1. Ani Retno Prijanti Renal and Body Fluids Module

2.  Body fluid  Regulation of Acid – Base Balance  Chemical buffer content and function  Acidosis and alkalosis

5.  To remain properly hydrated, water intake must equal water output.  Water intake sources  Ingested fluid (60%)  Solid food water (30%)  Metabolic water or water of oxidation (10%)

6.  Water output Urine (60%) and feces (4%) Insensible losses (28%), sweat (8%)  Increases in plasma osmolality trigger 1. Thirst 2. Release of antidiuretic hormone (ADH)

8. The hypothalamic thirst center is stimulated:  By a decline in plasma volume of 10%–15%  By increases in plasma osmolality of 1–2%  Via baroreceptor input, angiotensin II, and other stimuli

9. Thirst is quenched as soon as we begin to drink water Feedback signals that inhibit the thirst centers include:  Moistening of the mucosa of the mouth and throat  Activation of stomach and intestinal stretch receptors

11. Obligatory water losses include: Insensible water losses from lungs and skin Water that accompanies undigested food residues in feces Sensible water loss of 1500ml in urine Kidneys excrete 900-1200 mOsm of solutes to maintain blood homeostasis Urine solutes must be flushed out of the body in water

12. Water reabsorption in collecting ducts is proportional to ADH release Low ADH levels produce dilute urine and reduced volume of body fluids High ADH levels produce concentrated urine Hypothalamic osmoreceptors trigger or inhibit ADH release Factors that specifically trigger ADH release include prolonged fever; excessive sweating,vomiting, or diarrhea; severe blood loss; and traumatic burns

13. Electrolytes are salts, acids, and bases, but electrolyte balance usually refers only to salt balance Salts are important for: Neuromuscular excitability Secretory activity Membrane permeability Controlling fluid movements Salts enter the body by ingestion and are lost via perspiration, feces, and urine

14. Changes in plasma sodium levels affect: Plasma volume, blood pressure ICF and interstitial fluid volumes Renal acid-base control mechanisms are coupled to sodium ion transport.

16. Sodium reabsorption 65% of sodium in filtrate is reabsorbed in the proximal tubules 25% is reclaimed in the DCT When aldosterone levels are high, all remaining Na+ is actively reabsorbed Water follows sodium if tubule permeability has been increased with ADH

17. The renin-angiotensin mechanism triggers the release of aldosterone This is mediated by the juxtaglomerular apparatus, which releases renin in response to:  Sympathetic nervous system stimulation  Decreased filtrate osmolality  Decreased stretch (due to decreased blood  pressure) Renin catalyzes the production of angiotensin II, which prompts aldosterone release Renin  angiotensin  aldosteron  Sodium reabsorption

18. Low aldosterone cause Na excretion and water will follow it High aldosterone levels will cause Na absorption. For the water to be absorbed ADH must also be present Adrenal cortical cells are also directly stimulated to release aldosterone by elevated K+ levels in the ECF Aldosterone brings about its effects (diminished urine output and increased blood volume) slowly

19.  Acid-base balance is defined by the concentration of hydrogen ions.  In order to achieve homeostasis, there must be a balance between the intake or production of hydrogen ions and the net removal of hydrogen ions from the body.

20.  Molecules containing hydrogen atoms that can release hydrogen ions in solutions are referred to as an acid.  An example of an acid is hydrochloric acid (HCL)

21.  A base is an ion that can accept a hydrogen ion.  An example of a base is is the bicarbonate ion.( HCO3 - )

22.  Hydrogen ion concentration is expressed on a logarithm scale using pH units (part/percentage hydrogen).  7.0 being neutral  Body systems carefully control pH of the body within the range of 7.35-7.45

23. [ HCO 3 - ] pH = 6.10 + log ———————— 0.0301 P CO2

24.  pH = - log [H + ]  Range 0-14  A low pH corresponds to a high hydrogen ion concentration  The term “Acidosis” refers to the addition of excess hydrogen ions and the body has a pH that falls below 7.35

27.  A high pH corresponds to a low hydrogen concentration  The term “Alkalosis” refers to excess removal of hydrogen ions from the body and has a pH that rises above 7.45

29.  It’s important to maintaint pH of the body fluid because change of body fluid pH cause:  Change the enzym activity in the cells and vital organs: brain and heart  Influence to the exitability of nerves and muscles: decrease/increase pH could cause exitability

30. Our body produce more acid than base  Acid available from fuel/food  Protein metabolism produces sulphates & phosphates  Fatty acid metabolism produces keton bodies  Anaerobic Glycolisis produce lactic acid  Aerobic glycolisis produce CO 2 (see Henderson Haselbalch equation)  Cellular metabolism produce CO 2 (idem)

31. Acids produced in the body are  Carbonic acids  Sulphates  Phosphates  Lactic acid  Cytric acid  Ammonium ion  Keton bodies: Acetoacetic acids  -OH butiric acid Aceton

