A&P Lecture 2. Homeostasis (PDF)

Homeostasis: Volume and Composition of Body Fluid Compartments Baha ADAM, MD, MSc, Ph.D., DABCC Professor, Basic Pharmaceutical Science Physician Assistant Program College of Pharmacy, Xavier University of Louisiana  The outline...

Homeostasis: Volume and Composition of Body Fluid Compartments Baha ADAM, MD, MSc, Ph.D., DABCC Professor, Basic Pharmaceutical Science Physician Assistant Program College of Pharmacy, Xavier University of Louisiana  The outline of this chapter: Concept of steady-state balance Alterations in sodium, chloride, Distribution of body fluids and and water balance electrolytes Isotonic alterations Water movement between plasma Hypertonic alterations and interstitial fluid Hypotonic alterations Water movement between ICF and Alterations in potassium and ECF other electrolytes Alterations in water movement Membrane potential Na+, K+, and Cl-, and water balance Principles of epithelial transport  Homeostasis Volume and composition of body fluid compartments: Normal cellular function requires that the intracellular composition—with regard to ions, small molecules, water, pH, and a host of other substances—be maintained within a narrow range. This is accomplished by the transport of many substances and water into and out of the cell via membrane transport proteins.  Homeostasis Volume and composition of body fluid compartments: In addition, each day, food and water are ingested, and waste products are excreted from the body. In a healthy individual, these processes occur without significant changes in either the volume of the body fluid compartments or their composition. The maintenance of constant volume and composition of the body fluid compartments is termed homeostasis (steady-state balance). The human body has multiple systems designed to achieve homeostasis.  Homeostasis Concept of Steady-State Balance: The human body is an “open system,” which means that substances are added to the body each day and, similarly, substances are lost from the body each day. The amounts added to or lost from the body can vary widely, depending on the environment, access to food and water, and disease processes. In such an open system, homeostasis occurs through the process of steady-state balance.  Homeostasis To understand steady-state balance as it applies to the human body, the following key concepts are important. There must be a “set point” so that deviations from this baseline can be monitored The sensor that monitor deviations from the set point must generate “effector signals” that can lead to changes to maintain the desired set point “Effector organs” must respond in an appropriate way to the effector signals generated by the set point monitor. The sensitivity of the system which depends on several factors.  Homeostasis To understand steady-state balance as it applies to the human body, the following key concepts are important. It is important to recognize that deviations from steady-state balance do occur. When input is greater than output, a state of positive balance exists. When input is less than output, a state of negative balance exists. Although transient periods of imbalance can be tolerated, prolonged states of positive or negative balance are generally incompatible with life.  Whole-Body Steady-State Water Balance There are multiple inputs and outputs of water, many of which can vary but nevertheless cannot be regulated. The amount of water lost through the lungs depends on the humidity of the air and the rate of respiration. The amount of water lost as sweat varies according to ambient temperature and physical activity. Of these inputs and outputs, the only two that can be regulated are increased ingestion of water in response to thirst and alterations in urine output by the kidneys  Homeostasis Concept of steady-state balance: Water balance determines the osmolality of the body fluids. Cells within the hypothalamus of the brain monitor body fluid osmolality for deviations from the set point (normal range: 280- 295 mOsm/kg H2O). When deviations are sensed, two effector signals are generated. Neural and relates to the individual's sensation of thirst. Hormonal (antidiuretic hormone) regulates the amount of water excreted by the kidneys. With appropriate responses to these two signals, water input, output, or both are adjusted to maintain balance and keep body fluid osmolality at the set point.  