Urinary Session 6 Flashcards
What ensures tight regulation of the narrow range of hydrogen ion concentration needed to control pH?
Kidney via variable recovery of HCO3- and active secretion of H+
Is alkalaemia or acidaemia more severe?
Alkalaemia
What happens in alkalaemia?
Calcium crystallises causing hypocalcaemia and thus increased neuronal excitability –> parasthesia and tetany
What causes respiratory alkalaemia?
Hyperventilation –> hypocapnia –> increased pH
What happens in acidaemia?
Increases plasma potassium concentration affecting RMP –> arrythmias
Denatures proteins –> deranged muscle contractility, glycolysis and hepatic function
What causes respiratory acidaemia?
Hypoventilation –> hypercapnia –> decreased pH
How are changes in pH detected by the body?
Peripheral chemoreceptors detect pCO2 and pH causing rapid but small effect
Central chemoreceptors detect pCO2 changes and take longer to come into effect but are responsible for 80% of effect
What is the normal range of blood pH?
7.35-7.45
What is the main site of HCO3- production?
Erythrocytes
What controls HCO3- concentration?
Kidneys
How do the kidneys keep pH stable?
Compensate for changes in HCO3- concentration to keep [HCO3-]/[CO2] constant
What is the kidney reaction to respiratory alkalaemia?
Decrease [HCO3-]
Why is kidney control of [HCO3-] in respiratory alkalosis/acidosis correction as opposed to control?
Primary cause has not been altered
What happens when a decrease in pH is detected by peripheral chemoreceptors?
Stimulates respiratory neurones in medulla –> increases ventilation to decrease pCO2 –> shifts eqm to correct pH
What causes decreased [HCO3-] in metabolic acidosis?
Acid from tissues reacting with and thus removing HCO3-
Why does increasing ventilation compensate for metabolic acidosis?
Removes additional carbon dioxide which is formed due to reaction of acid from tissues and HCO3-
How does repeated vomiting lead to an increase in pH?
Loss of H+ –> increased H+ production for replacement –> increased HCO3- as a by product
What detects the decrease in pH seen in metabolic alkalosis?
Peripheral chemoreceptors
What can metabolic alkalaemia only be partially compensated for by decreasing ventilation?
Risk of hypoxia
What corrects metabolic driven changes in pH?
Kidneys
How can the kidneys decrease [HCO3-]?
Easily by not recovering all that is filtered
What must the kidney do in order to increase [HCO3-]?
Recover all filtered HCO3- and make new HCO3-
How does the kidney make new HCO3-?
Due to high metabolic rate produce lots of CO2 which reacts with water to form HCO3- which moves into the plasma
How can amino acids be used to make HCO3-?
a.a. –> HCO3- + NH4 + alpha-ketoglutarate
Where does formation of HCO3- from amino acids take place?
PCT
Where does 80% of HCO3- reabsorption occur?
PCT
How does the sodium gradient set up by Na-K-ATPase allow for reabsorption of HCO3-?
Drives H+ out via NHE-3 which reacts in the lumen with HCO3- to form CO2 –> CO2 moves into cell and reacts with water to reform HCO3- which moves into the ECF via Na-HCO3 co transporter
What needs to happen in order for cells producing CO2 to continue HCO3- production?
H+ needs to be secreted and buffered
How is H+ removed from the DCT?
Actively by H+ATPase
How is urine pH buffered so that it remains >4.5 to prevent damage to cells lining the urinary tract?
H+ in lumen reacts with HPO4+ and excreted NH3+
Ammonia diffuses freely but ammonium does not, why?
Ammonium has a positive charge
What change in pH can tubular cells detect?
Intracellular
What happens in the tubular cells if ECF [HCO3-] decreases?
More HCO3- moves out of the cells into the ECF –> more H+ in cells
What happens in the tubular cells if ECF [HCO3-] increases?
Tubular cell pH increases –> increased H+ secretion and deceased HCO3- recovery
Describe the action of NHE in volume depletion.
Works to reabsorb sodium thus favouring H+ secretion and HCO3- recovery
How is H+ buffered in the proximal tubule?
Ammonium formed by HCO3- production dissociates into NH3+ and H+ –> NH3+ diffuses out of cell and reacts with H+ in the lumen to reform NH4+
What are the tubular cellular responses to acidosis?
Na+/H+ exchanger activity increases
Enhanced breakdown of glutamine and therefore enhances ammonium production
Enhanced H+ATPase activity in DCT
What is the overall result of the tubular cellular responses to acidosis?
Increased capacity to export HCO3- from tubular cells to ECF
How is the anion gap calculated?
([Na+] + [H+]) - ([Cl-] + [HCO3-])
What increases the anion gap?
Other anions from metabolic acids replace HCO3- E.g. Lactate in profound shock
Do all forms of metabolic acidosis create and anion gap?
No, in renal problems HCO3- is replaced with Cl- therefore the gap is constant but [HCO3-] is decreased
What post assign disturbance does metabolic acidosis lead to?
