Physiology Flashcards
describe the structure of insulin
two polypeptide chains, an A chain and a B chain, covalently linked by two inter-chain disulphide bridges. There is a third, intra-chain disulphide bridge.
where is insulin synthesised
beta cells in the islets of Langerhans
what can be used as a measure of endogenous insulin production
C peptide
key points of the production of mature insulin (4)
prepoinsulin is synthesised in the RER of pancreatic b cells
removal of signalling peptide during insertion into the endoplasmic reticulum generates proinsulin
proinsulin = A chain + B chain + connecting peptide in the middle (C peptide)
endopeptidases excise the C peptide generating mature insulin
how can synthetic insulin preparations be created
by changing the amino acid sequence of endogenous insulin
secretion of insulin (5)
glucose enters b cells through the GLUT2 glucose transporter and is phosphorylated by glucokinase
increased metabolism of glucose leads to increase in ATP
ATP inhibits the ATP-sensitive K+ channel
depolarisation of the membrane causes opening of voltage gated Ca2+ channels
fusion of secretory vessels containing insulin with the cell membrane
what are the 2 types of insulin release
basal insulin release
post-prandial insulin release
describe post prandial insulin secretion
biphasic pattern
why is post-prandial insulin release biphasic
5% is immediately available for release to prevent a sharp increase in glucose
reserve pool requires preparation and mobilisation before its available for release
what does insulin release cause to decrease (2)
lipolysis
gluconeogenesis in the liver
what does insulin release cause to increase (7)
- Amino acid uptake in muscle
- DNA synthesis
- Protein synthesis
- Growth responses
- Glucose uptake in muscle and adipose tissue
- Lipogenesis in adipose tissue and liver
- Glycogen synthesis in liver and muscle
where in the islets are b cells found
close to blood vessels to allow easy identification of blood glucose conc
name the 5 types of cells found in the islets of langerhans
- α-cells secrete glucagon
- β-cells secrete insulin
- δ-cells secrete somatostatin
- PP-cells secrete pancreatic polypeptide(PP)
- ε-cells secrete Ghrelin
how does T2DM affect beta cells
number of secretory granules per β-cell is reduced
what happens to alpha cells at low glucose (4)
- KATP channels open
- Voltage-gated sodium channels (NaV) contributes to action potentials
- P/Q type voltage gated calcium channels (CaV) enable calcium influx
- Glucagon exocytosis triggered
role of glucagon
acts on the liver to promote hepatic glucose
production, raising blood glucose
what is the incretin effect
greater increase in insulin production in response to oral glucose than in response to IV glucose
who has an impaired incretin effect
patients with T2DM
what are incretins
intestinal secretion of insulin
name the 2 key incretin hormones
GIP, GLP1
where is GIP secreted from
K cells in the intestinal epithelial layer
where is GLP1 secreted from
L cells after eating
role of GLP1 (3)
increases glucose-induced insulin release by β-cells
promotes beta cell proliferation
suppress glucagon secretion at depolarising glucose concentrations
response of pituitary gland to increased plasma osmolarity
increased ADH
consequence of increased ADH (3)
more aquaporins in DCT and CD cells of the kidney → more water reabsorbed in kidney → small volume of concentrated urine
response of pituitary gland to decreased plasma osmolarity
decreased ADH
consequences of decreased ADH (3)
less aquaporins in DCT and CD cells of the kidney → less water reabsorbed in kidney → large volume of dilute urine
what does concentrated urine mean for osmolarity
high osmolarity
what does diluted urine mean for osmolarity
low osmolarity
how does mineralocorticoid activity affect Na+ balance
too much means sodium gain
too little means sodium loss
where is sodium confined to (body compartments)
extracellular fluid
state some clinical signs of hyponatraemia
- Increased pulse
- Dry mucous membranes
- Soft/sunken eyeballs
- Decreased skin turger
- Decreased consciousness
- Decreased urine output
