Blood pressure & osmolarity regulation Flashcards
What does short term regulation of blood pressure?
barroreceptor reflex and changing CO and TPR accordingly
What does mid- long term regulation of blood pressure?
the neurohormonal response, which changes salt and water balance
What two systems detect blood pressure change?
- baroreceptors in carotid sinus, aeorta and afferent arteriole
- Macular densa cells detecting changes in NaCl delivery
What things activate the RAAS system?
- reduced perfusion to AA
- Sympathetic stimulation to the JGA
- reduced perfusion to JGA
(hypovolaemia)
What cells release renin?
Juxtaglomerular or granulosa cells on the afferent arteriole
Describe the RAAS pathway (not its effects)
- Renin converts angiotensinogen to angiotensin 1
- ACE from the lungs converts angiotensin 1 to angiotensin 2
- Angiotensin 2 has range of affects, one of which is stimulating aldosterone release
What effects does angiotensin 2 have generally?
- ADH release
- sympathetic stimulation
- aldosterone release
- systemic vasoconstriction
- cardiac hypertrophy
What affects does angiotensin 2 have in the kidneys? (3)
- Enhances NHE and Na/K/ATPase in the PCT so more Na+ and so water reabsorbtion
- Vascoconstricts the EA so GFR maintained
- It also increases the NCCT in the early DCT for more salt and water reabsorption
What effects does aldosterone have?
- Increases ENaC and Na/k/ATPase in both kidneys and gut meaning more salt and water reabsorption
What affects does sympathetic stimulation have which increase blood volume?
- Directly increases NHE and Na/K/ATPase activity in the PCT
- Stimulates renin release
Angiotensin 2, ADH and noradrenaline all stimulate prostaglandin release from the granulosa cells. What effect does this have?
They locally vasodilate- so vasodilate the AA. They do not spread far enough to be able to vasodilate the EA. This means that they increase hydrostatic pressure in the glomerulus to increase GFR
When is ANP released and what effects does it have?
- When atria dilates due to increased blood pressure
- Cause vasodilation
- Also inhibits ENaC to an extent
If Na+ content of the ECF increases, what will happen to its volume?
Also increase
Are we better at preserving or excreting Na+?
Better at preserving Na+, because diets used to be low in sodium. Now theyre very high in sodium and were not good at excreting it- leads to hypertension.
Which aquaporins are found in the PCT, descending limb and collecting ducts? What is their role?
PCT= AQP 1 and 2
Descending limb= AQP1
Collecting ducts= AQP 2,3 and 4
They allow water to move with the ions
Describe sodium reabroption in the loop of henle?
- In descending limb, aquaporins and loose junctions allow water to move out due to the corticomedullar concentration gradient
- but no ion channels to ions remain within the lumen
- in thin ascending limb, Na+ passively diffuses into intersitium because the water moving out has made the lumen hyperosmotic
- In thick AL, NKCC2 moves sodium out lumen
What are the two types of collecting duct cells and what is each of their roles?
- principle cells- reabsorption of Na by ENaC
2. intercalated cells- reabsorb Cl- and also variably secrete H+/ HCO3- for acid base balance
What can cause secondary hypertension? (4)
- Renovascular hypertension/ stenosis
- Coarctation of the aeorta (stenosis of aortic arch)
- Primary hyperaldosteronism (conns syndrome)
- Cushings syndrome
- Phaeochromocytoma, acromegaly, hyperthyroidism all cause hypertension but dont involve the RAAS
What normally prevents cortisol from binding to mineralcorticoid receptors in the kidney intended for aldosterone?
It is normally broken down to cortisone in the kidneys. This sysem is overwhelmed in cushings. It is also inactivated by liquorice.
Why do you not normally get fluid overloaded in renovascular hypertension?
Because although RAAS is activated and more fluid is reabsorbed, the other good kidney has good enough perfusion to excrete what the other retains. However you still get hypertension due to the other effects of RAAS and sympathetic stimulation.
