病理生理学课件：03 水盐代谢紊乱

1、Fluid and Electrolyte Balance and Imbalance CHAPTER 2 Ning Sun Office：Room 256, Building 7, West campus Phone: 54237781 E-mail: Chapter 2 Disorders of potassium metabolismDisorders of potassium metabolism Body Fluid and Body Fluid and Electrolyte BalanceElectrolyte Balance 1 1. .Volume, Distribution

2、 and Composition of Body FluidsVolume, Distribution and Composition of Body Fluids 2.2.Osmolality of Body fluidsOsmolality of Body fluids 3.3.Mechanisms for Regulating Body Fluid and Electrolyte BalanceMechanisms for Regulating Body Fluid and Electrolyte Balance Disorders of Water and Disorders of W

3、ater and Sodium MetabolismSodium Metabolism Water intoxiatonWater intoxiaton EdemaEdema HypertonicHypertonic HypotonicHypotonic IsotonicIsotonic DehydrationDehydration Water excessWater excess Environment: Outside: stable temperature and atmosphere Inside: stable temperature and fluid/solutes balanc

4、e-homeostasis Normal Body Fluid and Electrolyte Balance Water within the body and the substances dissolved in it. Function of body water Osmolality of the Body Fluid Total Fluid Volume Body Fluid Distribution Body Fluid Composition Body Fluid Homeostasis Total Fluid Volume Body fluids/Total body wat

5、er 60% of the body weight Determining factors affecting water content in different individuals Body fluid TBW (%) Adult female TBW(%) Adult male TBW(%) Infant Lean607080 Normal506070 Obese425060 q age, gender, the content of adipose tissue Body Fluid Distribution Intracellular fluid (ICF) 40 Extrace

6、llular fluid (ECF) ISF 15 Interstitial fluid(ISF) 4% Plasma Transcellular fluid (Third space) The cytosol of cells The ECF and the ICF are two distinct fluid compartment Cerebrospinal, pericardial, pleural, peritoneal, synovial, gastrointestinal fluids 1% Body Fluid Composition ECF: Na+、Cl-、 HCO3- I

7、CF: K +、 Mg2 +、 HPO42- Pr- SerumNa 140 mmol/L SerumCl 104 mmol/L SerumHCO3 24 mmol/L Semipermeable Figure 27.2 Osmolality of the Body Fluid Water movement outside-inside of driven by osmolality cellcapillarybody Semipermeable membrane 1. Water movement between outside-inside of cell Water, oxygen an

8、d carbon Water, oxygen and carbon dioxide can move freely, but dioxide can move freely, but electrolytes and proteins not.electrolytes and proteins not. Cell membrane: Semipermeable Aquaporins (AQPs) A family of small, hydrophobic proteins forming water-selective channels(AQP0-12) Cells with aquapor

9、ins Cells without aquaporins embedded in the cell membrane The plumbing system for cells 2. Water movement between outside-inside of capillary Water, glucose, oxygen, carbon Water, glucose, oxygen, carbon dioxide and electrolytes dioxide and electrolytes can pass freelycan pass freely through the ca

10、pillary wall.through the capillary wall. Proteins Proteins are confined toare confined to the the intravascular ravascular space. Daily intake:2,500ml Minimum water output: 1,500ml 850ml 500ml 150ml Daily output:2,500ml 3. Water movement between outside-inside of body How is body fluid and

11、electrolyte balance regulated? Mechanisms? 1. 1. Thirst The thirst center ECF osmolalityosmolality Blood volume Blood volume angiotensinangiotensin The neuronal cells in the anteroventral wall of the third ventricle and the anterolateral perioptic hypothalamus thirst 2.2. Antidiuretic hormone, ADH (

12、arginine vaspressin AVP) Osmolality of ECFOsmolality of ECF OsmoreceptorsOsmoreceptors ADH Reabsorption of Reabsorption of water by kidneywater by kidney ECF volumeECF volume osmolalityosmolality Angiotension II Emotional stress Pain ADH promotes the reabsorption of water in the late distal tubule a

13、nd collecting duct Hypotension Hypovolemia Baroreceptor Volume receptor Efferent arterioleEfferent arteriole AQP-2 apical membrane Basolateral membrane The signal pathway following V2 receptor stimulation by ADH activated PKA PKA Adenylate cyclase Principle cells The late distal tubule and collectin

