Objectives
•Comment on thethenormal concentration and intake of Potassium, Calcium, Phosphate and magnesium.
•Explain the renal reabsorption and section of Potassium, Calcium, Phosphate and magnesium.
•Summarize the role of sodium in osmolarity and its renal regulation
•Discuss the hormonal effect of aldosterone, angiotensin, ADH and parathormoneon ions regulation
Potassium Regulation
•Normal ECF concentration =4.2±0.3mEq/L
•Increase up to 3-4mEq/L cause
–Cardiac arrhythmias
–Cardiac arrest and death
•Potassium concentration
–98% inside cell
–2% in ECF
•Damaged cells release K+
Regulation of K+ Distribution
•After ingestion of normal meal K+ level will rise to lethal, if rapidly do not move into ICF
•Food contains at least 50mEq/L potassium
•Remain in the ECF —-severe hyperkalemia
•Excessive loss—-hypokalemia
•Maintenance depends upon excretion
Regulation of K+ Distribution
•K+ absorption—40mEq/L in ECF
•Raise concentration by 2.9mEq/L if not moved to cells
•Kidney eliminate the excess
•Uptake in the cell by
1.Insulin
2.Aldosterone
3.β –Adrenergic Stimulation—-activation of β2 receptors
Factors
•Metabolic acidosis—-increases potassium in the ECF—hyperkalemia
•Metabolic alkalosis—-decreases potassium in the ECF—hypokalemia
•Related to hydrogen imbalance
•Inhibits Na+/K+ pump
•Decreases cellular uptake
•Increases ECF concentration
•Increase K+ is due to
–Cell lysis
–Sternousexercise
–Increased ECF osmolarity
Potassium Excretion
•Excretion determined by
–GFR
–Potassium reabsorption
–Potassium secretion
•GFR(K+ )=180×4.2=756mEq/day
•If GFR decreases in renal diseases severe hyperkalemia
Potassium Excretion
Potassium Reabsorption
•K+ reabsorption
•65% reabsorbed in PCT
•25-30% –Thick ascending limb of Henle
–Cotransport with Na+
•Daily variation does not occur in these segments
•90% epithelial cells —-principal cells
•Two step process
–Uptake in to the cells Na+/K+ pump
–Passive diffusion of K+ in to the cell
•Intercalated cells—reabsorb K+
•When K+ is less
•From tubular lumen to cell to blood when in need
•Na+/K+ pump
•Via special transporters operate in depletion
•K+ secretion occurs in
–Principal cells of late DCT and CCT
•Intake of K+—-100mEq/day
•Excretion
–92mEq/day in urine
–8mEq/day in feces
•Decrease K+ —<1mEq/L
–Decrease secretion by principal cells
–Increase reabsorption by intercalated cells
•Variation occur in this segment
Potassium Secretion
•Increased ECF potassium
–Stimulates Na/K pump
–Increased synthesis of K channels
–Aldosterone secretion
•Increased Aldosterone
–Secretion of K ions in tubular fluid
–Luminal K channels
•ROMK
•BK
•High tubular flow rate
Aldosterone K feedback
Potassium Balance
Calcium Regulation
•Normal level 2.4m Eq/L
•Hypocalcemia
–Excitability of Na
–Leads to extreme TETANY
•Hypercalcemia
–Depressed nerve & muscle excitability
–Cardiac arrhythmias
•Plasma calcium
–50% in unionized form at cell membrane
–40% bound to plasma protein
–10% with anions
•In acidosis—hypercalcemia—less bound to plasma protein
•In alkalosis—hypocalcemia —more bound to plasma protein—TETANY
Calcium Regulation
•99% of total calcium is in bones
•1% in plasma
•Important regulator is PTH
Calcium Regulation
Calcium Excretion
•Ca+2 reabsorption 99% reabsorbed
•Most is reabsorbed in PCT
–80% paracellular
–20% transcellular
•Thick ascending limb of Henle under effect of PTH and VitD
–50% paracellular
–50% transcellular
Calcium Excretion
Phosphate Regulation
•Another factor is phosphate
•Stimulates PTH
•Reabsorbs Calcium
•Overflow mechanism
•T max = 0.1m M/min reabsorbed
•More than it excreted
•Less than it is reabsorbed
•PCT reabsorption 75-80%
•10% in DCT & CT
•Less amounts are reabsorbed in LOH
•10% excreted in feces
