Physiology Flashcards
(133 cards)
1
Q
Where is insulin synthesised?
A
beta cells in the pancreatic islet
2
Q
what is the role of insulin?
A
lowers the plasma glucose level
3
Q
what stimulates the release of insulin?
A
high plasma glucose level
4
Q
where is glucagon synthesied?
A
alpha cells in the pancreatic islet
5
Q
what is the role of glucagon?
A
raises the plasma glucose level
6
Q
what stimulates the release of glucagon?
A
low plasma glucose level
7
Q
what is proinsulin?
A
molecule which is the form insulin takes up inside the beta cell before being released
in this molecule insulin is cleaved to c peptide
8
Q
why is c-peptide a useful way to measure endogenous insulin secretion?
ii. why may it not be useful?
A
It is co-secreted with insulin but not part of injected insulin. Therefore if c-peptide is present in the blood it must be coming from the person’s beta cells
Useful in diagnosing patients for Type 1 (should be after 3 years of diagnosis)
ii.The test may be less helpful close to diagnosis, particularly where a patient is overweight and insulin resistant, as levels close to diagnosis in Type 1 diabetes may be high and overlap with those seen in type 2 diabetes
9
Q
What is HbA1c and why is it useful in measuring glucose levels?
A
It is glycated haemoglobin
it forms when haemoglobin is exposed to glucose and become glycated
amount of glycation is proportional to the glucose level
10
Q
why is HbA1c not useful when patients have anaemia?
A
RBCs normally live for 120 days and HbA1c gives a reasonable understanding of the patients glucose level for the past 3 months
Anaemia reduces the RBC turnover therefore will give a low HBA1c result which may be misleading
11
Q
what is the HbA1c value which signifies the patient has diabetes?
A
48 mmol/mole or 6.5%
remember that each 1% increase there is an 11 mmol/mole increase
12
Q
what are the the different endocrine cell types found in the islets of langerhans?
A
alpha cells
beta cells
delta cells
Pancreatic polypeptide cells (PP)
Epsilon cells (ε-cells)
13
Q
what is the role of delta cells?
A
secretes somatostatin
14
Q
what is the role of pancreatic polypeptide cells?
A
secretes pancreatic polypeptide
15
Q
what is the role of Epsilon cells (ε-cells)?
A
Ghrelin
16
Q
what happens to the normoglycaemia if a person fasts/exercise?
A
- lowers - can become hypoglycaemic (hypolipidaemia too)
- Glucagon is triggered and insulin is inhibited
- glucose is produced (Lipolysis)
n. b. adrenaline can be used to increase glucose production in its own pathway
17
Q
what happens to the normoglycaemia if a person eats?
A
- raise blood glucose - can become hyperglycaemic (hyperlipidaemia too)
- Insulin is triggered and glucagon is inhibited (lipid storage)
- glycogen synthesis
18
Q
what else apart from glucose do Beta cells respond to?
A
- Amino acids
- fatty acids
- IL6
- Leptin
- Glucagon
- GLP1
- GIP
- Acetylcholine
- Igf1
19
Q
How does a beta cell release insulin?
A
in a biphasmic manner
1st phase is very important as it releases insulin within 2 minutes of glucose secretion.
it is the first sign that a patient has beta cell disfunction due to lack of response
20
Q
Give example of essential molecular components in beta cells for glucose sensing.
A
- Glucose transporters (GLUT1/2)
- Glucokinase (GCK)
- oxidative metabolism
- k ATP-channels
- L type voltage dependant channels
- Exocytotic machinery
21
Q
what happens in alpha cells when there is low glucose?
A
- Glucose uptake and metabolism low.
- katp channels open
- Voltage-gated sodium channels contribute to action potentials
- P/q type voltage gated calcium channels enable calcium influx
- Glucagon exocytosis triggered
22
Q
what happens in alpha cells when there is high glucose?
A
- Glucose uptake and metabolism high
- katp channels closed, cell depolarised
- Presence of SGLT2 glucose transporters contributes to non-voltage-regulated sodium ion influx
- NAV and CAv channels closed and Glucagon not released
23
Q
Give examples of islet defects in type 2 diabetes?
