Potassium and Sodium Metabolism

Dr Zahid AzeemAJK Medical College

Muzaffarabad

For. . MBBS- batch-2018

DEFINITION Sodium is the most abundant ion of the

extra cellular compartment.

Water is the most abundant constituent of the body 50% of body weight in women & 60% of the body wt in men is water, out of which 40% is intracellular and 20% is in extracellular compartment.

Total body water (60% of body wt

I.C.F. (40 of body wt)

E.C.F. (20% of body wt)

Interstitial fluid 15% Intravascular 5%

IONIC COMPOSITION OF DIFFERENT

BODY FLUID COMPARTMENTS

SODIUM • Sodium -> the a abundant cation of ECF

• Sodium salts -> important part of osmotically active solutes in plasma & interstitial fluid.

• Sodium and its corresponding anions represent almost all of the osmotically active solutes in the extracellular fluid under normal conditions…………. Tonicity

.

Small changes in osmolality are counteracted by thirst regulation,

antidiuretic hormone (ADH) secretion, and renal concentrating or diluting

mechanisms.

Preservation of normal serum osmolality (i.e., 285-295 mOsm/L) guarantees

cellular integrity by regulating net movement of water across cellular

membranes.

ADHIts mechanism of action

•ADH is also called arginine vasopressin or simply vasopressin.

•ADH is a small peptide hormone produced by the hypothalamus that binds

to the vasopressin 1 and 2 receptors(V1 and V2).

•Vasopressin release is regulated by osmoreceptors in the hypothalamus, which

are sensitive to changes in plasma osmolality of as little as 1 % to 2%.

•Under hyperosmolar conditions, osmoreceptor stimulation leads to stimulation

of thirst and vasopressin release.

These two mechanisms result in increased water intake and retention, respectively.

•Vasopressin release is also regulated by

baroreceptors in the carotid sinus and aortic arch; under conditions of hypovolemia, these receptors stimulate vasopressin release to

increase water retention by the kidney.

Regulatory systems Detects ECF volume changes Detects Sodium concentration

Modify rate of sodium

absorption/excretion SODIUM HOMEOSTASIS

DEFENSE OF ECF VOLUME AND DEFENSE OF ECF VOLUME AND IONIC COMPOSITION OF THE BODYIONIC COMPOSITION OF THE BODY

Angiotensin

Angiotensin -I

Angiotensin -II

Hypothalamus

ADH

Thirst

Hypovolemia

Hyperosmalarity

Vasoconstriction

Adrenal cortex

Aldosterone

Kidney

Na+, water retention

Renin

ACE

KIDNEY -- > homeostasis

At a GFR of 125 ml/ min & serum sodium -> 145 mmol/L , kidney filters > 26 mol/ day of sodium ( 1.5

kg of NaCl )

More than 99% of filtered sodium is reabsorbed along nephrons

In KIDNEY :

Sodium is reabsorbed along different

segments of nephrons :

1) 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%

4) Distal convoluted tubule: i) early DCT : 5-10% reabsorption by NaCl

co transporter ii) late DCT : 2-5% enters here * fine regulation, under control of

Aldosterone * Although sodium reaching here is a small

fraction of filtered sodium, it is here where it is decided how much sodium will be excreted

Hyponatremia

Hyponatremia is defined as a serum sodium concentration lower than 136 mmol/L.

Hyperglycemia can also cause hyponatremia, via osmotically induced water movement from cells into the blood (translocational hyponatremia)

Hyponatremia in a patient with hypovolemia

Hypovolemic hyponatremia represents a decrease in total body sodium in excess of

a decrease in total body water. REASONS;

Simultaneous sodium and water loss can be due to renal

(such as diuretic use) or extrarenal causes.

Hypovolemia results in a decrease in renal perfusion, a decrement in the glomerular filtration

rate, and an increase in proximal tubule reabsorption of

sodium and water;

How does hypervolemic hyponatremia differ from

hypovolemic hyponatremia?