•Effects of PTH
–Promotes bone resorption
–Decreases transport maximum
–Overall decreases phosphate in ECF
Magnesium Regulation
•More than 50% in bones
•49% resides in cells
•1% in ECF
•Plasma concentration1.8mEq/L
•Free ionized concentration is 0.8mEq/L
•Intake 250-300mg/day
•PCT reabsorption 25% of filtered
•65% in LOH
•5% in DCT & CT
Sodium Regulation
•Sodium —Most abundant cationof ECF
•Sodium salts —Important part of osmoticallyactive solutes in plasma & interstitial fluid
•The amount of sodium in the body -a prime determinant of ECF volume
•ECF changes and NaClchanges are parallel
•Plasma Osmolarity = 2.1 X serum Na+
•Provided the ADH-thirst mechanism is active
•Excretion is dependent upon the intake
•The amount of sodium excreted = amount of sodium ingested over a wide range of dietary intakes allowing individuals to stay in sodium & volume balance
•Internal renal adjustments
Regulatory systems
Detects ECF volume changes
Detects Sodium concentration
Modify rate of sodium absorption/excretion
SODIUM HOMEOSTASIS
Sodium Regulation
•GFR —-180L/day
•Tubular reabsorption —178.5L/day
•Excretion —1.5L/day
•If GFR increases 5%, no change in tubular reabsorption
•Urine volume 9L/day (additional)
•Compensated by
–Glomerulotubularbalance
–Macula dansa feedback
Sodium Handling by Kidney
Sodium is reabsorbed along different segments of nephrons :
1.PCT -> 50-75 % of filtered sodium reabsorbed via secondary active co transporters
2.Thin ascending loop of Henle doesn’t reabsorb sodium
3.Thick ascending loop of Henle reabsorbs 20-25%
- Distal convoluted tubule:
i)Early DCT : 5-10% reabsorption by NaClco transporter
ii)Late DCT : 2-5% enters here
•Fine regulation, under control of Aldosterone
•Here potassium sparing diuretics acts & blocks sodium reabsorption
Sodium Regulation
•Mechanism for control of blood/ECF volume affects sodium and water excretion —Pressure diuresis and natriuresis
•Pressure diuresis—-refers to water excretion
•Pressure natriuresis—-refers to sodium excretion
•Both mechanism work in parallel
Pressure Diuresis
•Is a phenomena which shows that even a small increase in arterial pressure often causes marked increase in urinary excretion of water.
•Increased urinary excretion of water when arterial pressure increases, a compensatory mechanism to maintain blood pressure within the normal range
Control of ECF volume
Change in blood volume
Changes in cardiac output
Changes in blood pressure
Changes in urine output
Edema
•Elevated capillary pressure
•Decreased plasma colloid osmotic pressure
•Increased interstitial fluid colloid osmotic pressure
•Increased permeability of the capillaries
•Low tissue compliance, negative interstitial fluid pressure
•Increased lymphatic flow
•Washout of proteins from interstitial space
Volume and Sodium Regulation
•Sympathetic stimulation
•Aldosterone
•Angiotensin II
•Anti diuretic Hormone
Angiotensin II
•Effects of Angiotensin II:
–Stimulates aldosterone secretion
–Constrict the arterioles and ↑ arterial pressure
–Stimulates Na+ reabsorption, mainly in the proximal tubulles
–Constrict efferent arterioles
–Facilitates release of ADH
–↑ thirst
Aldosterone
•Stimulus Na, K and Angiotensin II
•Enhances sodium and waterreabsorption and K+ secretion
•Aldosterone escape: despite high levels of aldosterone pressure natriuresisand diuresis take place returning BP back to normal
•Deficiency : circulatory shock
Sodium regulation
1.Activation of low pressure receptor reflexes
2.Small increases in arterial pressure, caused by volume expansion, raise sodium excretion through pressure natriuresis
3.Suppression of angiotensin II formation
4.Stimulation of natriuretic systems, especially ANP