The role of kidney in the regulation of

THE ROLE OF KIDNEY IN THE REGULATION OF;

BODY FLUIDSOSMOLARITY

ELECTROLYTES ERYTHROPOIESIS

July 13, 2015 Year - II Medical Students of AAU

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Overview

Renal mechanisms for control of body fluid Overall control of extracellular fluid volume

and sodium excretion Renal control of extracellular fluid

osmolarity the osmoreceptor-ADH feedback system the thirst mechanism

Renal regulation of electrolytes Potassium, Magnesium, Calcium, Phosphate

Renal regulation of erythropoiesis

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Renal Mechanisms for Control of Extracellular Fluid Volume

To control of extracellular fluid volume, consider factors that regulate the amount of NaCl in ECF

because electrolytes content usually parallels the extracellular fluid volume

i.e. provided the antidiuretic hormone (ADH)-thirst mechanisms are operative

Burden of EC volume regulation is on KIDNEY, which must adapt their excretion to match varying intakes of

salt and water.

Sodium excretion is precisely matched with sodium intake under steady-state conditions.

i.e. Even with disturbances that cause major changes in renal excretion of sodium, the balance between intake and

excretion is usually restored within a few days

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…Cont’d

The kidney alters sodium and water excretion by changing the rate of filtration, the rate of tubular reabsorption, or both, as follows:

Excretion = Glomerular Filtration - Tubular Reabsorption

i.e. GF and tubular reabsorption are both regulated by multiple factors, including hormones, sympathetic activity, and arterial

pressure.

Normally….H2O, GFR = 180 L/day, tubular reabsorption = 178.5 L/day, urine excretion = 1.5 L/day.

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Even with disturbances that alter the GFR or tubular reabsorption, changes in urinary excretion are minimized by various intrarenal buffering mechanisms: Glomerulotubular balance Macula densa feedback

• i.e. NOT PERFECT--> systemic feedback mechanisms such as changes in blood pressure

and changes in various hormones—that eventually return sodium excretion to equal intake

…Cont’d

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Renal Control of Extracellular Fluid Osmolarity

The regulation of ECF osmolarity and Na concentration are closely linked Na is the most abundant cation in the EC

compartment

Two primary systems are particularly involved the osmoreceptor-ADH feedback system the thirst mechanism

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Osmoreceptor-ADH Feedback System When osmolarity increases above normal:

Stimulates osmoreceptor cells in the anterior hypothalamus,

AP to the posterior pituitary stimulate release of ADH,

ADH via blood to kidneys, increases water permeability of the late distal tubules,

cortical collecting tubules, and medullary collecting ducts Increased water reabsorption Excretion of a small volume of concentrated urine

This causes dilution of solutes in extracellular fluid, thereby correcting the initial excessively concentrated extracellular fluid.

…Cont’d

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The thirst mechanism Fluid intake is regulated by the thirst mechanism,

Stimuli for thirst (the conscious desire for water) are: ed ECF osmolarity ed ECF volume and arterial pressure Angiotensin II

Other factors …short lived dryness of the mouth and mucous membranes of the

esophagus the degree of gastric distention

…Cont’d

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The ADH and thirst mechanisms operate together to regulate extracellular osmolarity. Normally, these two mechanisms work in parallel to regulate

ECF osmolarity and Na concentration precisely, despite the constant challenge of dehydration.

If both the ADH and thirst mechanisms fail simultaneously, however, neither sodium concentration nor osmolarity can be adequately controlled.

In the absence of these mechanisms, there are no other feedback mechanisms in the body capable of precisely regulating plasma osmolarity.

…Cont’d

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Renal Regulation of Electrolytes

Potassium• Storage

• 98% -- IC• 2% -- EC …..

(4.2mEq/L)

IC K+ is ed by: Insulin aldosterone, Metabolic alkalosis

EC K+ is ed by: Cell injury Sternous exercise ed ECF osmolarity Metabolic acidosis

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Daily variations in potassium excretion are controlled mainly by changes in secretion in distal and collecting tubules.

Maintaining potassium balance depends primarily on renal excretion which is determined by: the rate of potassium filtration the rate of potassium reabsorption by the tubules the rate of potassium secretion by the tubules

i.e. About 65% of the filtered potassium is reabsorbed in the proximal tubule and another 25% to 30% in the

ascending loop of Henle.