What may cause renovascular stenosis?
Atheroma Fibromusclar dysplasia (makes renal artery look like beads on a string on MRI)
How are changes in plasma osmolarity (eg when we drink lots of water) adjusted for?
By changing the amount of water we reabsorb in the collecting ducts
What senses changes in plasma osmolarity?
osmorereceptors in the OVLT of the hypothalamus, also some input from the baroreceptors
What are the two responses to increases in plasma osmolarity?
- Secrete ADH
- Stimulate thirst
What affects does ADH have?
- Increases expression of AQP2 in collecting ducts
- This increases ability for water to diffuse into blood
- Also increases urea transport/ recyling to maintain corticomedullary concentration gradient
WHere is ADH released from? How much does plasma osmolarity have to change by for it to be released?
ADH is produced in the hypothalamus and released form the posterior pituitary.
Osmolarity only needs to change by 1% for it to be released- therefor its almost always being secreted but in different quantities
What happens to the threshold for ADH release when blood volume decreases?
It decreases- the body would rather maintain blood volume than blood osmolarity so ADH is released more readily just to get more fluid in, even if the blood ends up being hypoosmotic as a result.
How is the corticomedullary concentration gradient established?
- ascending limb extrudes ions and makes interstitium hyperosmotic
- water leaves descending limb to make its osmotic pressure equal to the interstitium
- filtrate in descending limb now hyperosmotic
- this filtrate moves round where yet more ions are removed (more hyperosmotic)
- the same thing happens again and again until the bottom of loop is 1,200 mOsm more concentrated than the top
- the gradient is maintained by removal of ions from the ascending limb and then removal of water from the descending limb (counter current exchange)
Describe the role of urea recycling when ADH is released
- If ADH only allowed water movement, water would move into the medulla and reduce its concentration, thus removing the corticomedullary concentration gradient
- ADH therefor also allows urea to move with the water and so ensure the medullar maintains the same osmolarity
Where is urea reabsorbed during urea recyling?
the loop and the vasa recta
What is diabetes insipidus?
Lack of ADH secretion, usually due to head trauma, surgery or tumours. It means you wee lots and have high serum [Na+] because youre excreting all your water
What is nephrotic diabetes insipidus?
Insensitivty to ADH. It is usually genetic but can be induced by some drugs.
What is SIADH and what could cause it?
syndrome of inappropriate ADH secretion.
Usually due to head trauma, small cell lung cancers, sarcoidosis, brain tumours and infections ect
Although rare, what may cause a true hyponaturaemia (low levels of Na+ in blood, because of low Na+ rather than high blood volume)
Diarrhoea, vomiting, diuretics, peritonitis, burns
Other than SIADH, what may cause relative hyponaturaemia (low serum Na+ conc, but due to high blood volume)?
SIADH, heart failure (more ADH produced), kidney disease, liver failure, ACE inhibitors
How will hyponaturaemia present?
- confusion because neurones swell and demyelinate
- symptoms of cause- odema, high BP, polyuria, polydipsia ect
- blood results: serum na+ low, blood osmolarity low,
- urine: osmolarity and na+ high if due to excess ADH
What would happen to ECF and ICF volumes during isoosmotic volume loss (bleed, diarrhoea)
- ECF vol decrease
- ICF stays the same as iso osmotic loss so no ion movement so no water movement
What would happen to ECF and ICF volumes during hypo-osmotic volume loss (eg sweat)
Water is lost but solute remains
- ECF osmolarity increases and volume decreases
- Fluid moves out of ICF to ECF
- Therefor ICF volume decreases and osmolarity increase also
Why is it that you often need to urinate after a swim of longer than 30-45 mins or so?
The pressure exerted by the water on your peripheral blood vessels tricks the body into perceiving an increase in BP. This means you stimulate water loss to correct the perceived hypervolaemia.