- Postural decrease in blood pressure
state some clinical signs of hypernatremia
- Coughing, shortness of breath
- Tiredness
- Pulmonary oedema
- Pleural effusion
- Ascites
- Swelling in ankles and legs
what can cause hyponatraemia
too little sodium or too much water
what can cause hypernatremia
too much sodium or too little water
what is the most common cause of low Na+
SIADH
what is the most common cause of high Na+
low water intake
management of low Na+ (2)
- If due to too little sodium - give sodium IV as saline or orally
- If due to too much water - remove water through fluid restriction
management of high Na+
- If due to too little water - give water as IV dextrose
- If due to too much sodium - remove sodium through diuretics
what does SIADH stand for
Syndrome of Inappropriate Antidiuretic Hormone Secretion
what happens in SIADH
excessive release of ADH causing an abnormal and excessive retention of water
describe the hypothalamic-pituitary-thyroid axis (5)
- hypothalamus produces TRH
- stimulates anterior pituitary to produce TSH
- binds to receptor on thyroid epithelial cells
- production of cAMP increases production and release of T3 and T4
- circulate in bound and free forms and suppress the production of TRH and TSH
state the 2 gonadotrophic hormones secreted by the pituitary
follicle stimulating hormone
luteinizing hormone
role of FSH in men
causes the testes to produce sperm
role of FSH in women
causes the growth of ovarian follicles and causes the ovary to secrete oestrogen which thickens the endometrium
role of LH in men
causes the testes to secrete testosterone
role of LH in women
causes ovulation and causes progesterone production by the corpus leutum
what is GnRH
gonadotrophin releasing hormone
describe the release of GnRH
pulsatile manner
where is GnRH synthesised and released from
hypothalamus
role of GnRH
causes the release of FSH and LH from the anterior pituitary
what is GnRH pulsatility regulated by
oestrogen and progesterone/testosterone
effect of progesterone on GnRH
increase in progesterone reduces the frequency of GnRH pulses
effect of oestrogen on GnRH
increase in oestrogen will increase pulsatility of GnRH driving the release of LH
what are the 3 key events in the menstrual cycle
follicular growth
ovulation
luteal phase
frequency of GnRH pulses throughout the menstrual cycle
more frequent during early follicular phase and less during the luteal phase
what does a follicle consist of
an oocyte surrounded by follicular cells
what causes endometrium to thicken
oestrogen
what causes endometrium to become a secretory tissue
progesterone
what does early stage follicular growth depend on
NOTHING
when does the LH surge happen
34-36 hours before ovulation
what influences the formation of the corpus leutum
LH
what happens during the formation of the corpus luteum (2)
increase in progesterone production
granulosa and theca cells transform to luteal cells
name some functions of oestrogen
regulates LH surge
reduces vaginal pH
decreases viscosity of cervical mucous to facilitate sperm penetration
what secretes oestrogen
ovaries and adrenal cortex
and placenta during pregnancy
what secretes progesterone
corpus luteum
placenta during pregnancy
what is the main function of progesterone
maintains pregnancy - inhibits the secretion of LH
how is progesterone pro-gestation
maintains thickness of the endometrium
relaxes the myometrium
increases basal body temperature
name 3 ways we can predict ovulation
spinnbarkeit
ovulation kits
basal body temperature
what is spinnbarkeit
describes the property of cervical mucous which changes in response to oestrogen levels around the time of ovulation
how do ovulation kits work
use the LH surge to predict the onset of ovulation
when should basal body temperature be measured
in the morning before moving about or eating after at least 6 hours of sleep
what regulates sperms ability to penetrate cervical mucous (4)
thickness of the mucous
motility of the sperm
interaction with ROS
interaction with mucins
histology of the stroma of the cervix
fibroblast cells surrounded by a collagen matrix
histology of epithelium of the cervix
