Tubular Processing & Electrolyte Balance Flashcards
What is the key process in the kidneys to fine tune volume/composition of urine and to avoid high fluid and solute losses?
Tubular processing
What is more important for most substances; reabsorption or secretion?
Reabsorption
What are the 2 properties of tubular reabsorption?
- Quantitatively large
2. Highly selective; allows independent regulation of solute excretion
What 2 types of transport does tubular reabsorption utilise to move fluid/solutes from tubule lumen to peritubular capillary?
Passive
Active
What do luminal and basal surfaces of tubule epithelial cells have on them and what does this achieve?
Transporters -> establish concentration gradients e.g. Na+/K+ ATPase
How is water reabsorbed in the nephron?
Linked closely to Na+ (main osmotically active substance) reabsorption and permeability of the different parts of the nephron
Where does the majority of reabsorption occur?
Proximal convoluted tubule
Where does fine tuning of water and solute excretion occur and via what?
More distal parts of nephron under hormonal control
What occurs in the Proximal Convoluted Tubule (PCT) and what characteristics does it have to do this?
Roles:
Majority of Na+ and water (~65%) & glucose and AA reabsorption
Site of secretion of metabolic acids/bases, drugs etc.
Characteristics:
Fluid leaving PCT is isosmotic as epithelium freely permeable to water
Brush border increases SA
Mitochondria provide energy
How are glucose and amino acids reabsorbed in the PCT?
- Secondary active transport linked to Na+ reabsorption -> Na+ glucose co-transporters (SGLT2 mainly) on luminal side move glucose against concentration gradient into cell -> glucose transporters (GLUT) on basal side allow facilitated diffusion into interstitial fluid
- Similar process for AAs but different transporters used to move them from tubular lumen to interstitial fluid
What happens if the amount of glucose appearing in the filtrate increases?
Finite number of SGLT transporters on proximal tubule cells and because glucose should all be reabsorbed, if too much glucose gets into filtrate they reach a transport maximum (Tm) where reabsorption cannot go faster -> glucose lost in urine + water retained in tubule lumen getting excreted too (osmotic diuresis)
How are H+ ions secreted?
Na+ reabsorption linked to secondary active transport of H+ into tubular lumen using a Na+/H+ exchanger (NHE) where Na+ goes into tubular cells and H+ is secreted into tubular lumen (important for HCO3- reabsorption in proximal tubule)
What are the 3 main parts of the Loop Of Henle and there functional characteristics?
- Thin descending limb: water permeable + no active reabsorption/secretion of solutes
- Thin ascending limb: water impermeable + barely any reabsorption/secretion of solutes
- Thick ascending limb: water impermeable, active reabsorption of Na+/others + dilutes luminal fluid (hypo-osmotic)
How does reabsorption + dilution of luminal fluid occur in the thick ascending limb of the Loop Of Henle?
Reabsorption from tubule lumen occurs primarily by Na+K+2Cl- co-transporters (all 3 move into tubular cells)
+ve charge in lumen encourages paracellular reabsorption of cations e.g. Ca2+, Mg2+
Water cannot solutes into tubular cells as it is impermeable to water so tubular lumen fluid becomes diluted + hypo-osmotic (solution with lesser concentration of solutes)
What occurs in the early distal tubule?
Macula densa cells in 1st portion -> part of JGA involved with feedback control of GFR/BP + sensitive to [NaCl]
Impermeable to water so contributes to filtrate dilution
Active reabsorption of Na+ utilising Na+Cl- co-transporter on luminal side further diluting tubular luminal fluid
What happens in the late distal & cortical collecting tubule?
Water permeability under hormonal control by ADH i.e. water permeable when ADH present and vice versa
2 main cell types:
1. Principal cells: Na+ reabsorption & K+ secretion
2. Intercalated cells: K+ reabsorption & H+ secretion
What do principal cells do?
Na+ enter cells through epithelial Na+ channels (ENaC) on luminal side -> transported out of tubular cells via Na+/K+ ATPase to maintain concentration gradient - no. of ENaC channels & Na+/K+ activity controlled by aldosterone hormone e.g. high aldosterone = increase in channels -> more ion movement - as Na+ is reabsorbed, water follows + K+ is secreted in collecting tubule & duct
What happens in the medullary collecting duct?
Final site for urine processing; key role in regulating degree of [urine]
Water permeability controlled by ADH i.e. ADH increases water reabsorption
Surrounded by medullary interstitium with a high [solutes]
Urea permeability allows medullary interstitium to remain concentrated
Close relationship to Loop Of Henle aids these processes
How are tubular processes regulated?
