role:
- Secondary male sexual characteristics
| - Spermatogenesis
116
Oestrogen role: (2)
- Secondary sexual characteristic development
| - Growth of ovarian follicles/proliferation of endometrium
117
Progesterone role:
- Prepares the uterus for ovulation, thickens wall lining etc.