Increase in total body water exceeds increase in total body sodium. Patients are edematous.

RENAL CAUSES(urinary sodium > 20mEq/L): Acute or Chronic renal failure

NON RENAL CAUSES: CHF, Cirrhosis, nephrotic syndrome

Hypervolemic Hyponatremia

In general, hypervolemic hyponatremia due to an extrarenal cause is

characterized by a low urine sodium concentration (<10 - 20 mEq/L)

This distinguishes it from hypervolemic hyponatremia due to intrinsic renal

causes, where the urine sodium is > 20 mEq/L

{ In renal causes, kidney can not re-absorb Na } .

Patient has a normal store of sodium but an excess of total body water

The most common form seen in hospitalized patients. The most common cause is the inappropriate administration of hypotonic fluid

The syndrome of inappropriate antidiuresis is the most common cause of euvolemic hyponatremia

Euvolemic Hyponatremia

Clinical Signs of Hyponatrema

Nausea, vomiting, anorexia, muscle cramps, confusion, and lethargy, and culminate ultimately in seizures and coma.

Seizures are quite likely at [Na+] of 113 mEq/L or less.

Hypernatremia

Defined as a serum sodium concentration greater than 145

mEq/L, occurs when too little total body water exists relative to the

amount of total body sodium, thereby raising the sodium concentration.

An increase in serum sodium concentration is almost always a reflection of water loss rather than sodium gain.

Water loss results in the development of plasma hyperosmolality; via hypothalamic sensors, this acts as a stimulant to thirst and production of ADH.

•Given that even small rises in the serum osmolality trigger the thirst mechanism, •Hypernatremia is relatively uncommon

unless the thirst mechanism is impaired or access to free water is restricted.

As a result, hypovolemic hypernatremia tends to occur in the very young, the very

old.

It is typically due to extracellular fluid losses accompanied by inability to take in adequate amounts of free

water.

Febrile illnesses, vomiting, diarrhea, and renal losses are

common causes.

Hypervolemic hypernatremia

Although uncommon. Sodium bicarbonate injection during cardiac arrest,

administration of hypertonic saline solution and inappropriately prepared infant

formulas are several examples of induced hypernatremia.

Regulation of Na/K

How much sodium does the patient need?

Sodium deficit = Total body water x (desired Na – actual

Na)

Total body water is estimated as lean body weight x 0.5 for

women or 0.6 for men

Question:In elderly patients : Decreased GFR with age limits ability to

excrete sodium prone to over expansion of ECF

Why Hyponatremia?????????????

Impaired thirst mechanism with decreased ability to concentrate urine

Why Hypernatremia????????

Thanx

BODY POTASSIUM

-K+ is the major intracellular ion

-serum potassium is normally regulated within a narrow range of 3.5 to 5.0 mmol/L.

-75% of which is in skeletal muscles

-K+ is taken up by all cells via the Na-K ATPase pump

-K+ is one of the most permeable ion across cell membranes and exits the cells mostly via K channels (and in some cells via K-H exchange or via K-Cl cotransport)

Introduction The total body stores are approximately 50 to 55

meq/kg. The main intracellular cation. 98% located ICF,150 meq/L. 2% located ECF,4meq/L.90% readily exchangeable10% non exchangeableAmount ingested = up to 100meq/d = 2.5 gm/d92% urinary excretion8% GIT excretion

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Redistribution of K

potassium homeostasis External potassium balance is determined by rate of potassium intake

(100 meq/day) and rate of urinary (90 meq/day) and fecal excretion (10 meq/day).

Internal potassium balance depends on distribution of potassium between

muscle, bone, liver, and red blood cells (RBC) and the extracellular fluid (ECF).

