It is related to the rule of origin and evolution of disease process and the underlying mechanisms.

What is Pathophysiology?

Pandect of Pathophysiology

Fundamental Pathological process

Systemic Pathophysiology

Conspectus of the diseaseconcept /etiology/pathogenesis/ outcome of the disease

Typical Pathological process: an organic process occurring as a consequence of disease.

The common outcome for the diseases in a certain system.

Disorders of Water and Electrolyte Metabolism

Pathophysiology Department, Tongji Medical College, HUST

Part I: Normal Metabolism of Water

and SodiumVolume and distribution of body fluid

Major electrolytes and its distribution

Water balance and its regulation

Body fluid: the liquid parts of the body

—It contains water and a lot of solutes. —As we have studied, the metabolism of our body is taken

place in body fluid, so the fluid balance is an important

factor to maintain the normal metabolism and homeostasis.

Total body fluid varies with gender /age / body adipose content.

Men :60% of the body weight Women:50% of the body weight

Newborn infant > Adult > Old person

ICF40% ECF20%

The total body fluid is comprised of several different compartments.

Interstitial 15% Plasma 5%

Transcellular fluid

Transcellular fluid —is a small compartment that represents all those body

fluids which are formed from the transport activities of cells. —is contained within epithelial lined spaces. —includes cerebrospinal, pleural, pericardial, peritoneal,

intraocular, synovial fluid and of the secretions from the

digestive tract.

Solutes

Nonelectrolytes: Proteins, urea, glucose, oxygen,

carbon dioxide and organic acid etc.

Eletrolytes: cation(Na+, K+, Ca2+, Mg2+),

anion(Cl-,HCO3- ,HPO4

2-), etc.

Ka+,HPO42- Na+,Cl-

Pro

Osmosis and Osmotic Pressure

When a semi-permeable membrane (a membrane that allows solvent molecules to flow through but not the solute particles) separates two solutions of different concentrations, there will be a net flow of solvent molecules from the solution where its concentration is lower to the solution

where its concentration is higher. This phenomenon is called Osmosis and driving pressure is called as Osmotic pressure.

Osmotic pressure:Crystal osmotic pressure is formed by a lot of small molecular weight materials, such as electrolyte, Glucose, BUN and so on. Colloid osmotic pressure is formed by large molecular weight materials such as proteins.

Ka+,HPO42-

Na+,Cl-

Pro

Why the colloid pressure is very low?What is the effect of colloid osmotic pressure? What is the function of ECF Osmolarity?

Functions of electrolytes:

1 Maintaining the osmotic and acetic-alkali equilibrium.

2 Maintaining the resting membrane potential and generating the active membrane potential.

3 Taking part in metabolism and physiologic action.

Functions of body water:

It is essential to metabolism of the body.

It acts as a transport vehicle.

It is a good lubricant.

It is necessary for temperature regulation.

Water balance

40%BW15%BW5%BW

Interstitial

Plasma

ICF

吸收水分

Kidney(urine) 1500ml Intestine(feces) 200mlLung(water vapor) 400ml Skin(sweat and evaporation)400ml

排出水

分

Intake Output

Digestive tracts

Nutrients oxidation

Osmotic pressure of this lost water?

The Balance Concept: Input -Output = Storage/Depletion

InternalPool (ECFConcentration) of substance

Storage

MetabolicProduction

MetabolicConsumption

InsideBody

Inputs from environment

Excretion

Regulation of fluid volume and osmotic pressure

Disturbance

Volume

Osmotic pressure

ADHRAASANP

Thirst

Thirst ADHRAAS

Regulation pathway

The regulation of thirsty reaction

Thirsty center locates in the hypothalamus.

Stimulus: Increase of plasma Na+

Decrease of effective blood volume

Increase of ANGII

The regulation of RAAS

The regulation of ADH

ADH released

BP/Blood volume

+Stretch receptor

+

Plasma osmotic pressure

+Osmoreceptor

ADH enhances reabsorption of free water in renal tubules.