Hyperkalaemia
How does metabolic acidosis lead to a potassium disturbance?
Increased H+ outside cells –> increased movement in –> K+ move out into ECF
What effect does metabolic acidosis have on the distal nephron?
Increases potassium reabsorption
What potassium disturbance does metabolic alkalosis lead to?
Hypokalaemia
How does metabolic alkalosis lead to a potassium disturbance?
Decreased H+ outside cells causes movement out –> K+ moves into cells
What effect does metabolic alkalosis have on the distal nephron?
Decreases K+ reabsorption
How does hyperkalaemia effect HCO3- excretion?
Increased pH of tubular cells –> H+ move out into ECF –> HCO3 excretion favoured
How does hypokalaemia lead to an acid-base disturbance?
Decreased intracellular pH of tubular cells –> H+ into cells –> favours H+ excretion and HCO3- recovery –> metabolic alkalosis
Why are the anions usually at a lower level than the cations when calculating the anion gap in a normal pt?
Unaccounted for anions which are associated with metabolic acids
Where is the majority of K+ found in the body?
ICF of skeletal muscle, liver, bone and red blood cells
What is the effect of ECF [K+] on establishing resting membrane potential?
Increasing [K+]i and decreasing [K+]o means K+ moves out of cell taking +be charge with it, establishing RMP
What maintains the difference between ICF and ECF [K+] under tight control?
Na-K-ATPase
How does increasing and decreasing ECF [K+] affect the RMP of cells?
Decrease: increases K+ gradient –> more K+ leaves, hyperpolarising cell
Increase: reduces K+ gradient –> less K+ leaves so depolarises cell
What type of mechanism controls meal-driven kidney K+ excretion?
-ve feedback
What happens upon absorption of dietary K+ in the intestine and colon which leads to meal-driven kidney K+ excretion?
Substantial amount of K+ enters ECF –> plasma K+ increases –> excretion
What happens to 4/5ths of absorbed dietary K+?
Sequestered in liver and muscle cells
What happens upon activation of splanchnic sensors by absorption of dietary K+?
Feed forward regulation signals from vagus nerve to stimulate meal driven K+ excretion
Why does intracellular buffering have an important role in meal-driven potassium excretion?
Kidneys cannot excrete K+ fast enough
Give some examples of potassium rich foods.
Beans Raisins Fruit Potatoes Milk
What is internal balance of potassium regulation?
Net of 2 processes which shifts K+between ECF and ICF for immediate effects for moment to moment control
How does K+ move from the ECF into cells?
Via Na-K-ATPase
How does K+ move from cells into ECF?
ROMK
What factors increase potassium uptake by cells?
Hormones
Increase [K+] in ECF
Alkalosis
Which hormones increase K+ uptake by cells?
Insulin
Aldosterone
Catecholamines
How do insulin and aldosterone increase potassium uptake by cells?
Increased potassium levels in blood stimulate their release which then increases Na-K-ATPase activity
How does physiological stress increase potassium uptake into cells?
Stimulate catecholamine release –> beta-2-adrenoreceptors –> stimulate Na-K-ATPase
What factors cause increased potassium efflux from cells?
Exercise Cell lysis Increase in ECF osmolality Decreased ECF [K+] Acidosis
How does exercise increase potassium efflux from cells?
Potassium pump cannot keep up with increased demand so there is net post assist release during action potential recovery
Damage to myocytes causes potassium release
When might cell lysis causing increased efflux of potassium by cells occur?
Rhabdomyolysis
Intravascular heamolysis
Chemotherapy
How does an increase in ECF osmolality cause potassium efflux from cells?
Water moves out of cell thus increasing the ICF levels of potassium and creating a steeper gradient which the potassium moves down
When is potassium efflux due to an increase is ECF osmolality seen?
Diabetic ketoacidosis
How long does external balance of K+ regulation take to act?
6-12 hrs to excrete load
What is external balance of K+ regulation responsible for?
Control of total body potassium over the longer term
How do the kidneys adjust K+ excretion to match intake?
Controlling secretion
Where is the majority of potassium reabsorbed?
PCT and thick ascending limb of Henle’s loop
Where is potassium secreted?
DCT
Principal cells of cortical CD
In renal handling of potassium, what remains constant regardless of K+ levels in the blood?
% reabsorption
How are low-high K+ diets counteracted?
Variable K+ secretion by principal cells of DCT and cortical CD
What luminal factors affect potassium secretion in the distal tubule and collecting duct?
High distal tubular flow rate to wash away luminal potassium and maintain gradient
High sodium delivery to DCT causes more sodium reabsorption and therefore increased potassium loss
What tubular factors affect potassium secretion?
ECF [K+]
Aldosterone
Acid-base status
How does ECF [K+] affect potassium secretion?
Directly stimulates Na-K-ATPase
Increase permeability of apical K+ channels
Stimulates aldosterone secretion
How does aldosterone affect potassium secretion?
