Renal structure and function: salts Flashcards
What cation is found in largest quantities in ECF?
Na, around 140mM Na, 5mM K
What anion is found in the largest quantity in ICF?
K, around 140mM K, 5mM Na
_____ is the main ion that is tightly controlled in the ECF and _____ is the main ion tightly controlled in the ICF
Na
K
Total body Na _____ is sensed, not concentration.
Content
Why is sodium content measured rather than sodium concentration?
The amount of salt, i.e. salt content is what influences plasma osmolality. Osmolality is usually maintained at the expense of volume changes, thus usually remains within narrow limits. The osmoreceptors control water intake by altering thirst and control renal excretion by altering ADH release. Changes in Na influence osmolality, for example if an animal eats a food high in Na, plasma osmolality will rise, inducing thirst and water absorption from the collecting ducts. This increases body volume and reduces salt concentration, but does not alter the amount of Na present. Therefore osmoregulation controls plasma Na by altering water balance, but does not control body Na content.
What effect does altering Na concentration have on body volume?
If body Na is altered, the osmoregulatory system adjusts water balance and therefore body volume to maintain osmolality. Body volume can be controlled by altering Na content. The kidney controls Na excretion and therefore body volume
What is hypernatraemia?
High ECF Na
What are the potential complications of hypernatraemia?
Lots of fluid entering the blood due to increase osomolality of the blood can result in problems such as hydrocephalus
How would you treat hypernatraemia?
Induce natruesis to cause a net loss of Na
What is hypernatraemia?
Low ECF Na
What are the potential complications of hyponatraemia?
Too little fluid in the blood (hypovolaemia)
How would you treat hyponatraemia?
Induce Na retention to recover Na ions
Name the four key hormones that control ECF Na. 1. 2. 3. 4.
Aldosterone
ADH
Natriuretic peptide
RAAS
What biochemical class is aldosterone?
Mineralocorticoid
What is the action of aldosterone?
Promote Na reabsorption in the CD
Is aldosterone water or lipid soluble?
Lipid
What response is seen when aldosterone binds to its receptors?
Transcription and translation of more mineralocorticoid receptors
Aldosterone is inhibited in ______ and stimulated in ______
Hypernatraemia
Hyponatraemia
Aldosterone stimulates Na reabsorption in the CD, what effect does this have on ECF volume and blood pressure?
Increases both
What channels does aldosterone action act on?
Distal tubule Na/K-ATPases
CD apical ENAC
With Na retention, _____ follows. This is what restores blood volume.
Water
What effect does aldosterone have on the expression of Na/KATPases in the baolateral membrane of the cell?
Increases expression
What effect does aldosterone have on the expression of Na channel on the apical membrane?
Increases expression
Aldosterone does not markedly effect Na concentration, true or false?
True, this is because changes in osmolarity are largely maintained by a loss of water. Water and Na concentration is all relative, so if you get an increase in plasma concentration of Na, you will get a compensatory increase in water retention. The concentration may stay the same while the actual total body content of Na has increased.
Thirst and ADH have a greater effect than aldosterone at maintaining water and Na balance, true or false?
True
How does aldosterone act to counteract an increase in plasma K?
Increased release of aldosterone from the adrenal glands (ZG), increases renal secretion of K, resulting in increased excretion of K leading plasma K to come down to a normal level
What are the sites of K excretion in the kidneys?
CD and DT
How does secretion occur in the DT and CD?
Coupled to Na/K pumps
In which direction does K travel in the epithelial cells of the DT when being secreted?
From epithelial cells to the tubular lumen via ion channels
Plasma content of K is detected resulting in changes of aldosterone secretion, true or false?
False, K concentration is detected
What is another name of ADH?
Vasopressin
What biochemical class is ADH?
Peptide
Where is ADH made?
Hypothalamus
Where is ADH secreted from?
Posterior pituitary
What 5 factors stimulate ADH release? 1. 2. 3. 4. 5.
Hypovolaemia Hypotension Dehydration Angiotensin II Sympathetic activation
How does ADH conserve water?
Upregulates the amount of aquaporins in the apical membrane of principle cells in the collecting ducts and DT
Osmoreceptors in the _____ detect changes in osmolarity in the ECF
Hypothalamus
Increased ECF osmolarity _____ ADH secretion from the posterior pituitary
Increases
As well as changes in plasma osmolarity, what else can stimulate ADH release?
