Chapter 15 Fluid and Acid-Base Balance

Transcription

1 VI. Pag Chapter 15 Fluid and Acid-Base Balance V. Pag

2 Fluid Balance Water constitutes ~60% of body weight. All cells and tissues are surrounded by an aqueous environment. Most biochemical reactions inside the cell occurs in the cytosol. Body systems maintain homeostasis Homeostasis Fluid balance is critical for maintaining body homeostasis Cells make up body systems

3 Fluid Balance Disruption of normal fluid balance can disrupt cell function No net movement of water Water tends to move in causing cell swelling Water tends to move out of cell causing cell shrinking

4 Water Distribution Vessels Tissues Heart (pump) Cells In the human organism, water is distributed between: 1) The intracellular fluid (~62%) Circulating plasma (20% of extracellular fluid) Interstitial fluid (80% of extracellular fluid) Figure Page 364 Slide 30 2) The extracellular fluid that consist of plasma (6.6%) and interstitial fluid (26.4%)

5 Ionic Composition of Body Compartments

6 Ionic Composition of Body Compartments Barriers regulating body fluid composition in human body: 1) Capillary wall 2) Cell membrane

7 Fluid Balance Vessels Tissues Heart (pump) Cells Fluid balance is maintained by regulating: 1) Extracellular fluid volume. Effect on blood pressure Circulating plasma (20% of extracellular fluid) Interstitial fluid (80% of extracellular fluid) Figure Page 364 Slide 30 2) Osmolarity: measure of solutes dissolved in aqueous medium. Effect on cell volume

8 Fluid Balance Disruption of normal fluid balance can disrupt cell function No net movement of water Water tends to move in causing cell swelling Water tends to move out of cell causing cell shrinking

9 Regulation of Extracellular Fluid Volume is Important in the Regulation of Blood Pressure Reduction in EC volume causes a fall in blood pressure Short term regulation of blood pressure: 1) Baroreceptor reflex, and 2) Fluid shift between plasma and intestinal fluid Long term regulation of blood pressure: 1) Control of Na + ions filtration and reabsorption by the renin-angiotensin-aldosterone system

10 Baroreceptor Reflex Parasympathetic stimulation Heart Heart rate Cardiac output Blood pressure Sympathetic stimulation Heart Heart rate Contractile strength of heart Stroke volume Cardiac output Blood pressure Arterioles Vasoconstriction Total peripheral resistance Blood pressure Veins Vasoconstriction Venous return Stroke volume Cardiac output Blood pressure

11 Baroreceptor Reflex Consequences Compensations Figure Page 384 Slide 54

12 Fluid Shift Between Plasma and Interstitial Fluid Initial lymphatic vessel 11 mm Hg (ultrafiltration) Interstitial fluid -9 mm Hg (reabsorption) From arteriole Blood capillary To venule (See next slide)

13 Long Term Control of Blood Pressure: Na + Control 1) Regulation of Na + filtration in glomerulus by GFR 2) Regulation of Na + reabsorption by the renin-angiotensinaldosterone system

14 Long Term Control of Blood Pressure: Na + Control Decreased blood pressure or Na + load Decreased Na + filtration rate Decreased blood pressure or Na + load Increased renin production and insertion of Na + channels in luminal membrane and Na + /K + ATPase in basolateral membrane

15 Juxtaglomerular Apparatus Macula dense cells can detect changes in flow rate and release vasoactive substances (vasoconstrictors and vasodilators) that alter capillary blood flow. Granular cells sense changes in pressure and release renin. Sense changes in flow rate. Secrete vasoactive Substances (endothelin) Sese chages in blood pressure, NaCl volume. Secrete renin

16 Regulation of GFR by Baroreceptor Reflex and Sympathetic Activity Short-term adjustment for Arterial blood pressure Long-term adjustment for Arterial blood pressure Cardiac output Total peripheral resistance Detection by aortic arch and carotid sinus baroreceptors Sympathetic activity Generalized arteriolar vasoconstriction Notice that sympathetic nerve activation reduce filtration The idea coefficient here is to (and increase GFR) blood by volume stimulating when drop in contraction blood of pressure podocytes occurs Afferent arteriolar vasoconstriction Glomerular capillary blood pressure GFR Urine volume Conservation of fluid and salt Arterial blood pressure Figure Page 523 Slide 17