Increase transcription of Na-K-ATPase, K+ channels and ENaC therefore reabsorb more sodium and excrete more K+
How does acid-base status affect K+ secretion?
Acidosis decreases potassium secretion as it inhibits Na-K-ATPase and decreased K+ channel permeability
Alkalosis increased potassium secretion by having an opposing action
How is potassium absorbed by intercalated cells in DCT and cortical CD?
Active process mediated by H+-K+-ATPase in the apical membrane
What effect does acidosis have on K+ absorption by intercalated cells in DCT and cortical CD?
Increases pumping of K+ into cells
What can cause an external shift of potassium leading to hyperkalaemia?
Increased intake and renal dysfunction Inappropriate IV dose AKI/chronic kidney injury K+ excretion blocking drugs Decreased aldosterone state
What can cause an internal shift of potassium and lead to hyperkalaemia?
Diabetic ketoacidosis
Cell lysis
Metabolic acidosis/exercise
What effects of diabetic ketoacidosis cause an internal shift of potassium?
Lack of insulin
Plasma hyperosmolarity
Metabolic acidosis
How does Addison’s disease lead to hyperkalaemia?
Causes low aldosterone state hence low plasma sodium and high plasma potassium levels
What can cause an external shift of potassium leading to hypokalaemia?
Excessive GI loss in diarrhoea/bulimia/vomiting
Excessive renal loss by diuretics
Osmotic diuresis
High aldosterone state
What can cause an internal shift of potassium leading to hypokalaemia?
Metabolic alkalosis
What is the clinical relevance of hyperkalaemia on the heart?
Depolarises cardiac tissue –> more fast sodium channels in inactive form –> heart less excitable –> arrythmias and heart block
What is the clinical relevance of hyperkalaemia in the GI tract?
Neuromuscular dysfunction –> paralytic ileus
How is paralytic ileus identified O/E?
Decreased bowel sounds
What is the clinical relevance of hypokalaemia in the heart?
Hyperpolarises cardiac tissue –> more fast sodium channels in active form –> heart more excitable causing arrythmias
What is the clinical relevance of hypokalaemia on the GI tract?
Paralytic ileus
What is the clinical relevance of hypokalaemia in skeletal muscle?
Neuromuscular dysfunction –> muscle weakness
What is the clinical relevance of hypokalaemia on the kidneys?
Unresponsive to ADH –> neohrogenic diabetes incipidus
What are the progressive ECG changes seen in worsening hyperkalaemia?
High T wave –> increased PR, decreased ST, high T wave –> atrial standstill and IV block –> ventricular fibrillation
What are the progressive ECG changes seen in worsening hypokalaemia?
Low T wave –> low T wave, high U wave –> low T wave, high U wave, decreased ST
What is the emergency Tx for hyperkalaemia which should be carried out within 30 mins?
IV calcium gluconate
IV insulin and glucose
Nebulised beta-agonists (salbutamol)
Dialysis
Why is calcium gluconate used to treat hyperkalaemia?
Restores RMP of cardiac myocytes
Why is IV insulin used to treat hyperkalaemia?
Increases Na-K-ATPase activity
What is the longer-term treatment for hyperkalaemia?
Treat cause: stop medication, treat DKA etc
Decrease potassium intake
Remove excess K+ with dialysis in AKI/CKI or oral binding resins to increase loss via GI tract
How is hypokalaemia treated?
Treat cause
IV/oral potassium replacement
Potassium sparing diuretics in high mineralocorticoid activity
Why are potassium sparing diuretics used to treat hypokalaemia if mineralocorticoid activity is high?
Block action of aldosterone on principal cells
At what stage do the S/S of potassium balance disturbance present?
Late
What is the physiological role of intracellular potassium on cell volume maintenance?
Net loss of K+ –> cell shrinkage
Net gain of K+ –> cell swelling
What is the physiological role of intracellular K+ on intracellular pH regulation?
Net loss –> cell acidosis
Net gain –> cell alkalosis
What is the physiological role of intracellular potassium on cell enzyme function?
Some enzymes are potassium dependent, e.g. ATPases, succinct dehydrogenase
What is the physiological role of intracellular potassium on DNA/protein synthesis and growth?
Lack –> decreased protein synthesis –> stunted growth
What are the effects of decreased plasma potassium causing deranged neuromuscular activity?
Muscle weakness and paralysis
Intestinal distension
Peripheral vasodilation
Respiratory failure
What are the effects of increased plasma potassium affecting neuromuscular activity?
Increased muscle excitability –> muscle weakness –> paralysis
What effect does low plasma potassium have in cardiac activity?
Slowed conduction of pacemaker –> arrythmias
What effect does high plasma potassium have on cardiac activity?
Conduction disturbances
Ventricular arrhythmias and fibrillation
What affect does intracellular potassium have on vascular resistance?
Low plasma potassium –> vasoconstriction
High plasma potassium –> vasodilation
