Week 4 Flashcards
Adrenal medulla
Modified sympathetic ganglia, secreted catecholamines
Adrenal cortex
Steroid factory, it secretes steroid hormones
Main catecholamine
epinephrine, it is secreted in enough quantity to exert effects
chromaffin cell
post ganglionic sympathetic neuron
Catecholamines
Epinephrine, norepinhrine, dopamine
Stimulus for release of epinephrine
Activation of the sympathetic nervous system - fight or flight response
role of epinehrine in skin, intestine, kidney
intestine: muscle relaxation, arteriole contriction
skin and kidney: arteriole contriction
role of epinehrine in liver and fat
liver: glucose release (via glycogenolysis)
fat: fatty acid release
role of epinehrine in muscle, brain and resp
muscle: arteriole contraction (alpha receptors), arteriole relxation (beta receptors)
brain: increased alertness
resp: bronchodilator
Reactions of anaphylactic shock
bronochospasm (contriction of airways), decrease in blood pressure
How does epipen counteract symptoms of anaphylactic shock?
bronchodilation, vasoconstriction in skin, kidney, intestine and vasodilation in skeletal and cardian muscles.
Parts of adrenal cortex
Zona glomelurosa, zona facilutata, zona reticularis
what does zona glomerulosa secrete
aldosterone
what does zona fasciculata secrete
glucocorticoids - cortisol
Weak androgens
Less than 20% activity of testosterone but they are converted to more potent androgens and estrogens in peripheral tissue
what does zona reticularis secrete
sex steroids
What increases androgen production?
ACTH
physiological role of androgens in children
Male prenantal development, also contribute to andrenarche - pubic hair, body odor, oily skin, acne - for both males and females
physiological role of androgens in adult men
no physiological role - testes provide androgens for males
physiological role of androgens in women
although ovaries provide estrogen, androgens maintain pubic and axillary hair, source of estrogen after menopause
Aldosterone
its actd on the distal tubule of increase Na+ absorbtion and K+ secretion
Cortisol
Main glucocoricoid, secreted by zona fasiculata
role of cortisol
mediation long term stress
what is the control pathway of secretion of cortisol
hypothalamic-adrenal-pituatary pathway
diurnal rhythm
continious secretion of costisol
short term stress
nerve impulse –> spinal cord –> preganglionic sympathetic fibres –> adrenal medulla (secretes amino acid based hormones) –> catecholamines
short term stress response
- heart rate and blood pressure increases
- bronchioles dilate
- liver converts glycogen to glucose and releases glocse to blood
- blood flow chnages, reducing digestive system activity
- metabolic rate increases
prolonged stress
hypothalamus –> CRH released –> corticoptropic cells of anterior pituatary –> ACTH –> targets blood –> adrenal cortex –> steroid horones secreted
long term stress response
- kidneys retain sodium and water
- blood volume and blood pressure rise
- proteins and fats converted to glucose or broken down for energy
- blood glucose increases
- Immune system supressed
What is cortisol protective against?
Hypoglycemia through the permissive effect
Metabolic effect of cortisol
they primarily catabolic
1. promotes glucogenesis
2. brakdown of skeletal muscle proteins
3. enhances lipolysis
4. supresses the immune system
How is cortisol used as a drug to supress the immune system?
- inhibit inflammatory responses
specififc uses: poison ivy, allergies, asthma
cortisol regulation
it is regulated through the negative feedback loop.
cortisol supresses both CRH and ACTH production, inturn stopping its own production.
what can long term use of cortisol drugs do
inhibition of ACTH secretion and atrophy cortisol secretig cells
addisons disease (adrenal insifficiency)
hyposecretion of adrenal steroid hormones.
it causes destruction of the adrenal by autoimmunity, sometimes infection
symptoms of addisons disease
hypotension (low aldosterone –> low Na + reabsorbtion –> increased water loss –> low blood volume) , hypoglycemia. (low cortisol –> low blood glucose levels)
Cushings syndrome - excess cortisol
caused by tumours, cortisol therapy
symptoms of cushings syndrome
hyperglycemia, muscle protein breakdown, lipolysis but build up of fat on trunk and facem increased apetite, mood elevation but then followed by depression and problems with learning
What does excessive water loss do?
It can cause disease (hypotension/shock)
there is less extracellular fluid –> decreased blood pressure
How is water distributed in the body?
