BIOL 2402 Acid Base Homeostasis

Transcription

1 Dr. Chris Doumen Collin County Community College BIOL 2402 Acid Base Homeostasis 1 Acid -Base Balance and Regulation Acid-Base Balance refers to the precise regulation of free hydrogen ion concentration in the body fluids Free hydrogen ions determine the acidity of the body fluids and ph is used as a specific H + indicator ph = -log [H + ] where [H + ] is the molar concentration H 2 O H + + OH - [H + ] = 10-7 M [H 2 O] = 55 M ph = - log [10-7 ] = 7 2 1

2 Acid -Base Balance and Regulation In physiology, 7.4 is considered neutral because it reflects the average blood ph ( concentration of H + = 40 nm; compare that with [Na + ] = 135 mm Acidosis or acidemia: A blood ph below 7.35 Alkalosis or alkalemia : A blood ph above 7.45 Death occurs within seconds when blood ph falls below 6.8 or above 8.0. Regulation of blood ph, more specifically H +, is thus a very important homeostatic factor in life. 3 Acid -Base Balance and Regulation Sources of H + in the body VOLATILE ACIDS : Carbon dioxide and carbonic acid CO 2 and H 2 CO 3 FIXED ACIDS : Inorganic acids (non carbonic acids ) from diet phosphoric acid, sulfuric acid, ammonia ~ mmoles of H + /kg/day ORGANIC ACIDS : resulting from metabolism citric acid, lactic acid, pyruvic acid, ketone body acids 4 2

3 Acid -Base Balance and Regulation Quantities of H+ produced per day Diet : nmoles/day Metabolism : nmoles/day Amount of protons free in solution in Blood plasma is around 40 nmol /L ( = ph 7.4)! Our body is thus constantly challenged by an enormous overload of protons. It requires different mechanism to keep the proton levels under control 5 Lines of defense against changes in ph Chemical Buffers Respiratory mechanism Renal mechanism Chemical buffers act immediately ; they bind excess protons but do not eliminate H + from the body. They can only soak up extra H + depending on the concentration of the chemical buffers present. When capacity is full, the additional H + needs to be removed from the body The lungs and kidneys aid in the removal of acids from the body. They act however more slowly, with the lungs being faster compared to the kidneys. 6 3

4 Lines of defense against changes in ph 7 Lines of defense against changes in ph 1. Chemical Buffers Chemical Buffers are composed out of compounds that minimize ph changes when acids or bases are added. The compounds come in pairs : a weak acid : releases H + a weak base : binds H + HY H + + Y - Weak acid Weak base 8 4

5 Lines of defense against changes in ph A. The most important buffer in ICF are the proteins Proteins contain both acid and basic groups and can thus bind H+ and release protons quite easily Hemoglobin in RBC also is important in binding H+ in the tissues and buffering blood ph. 9 Lines of defense against changes in ph If ph climbs, the carboxyl group of amino acid acts as a weak acid If the ph drops, the amino group acts as a weak base Hemoglobin in RBC also is important in binding H+ in the tissues and buffering blood ph. 10 5

6 Lines of defense against changes in ph B. The most important buffer in ECF is the bicarbonate buffer CO 2 + H 2 O H 2 CO 3 H + + HCO 3 - Has the following limitations: It cannot protect the ECF from ph changes due to increased or depressed CO 2 levels Only functions when respiratory system and control centers are working normally It is limited by availability of bicarbonate ions (bicarbonate reserve) 11 Lines of defense against changes in ph 12 6

7 Lines of defense against changes in ph c. Phosphate buffer is an important urinary buffer Na 2 HPO 4 + H + NaH 2 PO 4 + Na + Humans consume more phosphate than needed. The excess is filtered into the nephrons and is not re-absorbed by the kidney. The phosphate helps to buffer urine ph in the nephron. It binds the secreted protons and keeps the ph above 5. If it were not for this buffer, urine ph would be extremely acidic very fast ( below 4.5) and prevent the nephron from secreting H+. 13 Lines of defense against changes in ph 2. Respiratory Mechanism of H + regulation Regulation occurs by CO 2 removal and involves the bicarbonate reaction If not enough CO 2 is expelled by the lungs, more CO 2 stays behind in the blood CO 2 drives the bicarbonate reaction to the left and forms more Bicarbonate and protons and ph drops CO 2 + H 2 O H 2 CO 3 H + + HCO