Decline in blood volume and decline in blood pressure
Where are changes in blood volume detected, and what are they detected by?
Volume receptors in the wall of the atria and veins
Where are changes in blood pressure detected, and what are they detected by?
Baroreceptors in the aortic arch and carotid sinus
Although osmoreceptors are more sensitive when it comes to ADH regulation, volume receptors can give the _____ _____ in ADH.
Greatest rise
What does ANP stand for?
Atrial natriuretic peptide
What effect does ANP have on Na balance?
Increases Na loss
What are the major actions of ANP?
Renal vasodilation
Increase in GFR
Decreases renin release opposing the RAAS
Decrease aldosterone release
Decreased resorption/increased loss of Na
Decreased ADH release
Where is ANP stored and released from?
Right atrium
What causes ANP release?
Release is stimulated by stretch of the right atrium
Decreased blood volume results in ANP release, true or false?
False, increased blood volume results in ANP release
What does RAAS stand for?
Renin-angiotensin-aldosterone system
What level(s) does the RAAS work on?
Systemic and organ level
What does the RAAS detect to bring bring about a physiological change?
Fall in blood pressure or volume
Outline the physiological changes and how they activate the RAAS.
Fall in blood pressure is detected in the afferent arteriole, renin secreted from juxtaglomerular cells, renin converting angiotensinogen to angiotensin II which will act to increase blood pressure
On what tissues does angiotensin II act and what actions does it have?
Adrenal gland, release aldosterone
Pituitary, release ADH
Arterioles, causes vasoconstriction
Also acts on the PT (insertion of apical Na/H exchangers, basolateral Na/HCo3 ATPase and Na/K ATPases), TAL (insertion of apical Na/H and Na/K/2Cl exchangers) and CD (ENaC channels)
These result in increase blood pressure or volume
How does angiotensin II promote Na retention in the kidneys?
PT: insertion of apical Na/H exchangers, basolateral Na/HCo3 ATPase and Na/KATPases
TAL: Na/H and Na/K/2Cl exchangers
CD: ENaC channels
Roughly how much Na is reaborsbed in the PT?
65%
How does absorption of Na occur in the PT?
Na/KATPases, Na/H exchange transporters
Roughly how much Na is absorbed in the LOH?
25%
The thin ascending limb of the LOH is _____ to Na. Therefore, Na (and Cl) _____ out into the interstitial fluid.
Permeable
Diffuse
Which pump in the thick AL utilises the Na gradient to co-transport one Na, one K and 2 Cl?
Na/K/2Cl cotransporter
Ions are moved from the tubule lumen to the epithelial cells, but one ion passes back through to the lumen of the tubules through the energy requiring ROMK channel- which ion is this?
K
The net charge of the tubule lumen is _____ due to the net removal of one Na and two Cl. K passes back into the tubule lumen.
Positive
Roughly how much Na is reabsorbed from the DT?
5-8%
How is Na and Cl reabsorbed in the DT?
NCC channels
Roughly how much Na is reabsorbed in the CD?
5-10%
How is Na taken up in the CD?
ENaC channels in principle cells
When Na is taken up in the CD, what happens to the charge of the tubular fluid?
Becomes more negative
How does a more negative lumen in the CD (due to Na uptake by ENaC cells) influence Cl uptake?
Increases paracellular Cl uptake
Are principle cells responsive to ADH?
Yes
What type intercalated cells are present in the CD?
B-intercalated cells
What is present on B-intercalated cells in the CD that creates a gradient that is used to drive the secretion of HCO3- coupled to Cl absorption?
H+ATPases
What happens if an animal Na laods or ECF volume or blood pressure is high?
Renin secretion is inhibited
Aldosterone-dependant Na resorpton is inhibited
Excess Na is excreted in the urine (action of ANP)
Where is the majority of K found in the body?
ICF
What is a method of short term control K in the body?
ECF to ICF shifts of potassium
What are two mechanisms that controls K excretion longer term?
1.
2.
Renal excretion
GI excretion
Which of renal or GI excretion causes the most loss of K from the body?
Renal excretion
In the PT, _____% of K is reabsorbed.