17 Renin-Angiotensin-Aldosterone Regulates Na + Reabsorption Aldosterone acting on distal/collecting tubules, drives the insertion of new Na + channels and Na + /K + ATPases in tubular cells NaCl / ECF volume / Arterial blood pressure Liver Kidney Lungs Adrenal cortex Kidney H 2 O conserved Na + (and CI ) osmotically hold more H 2 O in ECF Renin Angiotensinconverting enzyme Angiotensinogen Angiotensin I Angiotensin II Aldosterone Na + (and CI ) conserved Na+ reabsorption by kidney tubules ( CI reabsorption follows passively) Vasopressin Thirst Arteriolar vasoconstriction H 2 O reabsorption by kidney tubules Fluid intake Figure Page 529 Slide 23

18 Aldosterone Function Aldosterone stimulates Na + reabsorption by promoting the insertion of new Na + channels in the luminal membrane and additional Na + /K + ATPase carriers in the basolateral membrane Brooks/Cole - Thomson Learning

19 Angiotensin-Aldosterone System NaCl / ECF volume / Arterial blood pressure Liver Kidney Lungs Adrenal cortex Kidney H 2 O conserved Na + (and CI ) osmotically hold more H 2 O in ECF Water conservation Renin Other Functions of the Renin- Angiotensinconverting enzyme Angiotensinogen Angiotensin I Angiotensin II Aldosterone Na + (and CI ) conserved Na+ reabsorption by kidney tubules ( CI reabsorption follows passively) Arteriolar vasoconstriction Water/fluid intake Vasopressin Thirst Arteriolar vasoconstriction H 2 O reabsorption by kidney tubules Fluid intake Figure Page 529 Slide 23

20 Fluid Balance Vessels Tissues Heart (pump) Cells Fluid balance is maintained by regulating: 1) Extracellular fluid volume. Effect on blood pressure Circulating plasma (20% of extracellular fluid) Interstitial fluid (80% of extracellular fluid) Figure Page 364 Slide 30 2) Osmolarity: measure of solutes dissolved in aqueous medium. Effect on cell volume: hypertonic and hypotonic extracellular fluid

21 Osmolarity-Induced Changes in Cell Volume No net movement of water Water tends to move in causing cell swelling Water tends to move out of cell. Cell shrinking

22 Ionic Composition of Body Compartments Between plasma and interstitial fluid, differences in osmolarity are due to unequal distribution of plasma proteins Between interstitial fluid and intracellular fluid differences in osmolarity are due to differences in ionic composition

23 Regulation of Osmolarity in Human Body Vessels Tissues Heart (pump) Cells Osmolarity can be regulated by: 1) Water intake (angiotensin-thirst) Circulating plasma (20% of extracellular fluid) Interstitial fluid (80% of extracellular fluid) Figure Page 364 Slide 30 2) Water output (vasopressin effect on kidneys)

24 Vasopressin Release Controls Water Secretion and Osmolarity

25 In the face of water deficit: vasopressin stimulates water movement out of distal/collecting tubules From proximal tubule Filtrate has concentration of 100 mosm/liter as it enters distal and collecting tubules Distal tubule Cortex Loop of Henle * Medulla * Collecting tubule * Concentration of urine may be up to 1,200 mosm/liter as it leaves collecting tubule = passive diffusion of H 2 O = active transport of NaCl * = portions of tubule impermeable to H 2 O = permeability to H 2 O increased by vasopressin

26 Plasma osmolarity ECF volume Plasma volume Osmolarity Hypothalamic osmoreceptors (dominant factor controlling thirst and vasopressin secretion) Figure 15.4 Page 569 Hypothalamic neurons Arterial blood pressure Left atrial volume receptors (important only in large changes in plasma volume/arterial pressure) Thirst Vasopressin Arteriolar vasoconstriction H 2 O intake H 2 O permeability of distal and collecting tubules H 2 O reabsorption Urine output

27 Angiotensin Regulates Thirst AND Water Intake NaCl / ECF volume / Arterial blood pressure Liver Kidney Lungs Adrenal cortex Kidney H 2 O conserved Na + (and CI ) osmotically hold more H 2 O in ECF Renin Angiotensinconverting enzyme Angiotensinogen Angiotensin I Angiotensin II Aldosterone Na + (and CI ) conserved Na+ reabsorption by kidney tubules ( CI reabsorption follows passively) Vasopressin Thirst Arteriolar vasoconstriction H 2 O reabsorption by kidney tubules Fluid intake Figure Page 529 Slide 23

28 Vasopressing and Angiotensin Also Regulate Total Peripheral Resistance Total peripheral resistance Arteriolar radius Blood viscosity Number of red blood cells Concentration of plasma proteins Local (intrinsic) control Extrinsic control Myogenic responses to stretch Vasopressin Heat, cold application (therapeutic use) Angiotensin II Histamine release (involved with injuries and allergic responses) Local metabolic changes in O 2, CO 2, other metabolites Sympathetic activity (exerts generalized vasoconstrictor effect) Major factors affecting arteriolar radius Epinephrine and norepinephrine Figure Page 354 Slide 23