14、g duct V2 Efferent arteriole Afferent arteriole Macula densa Mesangial cells 3.The Renin-Angiotensin-Aldosterone System(RAAS) Juxtaglomerular cells Juxtaglomerular apparatus The Renin-Angiotensin-Aldosterone System(RAAS) Retain Na+ Excrete K+ and H+ Aldosterone promotes the reabsorption of Na+/H2O i

15、n the late distal tubule and collecting duct 4.The Natriuretic Peptide Family4.The Natriuretic Peptide Family Atrial natriuretic peptideAtrial natriuretic peptide（ANPANP） Acute volume expansion ANP Provides a negative feedback against ADH in CNS and kidney Increase glomerular filtration rate Decreas

16、e plasma renin activity, aldosterone and endothelin release atrium diuresis、natriuresis、vascular dilation Summary Body organs and tissues cooperate to maintain the body fluid and electrolyte homeostasis by intricate mechanisms, such as Thirst、ADH、 RAAS、and ANP. The Integration of Fluid Volume Regula

17、tion and Sodium Ion Concentrations in Body Fluids The surface of bone crystals （40%） ECF （50%） 130150mmol/L ICF（10%） 10mmol/L Distribution of bodily sodium: : 4050mmol/kg Sodium constitutes 93% of the cations in the body (serum sodium concentration) Physiologic function of sodium vControls the volum

18、e of extracellular fluid in the body, regulates the osmotic pressure and maintains proper water balance within the body. vMaintains the acid-base equilibrium vNecessary to maintain electrical potentials(The rapid influx of sodium ions causes the action potential) The balance of sodium in the body Na

19、+ Diatery salt Absorbed in digestive tract blood Excreted through kidney Digestive fluid Interstitial fluid Perspiration Intake more, excrete more Intake less, excrete less Intake none, excrete none Disturbances of water and sodium metabolism Serum sodium concentration Classification and Termination

20、 of Disturbances of Water and Sodium Metabolism Normal serum sodium concentration （Isotonic） (130-150mmol/L) Hyponatremia （Hypotonic） Hypernatremia （Hypertonic） (150mmol/L) Body fluid volume Normovolemic Hypovolemic （dehydration） Hypervolemic edema Water intoxiation vDehydration Hypertonic Hypertoni

21、c Hypotonic Hypotonic IsotonicIsotonic vWater excess Water intoxication Water intoxication Edema Edema OUTLINE: Dehydration Refers to insufficient body fluid resulting either from inadquate intake or excessive loss of fluids or a combination of the the two. Water movement between outside-inside of b

22、ody Dehydration signs: Mild dehydration: a decrease of 2% in body weight Moderate dehydration: a decrease of 5% in body weight. Severe dehydration: a decrease of 8% in body weight. 1. 1. concept A hypernatremia with decreased extracellular fluid volume (hypovolemic hypernatremia) ( (一一) ) Hypertonic

23、 dehydration v water losssodium loss v serumNa+ 150 mmol/L v plasma osmotic pressure 310 mmol/L 2. Etiology2. Etiology (1) (1) inadequate water intakeinadequate water intake v impaired consciousnessimpaired consciousness v impaired thirstimpaired thirst v difficulty in swallowingdifficulty in swallo

24、wing v In environment of water deficit In environment of water deficit 1200ml lost if not drink per day, 2% of the total weight Infants lost 10% if not drink 2. Etiology2. Etiology (2) (2) excessive water lossesexcessive water losses vExtrarenal route:Extrarenal route: Diarrhea and vomitting-digesti

25、ve fluid lost, hypo or Diarrhea and vomitting-digestive fluid lost, hypo or isotonic fluidisotonic fluid Insensible evaporation and perspiration-Fever, excessive Insensible evaporation and perspiration-Fever, excessive sweating, Hyperthyroidism, 500ml loss per 1.5 degree increase sweating, Hyperthyr

26、oidism, 500ml loss per 1.5 degree increase in temperaturein temperature Excessive respiration-Hysteria, loss of water through Excessive respiration-Hysteria, loss of water through respiration without replenishrespiration without replenish vRenal pathway:Renal pathway: Diabetes insipidus Diabetes ins

27、ipidus Osmotic diuresis-high glucose or protein in blood Osmotic diuresis-high glucose or protein in blood Diabetes insipidus (DI) is a condition characterized by excessive thirst and excretion of large amounts of severely diluted urine, with reduction of fluid intake having no effect on the latter.