65%
Similar proportions of _____, _____ and _____ are reabsorbed in the PT
Na, K, water
What results in K being constantly pumped into the tubular epithelium?
Na/KATPases
Once pumped into the epithelium, K can have two fates, what are these?
Leak into interstitium
Pumped out of the epithelial cells by Cl/K pumps
Some K moves into the filtrate in the TDL, but this is countered by movement of K out of the loop and into the CDs. The net result is some _____ of K across the medullary interstitum.
Recycling
Roughly how much K is reabsorbed in the TAL?
30%
How does K enter the epithelial cells of the TAL?
Na/KATPases
What is the name of the transporters that transport Na, K and 2Cl into the epithelial cells?
NKCC2 transporters
Apart from the NKCC2 transporters, what other channels are present in the TAL that pump K into the epithelial cells?
Na/KATPases
What transporters pump K out of the epithelial cells of the TAL?
K/Cl transporters
By what other route can K be reabsorbed in the TAL?
Paracellularly due to the positive charge of the tubule contents
95% of K is reabsorbed before the filtrate reaches the CD’s, true or false?
True
There are two cell types in the collecting tubules and ducts with opposing actions with regards to K absorption and secretion. What are these cells called and what is their function?
Principle cells secrete K
Intercalated cells reabsorb K
_____ cells reabsorb K while _____ secrete K.
Intercalated
Principle
K _____ outweighs K _____ in the CD.
Secretion
Reabsorption
How is secretion of K mediated in the epithelial cells of the CD?
Driven by Na/KATPases in the basolateral membrane pumping K into the cell at the basolateral surface. At the apical surface, K enters the tubular fluid via KCC channels.
Why is there a negative charge in the tubular fluid?
Due to net Na reabsorption in the PT and LOH
How does flow rate effect K secretion?
If flow rate is high, lots of K can be secreted as this keeps the charge in the tubular lumen negative, which increases K secretion.
What are SK and BK channels and where are they found in the kidneys?
Big K channels
Collecting ducts
When are BK channels activated?
When flow rate of tubular fluid is high to promote K secretion
Type A intercalated cells are involved in the reabsorption of K in the CDs. How do they function?
Driven by apical H/KATPase which actively pumps K into the cell and H out of the cell. K ions then leave through basolateral K channels and are reabsorbed.
High plasma K results in the release of what hormone?
Aldosterone
What is the level does K have to get to in the serum for an animal to be considered hyperkalaemic?
5.5mmol/L
Clinical effects of hyperkalaemia are seen at 7.5mmol/L, true or false?
True
What is the most common reason for hyperkalaemia?
Impaired renal function
What are the four most common causes of hyperkalaemia?
Internal redistribution of K is impaired
Increased K leak in muscles
Structural abnormalities in the kidney
Functional abnormalities in the kidney
What can cause alteration in internal redistribution of K?
Insulin resistance, use of beta-blocker
What can cause high K leak within muscle cells?
Cell destruction, acidaemia
What are the consequences of structural abnormalities in the kidney?
Decreased filtration, reduced ability to compensate for rapid changes in K load (or any other ion)
What can cause functional abnormalities in the kidney?
Decreased luminal flow, metabolic acidosis, hypoaldosteronism
Chronic hyperkalaemia is largely due to reduced renal excretion. Name 5 causes of this. 1. 2. 3. 4. 5.
UT trauma UT obstruction Use of K sparing diuretics Hypoaldosteronism Hypoadrenocorticism Anuric renal failure Use of ACE inhibitors
What level in the blood does K have to reach before an animal is considered hypokalaemic?
Less than 3.5mmol/L
What conditions can cause hypokalaemia?
Anorexia, CKD, IV fluids on too high a flow rate
What are the four most common causes of hypokalaemia?
Increased renal loss
Increased gastric loss
Shift in biodistribution from ECF to ICF
Iatrogenic
What can cause increased renal loss of K?
CKD, inability to concentrate urine and reabsorb K
Diureteic therapy that increases tubular flow rate
Increased gastric loss of K is often caused by _____ and _____.
V+ and D+
What can cause changes in biodistribution of K?
Insulin treatment
Hyperthyroidism
What are some possible causes of iatrogenic damage resulting in hypokalaemia?
Use of nephrotoxic drugs, laxatives, too aggressive bicarbonate therapy when treating acidosis