A
- impaired insulin secretion
- dyregulated glucagon secretion:
i. lack of suppression of GCG secretion at high glucose
ii. May contribute to hyperglycaemia
24
Q
when is somatostatin 14 released?
A
it is a paracrine regulator in response to nutrient or hormonal stimulation
it suppresses beta cell and alpha cell function
25
what is paracrine signalling?
like endocrine release of hormones which travel through the blood stream to a target tissue but travels much shorter distance
26
what is the principle incretin hormone?
Glucagon Like peptide 1 (GLP1)
27
what is GLP1 released due to?
glucose
amino acids
fatty acids
28
which cells release GLP1?
L-cells - it is released biphasic manner
29
what is the role of GLP1?
1. potentiates insulin secretion from pancreatic beta cells
2. reduces apetite
3. inhibits glucagon secretion
4. delay gastric emptying
30
where are L cells found?
Ileum and colon
31
which gene is responsible for coding for GLP1?
glucagon
then creates pre protein Pro glucagon
then pro horomone convertase (PC1/3) makes GLP1
32
GLP1 has a very short half life true or false?
ii. what could be used instead for incretin treatment for T2 diabetes?
true- difficult therefore to give as a therapeutic due degradation by DPPIV
ii. however GLP1 analogue is useful which has an increased stability in serum or DPPIV inhibitors
33
what is the effect of bariatric surgery on incretin?
increased GLP1 response as nutrients reach L cells more quickly
34
what type of hormone is insulin?
anabolic
protein/peptide
35
how many molecules of ATP are produced after oxidative phosphorylation of one glucose molecule?
36
36
what type of target cells are involved in endocrine signalling?
distant target cell
37
what type of target cells are involved in autocrine signalling?
acting on itself
38
what type of target cells are involved in paracrine signalling?
surrounding (local) cells
39
what are the 3 main classes of hormones?
1. (glyco)proteins and peptides
2. steroids
3. tyrosine and tryptophan derivatives
40
what molecule are steroids derived from?
cholesterol
41
what type of hormone is oxytocin?
protein/peptide
42
what type of hormone is cortisol?
steroid
43
what type of hormone is aldosterone?
steroid
44
what type of hormone is adrenaline or epinephrine?
tyrosine/tryptophan derivatives
45
what type of hormones are the thyroid hormones?
tyrosine derivatives
46
what type of hormone is testosterone?
steroid
47
are amines pre-synthesised and stored or synthesised on demand?
pre-synthesised and stored
48
where are amines stored?
intracellular vesicles
49
Name all the glands and organs which make up the endocrine system.
1. Pineal gland
2. Pituitary gland
3. thyroid gland
4. Parathyroid glands
5. Thymus
6. adrenal glands
7. Pancreas
8. Ovaries
9. Testes
50
what does the thyroid gland tissue secrete?
Thyroxine (t4)
Tri-iodothyronine (T3)
Calcitonin
51
what do parathyroid glands secrete?
Parathyroid hormone (PTH)
52
what is the basic functional unit of the thyroid gland?
Follicle
53
what does the follicle consist of?
Follicular cells enclose a colloid.
Parafollicular cells located adjacent to the thyroid follicles and reside in the connective tissue. These cells are large and have a pale stain compared with the follicular cells.
54
How is T4 and T3 released in the thyroid gland?
Negative feedback system
1. signals start in the Paraventricular nucleus (PVN) of the hypothalamus
2. Hypothalamus releases thyrotrophin releasing hormone (TRH)
3. TRH stimulates the release of Thyroid stimulating hormone (TSH) in the pituitary gland
4. TSH stimulates thyroid gland to secrete T4 and T3
5. T4 and T3 is secreted into the peripheral tissues
6. If there is a high level of T4 and T3 in the peripheral tissue these hormones inhibit the hypothalamus and pituitary gland from releasing anymore hormones
55
what are the 6 steps of thyroid hormone synthesis?
1. Thyroglobulin synthesis - occurs in the follicular cells
2. Uptake and concentration of Iodide in the colloid
3. iodide is then oxidised to iodine
4. Iodination of thyroglobulin - iodine attaches to the tyrosine residues of the thyroglobulin . Thyroglobulin has to enter the colloid
5. Formation of MIT and DIT ( monoiodotyrosine unit and DI-iodotyrosine unit)
6. Coupling occurs: 1 MIT and 1 DIT = T3 or 2 DIT = T4
7. T3 and T4 stored in the the colloid thyroglobulin
56
what can inhibit iodination in the thyroid glands?