Local feedback & hormonal/neural mechanisms
Reabsorption of individual solutes can be adjusted independently via hormones acting on different parts of nephron (unlike GFR regulation)
Where/how is Atrial Natriuretic Peptide (ANP) produced and what does it do?
- Released by atrial muscle fibres in response to increased stretch of atria as a result of excessive blood volume (also pathologically raised e.g. in cardiac failure when there is increase in ECV)
- Decreases NaCl reabsorption in the distal tubule/collecting tubule and duct
- Causes small increases in GFR and decreases renal reabsorption
What does parathyroid hormone do?
Decreases phosphate (PO4) reabsorption and increases Ca2+ reabsorption in the proximal tubule, thick ascending loop of Henle/distal tubule
What does angiotensin II do?
- Increases NaCl + water reabsorption and H+ secretion in the proximal tubule, thick ascending loop of Henle/distal tubule + collecting duct (directly on renal tubule cells increasing activity of Na+ transporters & indirectly via increased aldosterone in adrenal gland)
- Vasoconstriction
- Indirectly increases thirst & ADH release in posterior pituitary
- > increase arterial BP
Where does ADH have its affects?
Distal tubule/collecting tubule + duct
Describe the 2 mechanisms via which receptors can detect high or low levels of electrolytes to keep levels balanced.
- Direct e.g. ECF [K+] has a direct effect on release of aldosterone
- Indirect e.g. baroreceptors indicate ECF volume so are a marker of Na+ levels as water tends to follow Na+ (however serum ECF samples do not necessarily reflect body content of any electrolyte due to water)
How is Na+ levels regulated?
Major EC electrolyte + determinant of ECF volume so kidneys help to maintain ECF volume by regulating amount of Na+ excreted in urine e.g. if Na+ is lot, water will follow + be lost decreasing ECF volume (normally reabsorb most Na+ filtered so only small amount excreted) - regulated by local, hormonal + neural factors
What is pressure diuresis/natriuresis?
Ability of kidney to increase urine output/Na+ excretion in response to increased arterial BP/volume - helps maintain blood volume over a wide range of fluid & Na+ intake
What do granular cells of the afferent arteriole of the JGA do?
Secrete an enzyme called renin in response to falls in ECV/low Na+ by utilising baroreceptors that detect a decrease in ECF volume and increase Na+ reabsorption and thus, water reabsorption
What are the 3 main triggers of renin release?
- Low afferent arteriole pressure
- Activation of sympathetic nerves that supply JGA
- Low [NaCl] in distal tubule
- > renin released by granular cells of afferent arteriole
What happens in the renin angiotensin aldosterone system (RAAS)?
Angiotensinogen (liver) -> converted to angiotensin I (produced due to decreased arterial BP which releases renin in kidneys to produce this) -> Angiotensin Converting Enzyme (ACE) in the lungs converts this to angiotensin II
What is the aim of the RAAS process?
Helps maintain ECV and arterial BP despite wide variations in dietary intake of Na+ e.g. if Na+ intake reduced decreasing ECF, RAAS activity increases and vice versa (also responds to situations where ECF and BP falls independently of salt intake)
What would happen in the RAAS system step-by-step if there was an increase in salt/Na+ intake?
Increased ECV -> increased arterial BP -> decreased renin + angiotensin -> decreased renal retention of salt + water -> return of ECV almost to normal + arterial BP almost to normal
Where is aldosterone produced + what does it do?
- Secreted by zona glomerulosa of adrenal cortex in response to increased angiotensin II or EC [K+]
- Increases Na+ reabsorption by acting on principal cells in late distal/cortical collecting tubule by binding to nucleus + increasing production of proteins e.g. ENaC & Na+/K+ ATPase which increases ability of cells to reabsorb Na+
Why does K+ levels need to be regulated?
K+ is the major determinant of resting membrane potential so small changes can cause life-threatening cardiac arrhythimas - most K+ is located IC so need rapid ways to regulate EC levels (performed mainly by kidneys)
Why is serum [K+] not a good reflection of total body K+?
Because there is only a small amount in the EC so a lot of it could be IC e.g. in diabetic ketoacidosis levels initially appear high but the amount in the body might actually be low
What 4 factors decrease the blood levels of K+ by driving it into cells decreasing EC [K+]?