300 mosm 300 mosm

No ADHNo water reabsorption

Diuresis

ADH enhances water reabsorption

H2O into blood

Anti-diuresis

High quantityLow osmotic pressure

Function of ADH

Low quantityHigh osmotic pressure

ADH is more sensitive to the change of osmotic pressure. 1-2% change of osmotic pressure will change the production of ADH.

At first, ADH will not be increased.

When blood volume is decreased >10%, ADH will be increased At this time, the decreased of blood volume may be life-threatening.

ADH released

BP/Blood volume

+Stretch receptor

+

Plasma osmotic pressure

+Osmoreceptor

+

Plasma osmotic pressure

-Osmoreceptor

-?

1. Inhibition of sodium reabsorption in the collecting duct2. Decrease in renin secretion from the macula densa and aldosterone secretion.3. Vasodilation

Stimulus ： Blood volume /pressure Serum Na+

ANGII

The regulation of ANP

Functions ：

Table. Differences Between Table. Differences Between Osmoregulation Osmoregulation and Volume Regulationand Volume Regulation

OsmoregulationOsmoregulation Volume regulationVolume regulation

What is being sensedWhat is being sensed Plasma Plasma osmolalityosmolality Effective circulating volumeEffective circulating volumeSensorsSensors Hypothalamic Hypothalamic osmoreceptorsosmoreceptors Carotid sinusCarotid sinus

Afferent arterioleAfferent arterioleAtriaAtria

EffectorsEffectors Antidiuretic Antidiuretic hormonehormone ReninRenin--AngiotensinAngiotensin--ThirstThirst aldosteronealdosterone systemsystem

Sympathetic nervous systemSympathetic nervous systemAtrial natriuretic Atrial natriuretic peptidepeptidePressure Pressure natriuresisnatriuresisAntidiureticAntidiuretic hormonehormone

What is affectedWhat is affected Water excretion and, via thirstWater excretion and, via thirst Urine sodium excretionUrine sodium excretionwater intakewater intake

Water Channels2003 Chemistry Nobel Prize

 

In mid-1980’s he studied various proteins found in the membrane of red blood cells and also found one in the kidneys and was able to determine the peptide sequence and the corresponding DNA sequence. (CHIP28 28kDa)

Agre’s Work

Water permeability in human erythrocytes: Identification of membrane proteins involved in water transport. Eur J Cell Biol, 1986,41(2):252-262.

Aquaporin,AQP

It is a family of protein in the cell membrane.

It located in the animal, plant and microorganism.

There are at least 11 aquaporins now.

AQP2 is also called as water channel of the collecting duct.

This is the only water channel which is found being regulated by hormone till now.

ADH can increase the number of AQP2 and water permeability.

The human aquaporin gene family. Current Genomics,2000,1(1):91-102.

Modulation of vasopression-elicited water transport by trafficking of aquaporin2-containing vesicles. Annu Rev Physiol, 1999, 61(1) : 683-697.

Part II:

Disorder of fluid volume and sodium

Classification of disorder of fluid volume and sodium

Volume

HypervolemiaNormovolemia Hypovolemia

< 130

Na+ mEq/L

135-145

> 150

Hypotonic dehydration

Isotonic dehydration

Hypertonic dehydration

Normal

Water intoxication

Edema

Hyponatremia

Hypernatremia

Dehydration: an excessive loss of body fluid.

(Hypovolemic hypernatremia)

Hypertonic dehydration

The dehydration in which the water loss is in excess of salt loss and the remaining ECF of the body is hypertonic is termed of hypertonic dehydration.

Concept:

Characteristics:—Loss of water more than sodium—Serum Na+ >150mmol/L—Plasma osmotic pressure> 310mmol/L

Etiology:

1. Insufficient water intake

2. Excessive water loss

Unable to obtain water

Deficient Thirst Reflex

Difficulty in swallowing

the skin(burns, excessive perspiration)

the lungs (hyperventilation of any cause)

the kidneys

the Intestine (GI hemorrhages, diarrhea, vomiting)

Through

Causes of polyuria and increased diuresis

Central causes: Primary (Psychogenic) polydipsia(烦渴 ) Central Diabetes Insipidus (中枢性尿崩症 )

Kidney and adrenal causes: ARF in polyuric phase Postobstructive diuresis Osmotic diuresis (mannitol, uncontrolled

Diabetes Mellitus) Nephrogenic Diabetes Insipidus (肾性尿崩症 ) Diuretics (the most common cause) Secondary and drug-induced

hypoaldosteronism(醛固酮减少症 ) .