8 Lines of defense against changes in ph The opposite occurs when too much CO 2 is expelled CO 2 + H 2 O H 2 CO 3 H + + HCO 3 - The Henderson-Hasselbalch equation for weak acids/bases dtermines ph levels. ph = pka + log {[Base]/[Acid]} ph = pka + log {[HCO 3- ]/[CO 2 ]} ph = pka + log {[HCO 3- ]/0.03 P CO2 } Blood ph is 7.4 and pka for Bicarbonate reaction is 6.1 [HCO 3- ]/0.03 P CO2 = 10 (ph - pka) = 10 (1.3) = Lines of defense against changes in ph So the ratio of [HCO 3- ] to {0.03 P CO2 } determines blood ph! The respiratory system uses this to adjust ph by regulating CO 2. Changes can occur within minutes ; changing AVR by 2 ( or 1/2) will change ph of the blood by 0.2 units Anything that impairs respiratory system may thus affect acid base balance of the body. When a change in acid base balance is due to a problem with the respiratory system, it is referred to as Respiratory Acidosis or Respiratory Alkalosis. 16 8

9 Lines of defense against changes in ph 17 Lines of defense against changes in ph 2. Renal Mechanism of H + regulation ph = pka + log {[HCO 3- ]/0.03 P CO2 } While the lungs take care of the CO 2 aspect of the equation, the kidneys adjust and regulate ph by regulating the bicarbonate levels in the body. Kidneys role in acid base is Excrete H + ions Reabsorb HCO 3 - ions Make new HCO 3 - ions 18 9

10 Kidneys role in Acid Base Excretion/secretion of H+ Amount of H + filtered = Plasma [H + } x GFR Since under normal circumstances, the amount of plasma H + is extremely low, only minute amounts of H+ are filtered. The majority of H + is secreted by the nephron. PCT, DCT and collecting ducts all participate in secretion of H +. Note : Urine ph = 6 or lower. If H + was only filtered, then urine ph = blood plasma ph. The fact that it is lower, indicates more acidity present; hence, secretion! 19 Kidneys role in Acid Base Secretion of H + is related to HCO - 3 and CO 2 concentrations CO 2 + H 2 O H 2 CO 3 H + + HCO 3 - H + generated from non-carbonic acids are buffered by HCO 3 - Loss of a bicarbonate ion to the urine, is equivalent to adding a H + to the plasma, since that buffering capacity has been lost. Thus the primary function of the kidneys is not only H + secretion but HCO - 3 reabsorption. The two are closely linked to each other

11 Kidneys role in Acid Base 21 Kidneys role in Acid Base Filtered load of HCO 3 - = Plasma [HCO 3- ]x GFR = 24 mmoles/l x L/min = 3 mmoles/min = 4320 mmoles/day PCT reabsorbs 85 % DCT reabsorbs 10 % Collecting ducts Reabsorb 5 % Excreted 0 mmol/day. Body makes 1 mmol of noncarbonic acids per day. Part of this reacts with HCO 3 and lost via CO 2 Part of that acid load is filtered and are excreted So, even though we absorb most of the HCO 3 -, some of it is lost as CO 2. This requires us to make new HCO 3 - or we cannot buffer the acids formed 22 11

12 Kidneys role in Acid Base Nephron Actions in H + /HCO 3 - regulation Proximal convoluted tubule Principal way of reclaiming HCO 3 - is via the Na/K pump (basolateral side) Na/H antiport (lumen side) Bicarbonate transporter ( basolateral side) Bicarbonate reaction both in lumen and inside PCT cell aided by Carbonic Anhydrase enzyme 23 PCT HCO 3 - Na + H + H + HCO 3 - Na + K + HCO 3 - H 2 O CO 2 H 2 O CO 2 CO 2 Net effect : For every Bicarbonate reabsorbed, a proton is excreted HCO 3 - are titrated against H + in proximal tubule 24 12