2/3 in intracellular fluid
1/3 in extracellular fluid - 75% interstitial and 25% plasma
Symptoms of excessive water loss
confused, chess pain, low blood pressure, no urine
What does too much water in the body do?
back up in legs, abdomen and lungs
it can cause difficulties walking and breathing
How is urine formed in the nephron?
Filtration, reabsoprtion and secretion
What is the nephron/kidney responsible for
- excreting waste
- regulating blood volume
- controlling electrolytes
- blood pH
- Vitamin D (via PTH)
Mechanism in nephron
- After fluid (isoosmotic) leaves the proximal tubule, it goes into the descending limb of the loop of henle. here the fluid gets more conc s only water is reabsorbed.
- in the ascending limb ions are reabsorbed (hypoosmotic)
- in the distal tubule, hormones manage the reabsorption of water and ions.
- lastly, urine osmolarity will depend on reabsorption in the collecting duct; most reabsorption happens here.
Osmolarity
Concentration of a solution expressed as total number of solute particles per litre
Function of Vasopressin
Increases water reabsorption in the kidneys - conserves body water, water balance and fluid homeostasis, increases blood volume and blood pressure
also regulates the permeability of cells in the kidney - increased permeability - high reabsorption and low urine output
Function of Aldosterone
increase Na+ reabsorbtion and K+ secretion
it acts on the distal tubule and collecting duct
Function of Atrial Netriuetic peptide and BNP
decrease Na+ and water reabsorption ( lowers blood pressure). Increase K+ reabsorption.
it suppresses renin, aldosterone and vasopressin
where is vasopressin synthesized and secreted from
Syntheisized in the hypothalamus and secreted from the posterior pituitary
Other name for vsaopressin
Antidiuretic hormone ADH
Bond in vsaopressin
disulfide bond between cys-cys
Stimuli for vasopressin release and how it is detected
Low blood pressure - detected by reduced stretch of atrial walls and aortic and carotid arteries
high plasma osmolarity - detected by osmoreceptors in hypothalamus - MODT IMP STIMULUS
Regulation of vasopressin release
- low blood pressure and high osmolarity are detected
- PASSES TO HYPOTHALAMIC neurosecretory cells
- passed neurosecretory terminals in pituitary
- ADH released
- increased H2O permeability and water reabsorption takes place in collecting duct
What does increase in vasopressin cause?
thirst
process of water pore binding and reabsorption of water
- vasopressin binds to receptor
- cAMP released - signal cascade caused
- aquaporin 2 water pores form on membrane of collecting duct lumen
- water is reabsorbed into blood
- osmolarity of blood reduces
Where does vasopressin insert water pores?
Vasopressin inserts water pores into distal convulated tubule or in collecting duct cell membranes
where is aldosterone sythesized?
adrenal cortex
How is aldosterone synthesis controlled?
it is controlled by negative feedback: simple (K+, osmolarity) and complex (renin-angiotensin II)
what are stimulators for aldosterone synthesis?
High K+ in plasma - most important stimulus
Angiotensin II (via blood pressure) - low bp
through RAAS - renin angiotensinogen pathway
regulation of aldosterone synthesis and action
- high K+ in plasma and low blood pressure (activates RAAS pathway) are the stimuli
- Causes adrenal cortex to synthesize aldosterone
- aldosterone goes to P cells of collecting duct
- this causes increased Na+ reabsorption and K+ secretion
what is the inhibitor for aldosterone synthesis?
high osmolarity in extracellular fluid
What does aldosterone act on?
distal tubule and collecting duct
What does aldosterone prevent degradation of?
Apical Na+ channel
MAIN aldosterone action
- aldosterone combines with a cytoplasmic receptor
- Hormone-receptor complex initiates transcription in the nucleus.
- Translation and protein synthesis make new channels and pumps.
- aldosterone-induced proteins module existing channels and pumps
- result is increased Na+ reabsorption and K+ secretion
Renal juxtaglomerular cells
they secrete the enzyme renin when blood pressure falls
What does aldosterone increase expression of
Na+ and K+ channels and Na+/k+ ATPase
Renin-angiotensin pathway
- the drop in blood pressure is sensed by the kidney
- renin is released
- renin cleaves angiotensinogen (produced by liver) to produce angiotensin I
- ACE produced by the lungs will cleave angiotensin I to produce angiotensin II
- angiotensin II is active and it
what does angiotensin do
- increases vsaopressin
- stimulates thirst
- potent vasoconstricutor
- increases proximal tube Na+ retention
BNP
in ventricles (myocardial cells) and neurons
Atrial Natriuretic peptide
in atria (myocardial cells) and neurons
CNP
in the brain, pituitary, vessels, and kidneys
ANP release
- increased blood volume causes increased atrial stretch
- myocardial cells stretch and release ANP
ANP effect on hypothalamus
less vasopressin
therefore, high NaCl and water excretion. decreased blood volume and decreased BP.