Carbimazole and propylthiouracil
57
Which thyroid hormone is synthesised more?
T4 - 90% of the thyroid hormone produced
58
How can T4 be converted to T3?
in the liver and kidney
59
which of the thyroid hormones is biologically active?
T3
60
How are thyroid hormones transported?
Serum proteins: Almost 100% of Thyroid hormones are carried this way
1. Thyroxine binding globulin (TBG) - 70% - has higher affinity for T4
2. Thyroxine binding pre-albumin (TBPA) - 20%
3. Albumin - 5%
unbound :
1. free T4
2. Free T3
Note: only unbound thyroid hormones enter the cells
61
which conditions increase TBG levels?
Increased TBG causes increase total T4 but not free T4
1. Pregnancy
2. Newborn state
3. Oral contraceptive pill
4. Tamoxifen
5. Hep A
6. Chronic hepatitis
7. Biliary cirrhosis
8. Acute intermittent porphyria
9. Genetically determined
62
Which conditions decrease TBG?
Decreased TBG causes decrease total T4 but not free T4
1. Androgens
2. Large doses of glucorticoids
3. Cushings syndrome
4. Acromegaly
5. Chronic liver disease
6. severe systemic illness
7. Nephrotic syndrome
8. Genetically determined
9. Pheytoin
63
what are the effects of thyroid hormones?
All cells:
1. Increases metabolic rate especially in neurons
2. increased glucose uptake especially in neurons
3. Increases thermogenesis
Liver:
1. Increased glycogenolysis and gluconeogenesis in the liver
2. Decreased glycogenosis
Adipose connective tissue:
1. Increased lipolysis
2. Decreased lipogenesis
Lungs
1. increased breathing rate
Heart
1. Increased heart rate
2. Increased force of contraction
Growth:
1. Thyroid hormones promotes the production and secretion of growth hormone releasing hormone (GHRH) from the hypothalamus
2. promotes release of Glucorticoid induced GHRH also
3 Growth hormones and Somatomedins require presence of thyroid hormone for activity
Development of foetal and neonatal brain
1. myelinogenesis and axonal growth require thyroid hormones
Normal CNS activity
1. Hyperthyroidism - causes nervousness, hyperkinesis and emotional lability
2. Hypothyroidism - slow intellectual functions
Others:
1. increases sensitivity to adrenaline and sympathetic NS neurotransmitter, noradrenaline by increasing number of receptors
64
How do the thyroid hormones increase metabolic rate?
1. increase number and size of mitochondria
2. Increase oxygen use and rates of ATP hydrolysis
3. Increase synthesis of respiratory chain enzyme
65
What are the three types of enzymes involved in the degradation of thyroid hormones?
De-iodinase:
DI - found mainly in liver and kidney
D2 - found mainly in heart, skeletal muscle, CNS, fat, thyroid and pituitary
D3 - found in fetal tissue, placenta and brain ( apart from pituitary)
66
How are the the thyroid hormones broken down into?
Occurs in circulation and peripheral tissues:
T4:
1. 45% is broken down by D3 into inactive reverse T3 which is rapidly excreted
2. 40% is broken down by D1 into T3. See T3 degradation.
3. 15% is broken by minor degradative pathways
T3:
1. Used up in reaction
2. Other T3 broken down is broken down by D3 into inactive t3
Brain and pituitary thyrotroph:
1. T4 is broken down by D2 into T3
2. T3 then is used in the negative feedback system preventing secretion of TRH and TSH
67
Name key reproductive hormones.
1. Gonadotropin-releasing hormone (GnRH)
2. Luteinizing hormone (LH)
3. Follicle-stimulating hormone (FSH)
4. Oestrogen
5. Progesterone
6. Testosterone
68
What gonadotrophic hormones does the anterior pituitary gland release?
