AIMST UNIVERSITY PHYSIOLOGY UNIT DR.P.SUNITHA

REGULATION OF FLUID VOLUME AND OSMOLARITY

Definition: Keeping the internal environment in a Steady state Homeostasis Definition: Keeping the internal environment in a Steady state It is controlled by Negative Feedback Mechanism

Body Fluids Fluid compartments Body Water Healthy adult 2 main ones Male = 60% Female = 50% Babies = 75% Elderly = 45% Calculation: 1 Kg = 1 L water volume 150# = 70Kg 60% of 70Kg = approx 40Kg 40Kg = 40L Fluid compartments 2 main ones ICF = 2/3 volume of fluid in body ECF = 1/3 volume of fluid in body Plasma = 20% Interstitial fluid = 80% Calculation: 40L = fluid volume 2/3 = 25L of ICF 1/3 = 15L of ECF NB: Blood = 3-4% of weight

Fluid and Electrolytes 60% of body consists of fluid Intracellular space [2/3] Extracellular space [1/3] Electrolytes are active ions: positively and negatively charged

Solution = Solute + Solvent Solution = the fluid compartment (ICF or ECF) Solvent = water Solutes: Electrolytes Charged ions They dissolve in water They can conduct an electric current Major cations: ECF = sodium ICF = potassium Major anions: ECF = chloride, bicarbonate ICF = proteins w/ neg charge Non-electrolytes Polar =those that are water soluble (sugars, proteins) Non-polar = those that are water insoluble (lipids)

Note: Insensible loss = 1000 cc/day Fluid balance Important in IV daily maintenance Intake & output ( I &O ) Note: Insensible loss = 1000 cc/day

Basic concepts relating to regulation of fluid & electrolytes Water moves passively in response to changes in solute concentration Key = water follows salt Thus, regulation of fluid balance & electrolyte balance are intertwined Fluid shifts occur between ICF & ECF in response to changes only in ECF Key to equilibrium is maintaining solute concentration (osmolality = # solute particles in one liter of solution & is the ability of that solution to cause osmosis) between ICF & ECF If change to hypertonic ECF, then water into ECF If change to hypotonic ECF, then water into ICF

Regulation of Body Fluid Compartments Osmosis is the diffusion of water caused by fluid gradient

Regulation of Body Fluid Compartments Diffusion is the movement of a substance from area of higher concentration to one of lower concentration “Downhill Movement”

Regulation of Body Fluid Compartments Osmolality reflects the concentration of fluid that affects the movement of water between fluid compartments by osmosis

Regulation of Body Fluid Compartments Osmotic pressure is the amount of hydrostatic pressure needed to stop the flow of water by osmosis

Control of Volume Kidneys maintain constant volume and composition of body fluids Filtration and reabsorption of Na Regulation of water excretion in response to ADH Water is freely diffusible Movement of certain ions and proteins between compartments restricted

Volume Control osmoreceptors - day to day control baroreceptors - respond to pressure change neural and hormonal efferents hormonal mediators

Baroreceptors Hormonal mediators aldosterone renin ANP dopamine Hormonal effect  ECF  Na and water reabsorption

Baroreceptors Neural mechanism Autonomic nervous system

Osmolarity Osmolality Osmolarity is the № of osmoles per liter of solution Eg. plasma. Osmolality is the № of osmoles per kg of water Affected by volume of the various solutes in the solution & temperature Not affected

Osmoregulation osmolality 289 mOsm/kg H20 osmoreceptor cells in paraventricular/ supraoptic nuclei osmoreceptors control thirst and ADH small changes in Posm - large response

Osmoregulation Excess free water (Posm 280) thirst inhibited ADH declines urine dilutes to Uosm 100

Osmoregulation Decreased free water (Posm 295) thirst increased ADH increases urine concentrates to Uosm 1200

Factors affecting ECF & ICF volumes Infusion of water Dehydration Intravenous infusion of different types of solutions Loss of large amounts of water from GIT by sweating through the kidney

The control of fluid balance What is monitored: Volume & Osmolality (osmotic pressure via solute conc.) Mechanisms: ADH (antidiuretic hormone) , osmoreceptors, & thirst mechanism Osmoreceptors in hypothalamus regulates secretion of ADH from posterior pituitary The higher the osmolality, the more ADH secreted ADH causes: (1) thirst center to be stimulated (2) kidneys to conserve water Aldosterone Secreted by adrenal cortex Causes kidneys to retain sodium (nb: water follows salt) Stimulated by: increase potassium, falling sodium, & renin-angiotensin Atrial natriuretic peptide (ANP) Released by distended atrial walls of heart Secretion caused by increased pressure and/or volume Antagonistic to aldosterone

ADH secretion Synthesis: SON & PVN, Stored & Released from Posterior pituitary Stimulus: Plasma Osmolarity Blood volume Surgical stress Site of action:-DCT & collecting ducts adenylcyclase - c-AMP  aquaporins open Water reabsorption

Antidiuretic hormone Stimulates reabsorption of water by the kidneys.