Physiological roles of potassium

1.Roles of intracellular K+: Cellular volume maintenance Intracellular pH regulation Cell enzyme function DNA/protein synthesis Cell growth2.Roles of transcellular K+ ratio: Resting cell membrane potential Neuromuscular excitability Cardiac pacemaker rhythmicity

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Potassium homeostasis

1.Internal balance ( ICF and ECF K+ distribution)2. External balance ( Renal excretion of K+)1.Internal balancePhysiological and pathological conditions can influence this

process.o Hormones like insulin , catecholamines ,aldosterone o Acid base imbalanceo Changes in osmolarityo Exerciseo Cell lysis

Hormonal control of K+ homeostasis Insulin and beta 2agonsists shifts K+ to the cell, by increase the

activity of Na+,K+-ATPase, the 1Na+-1K+-2Cl- symporter, and the Na+-Cl- symporter.

Aldosterone acting on uptake of K+ into cells and altering urinary K+ excretion.

Stimulation of α-adrenoceptors releases K+ from cells, especially in the liver.

insulin and epinephrine act within a few minutes, aldosterone requires about an hour to stimulate uptake of K+ into cells.

02/12/15 37Potassium homeostasis and its renal handling

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Hormonal control of K+ homeostasis

Miscellaneous factors …..1.Acid base imbalance Metabolic acidosis increases the plasma [K+].

Metabolic alkalosis decreases the plasma [K+] .2.Plasma osmolarity Hyperosmolarity associated with hyperkalemia . A fall in plasma osmolality has the opposite effect. 3.Cell lysiso Crush injury,burns,tumor lysis syndrome, rhabdomyolysis

associated with destruction of cells and release of K+ to ECF. 4. Exercise vigorous exercise, plasma [K+] may increase by 2.0 mEq/L.

…………Cont’d

Physiological: Keep Plasma [K+] Constant Epinephrine Insulin Aldosterone Pathophysiological: Displace Plasma [K+] from Normal Acid-base balance Plasma osmolality Cell lysis Exercise Drugs That Induce Hyperkalemia Dietary K+ supplements ACE inhibitors K+-sparing diuretics Heparin

Renal handling of potassium

The PCT reabsorbs about 67% of the filtered K+ under most conditions by K+-H+ exchanger and K+-Cl- symport.

20% of the filtered K+ is reabsorbed by the TALH.

The distal tubule and collecting duct are able to reabsorb or secrete K+.

02/12/15 Potassium homeostasis and its renal handling

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……….cont’d

The rate of K+ reabsorption or secretion by the distal tubule and collecting duct depends on a variety of hormones and factors.

Most of the daily variations in potassium excretion is caused by changes in potassium secretion in the distal and cortical collecting tubules.

02/12/15 Potassium homeostasis and its renal handling

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……………cont ’d

02/12/15 Potassium homeostasis and its renal handling

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K+ SECRETION BY PRINCIPAL CELLS

Secretion from blood into the tubule lumen is a two-step process:

1.uptake of K+ from blood across the basolateral membrane by Na+,K+-ATPase and

2. diffusion of K+ from the cell into tubular fluid via K+ channels.

Three major factors that control the rate of K+ secretion by the distal tubule and the collecting duct

A. The activity of Na+,K+-ATPase .B. The driving force (electrochemical gradient) for movement of

K+ across the apical membrane. C. The permeability of the apical membrane to K+ .

Cellular K buffering When K is added to the ECF, most of the added K is

taken up by the cells, reducing the ECF K+ increase If K is lost from the ECF, some K+ leaves the cells,

reducing the ECF K decline Buffering of ECF K through cell K uptake is impaired in

the absence of aldosterone or of insulin or of catecholamines

Cell K exit to the ECF increases when osmolarity increases (as in diabetes mellitus) and in metabolic acidosis, when it is exchanged for ECF protons (H+)

When cells die, they release their very high K content to the ECF

Copyright ©1998 American Physiological Society

Renal regulation of Potassium

Sources of K

Banana, orange, apple, pineapple Almond, dates, beans, potatoes