Really... huge apologies. I post this because a) I know some of you would actually understand it. b) I really don't have the energy to process it at the moment, but I'll forget to do so after the exams.
Just a note to help you: K+ is potassium. Anything in square brackets means "concentration of". Here we go. Deep breath:
At the end of this section you should be able to:
· Understand the need for tight regulation of extracellular fluid potassium concentration
· Understand what is meant by internal K+ balance and to list and briefly explain factors which influence it
· Describe the handling of K+ by the proximal tubule, thick ascending loop of Henle and the distal convoluted tubule and collecting duct
· Describe the mechanisms which regulate K+ excretion
· Explain how K+ homeostasis can be simultaneously achieved with osmoregulation and volume regulation
Plasma [K+] is closely regulated at around 4.5 mMolal. Both hyperkalaemia ( > 5.5 mMolal) and hypokalaemia ( < 3.5 mMolal) are dangerous conditions because extracellular [K+] affects cell membrane potential and so the activity of excitable cells. Acid base balance is also affected by failure of K+ homeostasis. The normal dietary intake of K+ is about 100 mMoles per day. About 10 mMoles is lost in the faeces and sweat (unregulated) and the remaining 90 mMoles is excreted in the urine (regulated). Aldosterone has an important role in regulating K+ secretion and so excretion. Changes in the flow rate of tubular fluid also play a part.
Internal potassium balance
In humans, about 4 Moles of K+ are present intracellularly ([K+]i = 150 mMolal) and only 50 mMoles in the extracellular fluids. Shifts of K+ between the two compartments can present major challenges to plasma [K+] regulation.
Hormones. The large intake of K+ after a meal would be fatal if all of it was present in the extracellular fluids at the same time. Temporary uptake by cells is essential since renal excretion of K+ is relatively slow. Insulin is the main factor promoting cellular uptake of K+ after a meal (larger [K+] rises in diabetes mellitus).
Adrenalin and aldosterone also promote K+ uptake by cells.
Acid base balance Metabolic acidosis increases plasma [K+] as H+ enter cells and K+ leave. The reverse occurs in metabolic alkalosis.
Plasma osmolality. A rise in extracellular osmolality causes cell shrinkage, so [K+]i rises and K+ leaves the cells. A fall in osmolality has the reverse effect.
Cell lysis The lysis of cells (e.g. severe burns) releases large amounts of K+ into the extracellular fluid.
Exercise. Plasma K+ rises during exercise as K+ leaves skeletal muscle cells during electrical activity. Adrenalin tends to oppose the effect (larger rises seen in people taking ß blockers).
External potassium balance: excretion by the kidney
Renal potassium handling
K+ is freely filtered. 67% is reabsorbed in the proximal tubule and 20% in the loop of Henle. These fractions are constant. The distal tubule and collecting duct can show net reabsorption (in hypokalaemia) or net secretion (normal and in hyperkalaemia) of K+. Normally, 15% of filtered K+ is excreted. This amount can vary between 1% and 80%. Regulation is on K+ secretion in the distal tubule and collecting duct.
Potassium reabsorption in the proximal tubule
K+ reabsorption in the proximal tubule is by paracellular diffusion, the gradient for which is created by water reabsorption (hence by Na+ reabsorption).
Potassium reabsorption in the thick ascending loop of Henle
K+ reabsorption in the thick ascending loop of Henle occurs partially transcellularly by secondary active transport (K+ crosses the luminal membrane on the Na+/2Cl-/K+ co-transporter and leaves across the basolateral membrane by co-transport with Cl-). The remainder of the K+ reabsorption in this segment is paracellular, driven by the lumen positive transepithelial potential.
Potassium transport in the distal tubule and collecting duct
The distal convoluted tubule and cortical collecting ducts are the segments where K+ homeostasis is achieved, and may show net secretion or reabsorption. K+ is secreted by the principal cells and reabsorbed by the type A intercalated cells. Regulation is achieved by varying the activity of the principal cells.
Secretion of K+ by the principal cells depends on:
· The activity of the basolateral membrane Na+/K+-ATPase.
· The electrochemical gradient for K+ exit across the luminal membrane.
· The permeability of the luminal membrane to Na+ (Na+ entry stimulates the Na+/K+-ATPase).
· The permeability of the luminal membrane to K+.
Reabsorption of K+ by the type A intercalated cells is driven by the luminal membrane H+/K+ ATPase . K+ leaves the cell down its concentration gradient via K+ channels.
Regulation of potassium excretion
Aldosterone. High plasma [K+] directly stimulates aldosterone synthesis and so release. Aldosterone increases the amount of Na+/K+-ATPase in the principal cells. The resulting increased pumping of K+ into the cells increases the gradient for K+ efflux across the luminal membrane. The K+ efflux is promoted by the aldosterone-evoked increase in luminal K+ permeability (increased K+ channel density). Also, the increased luminal Na+ permeability (increased Na+ channel density) favours Na+ reabsorption, so K+ secretion.
Plasma K+. Increased plasma K+, as well as stimulating aldosterone secretion, promotes the activity of the Na+/K+-ATPase and so K+ loss across the luminal membrane. In addition, luminal membrane K+ permeability appears to increase (independently of increased aldosterone) when plasma [K+] rises. The mechanism is unknown.
Tubular fluid flow rate. Increased flow rate increases K+ secretion, a fall in flow rate reduces it. As K+ enters the tubule lumen, [K+] rises, reducing the driving force for further K+ entry. A high flow rate reduces the [K+] rise, a slow flow rate increases it.
The effect of tubular flow rate on K+ secretion helps explain why simultaneous Na+ (ECF volume) and K+ homeostasis can be achieved although the same cells (the principal cells) and hormone (aldosterone) are involved in both. For example, in hypovolaemia, Na+ reabsorption is promoted by high aldosterone. This would be expected to lead to K+ loss. However, it does not since the greater reabsorption of Na+ and water in earlier segments (promoted by multiple mechanisms) greatly reduces the rate of fluid delivery to the distal convoluted tubule and collecting duct. This reduced flow rate opposes K+ secretion. The reverse applies to hypervolaemia.
Osmoregulation employing ADH might also be expected to disturb K+ homeostasis, but does not since ADH itself stimulates K+ secretion (by increasing luminal membrane K+ permeability). Hence in antidiuresis, when high ADH slows tubular flow rate, the effect of this in reducing K+ secretion is offset by the direct action of ADH on principal cell luminal K+ permeability. Equally, when ADH is low, the water diuresis does not increase K+ secretion since low ADH reduces the K+ permeability of the principal cell luminal membranes.
Evidence that aldosterone is a major potassium (not sodium) regulating hormone
Dogs are adrenalectomised to stop endogenous aldosterone secretion and infused with aldosterone to maintain the normal plasma level of the hormone seen in Na+ replete animals. They are able to regulate sodium balance and blood pressure when severely deprived of dietary Na+ (so other mechanisms can cope alone when [aldosterone] cannot vary). In contrast, they are unable to regulate plasma [K+] when the amounts of K+ in the diet are varied. The ability to regulate Na+ without changes in aldosterone is not surprising given the many alternative mechanisms available. These experiments indicate that changes in aldosterone are not essential for Na+ homeostasis, rather than that they are not normally involved.
Evidence that other factors are involved in potassium regulation
A steep relationship between plasma K+ and urinary K+ excretion is maintained even in adrenalectomised animals given constant aldosterone infusion. Direct effects of plasma [K+] appear to be responsible.