- Insulin increases Na+/K+ ATPase activity (why it is used as part of emergency treatment of hyperkalaemia)
- Aldosterone acts in the same way to effect urinary excretion of K+
- B-adrenergic sympathetic stimulation increases Na+/K+ ATPase activity too (why salbutamol for e.g. can cause low blood levels of K+ if used in excess)
- Alkalosis i.e. low EC [H+] possibly due to exchange of IC H+ for EC K+
What 7 factors decrease blood levels of K+ by shifting it out of cells increasing EC [K+]?
- Insulin deficiency e.g. DM
- Aldosterone deficiency e.g. Addisons disease
- B-adrenergic blockade
- Acidosis i.e. high EC [H+] reduces Na+/K+ ATPase activity possibly to exchange of IC K+ for extracellular H+
- Cell lysis releases IC K+ via damaged cell membrane
- Strenuous exercise via damaged cell membranes too
- Increased EC fluid osmolarity causing cellular dehydration - increases IC [K+] resulting in a larger concentration gradient to promote movement out of the cell
What is responsible for most of the variation in K+ excretion?
The amount of secretion in late distal tubule/cortical collecting tubule (controlled by aldosterone)
How is K+ secreted/excreted?
Na+/K+ ATPase moves K+ into principal cells from the renal interstitial fluid creating a high IC concentration -> K+ then passes through channels in luminal membrane into tubular lumen
What are the 3 factors that determine the rate of K+ secretion?
- Activity of Na+/K+ ATPase
- [K+] gradient between blood, principal cell + tubular lumen
- Permeability of luminal membrane to K+ e.g. number/amount in an open state of K+ transporters
What cells can reabsorb K+ during K+ depletion?
Intercalated cells
What are the 4 factors that regulate K+ secretion?
- Plasma K+ concentration
- Aldosterone
- Tubular flow rate
- [H+]
How does plasma [K+] affect rate of K+ excretion?
- Increases Na+K+ ATPase activity
- Increases [K+} gradient from blood to lumen
- Increases permeability of luminal membrane to K+ via increased no. of transporters
- Increase aldosterone release
= increased rate of K+ secretion/excretion
How does aldosterone affect rate of K+ excretion?
- Increases Na/K+ ATPase activity
- Increases permeability of luminal membrane to K+ via increased no. of transporters
= Increased K+ secretion in cortical collecting tubules + thus, excretion
How does tubular flow rate occur and how does it affect rate of K+ excretion?
- Can occur with volume expansion, high Na+ intake or some diuretics (loop/thiazide so side effect is hypokalaemia)
- Increases [K+] gradient from principal cell to tubular lumen (low levels in lumen)
- Increases permeability of luminal membrane to K+
= increased rate of K+ secretion/excretion
(useful mechanism as K+ excretion occurs independently of aldosterone which can be suppressed by high Na+ intake)
What happens if there is increased Na+ intake in terms of K+ secretion/excretion in a healthy person?
Aldosterone is suppressed which is trying to decrease K+ secretion in cortical collecting duct
GFR is increased + proximal tubular Na+ reabsorption is decreased increasing distal tubular flow rate which causes increased K+ secretion in cortical collecting duct
Thus, there is unchanged K+ excretion
How does [H+] concentration affect the rate of K+ excretion?
Increased [H+] acutely decreases Na+/K+ ATPase activity, lowering the concentration gradient + decreasing rate of K+ excretion
What is the normal range for EC [K+]?
3.5 - 5.3 mmol/L
What is hypokalaemia? Describe the signs/symptoms, general approach to causes & treatment.
EC [K+] below normal range with signs/symptoms including muscle weakness + cardiac arrhythimas (often asymptomatic though)
You should consider causes such as reduced intake, excessive losses (e.g. diuretics, severe diarrhoea, aldosterone excess) + altered body distribution
Thus, should address underlying cause and perhaps give K+ supplements
What is hyperkalaemia? Describe the signs/symptoms, general approach to causes & treatment.
EC [K+] above normal range with signs/symptoms including cardiac arrhythimas (tall T waves in ECG) (often asymptomatic though)
Should consider causes such as excessive intake, inadequate losses (e.g. kidney disease, aldosterone deficiency) + altered body distribution (e.g. acidosis)
Thus, should address underlying cause, restrict intake, give Ca gluconate (stabilise myocardium), give insulin (+ glucose, maybe salbutamol) (drive K+ into cells) & aid excretion via fluids, ion-exchange resins or dialysis (treatment depends on severity)
Why can altered body distribution affect the blood levels of K+?
The body may have distributed K+ into the cells which may make the blood result abnormal however, if you do more bloods, K+ may start to appear again