28、 Diabetes insipidus central DI deficiency of ADH insensitivity of the kidneys to ADH nephrogenic DI DI PolyuriaPolydipsia Water loss is greater than sodium loss, which causes hyperosmalality of ECF，and then fluid shift from the intracellular to the extracellular compartments, causing ICF decreased d

29、ominantly. 3. Pathogenesis3. Pathogenesis Blood plasma Interstitial fluid ICFICF Hypertonic Hypertonic dehydrationdehydration Cellular dehydration and shrinkage in the thirst center Hyperosmalality of ECF Fluid shift from the intracellular to the extracellular compartments Brain cell shrinkage ADH A

30、DH urinary urinary concentrationconcentration Twitching and Twitching and somnolence, coma, somnolence, coma, respiratory paralysis, respiratory paralysis, deathdeath 4. Alternation of Metabolism and Function4. Alternation of Metabolism and Function ThirstThirst Neurologic Neurologic manifestationsm

31、anifestations Dry tongue and mucous membraneDry tongue and mucous membrane Dehydration feverDehydration fever 5. Pathophysiological basis of prevention and treatment v Treat primary diseases v Replacement with normal/hypotonic saline solution v Replacement with potassium v Water replacement 1. 1. co

32、ncept A hyponatremia with decreased extracellular fluid (hypovolemic hyponatremia) ( (二二) ) Hypotonic dehydration v sodium loss water loss v serumNa+ 130 mmol/L v plasma osmotic pressure 280 mmol/L 2. Etiology vrenal losses: Inappropriate long-term use of diuretics Adrenocortical insufficiency Renal

33、 diseases, particularly tubulointerstitial disease Renal tubular acidosis(RTA) vgastrointestinal losses vskin losses vaccumulate in third space The dehydrated patients are treated with pure water to replace the losses, rather than a balanced salt solution. As a result, the osmolality of ECF decrease

34、d, and then fluid shift from ECF to ICF, causing ECF decreased dominantly. 3. Pathogenesis3. Pathogenesis Blood plasma Interstitial fluid ICFICF Hypotonic Hypotonic dehydrationdehydration Decreased skin turgor, postural hypotension, tachycardia, shock Hypoosmolality of extracellular fluid Fluid shif

35、t from the extracellular to the intracellular compartments ADH Water diuresisWater diuresis 4. Alternation of Metabolism and Function Cerebral cellular swelling Nausea, vomiting, twitching. Confusion, lethargy, stupor, coma Urinary sodium Urinary sodium contentcontent Urinary sodium Urinary sodium c

36、ontentcontent Renal losses Extrarenal losses 5. Pathophysiological basis of prevention and treatment vIsotonic salt solutions must be administered to restore ECF volume and blood pressure. vTreat primary diseases 1. concept ( (三三) ) Isotonic dehydration v sodium loss water loss v serumNa+ 130150 mmo

37、l/L v plasma osmotic pressure 280310 mmol/L lost isotonic fluid v gastrointestinal losses(vomiting、 diarrhea) v Hemorrhage v Burned area 2. Etiology Isotonic Isotonic dehydrationdehydration Symptom associated with hypovolemia ADH ADH ThirstThirst AldosteroneAldosterone Adaptive responses 3. Alternat

38、ion of Metabolism and Function Isotonic dehydration Insensible water losses through skin and lung Hypertonic dehydration Hypotonic dehydration If treated inappropriately with pure water Correct causative factors and administer isotonic salt solution Hypertonic dehydrationHypertonic dehydration Hypot

39、onic dehydrationHypotonic dehydration Isotonic dehydrationIsotonic dehydration The patients who got diarrhea and were treated with only The patients who got diarrhea and were treated with only pure water are susceptible to pure water are susceptible to The patients with extensive burns are susceptib

40、le toThe patients with extensive burns are susceptible to The patients with diabetes insipidus are susceptible toThe patients with diabetes insipidus are susceptible to The patients with heavy sweating are susceptible toThe patients with heavy sweating are susceptible to The patients with coma are s

41、usceptible toThe patients with coma are susceptible to Hyper Hyper Hyper Iso Hypo 二、二、Water excess Excess of body water 1. 1. concept A hyponatremia with increased extracellular fluid volume (hypervolemic hyponatremia) ( (一一) )water intoxication v Excess water sodium excess v serumNa+ 130 mmol/L v p

42、lasma osmotic pressure Experimental Pulmonary Edema in Rabbits Normal after diuretics treatment pulmonary edema Cutted lung tissue pulmonary edema pulmonary edema Left heart failure Right heart failure (caused by COPD) Chronic obstructive pulmonary disease (2) Decreased plasma colloid osmotic pressu