13 Kidneys role in Acid Base Note that in this process, the H + ends up in a H 2 O molecule and does not add to acidity of urine. Also note, that Bicarbonate needs to be in a 1:1 ratio with H + for reabsorption of HCO 3 - to proceed. Under normal conditions, the Kidneys secrete about 4400 mmol H + /day and 4320 mmol HCO 3 - /day. Thus in theory, under normal conditions, all bicarbonate gets to be reabsorbed and none should appear in the urine The excess of H + combines with urinary buffers and is excreted in urine ( = 80 mmol/day = noncarbonic acids made per day by the body). 25 Kidneys role in Acid Base Distal convoluted tubule/collecting Duct Under normal conditions, very little HCO 3 - is left in the distal parts of the nephron In these areas, H+ secretion is regulated by a proton pump. In addition, urinary buffers aid in soaking up these protons, allowing more H + to be secreted. The net result is that in this area, new bicarbonate ions are created and redirected into the bloodstream 26 13

14 Kidneys role in Acid Base In the distal tubules, protons are actively secreted via H + - ATPase. The net result is that new bicarbonate ions are synthesized in the tubule cells, as long as a sink for hydrogen ions (here HPO 4 2- ) is available. Peritubular capillary The pumps can only pump out protons until tubular fluid is 800 times more acidic than plasma. That s why ph of urine will never drop lower than Kidneys role in Acid Base Note that in this scheme, a H+/K+ pump exchanger is involved as well, which also explains the hyperkalemia when there is acidosis

15 Kidneys role in Acid Base Ammonia and H+ buffering Additional H + secretion occurs via Ammonia generation This involves Glutamine uptake from filtrate into tubule cells Uptake of Glutamine via symport with Na + from filtrate into tubule cells Transamination of Glutamine to form 2 NH 4 + and two HCO 3 - molecules. Transport of HCO 3 - towards the blood Transport of NH 4 + into the lumen in exchange for Na + 29 Kidneys role in Acid Base Once again, additional new bicarbonate ions are synthesized from catalysis of the amino acid glutamine. If a person is acidotic, the increased acidity stimulates renal glutamine metabolism, hence increases NH 4 + production and the new bicarbonate is used to buffer the additional hydrogen ions. Peritubular capillary 30 15

16 Kidneys role in Acid Base Summary of Renal actions Acidosis Means we have more protons than the HCO 3 - can buffer Thus nephron filtrate will have more protons than bicarbonate ions All bicarbonate ions will be reabsorbed, no bicarbonate spills over in urine New bicarbonate is made by means of the Phosphate and Glutamine buffering systems. Excess of H + filtered will combine with urine buffers and be excreted in urine. 31 Kidneys role in Acid Base Alkalosis Means we have more HCO 3 - compared to protons So, not every HCO 3 - is matched with a proton in the nephron filtrate. Bicarbonate ions will spill over in the urine. The loss of Bicarbonate ion has the same effect as adding a proton to the blood plasma. The buffers in the nephrons are very important. Without them, we would only be able to excrete 1% of the normally excreted protons

17 Acid/Base Disturbances and Compensations Acid/Base Disturbances are divided into 4 main categories Respiratory acidosis Respiratory alkalosis Metabolic acidosis Metabolic alkalosis Respiratory disturbance will be compensated for by renal actions, while metabolic deviations will be regulated by respiratory actions. 33 Acid/Base Disturbances and Compensations To find the reason for the disturbances, we need to remember who controls what and thus look at the factors responsible for a particular acid-base status. ph = pka + log {[HCO 3- ]/0.03 P CO2 } ph ~ [HCO 3- ] (controlled by kidneys) P CO2 (controlled by lungs) We thus need to look at the ratio of bicarbonate to CO 2 (which should be 20 to 1 in order to have a ph of 7.4) 34 17