columnar epithelial cells, site of mucus production
role of the stroma of the cervix
regulates the rigidity of the cervical wall
role of the epithelium of the cervix
site of mucous production
what is released once an embryo implants
HCG
what produces testosterone
leydig cells of the testis
where are sertoli cells found
seminiferous tubes
what is produced by sertoli cells
mature sperm
inhibin
where does spermatogenesis occur
in the testes
how long does the entire spermatogenic process take
70 days
what happens to testosterone when it reaches target tissues
converted to dihydrotestosterone and oestradiol
hypothalamic-pituitary -thyroid axis
hypothalamus produces TRH
stimulates anterior pituitary to produce TSC
thyroid gland produces and release T3 and T4
T3 and T4 supress the production of TRH and TSH
what cells does the thyroid gland consist of
follicles lined by cuboidal epithelial cells
which is the biologically active thyroid hormone
T3
what is the most common (in terms of amount) thyroid hormone
T4
role of T4
prohormone
converted to T3 by the liver and kidney to become biologically active
what is the most common hormone binding protein for T3 and T4
thyroxine binding globulin
which versions of T3 and T4 can enter cells
ONLY unbound hormones
name some states that can cause an increase in TBG
pregnancy, OCP, chronic active hepatitis and biliary cirrhosis
name some states that can cause a decrease in TBG
cushings, severe systemic illness, chronic liver disease
consequence of alterations in TBG levels
confusing total T4 levels - most levels measure free T4
effect of thyroid hormones on all cells
increase metabolic rate
increase glucose uptake
effect of thyroid hormone on liver tissue
increased glycogenolysis and gluconeogenesis
decreased gylcogenesis
effect of thyroid hormone on adipose tissue
increased lipolysis
decreased lipogenesis
effect of thyroid hormone on the lungs
increased breathing rate
effect of thyroid hormone on the heart
increased HR and force of contraction
how do thyroid hormones increase basal metabolic rate (3)
- Increase number and size of mitochondria
- Increase oxygen use and rates of ATP hydrolysis
- Increase synthesis of respiratory chain enzymes
key enzyme in the degradation of thyroid hormones
de-iodinases
where are type 1 de-iodinases found
liver and kidney
where are type 2 de-iodinases found
heart, skeletal muscle, fat, thyroid, and pituitary
where are type 3 de-iodinases found
foetal tissue, placenta, and brain (except pituitary)
role of type 3 de-iodinases
breaks down the majority of T3 into inactive T2 and T4 into inactive reverse T3
role of TRH
stimulates the anterior pituitary to release TSH and prolactin
role of CRH
stimulates the anterior pituitary to release ACTH
what is autocrine signalling
cell signals to itself
what is paracrine signalling
cell signals to its close neighbours
what is endocrine signalling
cell signals via molecules transported by the blood to target distant cells
give some examples of peptide hormones
oxytocin, ADH, GH, insulin
thyroxine binding globulin
binds thyroxine selectively and also some T3
another name for T4
thyroxine
another name for T3
triodothyronine
role of albumin
binds many steroids and thyroxine
role of transthyretin
binds thyroxine and some steroids
what controls the release of prolactin
tonic inhibition by hypothalamic dopamine
what inhibits prolactin secretion in non-pregnant women
prolactin inhibiting hormone (dopamine)
what regulates cortisol production
HPA axis
HPA axis
hypothalamus release corticotropin releasing hormone
anterior pituitary releases adrenocorticotropic hormone
adrenal cortex releases cortisol
what regulates aldosterone
RAAS
what activates RAAS
decreased blood pressure
RAAS run through
renin released from the kidneys
causes angiotensinogen from the liver to be converted to angiotensin 1
ACE from the lungs converts angiotensin 1 -> 2
angiotensin 2 acts on the adrenal gland to stimulate aldosterone
consequence of the release of aldosterone
acts on the kidneys to stimulate the reabsorption of salt and water
what is another role of angiotensin 2
acts directly on blood vessels to stimulate vasoconstriction