29 Acid-Base Balance Regulation of free H + in body fluids Acids are substances that generate free H + in solution Ex: H 2 CO 3 HCl Bases are substances that accept free H + in solution Ex: HCO 3- NaOH

30 Acids Release H + in Solution Strong Acid versus Weak Acid Strong acids undergo complete dissociation in solution Weak acids undergo incomplete dissociation in solution. At certain point, the amount of dissociated ions and whole molecule reach an equilibrium Concentration of each component in the reaction is regulated by the law of mass action and dissociation constant K

31 ph Acids are substances that generate free H + in solution How do we quantify the amount of H + present in a solution? ph is a number that allow us to quantify the amount of H + in solution: ph= log 1/[H + ]

32 ph Scale Since ph is inversely proportional to the H + concentration, an acidic solution will have a low ph and a basic solution will have a high ph Notice that a ph = 7 is considered a neutral ph. Pure water have a ph = 7 Physiologically, a ph = 7.4 is considered normal and correspond to the average ph of blood

33 ph Values For Some Substances and Body Fluids

34 Physiological Changes Induced By H + Fluctuations Blood ph = 7.4 Acidosis ph < 7.35 Alkalosis ph > 7.45 Death may occur if 6.8 < Blood ph <8

35 Physiological Changes Induced By ph Changes 1) Increased H + (acidosis) depresses nerve activity, whereas decreased H + causes overexcitability of the nervous system 2) Changes in H + concentration can modify protein structure and change enzymatic activity 3) Increased H + results in lower K + secretion in kidneys

36 K + and H + Secretion Basolateral pump can use K + or H + for Na + reabsorption. If body fluids become acidic then kidneys will secrete more H + and leave K + in blood Not good! H + H + H + H +

37 Sources of H + in Human Body 1) Carbonic acid formation (H 2 CO 3 ) 2) Inorganic acids produced during nutrients degradation (Sulfuric and phosphoric acid formation) 3) Organic acids produced during cell metabolism (Lactic acid, Fatty acids)

38 How Does The Human Body Avoid Dramatic Changes in [H + ] 1) Chemical buffers 2) Respiration 3) Renal function

39 How Does The Human Body Avoid Dramatic Changes in [H + ]: Role of Chemical Buffers A Chemical buffer is a mix of a weak acid and its salt that can minimize ph changes when strong acids or bases are added. Effect of law of mass action. Addition of a one component will shift equilibrium and partially compensate for changes in ph. oons5.htm

40 Chemical Buffers in Human Body Carbonic acid-bicarbonate buffer (H 2 CO 3 /HCO 3- ) is the most important system that control blood ph Protein Buffer (Intracellular buffer) Hemoglobin buffer Phosphate buffer (Intracellular buffer)

41 Carbonic Acid-Bicarbonate Buffer Use to buffer extracellular fluid and changes in ph caused by fluctuations of H + non related to CO 2 formation HCO 3- + H + H 2 CO 3

42 The Henderson-Hasselbalch Equation describes the relationship between H + and the other members of the buffer CO 2 + H 2 O H 2 CO 3 HCO 3- + H + ph = pk + log ([HCO 3- ]/ [CO 2 ]) ph = 7.4 (normal ph) pk is a constant, for H 2 CO 3 = 6.1 [HCO 3- ]/ [CO 2 ] = 20/1 (normal) [HCO 3- ] is regulated by the kidneys [CO 2 ] is regulated by lungs

43 Protein Buffer Proteins contain acidic or basic groups that can give up or take up H +. These groups can be used to buffer H + changes in the intracellular fluid

44 Hemoglobin Buffer Use to buffer H + generated from carbonic acid Hb + H + HHb

45 Phosphate Buffer Use to buffer urine and intracellular fluids Na 2 HPO 4 + H + NaH 2 PO 4 +Na + (basic phosphate salt) (acid phosphate salt)

46 How Does The Human Body Avoid Dramatic Changes in [H + ] Regulation of ph by Respiration CO 2 + H 2 O H 2 CO 3 HCO 3- + H +

47 Effect of CO 2 on ventilation

48 How Does The Human Body Avoid Dramatic Changes in [H + ] Chemical buffers (can regulate plasma ph instantly) Respiration (is involved in the minute-to-minute regulation of plasma ph, but can not fully compensate for charges in ph) Renal function (is involved in the long term regulation of ph- from hours to days)

49 How Does The Human Body Avoid Dramatic Changes in [H + ] Notice that chemical buffers just mask any excess of H + (H + ions do not disappear but are converted into something else) The respiratory and renal systems are the only systems that actually can eliminate H + from the body