Mechanism of action of ADH ADH binds to V2 receptors in the DCT, & CD epithelia  formation of c-AMP activates protein kinases  stimulates the movement of an intracellular protein called Aquaporin-2 to the luminal side of the cell membranes

Mechanism of action of ADH The molecules of AQP2 cluster together & fuse with the cell membrane by exocytosis form water channels that permit rapid diffusion of water through the cells. The AQP-3, AQP-4 in the basolateral side provide a path for water to leave the cell

Renin-angiotensin Renin secreted when drop BP drop Na delivery to kidney increased sympathetic tone

Aldosterone Release stimutlated by Effect Angiotensin II increased K ACTH Effect Na and water absorption in distal tubular segments

Atrial Natriuretic Peptide A. Source:- Secretory granules on Atrial muscle & ventricular muscle B. Site of action:- Kidney tubules. C. Action:- a. Slight increase in GFR b. Inhibit sodium reabsorption in collecting ducts. c. Increases excretion of sodium D. Stimulus:- Stretching of atrial muscles by a. Inc. in central venous pressure b. High sodium in blood

Plasma volume Activity of renal sympathetic nerves Arterial pressure GFR & flow to macula densa Renal juxta glomerular cells NaCl delivery to macula densa Plasma renin Plasma angiotensin II Adrenal cortex Aldosterone secretion Plasma aldostrone Cortical collecting ducts Na+ & H2O reabsorption Na+ & H2O excretion

Water deficit Osmoreceptor-ADH feedback mechanism for regulating ECF osmolarity in response to a water deficit Extracellular osmolarity + Osmoreceptors ADH secretion (Posterior pituitary) Plasma ADH H2O permeability in distal tubules,& collecting ducts H2O reabsorption H2O excreted

Juxtaglomerular apparatus Decreased delivery of Na+ and Cl- to the distal tubules is associated with increased renin secretion. Juxtaglomerular apparatus

Mechanisms of glomerulotubular balance and tubuloglomerular feedback Renal arteriolar pressure Glomerular capillary pressure GFR Solute reabsorption in PCT Solute reabsorption in thick ascending limb Salt & fluid delivery to the distal tubule Glomerulo tubular balance Tubulo glomerular feed back Mechanisms of glomerulotubular balance and tubuloglomerular feedback

Osmoregulation (Water & Mineral salts) After having a very salty meal produce concentrated urine to remove excess salts in solution form extra water is needed to be excreted along with the excess salts sensation of thirst (drink more water to compensate for the water loss)

Reabsorption of Salt and Water

The Homeostatic Regulation of Normal Sodium Ion Concentrations in Body Fluids Figure 27.4

Electrolytes & Their Imbalances Sodium (Na+) Sodium balance Sodium = major cation in extracellular fluid (ECF) Sodium = most common problem with electrolyte balance Key to balance: ingestion via G-I tract = excretion via kidney Aldosterone controls sodium levels via the kidney Remember aldosterone’s antagonist = ANP Sodium contributes to resting membrane potential Sodium rushing into cell via open channels causes depolarization of nerves and muscles

Potassium K+ Most abundant cations in ICF Key role in establishing resting membrane potential in neurons and muscle fibers Also helps maintain normal ICF fluid volume Helps regulate pH of body fluids when exchanged for H+ Controlled by aldosterone – stimulates principal cells in renal collecting ducts to secrete excess K+

5. Potassium reabsorption and secretion

Clinical implications – Diabetes insipidus Sites of lesions that cause deficiency of ADH secretion Symptoms: Polyuria- large volume of dilute urine, Polydipsia, Intact thirst mechanism is important

Signs of sodium imbalance hyponatremia hypernatremia Weakness & fatigue weakness & agitation G-I: anorexia, nausea, cramps G-I: thirst, dry mucosa Hypotension hypertension & edema Mental confusion & ? Seizures (from fluid shift into brain cells) Causes of hyponatremia Excess sweating, vomiting, diarrhea Diuretics Renal failure Excess water intake (water intoxication) Hormonal imbalances Causes of hypernatremia Watery diarrhea Long periods of rapid respiration Loss of thirst mechanism

Hyponatremia Sodium level less than 135 mEq/L May be caused by vomiting, diarrhea, sweating, diuretics, etc.

Fluid Volume Disturbances Fluid Volume Deficit (Hypovolemia)

After Sweating Concentrated Blood Concentrated Urine is produced Concentrated Blood Normal Water Content in Blood Larger proportion of water is reabsorbed

Smaller proportion of water is reabsorbed After Drinking Diluted Blood Diluted Urine is produced Normal Water Content in Blood Smaller proportion of water is reabsorbed

Fluid Volume Deficit Mild – 2% of body weight loss Moderate – 5% of body weight loss Severe – 8% or more of body weight loss

Fluid Volume Deficit 2 Clinical manifestations Acute weight loss Decreased skin turgor

Fluid Volume Disturbances 2 Fluid Volume Excess (Hypervolemia)

Fluid Volume Excess 2 Clinical manifestations – edema, distended neck veins, crackles, tachycardia, increased blood pressure, increased weight

HAVE A HEALTHY KIDNEY HAVE A NICE DAY

Learning objectives Role of kidneys in regulation of osmolality of body fluids: the need to regulate osmolality of body fluids; osmoreceptors; humoral mechanisms affecting renal excretion of water – special reference to the role of antidiuretic hormone.

Learning outcomes Describe the release, mechanism of action & functions of ADH. Explain how the body fluid osmolarity is regulated. Describe the disorders of ADH secretion