1. FSH
Male - causes testes to produce sperm (Spermatogenesis)
Females - causes growth of ovarian follicles (oogenesis) and it causes the ovary to secrete oestrogen
2. LH
Male : causes secretion of testosterone from testes
Female: causes ovulation and it causes progesterone production by corpus luteum
corpus luteum - is a temporary endocrine structure in female ovaries and is involved in the production of relatively high levels of progesterone LH causes cholesterol to be stacked in the follicle. Cholesterol acts as substrate for progesterone)
69
what is the role of GnRH?
Responsible for the release of FSH and LH from anterior pituitary gland
70
what type of hormone is GnRH?
ii. where is it synthesised?
neuropeptide hormone ( made out of peptide but released from the neuron)
ii. GnRH neurons in the hypothalamus
71
Describe the releasing pattern of GnRH.
Released in a pulsatile pattern
Males - released in pulses at a constant frequency
Females - varies during the menstrual cycle ( fast at early follicular phase and decreases up to the luteal phase)
Remember LH and FSH are released by same cells in Anterior pituitary therefore:
high frequency GnRH pulses stimulate LH release
Low frequency GnRH pulses stimulate FSH release
72
what is oestrogens effect on the GnRH pulse pattern?
oestrogen enters circulation and it enters hypothalamus
This increases pulsatile frequency of GnRH
causes drive in release of LH
73
what is progesterone effect on the GnRH pulse pattern?
enters circulation and it enters hypothalamus
decreases pulsatile frequency of GnRH
causes drive in release of FSH
74
What is the role of Kisspeptin neurons?
found in the hypothalamus, they are an upstream regulator of GnRH which stimulates it's secretion
oestrogen and progesterone influence Kisspeptin neurons which in turn effects GnRH neuron response
75
what are the phases of the menstrual cycle?
approximately 28 days
Phase 1 - follicular phase (proliferative phase) - when follicles are starting to grow. Only one should typically ovulate . typically 14 days
Phase 2 - luteal phase (secretory phase) - corpus luteum is forming in the ovaries. more constant in number of days in comparison to follicular phase
76
Describe the hormone changes in the menstrual cycle.
female Hypothalamic - Pituitary - Gonadal Axis (HPG Axis).
1. FSH stimulates growth of ovarian follicles (associated with an increase in oestrogen levels)
2. Rising oestrogen levels in turn exert negative feedback regulation ( level of hypothalamus and pituitary) to lower FSH levels (temporarily)- functionally important in selecting one follicle for ovulation
3. Once oestrogen reaches a certain concentration it exerts positive feedback regulation resulting in an increase in FSH levels and the LH surge
4. LH surge eventually leads to ovulation and regulates the formation of the corpus luteum and progesterone production and secretion
5. Increasing progesterone decrease LH secretion by influencing GnRH pulsatility
77
Describe what is happening in the ovary and endometrium during the menstrual cycle?
1. Follicle consists of an oocyte surrounded by follicular cells ( granulosa cells and theca cells). FSH doesn't directly act on egg but rather the follicular cells
2. Growth entails (FSH effect) an increase in the number of follicular cells ( not oocyte).
3. Accumulation of follicular fluid both result in an increase in the diameter and overall size of the follicle
4. Endometrium thickens under the influence of oestrogen and becomes a secretory tissue under the influence of progesterone
78
what are the two Specialised types of follicular cells?
theca cells
granulosa cells
79
What happens if LH binds to Theca cells?
converts Cholesterol to androgen
Gives androgen to Granulosa cells
80
what happens if FSH binds to Glanulosa cells?
uses androgen from theca cells and converts it to oestrogen
catalysed by aromatase
81
What occurs in folliclogenesis?
Early stages of follicle growth occurs independently of gonadotrophins
Once a follicle reaches a certain size (2mm) becomes gonadotrophin dependent. Has to occur as FSH rises in early follicular phase otherwise it becomes atretic
3. Follicle number keeps growing under influence of FSH but only 1 (dominant follicle) will be selected for ovulation. Totally dependent on FSH levels
possible reason for follicle selection: As FSH levels decrease ( due to negative feedback). Most follicles die and the largest Follicle ( more receptors/ better blood supply) which is able to survive.
82
What are early follicles called?