Diabetes Insipidus

Central diabetes insipidus is characterized by decreased secretion of antidiuretic hormone (ADH) that results in polyuria and polydipsia by diminishing the patient's ability to concentrate urine.

Nephrogenic diabetes insipidus is characterized by a decrease in the ability to concentrate urine due to a resistance to ADH action in the kidney.

No ADHNo water reabsorption

Diuresis

ADH enhances water reabsorption

H2O into blood

Anti-diuresis

High quantityLow osmotic pressure

Low quantityHigh osmotic pressure

Hypertonic dehydration

Effects on the body:

1Thirsty

ADH release Drink water

Blood volume

Serum Na+

Water reabsorbed from tubular

。 。 。 。 。 。 。 。 。 。

。 。 。 。。 。

。 。 。。 。 。

。。 。 。 。 。

。ICF Interstitial Plasma

2

1) ECF is decreased.

2) ICF is transported to outside of the cell.

3) Blood is condensed.

Cell dehydration

Degree Volume of water loss Clinical manifestation

(% of body weight)

Mild 2-5 Thirst, Oliguria

Moderate 5-10 Severe thirst,dryness of mucosa,fever

Sever 10-15 Delirium, stupor, coma

Clinical Manifestation of Hypertonic Dehydration

Principles of Therapy:

Treating the primary disease

Supplying 5%-10% Glucose

Adding a small amount of NaCl solution

Adding K+ properly

Hypotonic dehydration

(Hypovolemic hyponatremia)

The dehydration in which the salt loss is in excess of water loss and the remaining ECF of the body is hypotonic is termed of hypotonic dehydration.

Characteristics:—Loss of salt more than water—Serum Na+ <130mmol/L—Plasma osmotic pressure< 280mOsm/L

Concept:

Etiology:

Excessive amount of sodium can be lost in gastrointestinal secretions. (Vomiting, diarrhea or gastric suction)

Sodium deficit may result from excessive sweating.

Sodium deficit may result from excessive water loss from kidney (prolonged diuretic therapy, adrenal deficiency or low aldosterone or renal tubular acidosis)

Most of conditions occurs when the fluid loss is replaced with water only.

Effects on the body:

1Thirsty not obvious

ADH release is inhibited due to the decreased osmolarity of ECF

Mild dehydration

Moderate-severe dehydration

ADH is released due to the decreased volume of ECFAld is released due to the decreased volume of ECF

Water reabsorbed from tubular

。 。 。 。 。 。 。 。 。 。

。 。 。。 。 。。 。 。

。 。 。 。 。 。 。 。 。 。 。 。 。 。 。。 。 。 。 。。 。 。 。 。。 。 。 。 。。 。 。 。 。。 。 。 。 。。 。 。 。 。。 。 。 。 。

ICF Interstitial Plasma

2

1) ECF is decreased.

2) ECF is transported to the cell.

3) Blood is condensed.

Cell edema

Degree Volume of water loss Clinical manifestation

(per kg of body weight)

Mild 0.5g/Kg Fatigue, dizziness, pale

Moderate 0.5-0.7g/Kg Loss of skin turgor, cramps,

apathy, hypotension

Sever 0.75-1.25g/Kg Oliguria, shock, stupor

Clinical Manifestation of Hypotonic Dehydration

Principles of Therapy:

Treating the primary disease

Supplying 5%Glocose or 0.9% NaCl solution

Isotonic dehydration

The dehydration in which the salt loss is identical to water loss and the remaining ECF of the body has the normal osmolality is termed of isotonic dehydration.

Concept:

Effects on the body:

Hypertonic dehydration Hypotonic dehydration

Thirsty

ECF

ICF transported to ECF

Blood condensed

stupor, coma

ECF

ECF transported to ICF

Blood condensed

Interstitial transported into vessel

Which type of dehydration is more common?

Which type of dehydration tends to cause shock?