Homeostasis Concept of steady-state balance: The cells of the body live in a fluid environment where electrolyte and acid–base concentrations are maintained within a narrow range. Changes in electrolyte concentration affect the electrical activity of nerve and muscle cells, resulting in fluid shifts from one compartment to another. Alterations in acid-base balance disrupt cell functions. Fluid fluctuations also affect blood volume. Disturbances in these functions are common and can be life-threatening.  Distribution of Body Fluids and Electrolytes Total body water = 0.6 x (body weight) ICF = 0.4 x (body weight) ECF = 0.2 x (body weight)  Distribution of body fluids Table 1. Distribution of Body Water (70-kg Adult) Fluid Compartment % of Body Weight Volume (L) Total body water 60 (males) 42 (TBW) 50 (females) 35 Intracellular fluid 40 (males) 28 (ICF) 30 (females) 21 Extracellular fluid 20 male and female 14 (ECF) Interstitial 15 11 Intravascular 5 3 The distribution of intracellular water in females is less due to larger amounts of subcutaneous tissue and smaller muscle mass.  Distribution of Body Fluids and Electrolytes Body fluids are distributed among functional compartments: Intracellular fluid (ICF) Extracellular fluid (ECF) The interstitial fluid is the fluid found in the spaces between cells but not within the blood vessels. The intravascular fluid is the fluid found within blood vessels; it is more commonly known as the blood plasma.  Distribution of Body Fluids and Electrolytes Body fluids are distributed among functional compartments: The transcellular fluids, the smallest component of extracellular fluids, are the fluids contained within epithelial-lined cavities of the body. Examples of transcellular fluid include synovial fluid, cerebral spinal fluid, gastrointestinal fluids, pleural fluids, pericardial fluids, peritoneal fluids, and urine. Sweat is yet another component of the extracellular fluid. Distribution of the Electrolytes ECF (mEq/L) ICF (mEq/L) electrolytes Cations Sodium 142 12 Potassium 4.2 150 Calcium 5 0 Magnesium 5 24 TOTAL 153.2 186 Anions Bicarbonate 24 12 Chloride 103 4 Phosphate 2 100 Proteins 16 65 Other anions 8 6 Total 153 187 Electrolytes and other solutes are distributed throughout the intracellular and extracellular fluids The extracellular fluid contains a large amount of sodium and chloride and smaller amounts of potassium. The intracellular fluid contains larger amounts of potassium with smaller amounts of sodium and chloride. The concentrations of phosphates and magnesium are greater in the intracellular fluid; the concentration of calcium is greater in the extracellular fluid. An active energy-requiring physiologic pump maintains these differences in the electrolyte concentration. Electrolytes and other solutes are distributed throughout the intracellular and extracellular fluids These differences in electrolyte concentration are important in maintaining several physiologic functions: electroneutrality between the extracellular and intracellular compartments, the transmission of electrical impulses, and the movement of water among body compartments. Electrolytes and other solutes are distributed throughout the intracellular and extracellular fluids Although the amount of fluid within the various compartments is relatively constant, solutes and water are exchanged between compartments to maintain their unique compositions. The percentage of TBW varies with the amount of body fat and age. Fat is hydrophobic (water-repelling), and very little water is contained in adipose (fat) cells. Individuals with more body fat have proportionately less TBW and tend to be more susceptible to dehydration. Normal Water Gains and Losses (70-kg Adult) Daily Intake (mL) Daily Output (mL Drinking 1400–1800 Urine 1400–1800 Water in food 700–1000 Stool 100 Water of oxidation 300–400 Skin (sweating) 300-500 Lung 600-800 TOTAL 2400–3200 TOTAL 2400–3200 Sweating and lung ventilation are two major sources of insensible fluid loss. Insensible losses must be replaced regularly, usually by drinking fluids, to maintain fluid balance.  Homeostasis Net filtration or Starling forces: Capillary hydrostatic pressure (blood pressure) facilitates the movement of water from the capillary into the interstitial space. Capillary (plasma) oncotic pressure osmotically attracts water from the interstitial space into the capillary. Interstitial hydrostatic pressure facilitates the inward movement of water from the interstitial space into the capillary. Interstitial oncotic pressure osmotically attracts water from the capillary into the interstitial space.  