Primordial follicles
there are roughly 7 million in each ovary
drops to 2 million at birth
0.5 million at puberty
83
Why is the LH surge useful in timing of ovulation?
the Surge occurs before ovulation by approx 34-36 hours
84
what is the threshold of oestrogen required for an increase in GnRH pulsatility and therefore LH surge?
200pg/ml
85
Describe the process of the formation of the corpus luteum.
Occurs under the influence of LH
Granulosa and theca cells transform to luteal cells
Increase in progesterone production:
LH stimulates angiogenesis - blood vessel formation (ensures efficient delivery of cholesterol )
LH stimulates enzymes involved in conversion of cholesterol to progesterone
After LH levels decrease hCG takes over role and maintains conversion of cholesterol to progesterone
86
what does the corpus luteum turn into during pregnancy?
corpus albicans - broken down by macrophages, fibroblasts lay down type I collagen, forming it
87
what is the role of oestrogen?
Increase thickness of vaginal wall
regulate the LH surge
Reduce vaginal pH - increases lactic acid production
decrease viscosity of cervical mucus to facilitate sperm penetration
88
What is the role of progeseterone?
Maintains pregnancy - pro gestation
Maintains the thickness of the endometrium
Responsible for infertile thick mucus ( prevent sperm transport and help prevent infection)
Relaxes the myometrium ( smooth muscle). Functional progesterone withdrawal though to regulate parturition (birth).
89
what is the role of stroma in the cervix?
it consists of collagen matrix and fibroblasts.
Regulates the rigidity of the cervical wall
90
What type of epithelial cells are found in the the cervix?
Columnar epithelial cells.
Site of mucus production
91
Describe the sperm transport through the cervix.
1. Sperm enter the cervical canal rapidly where they encounter cervical mucus
2. Sperms ability to the mucus is regulated by:
Motility of the sperm - poor motile cells get stuck
Thickness of the mucus - hydration of cervical mucus under hormonal control
Interaction with reactive oxygen species - produced by leukocytes that have infiltrated the cervical mucus
Interaction with mucins
92
compare oestrogen and progesterone in terms of what they do to the cervical mucous?
oestrogen: makes fertile mucous
progesterone: makes (thick) infertile mucous
93
What does the human cervix contain?
Cervical canal
Primary grooves
Secondary grooves
Mucus thicker in the cervical canal
immune cells concentrated in the cervical canal
94
what is spermatogenesis?
creation of sperm - occurs in testes
95
how long does spermatogenesis occur?
73 days
96
What does testicular organisation consist of?
1.Extratubular compartment:
interstitial component
intravascular component
2. Intratubular compartment:
basal comparment
Adluminal compartment : contain
sertoli cells - they respond to FSH and help drive the development of spermatozoa. Like granulosa cells in ovaries
germ cells -
97
what is the role of Blood testes barrier?
prevent auto immune attack of sperm cells.
Sperm cells are only produced in puberty so can be viewed as a new cell and therefore a threat.
contains tight junction between adjacent sertoli cells
98
What is the role of leydig cells in the interstitium?
form testosterone
99
Describe the hormone action in the testes.
HPG - male axis
1. FSH influences spermatogenesis together with testosterone
2. FSH stimulates sertoli cells which are in seminiferous tubules secretes androgen binding globun (ABG and inhibin)
3. Inhibin decreases secretion of FSH
4. LH stimulates interstitial leydig cells to secrete testosterone
5. Testosterone decreases release of GnRH and LH
6. ABG sequests testosterone within the seminiferous tubules and so can go into circulation
7. Testosterone also causes release of mature spermatozoa from Sertoli cells by influencing peritubular myoid cells
8. Testosterone also forms dihydrotestosterone which is involved in:
Enlargement of male sex organs
secondary sexual characterisitics
anabolism
100
what hormones are secreted by the anterior pituitary gland?
ACTH
TSH
GH
PRL - prolactin
FSH
LH
MSH - melanocyte stimulating hormone
101
what hormones are secreted by the posterior pituitary gland?
ADH
Oxytocin
102
what effect does cortisol have on the body?
Regulates glucose levels
Increases fat in the body
Helps to defend the body against infection
Helps the body respond to stress
103
Discuss the feedback system which leads to the synthesis of Cortisol?