ANP effect on kidney
tubule: less Na+ reabsorption
afferent arteriole: greater glomerular filtration rate and decreased renin ( low blood pressure) - also decreased aldosterone
ANP effect of adrenal cortex
less aldo sterone - greater nacl and water excretion, decreased blood volume, decreased blood pressure
ANP effect on medulla oblongata
decreased sympathetic output - decreased blood pressure.
Why is calcium critical for normal physiology ?
- intracellular signalling
- hormone secretion
- blood clotting
- neural excitability
- muscle contraction
- building and maintaining bone
descibe calcium in bone
calcium in bone is mainly in crystals - hydroxyapatite
A small fraction is ionized and readily exchangeable with ECF and plasma.
locations of calcium
- extracellular matrix
- extracellular fluid
- intracellular Ca2+
Where does calcium have the ability to move?
between bone and ECF (both ways), kidney and ecf (both ways), cell and ecf (both ways), small intestine to ecf
3 cells in bones
osteoblasts, osteoclasts and osteocytes
osteoblasts
bone forming cells
osteoclasts
break down bone
1. they are attached to bone matrix
2. they secrete HCl and proteases - low pH
3. acid and proteases break down the matrix
4. Ca2+ released becomes part of ionised Ca2+ pools - enters bloodstream
osteocytes
maintain bone, they are retired osteoblasts that are surrounded by bone matrix
making bone
creating calcium phosphate complexes ( calcium crystallization)
bone dynamics
- osteoclast precursors –> osteoclast - they create pits - ACTIVATION
- osteoblast precursors fill in the pit, forming osteoid - REVERSAL and BONE FORMATION
Osteoclast formation
RANKL on osteoclasts interact with RANK on osteoclast precursors.
differentiation nd fusion takes place forming osteoclast.
RANK
receptor activator of nuclear factor kappa B
RANKL
RANKL
Osteoproteregin (OPG)
Secreted by osteoblasts, it blocks RANK and RANKL interaction - preventing formation of osteoclasts
Action of Denosumab
- it specifically binds to RANKL
- mimics the effect of OPG
- mops up RANKL not letting it bind to osteoclasts
3 hormones that control plasma Ca2+ levels and what do they act on
parathyroid hormone, calcitriol, and calcitonin
act on: bone kidneys digestive tract
Where is parathyroid hormone released from
parathyroid glands - 4 tiny glands
function of parathyroid hormone
increases plasma Ca2+ conc by effluc of Ca2+ from bone and decreased loss of Ca2+ in urine.
stimulus: low plasms conc
What happens when Ca2+ is bound to Gq receptor
PTH secretion is inhibited
PTH synthesis is reduced
PTH effects on bone
- PTH acts on osteoblasts by increasing cAMP to increase RANKL and decrease OPG expression
- More osteoclasts form leading bone resorption
Organs critical in the development of cacitriol
Skin, Liver, Kidney
What does calcitriol target to increase serum calcium?
intestine, bone, kidney
Formation of calcitriol
- precursor of vit D3 (7-dehyrocholestrol) in skin needs UV light to transform to cholecalciferol (vit D3)
- In liver cholecalciferol transforms to 25-hydroxycholecalciferol.
- PTH acts on it and in kidney it becomes calcitriol (vitamin D3 hormone).
How does cacitriol act?
- it increases Ca2+ uptake from small intestine
- renal Ca2+ reabsorption and mobilization from bone.
Calcitriol and vitamin D nuclear receptor binding
- Calcitriol and vitamin D nuclear receptor bind
- in nucleus. the complex and retinoic acid receptor become a heterodmer.
- they then bind to the vitamin D response element on DNA
- transcription stimulated, mRNA formed.
how is blood phosphate controlled?
PTH: increases phosphate release from bone and decreases phosphate reabsorption form kidney
calcitriol: increases phosphate absorption by intestine and reabsopriton by kidney.