Homeostasis The forces controlling the movement of fluid across the capillary wall are summarized by these equations: Net filtration = (Forces favoring filtration) – (Forces opposing filtration Forces favoring filtration = Capillary hydrostatic pressure and interstitial oncotic pressure Forces opposing filtration = Capillary oncotic pressure and interstitial hydrostatic pressure  Homeostasis Net Filtration: At the arterial end of the capillary, hydrostatic pressure exceeds capillary oncotic pressure; thus fluid moves into the interstitial space (filtration). At the venous end of the capillary, oncotic pressure within the capillary exceeds capillary hydrostatic pressure; thus, fluids move into the capillary to enter into the circulation (reabsorption). Net Filtration  Homeostasis Net Filtration: Interstitial hydrostatic pressure promotes the interstitial fluid, along with small amounts of protein, into the lymphatics. Once the fluid enters the lymphatic system, it travels through progressively larger lymphatic vessels until it enters the systemic circulation where the lymphatic thoracic duct joins the left subclavian vein.  Homeostasis Water movement between ICF and ECF: Water moves between ICF and ECF compartments primarily as a function of osmotic forces. Water moves freely by diffusion through the lipid bilayer cell membrane and through aquaporins. Sodium is responsible for the osmotic balance of the ECF, and potassium maintains the ICF osmotic balance. The osmotic force of ICF proteins and other nondiffusible substances is balanced by the active transport of ions out of the cell.  Homeostasis Water movement between ICF and ECF: Under normal conditions, the ICF is not subject to rapid changes in osmolality; however, when the ECF osmolality changes, water moves from one compartment to another until osmotic equilibrium is reestablished. A shift of fluid from the capillaries or lymphatic vessels into the tissues results in an excessive accumulation of fluid within the interstitial spaces called edema. Physiologic conditions that promote fluid flow into the tissues include (1) increased capillary hydrostatic pressure , (2) decreased plasma oncotic pressure , (3) increased capillary membrane permeability , and (4) lymphatic channel obstruction.  Mechanisms of edema formation. Alterations in Water Movement: Edema Pitting Edema Lymphedema  Homeostasis Sodium, chloride, and water balance: The combined influences of the renal and endocrine systems have a central role in maintaining sodium and water balance. Because water follows the osmotic gradients established by changes in salt concentration, the sodium concentration and water balance are integrally related. The sodium concentration is regulated by the renal effects of aldosterone. Water balance is regulated primarily by antidiuretic hormone (ADH), also known as vasopressin.  Homeostasis Sodium, chloride, and water balance: Na+ accounts for 90% of the ECF cations (positively charged ions). Na+ in concert with chloride and bicarbonate, the two major anions acts to regulate water balance by contributing to extracellular osmotic forces. Na+ has an important role in several other physiologic functions, including nerve impulse conduction, regulation of the acid–base balance, cellular biochemistry, and the transport of substances across the cellular membrane.  Homeostasis Sodium, chloride, and water balance: The serum Na+ concentration normally is maintained within a narrow range by renal tubular reabsorption within the kidney in response to neural and hormonal influences. Hormonal regulation of sodium (and potassium) balance is mediated by aldosterone. Aldosterone is a component of the renin-angiotensin- aldosterone system. Aldosterone secretion is influenced by a number of factors, including circulating blood volume , blood pressure , and plasma concentrations of sodium and potassium. The Renin-Angiotensin-Aldosterone System  Homeostasis Sodium, chloride, and water balance: When the circulating blood volume or blood pressure is reduced, renin, an enzyme secreted by the juxtaglomerular cells of the kidney, is released. Renin also is released when sodium levels are depressed or potassium levels are increased. Once released, renin stimulates the formation of angiotensin I from angiotensinogen, a substance secreted by the liver. Angiotensin-converting enzyme (ACE), found primarily in pulmonary vessels and to a lesser extent in endothelial and renal epithelial cells, converts angiotensin I to angiotensin II, a potent vasoconstrictor.  