32. Acids grouping are as follow A. Volatyl acids: H 2 CO 3 Almost CO 2 change to be Carbonic acid PCO2 conversely related to pH  therefore PCO2 is the important factor influences to pH. B. Fixed acids: H2SO4, H3PO4 they are fixed in the solution C. Organic acid: lactic acid Produced in anaerobic metabolisms

33. Three Systems in the body classified as follow Short term regulation Buffers in the blood Long term regulation 1. Respiration through the lungs 2. Excretion by the kidneys

34.  Buffers are substances that neutralize acids or bases  Bicarbonate which is a base and carbonic acid in the body fluids protect the body against changes in acidity  These buffer systems serve as a first line of defense against changes in the acid- base balance

35.  Carbon Dioxide which is formed during cellular metabolism forms carbonic acid in the blood decreasing the pH  When the pH drops respiration rate increases this hyperventilation increases the amount of CO2 exhaled thereby lowering the carbonic acid concentration and restoring homeostasis

36.  The kidneys play the primary role in maintaining long term control of Acid- Base balance  The kidney does this by selecting which ions to retain and which to excrete  The kidneys adjust the body’s Acid-Base balance

37.  Can be quickly realized if one considers the low concentration of hydrogen ions in the body fluids and the relatively large amounts of acids produced by the body each day  Example: 80 milliequvilalants of hydrogen is either ingested or produced each day by metabolism.  Whereas the hydrogen ion concentration of the body fluids normally is only about.0004meq/L

38.  Normal pH 7.35 – 7.45  Alkalosis or alkalemia – arterial blood pH rises above 7.45  Acidosis or acidemia – arterial pH drops below 7.35 (physiological acidosis)

39. Most hydrogen ions originate from cellular metabolism Breakdown of phosphorus-containing proteins releases phosphoric acid into the ECF Anaerobic respiration of glucose produces lactic acid Fat metabolism yields organic acids and ketone bodies Transporting carbon dioxide as bicarbonate releases hydrogen ions

40. Concentration of hydrogen ions is regulated sequentially by: Chemical buffer systems – act within seconds The respiratory center in the brain stem – acts within 1-3 minutes Renal mechanisms – require hours to days to effect pH changes

41. Strong acids – all their H+ is dissociated completely in water Weak acids – dissociate partially in water and are efficient at preventing pH changes Strong bases – dissociate easily in water and quickly tie up H+ Weak bases – accept H+ more slowly (e.g.,HCO3¯ and NH3)

43. One or two molecules that act to resist pH changes when strong acid or base is added Three major chemical buffer systems Bicarbonate buffer system Phosphate buffer system Protein buffer system Any drifts in pH are resisted by the entire chemical buffering system

44. A mixture of carbonic acid (H2CO3) and its salt, sodium bicarbonate (NaHCO3) (potassium or magnesium bicarbonates work as well) If strong acid is added: Hydrogen ions released combine with the bicarbonate ions and form carbonic acid (a weak acid) The pH of the solution decreases only slightly HCl + NaHCO3 = H2CO3 + NaCl

45. If strong base is added: It reacts with the carbonic acid to form sodium bicarbonate (a weak base) The pH of the solution rises only slightly NaOH + H2CO3 = NaHCO3 + H2O This system is the only important ECF buffer

46. Nearly identical to the bicarbonate system Its components are: Sodium salts of dihydrogen phosphate (H2PO4¯), a weak acid Monohydrogen phosphate (HPO42¯), a weak base HCl + Na2HPO4 = NaH2PO4 + NaCl NaOH + NaH2PO4 = Na2HPO4 + H2O This system is an effective buffer in urine and intracellular fluid

47. Plasma and intracellular proteins are the body’s most plentiful and powerful buffers Some amino acids of proteins have: Organic acid groups (weak acids) –COOH (carboxyl) R-COOH  RCOO- + H+ Groups that act as weak bases –NH2 (amino) R-NH2  R-NH3 Amphoteric molecules are protein molecules that can function as both a weak acid and a weak base

48. The respiratory system regulation of acid- base balance is a physiological buffering system There is a reversible equilibrium between: Dissolved carbon dioxide and water Carbonic acid and the hydrogen and bicarbonate ions CO2 + H2O ↔ H2CO3 ↔ H + + HCO3¯

49. During carbon dioxide unloading, hydrogen ions are incorporated into water When hypercapnia or rising plasma H+ occurs: Deeper and more rapid breathing expels more carbon dioxide Hydrogen ion concentration is reduced Alkalosis causes slower, more shallow breathing, causing H+ to increase Respiratory system impairment causes acid-base imbalance (respiratory acidosis or respiratory alkalosis)

50. Chemical buffers can tie up excess acids or bases, but they cannot eliminate them from the body The lungs can eliminate carbonic acid (volatile acid) by eliminating carbon dioxide Only the kidneys can rid the body of metabolic acids (phosphoric, uric, and lactic acids and ketones) and prevent metabolic acidosis The ultimate acid-base regulatory organs are the kidneys