18 Acid/Base Disturbances and Compensations 35 Acid/Base Disturbances and Compensations 36 18

19 RESPIRATORY ACIDOSIS 37 RESPIRATORY ALKALOSIS 38 19

20 METABOLIC ACIDOSIS 39 METABOLIC ALKALOSIS 40 20

21 Acid/Base Disturbances and Compensations Steps to consider 1. First look if we have an acidosis or alkalosis problem 2. A change in ph with a respiratory origin will have abnormal CO 2 values, giving rise to the abnormal ph. Normal plasma values for P CO2 = 40 mm Hg So, if we have a P CO2 of 50 mmhg, the expectations are that the person will become acidotic 3. A change in ph with a metabolic origin will have abnormal HCO 3 - values, giving rise to the abnormal ph. Normal plasma values for HCO 3 - = 24 meq/l So, if we have a HCO 3 - of 20 meq/l, the expectations are that the person will become acidotic 41 Acid/Base Disturbances and Compensations [CO 2 ] [HCO 3 -] ph = pka + log {[HCO 3- ]/0.03 P CO2 } ph = pka + log {20/1} = = 7.4 ph = pka + log {20/2} = = 7.1 Acidosis is of a Respiratory origin 42 21

22 Acid/Base Disturbances and Compensations [CO 2 ] [HCO 3 -] ph = pka + log {[HCO 3- ]/0.03 P CO2 } ph = pka + log {20/1} = = 7.4 ph = pka + log {10/1} = = 7.1 Acidosis is of a Metabolic origin 43 Normal Patient ph Pco 2 40 mm Hg 27 mm Hg [HCO 3- ] 24 meq/l 11 meq/l 1. Patient is acidotic 2a. Is Acidosis due to too much CO 2 retention? 2b. Is Acidosis due to too much HCO 3 elimination? Nope 3. It is thus Metabolic Acidosis ; the body is compensating via Respiratory system and is eliminating more CO 2! Yep 44 22

23 Normal Patient ph Pco 2 40 mm Hg 27 mm Hg [HCO 3- ] 24 meq/l 11 meq/l 1. Patient is alkalotic 2a. Is it due to retention of too much HCO 3? Nope 2b. Is this due to too much CO 2 elimination? Yep 3. It is thus Respiratory Alkalosis ; the body is compensating via Renal system and is eliminating more HCO 3! 45 Acid/Base Disturbances and Compensations 46 23

24 47 Causes of Acid Base Disturbances Respiratory Disturbances They all involve a change in CO 2 Respiratory Acidosis Lung diseases that prohibit enough CO 2 expiration Drugs that depress respiratory centers Nerve/muscle disorders that reduce respiratory muscle actions Result is increase in CO 2 levels above normal and drop in ph Note that the bicarbonate reaction will produce H + and HCO 3 -. However, concentrations of HCO 3 - is 600,000 times that of H +. So, H + will change rapidly but HCO 3 - concentration will barely change

25 Causes of Acid Base Disturbances Respiratory alkalosis Relatively rare condition Most of the times the result of hyperventilation Fever, anxiety, aspirin poisoning High altitude Result is decrease in CO 2 levels from normal and increase in ph 49 Causes of Acid Base Disturbances Metabolic Disturbances Metabolic acidosis ( low HCO 3 - and ph ) All acidosis conditions that are not caused by CO 2 changes Severe diarrhea Bicarbonate is lost via digestive tract (bile makes lots of HCO 3 -) If loss of Bicarbonate is greater than loss of NH4+ by kidneys, H+ will accumulate Max. Rate of NH4+ excretion by Kidneys ~ 200 mmoles/day [HCO 3 -] in diarrhea fluid ~ 50 mmol / L Diabetes mellitus : excess ketoacids in blood Strenous exercise : excess lactic acids in blood Renal failure : can t get rid of H+, can t conserve HCO

26 Causes of Acid Base Disturbances Metabolic alkalosis ( high HCO 3 - and high ph ) Vomiting Ingestion of alkaline drugs ( such as baking soda) 51 26