The effects of angiotensin II (is an α-2-globulin) Angiotensin is a peptide hormone  Homeostasis Sodium, chloride, and water balance: Vasoconstriction elevates blood pressure and restores renal perfusion. Restoring renal perfusion inhibits further release of renin. Angiotensin II also stimulates both the secretion of aldosterone from the adrenal cortex and antidiuretic hormone from the posterior pituitary. Aldosterone promotes sodium and water reabsorption, in addition to the excretion of potassium within the renal tubules. The net effect is to increase blood volume. Cooperative roles of antidiuretic hormone (ADH) and aldosterone in regulating urine and plasma volume.  Homeostasis Sodium, chloride, and water balance: Drugs used for the treatment of hypertension include angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers, which are well-tolerated. Both of these classes of drugs inhibit the renin-angiotensin- aldosterone system and lower blood pressure. Direct renin inhibitors are a third class of antihypertensive drugs. They are used less commonly because of their less favorable safety profile.  Homeostasis Sodium, chloride, and water balance: Natriuretic peptides are hormones primarily produced by the myocardium. Atrial natriuretic hormone (ANH) is produced by the atria. B-type natriuretic peptide (BNP) is produced by the ventricles. Natriuretic peptides are released when the transmural atrial pressure increases, which commonly occurs with congestive heart failure (CHF) or when the mean arterial pressure increases. BNP is a diagnostic marker for CHF.  Homeostasis Sodium, chloride, and water balance: Chloride (Cl−) is the major anion in the ECF and provides electroneutrality, particularly in relation to sodium. Chloride transport generally is passive and follows the active transport of sodium. Increases or decreases in chloride concentration are proportional to changes in sodium concentration. Chloride concentration tends to vary inversely with changes in the concentration of bicarbonate, the other major anion.  Homeostasis Sodium, chloride, and water balance: Water balance is regulated by the secretion of ADH, also known as vasopressin. ADH is produced in the posterior pituitary and secreted when plasma osmolality increases or circulating blood volume decreases, causing a drop in blood pressure. Increased plasma osmolality occurs when there is a decrease in water or an excess concentration of sodium in relation to total body water.  Homeostasis Sodium, chloride, and water balance: The increased osmolality stimulates hypothalamic osmoreceptors, resulting in thirst. Thirst, in turn, stimulates the individual to consume liquids, thus increasing total body water. In addition to stimulating thirst, the osmoreceptors signal the posterior pituitary gland to release ADH, ADH increases water reabsorption from the renal distal tubules and collecting ducts into the plasma.  Homeostasis Alterations in sodium, chloride, and water balance: Alterations in sodium and water balance are closely related. Sodium imbalances occur with gains or losses of body water. Water imbalances develop with gains or losses of salt. These alterations can be classified as changes in tonicity (i.e., the change in the concentration of solutes in relation to the amount of water present). Normal plasma osmolality is 280 milliosmoles [mOsm)/kg.  Homeostasis Alterations in sodium, chloride, and water balance: Solutions are classified as isotonic, hypertonic, or hypotonic as a function of the solute concentration compared with that of normal body cells. isotonic solutions (A) have solute concentrations that are equal to that of normal cells; hypotonic (B) solutions have less solute concentration. hypertonic (C) solutions have more solute concentration.  Homeostasis Alterations in sodium, chloride, and water balance: Changes in tonicity affect the volume of water within the intracellular and extracellular compartments, resulting in Isovolemia: normal volume Hypervolemia: excess volume than normal volume in the blood Hypovolemia: less than normal volume in the blood. Table 3. Water and Solute Imbalances Tonicity Mechanism Isotonic imbalance Gain or loss of ECF resulting in concentration Serum osmolality = equivalent to (normal saline); no shrinking or 280–294 mOsm/kg swelling of cells Hypertonic imbalance Imbalances that result in ECF concentration Serum osmolality >0.9% salt solution (i.e., water loss or solute >294 mOsm/kg gain); cells shrink in hypertonic fluid Hypotonic imbalance Imbalance that results in ECF