51. The most important renal mechanisms for regulating acid-base balance are: Conserving (reabsorbing) or generating new bicarbonate ions Excreting bicarbonate ions Losing a bicarbonate ion is the same as gaining a hydrogen ion (the blood becomes acidic); reabsorbing a bicarbonate ion is the same as losing a hydrogen ion (the blood becomes alkaline)

52. Hydrogen ion secretion occurs in the PCT and in the collecting ducts Hydrogen ions come from the dissociation of carbonic acid

53. Carbon dioxide combines with water in tubule cells, forming carbonic acid Carbonic acid splits into hydrogen ions and bicarbonate ions For each hydrogen ion secreted, a sodium ion and a bicarbonate ion are reabsorbed by the PCT cells Secreted hydrogen ions form carbonic acid; thus, bicarbonate disappears from filtrate at the same rate that it enters the peritubular capillary blood

54. Carbonic acid formed in filtrate dissociates to release carbon dioxide and water Carbon dioxide then diffuses into tubule cells, where it acts to trigger further hydrogen ionsecretion

55. Two mechanisms carried out collecting ducts cells generate new bicarbonate ions Both involve renal excretion of acid via secretion and excretion of hydrogen ions or ammonium ions (NH4+)

56. Dietary hydrogen ions must be counteracted by generating new bicarbonate The excreted hydrogen ions must bind to buffers in the urine (phosphate buffer system) Collecting duct cells actively secrete hydrogen ions into urine, which is buffered and excreted Bicarbonate generated is: Moved into the interstitial space via a cotransport system Passively moved into the peritubular capillary blood

57. In response to acidosis: Kidneys generate bicarbonate ions and add them to the blood An equal amount of hydrogen ions are added to the urine

58. This method uses ammonium ions produced by the metabolism of glutamine in PCT cells Each glutamine metabolized produces two ammonium ions and two bicarbonate ions Bicarbonate moves to the blood and ammonium ions are excreted in urine

60. When the body is in alkalosis, type B intercalated cells of collecting ducts : Exhibit bicarbonate ion secretion Reclaim hydrogen ions and acidify the blood The mechanism is the opposite of type A intercalated cells and the bicarbonate ion reabsorption process Even during alkalosis, the nephrons and collecting ducts excrete fewer bicarbonate ions than they conserve

61. Result from failure of the respiratory system to balance pH PCO2 is the single most important indicator of respiratory inadequacy PCO2 levels Normal PCO2 fluctuates between 35 and 45mm Hg Values above 45 mm Hg signal respiratory acidosis Values below 35 mm Hg indicate respiratory alkalosis

62. Respiratory acidosis is the most common cause of acid-base imbalance Occurs when a person breathes shallowly, or gas exchange is hampered by diseases such as pneumonia, cystic fibrosis, or emphysema Respiratory alkalosis is a common result of hyperventilation

63. All pH imbalances except those caused by abnormal blood carbon dioxide levels Metabolic acid-base imbalance – bicarbonate ion levels above or below normal (22-26 mEq/L) Metabolic acidosis is the second most common cause of acid-base imbalance Typical causes are ingestion of too much alcohol and excessive loss of bicarbonateions Other causes include accumulation of lactic acid, shock, ketosis in diabetic crisis, starvation, and kidney failure

64. Rising blood pH and bicarbonate levels indicate metabolic alkalosis Typical causes are: Vomiting of the acid contents of the stomach Intake of excess base (e.g., from antacids) Constipation, in which excessive bicarbonate is reabsorbed

65. Acid-base imbalance due to inadequacy of a physiological buffer system is compensated for by the other system The respiratory system will attempt to correct metabolic acid-base imbalances The kidneys will work to correct imbalances caused by respiratory disease

66.  Metabolic acidosis has low pH:  Bicarbonate level is low  PCO 2 is falling below normal to correct the imbalance  The rate and depth of breathing are elevated

67. Metabolic alkalosis has high pH: High levels of bicarbonate Correction is revealed by: Rising PCO2 Compensation exhibits slow, shallow breathing, allowing carbon dioxide toaccumulate in the blood

68.  To correct respiratory acid-base imbalance, renal mechanisms are stepped up  Respiratory Acidosis has low pH Has high PCO2 (the cause of acidosis) In respiratory acidosis, the respiratory rate is often depressed and is the immediate cause of the acidosis High bicarbonate levels indicate the kidneys are retaining bicarbonate to offset the acidosis

69.  Respiratory Alkalosis has high pH  Low PCO2 (the cause of the alkalosis)  Low bicarbonate levels The kidneys eliminate bicarbonate from the body by failing to reclaim it or by actively secreting it

70.  Water content of the body is greatest at birth (70-80%) and declines until adulthood, when it is about 58%  At puberty, sexual differences in body water content arise as males develop greater muscle mass  Homeostatic mechanisms slow down with age  Elders may be unresponsive to thirst clues and are at risk of dehydration  The very young and the very old are the most frequent victims of fluid, acid-base, and electrolyte imbalances