Renal Module

1. Potassium and Sodium Metabolism
Dr Zahid Azeem
AJK Medical College
Muzaffarabad
For. . MBBS- batch-2018

2. 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%

3. IONIC COMPOSITION OF DIFFERENT
BODY FLUID COMPARTMENTS

4. 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
.

5. 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.

6. ADH
Its 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%.

7. •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.

8. Regulatory systems
Detects ECF volume changes
Detects Sodium concentration
Modify rate of sodium
absorption/excretion
SODIUM HOMEOSTASIS

9. DEFENSE OF ECF VOLUME ANDDEFENSE 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

11.  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

12. 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%

13. 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

14. 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)

15. 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.

16. 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;

17. How does hypervolemic
hyponatremia differ from
hypovolemic
hyponatremia?

18.  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

19. 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 } .

20.  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

21. 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.

22. 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.

23.  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.

24. •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.

25. 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.

26. 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.

27. Regulation of Na/K

28. 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

29. 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????????

30.  Thanx

31. 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)

32. 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 exchangeable
10% non exchangeable
Amount ingested = up to 100meq/d = 2.5 gm/d
92% urinary excretion
8% GIT excretion
32

33. Redistribution of K

34. 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).

35. Physiological roles of potassium
1.Roles of intracellular K+:
 Cellular volume maintenance
 Intracellular pH regulation
 Cell enzyme function
 DNA/protein synthesis
 Cell growth
2.Roles of transcellular K+ ratio:
 Resting cell membrane potential
 Neuromuscular excitability
 Cardiac pacemaker rhythmicity
35

36. Potassium homeostasis
1.Internal balance ( ICF and ECF K+ distribution)
2. External balance ( Renal excretion of K+)
1.Internal balance
Physiological and pathological conditions can influence this
process.
o Hormones like insulin , catecholamines ,aldosterone
o Acid base imbalance
o Changes in osmolarity
o Exercise
o Cell lysis

37. 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

39. 39
Hormonal control of K+
homeostasis

40. 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 lysis
o 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.

41. …………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

42. 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
42

43. ……….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
43

44. ……………cont’d
02/12/15 Potassium homeostasis and its
renal handling
44

45. 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+
.

47. 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

48. Copyright ©1998 American Physiological Society
Renal regulation of Potassium

49. Sources of K
 Banana, orange, apple, pineapple
 Almond, dates, beans, potatoes