Potassium …Cont’d

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Secretion of potassium from the peritubular capillary blood into the lumen of the distal and collecting tubules is a three-step process: 1. passive diffusion of potassium from blood to

the renal interstitium, 2. active transport of potassium from interstitium

into tubular cells by the Na-K ATPase pump at the basolateral membrane, and

3. passive diffusion of potassium from the cell interior to the tubular fluid

Potassium …Cont’d

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Renal K+ secretion is increased by: ed

aldosterone ed EC K+ ed tubular

flow rate Acute in H+

(alkalosis)

Potassium …Cont’d

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Calcium Majorly excreted in the feces Storage

99% -- bones 1% -- ICF and 0.1% -- ECF

Parathyroid hormone(PTH) is an important regulator of bone uptake and release of calcium: Initially by directly acting on bone (resorption) Over the long term, must be balanced with calcium

excretion by the gastrointestinal tract and kidneys

Calcium …Cont’d

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PTH regulates the plasma calcium concentration through three main effects: Stimulating bone resorption; Stimulating activation of vitamin D, which

increases intestinal absorption of calcium; Directly increasing renal tubular

calcium reabsorption

Calcium …Cont’d

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i.e. Calcium is not secreted by the renal tubules, and its excretion rate is therefore determined by the

rate of calcium filtration and tubular reabsorption.

ed PTH >>> there is ed calcium reabsorption through the thick ascending loop of Henle and distal tubule>>> ed calcium urinary excretion

ed plasma phosphate concentration stimulates PTH, Calcium reabsorption is also stimulated by metabolic

acidosis and inhibited by metabolic alkalosis

Calcium …Cont’d

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Magnesium Storage

More than half --- in the bones the rest --- resides within the cells, < 1% --- in the extracellular fluid

More than one half of total plasma Mg concentration (1.8 mEq/L) -- bound to plasma proteins

Free ionized concentration of Mg = 0.8 mEq/L

Magnesium …Cont’d

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Only about one half of Mg intake is absorbed by the gastrointestinal tract.

i.e. the kidneys must excrete about one half of the daily intake of magnesium,

10 - 15 % of the magnesium in the glomerular filtrate is excreted.

Magnesium …Cont’d

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Regulation of magnesium excretion is achieved mainly by changing tubular reabsorption. 25% -- by the proximal tubule 65% -- by loop of Henle < 5% -- by distal and collecting tubules

i.e. The mechanisms that regulate magnesium excretion are not well understood, but the following disturbances lead to increased magnesium excretion:

increased ECF Mg concentration EC volume expansion increased ECF Ca concentration

Magnesium …Cont’d

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Phosphate Controlled by an overflow mechanism

maximum phosphate reabsorbed @ 0.1 mM/min

the excess is excreted into the urine

i.e. Because most people ingest large quantities of phosphate in milk products and meat, the

concentration of phosphate is usually maintained above 1 mM/L, a level at which there is continual

excretion of phosphate into the urine.

Phosphate …Cont’d

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PTH can play a significant role in regulating phosphate concentration through two effects: PTH promotes bone resorption,

thereby dumping large amounts of phosphate ions into the ECF from the bone salts,

PTH decreases the transport maximum (Tm) for phosphate by the renal tubules, so that a greater proportion of the tubular

phosphate is lost in the urine

Phosphate …Cont’d

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Renal regulation of Erythropoiesis

The direct control of erythrocyte production (erythropoiesis) is by a hormone -- ERYTHROPOIETIN secreted into the blood mainly by a particular group of

hormone-secreting connective tissue cells of fibrocytes in the cortex of kidneys

Acts on the bone marrow to stimulate the proliferation of erythrocyte progenitor cells and their differentiation into mature erythrocytes.

Secreted in relatively small amounts (but adequate enough for its function) Increased if oxygen delivery to the kidneys is

decreased

i.e. Testosterone, the male sex hormone, also stimulates the release of erythropoietin accounting for the higher

hematocrit in men than in women.

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Reference materials

- Guyton text book of medical physiology, 11th edition

- Vander, Sherman and Lucian’s human physiology, 9th edition

Group – 2AUrinary system and Toxicology Module (X)(USTX2091)Physiology Seminar

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