50 Kidneys Control ph by Adjusting: 1) H + excretion (H + filtration is very low) 2) HCO 3- filtration-reabsorption 3) NH 3 secretion HCO 3 - HCO 3 - H + CO 2 H + HCO 3 - NH3

51 Kidneys Regulate ph More Effectively Than the Lungs (Lungs only regulate CO 2. Beside regulating HCO 3-, kidneys regulate H + formed as a result of metabolic activity: lactic & fatty acids formation) Notice there is no H + reabsorption in kidneys. There is only HCO - 3 reabsorption

52 Kidneys Control ph by Adjusting: 1) H + excretion (H + enter kidneys by secretion resulting in a very acid urine, there is very little filtration WHY?) Basolateral pump can use K + or H + for Na + reabsorption. If body fluids become acidic then kidneys will secrete more H + H + H + in urine is buffered by phosphate buffers and NH 3

53 H + excretion is influenced by: 1) [H + ] in plasma 2) [CO 2 ] in plasma HCO 3 - H + HCO 3 - H + HCO 3 - CO 2 The ability of the kidneys to regulate H + and CO 2 independently allows regulation of free H + produced as a result of respiratory and/or metabolic activity. There is no neuronal/hormonal control

54 HCO 3- Regulation 1) Kidneys regulate HCO 3- by variable reabsorption of filtered HCO 3-2) Or variable addition of new HCO 3- to plasma

55 Kidneys Control ph by Adjusting: 1) Kidneys regulate HCO 3- by variable reabsorption of filtered HCO 3 - HCO 3- is filtered but can not cross the luminal membrane. Notice however that HCO 3- can cross the basolateral membrane There is a indirect reabsorption of filtered HCO 3 -

56 HCO 3- Regulation 2) Variable addition of HCO 3- to plasma (Buffering of H + with phosphate allows release of new HCO 3- from peritubular capillaries)

57 Difference Between New and Reabsorbed HCO 3 - Notice differential permeability of luminal and basolateral membrane of tubular cells to HCO 3 - Luminal membrane is impermeable to HCO 3 - Basolateral membrane is permeable to HCO 3 -

58 How Do the Kidneys Buffer Secreted H +? 1) Phosphate Buffer (Na 2 HPO 4 ) 2) NH 3 secretion Na 2 HPO 4 Na 2 HPO 4 + H + NaH 2 PO 4 + Na + H + H +

59 Why Is The Kidney Excreting Na 2 HPO 4 Continuously? (Chapter 14) [Glucose] 125 mg [Na 2 HPO 4 ] 300 mg Carrier saturation limits transport of a substance in tubules- tubular maximum If concentration of substance in tubules goes above tubular maximum excretion will take placerenal threshold Kidneys regulate Na 2 HPO 4 plasma levels

60 How Do the Kidneys Buffer Secreted H +? 1) Phosphate Buffer (Na 2 HPO 4 ) 2) NH 3 secretion NH 3 + H + NH 4 + Notice: NH 3 is formed and released into the lumen by tubular cells NH + 4 is impermeable to luminal membranes H + NH 3 H + NH 3

61 Acid-Base Imbalances Arise From: 1) Respiratory Disturbance 2) Metabolic Disturbance HCO 3 - HCO 3 - Respiratory disturbance may cause: Respiratory acidosis (too much CO 2 ) Respiratory alkalosis (too little CO 2 HCO 3 - H + H + CO 2 Metabolic disturbance may cause: Metabolic acidosis (too little HCO 3- ) Metabolic alkalosis (to much HCO 3- )

62 Acid-Base Imbalance Notice: kidneys control HCO - 3 and H + by regulating the creation of new HCO - 3 or the reabsorbtion of filtered HCO - 3 During respiratory acidosis (+CO 2 ) kidneys conserve more HCO 3- and add more new HCO 3- while secreting more H + During respiratory alkalosis (- CO 2 ) kidneys conserve more H + and excrete more HCO 3 -

63 Acid-Base Imbalance Respiratory Respiratory Metabolic Metabolic Acidosis Alkalosis Acidosis Alkalosis Too much CO 2, hypoventilation Too little CO 2, hyperventilation Fall in HCO 3 - Increase in HCO 3 - Cause: Lung disease Depression of respiratory center Respiratory motor dysfunction Anxiety Aspirin poisoning High altitude Diarrhea Diabetes mellitus Strenuous exercise Renal failure Vomiting Ingestion of alkaline compounds Compensation: Chemical buffers Kidneys (notice that damaged lungs can Chemical buffers Lungs Kidneys Chemical buffers Lungs Kidneys Chemical buffers Lungs Kidneys