43、re Protein malnutrition Hepatic disease (inadequate albumin synthesis ) Renal disease (protein loss in urine) Chronic debilitating diseases Intake Synthesis Output Utilization Hypoproteinemia (3) Increased capillary permeability Inflammation or allergy leakage of abnormally large quantities of prote

44、ins from capillaries (4) Obstruction of lymphatic flow Malignant obstruction of lymphatic structures Surgical removal of lymph nodes Blockage by infection, e.g. in filariasis FILARIASIS Elephantiasis GFR Reabsorption of sodium and water Reabsorption of sodium and water Reabsorption of sodium and wat

45、er Reabsorption of sodium and water GFRGFRGFR N N N N BalanceGlomerular-tubular imalance The renal retention of sodium and waterThe renal retention of sodium and water Decreased glomerular filtration rate Acute and chronic glomerulonephritisAcute and chronic glomerulonephritis Congestive heart failu

46、re, nephrotic syndromeCongestive heart failure, nephrotic syndrome decrease in the effective circulating blood volumedecrease in the effective circulating blood volume stimulation of sympathetic nervous system stimulation of sympathetic nervous system activation of renin-angiotensin system activatio

47、n of renin-angiotensin system reduce blood flow to reduce blood flow to the kidneythe kidney GFR (1) (2) A physical factor Efferent arterioleEfferent arteriole Congestive heart failure/renal blood flow decreasesCongestive heart failure/renal blood flow decreases Efferent arteriole resistance increas

48、esAfferent arteriole resistance Efferent arteriole resistance increasesAfferent arteriole resistance increasesincreases GFR increase relativelyGFR increase relatively Filtration fractionFiltration fraction Glomerular filtration rateGlomerular filtration rate Renal plasma flowRenal plasma flow（FF） Th

49、e nonfiltered blood passing through the glomerulus is concentratedThe nonfiltered blood passing through the glomerulus is concentrated The osmotic pressure in the capillaries near the proximal tubules elevates The osmotic pressure in the capillaries near the proximal tubules elevates and capillary h

50、ydrostatic pressure decreasesand capillary hydrostatic pressure decreases The sodium and water reabsorptionThe sodium and water reabsorption (3) Effective circulating blood volume The renal water and sodium retention ADHAldosterone Alternation of Metabolism and Function （1） Consistency of edema flui

51、d TransudatesExudates CausesNon-inflamation Inflamation Appearance ClearCloudy 1.015 2.5g% 1.018 3g%-5g% 500/100ml Yes Specific gravity Proteins Cells Bacteria Capillary permeabilityNormalIncrease （2 2）Dermal manifestation of edemaDermal manifestation of edema vpitting edema vrecessive edema （3 3）Di

52、stribution of edema fluidDistribution of edema fluid Generalized edema Distribution of edema fluid Pathogenesis Cardiac edema Affected by gravity The swelling of the ankles Increased capillary hydrostatic pressure ADH and aldosterone-induced retention of sodium and water Decreased GFR due to decreas

53、e in cardiac output and effective arterial blood volume Renal edema The swelling of eyelids and face Decrease in GFR The retention of sodium and water Hepatic edema Ascites Increased portal venous pressure Overflow of hepatic lymph The decreased effective circulating blood volume and hypoalbuminemia

54、 （4 4）The effect of edema fluid on the The effect of edema fluid on the bodybody v Protective effectsProtective effects： ( inflammatory edema)( inflammatory edema) dilute and neutralize toxin dilute and neutralize toxin transport the antibodies transport the antibodies v Harmful actionHarmful action

55、： impedes nutritional supply to cellsimpedes nutritional supply to cells impairs/damages the functions of specific organsimpairs/damages the functions of specific organs 84 year old woman admitted for knee replacement. On thiazide diuretic for hypertension. Preoperative serum sodium 134 mmol/L (135-

56、145). Postoperatively had frequent vomiting. Given 6 litres of 5% dextrose in saline for 2 days (i.e. 2/3-1/3 at 125 ml/h). After 48 hours became comatose, serum sodium was 115 mmol/L. Sodium concentration was corrected over 5 days but patient was left with permanent cognitive deficit. Case 1 She de

57、veloped hyponatremia because she received: A.Too much IV fluid B.Too much of the wrong IV fluid C.The wrong IV fluid D.Hydrochlorthiazide She developed hyponatremia because she received: A.Too much IV fluid B.Too much of the wrong IV fluid C.The wrong IV fluid D.Hydrochlorthiazide How should she have been