Cortico-trophin Releasing hormone (CRH) is released from the hypothalamus
This stimulates the release of Adrenocorticotropic hormone (ACTH) from the anterior pituitary gland
ACTH enters circulation and travels to the adrenal gland
Stimulates the release of cortisol
High levels of cortisol causes negative feedback inhibiting further synthesis of CRH and ACTH
104
Give examples of Hypothalamic hormones.
CRH - cortico-releasing hormone
TRH- Thyrotropin releasing hormone
GnRH - Gonadotropin-releasing hormone
GHRH- Growth hormone–releasing hormone
DA- dopamine
105
Which Pituitary hormone does TRH stimulate?
TSH
106
Which peripheral hormones does TSH stimulate?
Thyroxine and Triiodothyronine
107
Which pituitary hormones does GnRH stimulate?
LH
FSH
108
Which pituitary hormone does GHRH stimulate?
Growth hormone
109
Which pituitary hormone does Dopamine effect?
ii. what is different about dopamine in comparison to the other hypothalamic hormones?
Prolactin
ii. It inhibits prolactin. Other hypothalamic hormones stimulate their pituitary counterparts
110
Which peripheral hormones does growth hormone stimulate?
IGF-1
111
Give examples of stimulation tests.
1. Synacthen tests (Synthetic ACTH):
given Intra muscular - check cortisol at 0 min, 30 min and 60 min
Normal: cortisol rises by 150 and reaches 500 - if not they are deficient in cortisol
2. Insulin stress test:
Patient is given insulin and makes patient hypoglycaemic
Hypoglycaemia stimulates Cortisol and GH
Normal: >500 cortisol GH: >7 ug/l
3. Water deprivation test
dont give someone water for 8hrs. Expect ADH levels to go up
check serum and urine osmolalities for 8hrs and then 4hs
Normal: urine osmolality but not the serum osmolality
ratio should be >1.9
112
What is PTH normally secreted in response to?
Low ionised Ca2+ levels
113
what cells are the parathyroid glands composed of?
chief cells supported by oxyphil cells
114
what happens in response to PTH?
1. Increased osteoclast activity releasing Ca2+ and Po43- from the bones
2. Increased reabsorption of Ca2+ and decreased reabsorption of PO43- in the kidneys
3. causes osteoblasts to increase production of RANK-L, which causes osteoclastic formation and activation, thus leading to bone degradation and calcium release.
overall: increase in Ca2+ and decrease in PO43- levels
115
what type of hormones are produced from the adrenal cortex?
steroid hormones
116
what type of hormones are produced from the adrenal medulla?
catecholamine hormones
117
what are the 3 zones of the cortex?
zona glomerulosa
zona fasciculata
zona reticularis
118
what are the main hormones secreted by the zona glomerulosa of the adrenal cortex?
mineralocorticoids
| eg aldosterone
119
what are the main hormones secreted by the zona fasciculata of the adrenal cortex?
glucocorticoids
| eg cortisol
120
what are the main hormones secreted by the zona reticularis of the adrenal cortex?
androgens
| sex steroids and glucocorticoids
121
what is the adrenal medulla innervated by?
pre-synaptic fibres from the sympathetic nervous system
122
what cells within the medulla secrete catecholamines?
chromaffin cells
123
what are phaeochromocytoma cells derived from?
chromaffin cells of the adrenal medulla
124
what hormones do phaeochromocytomas secrete?
carecholamines
125
what system regulates the aldosterone levels within the body?
the renin-angiotensin system
126
Which controlling system effects the hormone production of the Zona glomerulosa?
Renin angiotensin system
127
what effect does mineralocorticoids have?
Increased sodium and water reabsorption
increased potassium secretion
128
which hormones control the release of Glucocorticoids in the zona fasculata?
CRH - hypothalamus
ACTH - anterior pituitary
129
What effect does glucocorticoids have?
Increase metabolsim
Increased BP
Anti inflammatory effects
130
Which hormones control the release of Androgen precursors in the zona reticularis?
CRH
ACTH
131
what effects does the androgen precursors have?
precursors used to produce sex steroids, namely testosterone
132
what is the half life of insulin?
less than 30 mins
133
what increases the secretion of somatostatin?
glucagon
