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Chapter 4,ACID-BASE DISTURBANCES,Acid-base balance is one of the most important requirement of life. Maintenance of a constant homeostasis, is crucial for our valuable life.,Maintenance of acid-base balance,Maintenance of acid-base balance actually means regulations of hydrogen ion concentration H+ in the body fluids. When H+ is high, the fluids are acidic; when H+ is low, the fluids are basic (or alkaline).,1. Concepts in Acid-Base balance,1) An acid is a H+ donor when dissolved in water, (H2CO3 NH4+ ) a base (or alkali) is a H+ acceptor (HCO3- NH3 ) -combines with H+ to form an acid : HA H+ + A- NH4+ NH3 H2CO3 HCO3- (acid) (base),2. Term of pH,H+f = 4 10-8 mol/L. - tedious way of expressing H+ - convenient to denote H+ in term of pH, where pH = - lg H+ = l g 1 / H+ N plasma : a pH of 7.35 7.45. PH = Pka + log HCO3- / H2CO3 = Pka + HCO3- / 0.03PCO2 = 6.1+ log 24 mmol/L / 1.2 mmol/L = 6.1+ log 20/1 = 6.1+ 1.301 =7.401,3. Sources of Acids & Bases,3.1 Origin of Acids: 3.1.1 volatile 3.1.2 non-volatile,3.2 Sources of Bases,Metabolic process can also produce some bases: NH3 Sodium citrate Sodium lactate etc,4. Regulation of acid-base balance,4.1 Buffer systems containing in the body : 4.1.1 Bicarbonate buffer systems a. - interaction with H+ : HCO3- + H+ = H2CO3- = CO2 + H2O b. - first line of defense against addition of acid / base to the body c. - be effectively regulated by kidney & lung. - special physiologic significance. 4.1.2 phosphate buffer systems. 4.1.3 Protein 4.1.4 hemoglobin ,4.2 Respiratory control One of the functions of respiration is to expel CO2. Respiration removes CO2 at the same rate as it is being formed.,In transportation of CO2 , buffer action of hemoglobin & chlorion shift,Tissue plasma RBC RBC plasma Air sac,CO2 CO2 +H2O H2O + CO2 CO2 CO2,H2CO3 HbO2- O2 HCO3- H+ Hb- Cl- HHb,CO2,H2CO3 Hbo2- H+ HCO3- HCO3- Na + O2 K , Cl- Cl- H Hbo2 H Hb,A B,HCO3- Cl-,O2,4.3 Renal regulation of pH,Kidneys play a major role, which has two essential functions: (1) To reabsorb HCO3- filtered by glomerulus (2) To excrete the net acid at a rate = rate of extra-renal net acid production.,4.3.1 Reclaimation of HCO3-,Proximal HCO3- reabsorption is effected primarily by: Na+ -H + exchange - driven by lumen-to-cell Na +gradient.,4.3.2 Distal convoluted tubule - reclaim HCO3- 4.3.3 Excretion of titratable acids,4.3.4 Nonionic diffusion of NH3 - Participating in the process of ammonia secretion / titration,Extra- & intra-cellular buffers bear a fairly close relationship by means of: ions exchange processes. They cooperate in blunting of the changes in both: H+ i H + e,4.3.5 Regulation function of tissues & cells,5. Laboratory Parameters of Acid-Base Balance,pH PaCO2 SB BE AB CO2 CP BB AG,Lab. parameters of acid-base balance,Henderson-Hasselbalch equation,In Henderson-Hasselbalch equation, PH= 6.1+ log HCO3- / H2CO 3 Acid-base status should be derived clearly from the three variable values: pH PaCO2 HCO3-,5.1 pH,Normal pH = 7.4,PH 7.45 alkalosis, un-compensation a. HCO3- - metabolic alkalosis b. H2CO3- respiratory alkalosis pH=7. 357 . 45, pH=7. 357 . 45,A normal range of pH may represent 3 different situations: 1) normal -Acid-base balance; 2) Acidosis or alkalosis with complete compensation; 3) A mixed acidosis and alkalosis, both events have opposite effects on pH, may also have a normal pH. In latter two situations, acidosis or alkalosis exists but with no acidemia or alkalemia.,5.2 PaCO2 -the best respiratory parameter,a. Tension inducing from the CO2 of physical dissolution in plasma Determined by : rate of CO2 production / elimination. C. Mainly affected by CO2 elimination ( by respiration) = serum H2CO3 / main respiratory parameter (if no metabolic disorders !),PaCO2,a. = 40 +/ - 5 mmHg - normal b. 45 - CO2 retention - respiratory acidosis c. 35 - CO2 elimination - respiratory alkalosis (- hyperventilation),5.3 SB, AB, BE, CO2CP ( Designed for HCO3- in plasma),1). SB /BE are measured under “standard condition”* 2). AB / CO2CP are measured under “actual condition“. * * Standard condition : T: 38C O2 saturation of Hb: 100% PCO2: 5.32 kPa (=40mmHg ). * Actual condition: blood sample : sealed off from air O2 saturation of Hb & PCO2 : original actual levels.,Difference between two cases :,SB : rules out the respiratory effect on HCO3- measurement AB: does not, comparing them - help the differential diagnosis on respiratory acid-base disorders from metabolic ones.,AB SB - CO2 retention- respiratory acidosis (P CO2 40 mmHg) AB SB - CO2 elimination- respiratory alkalosis (hyperventilation, P CO2 40 mmHg ) AB = SB = normal value - normal - metabolic alkalosis - metabolic acidosis (metabolic disorders),5.4 BB,Sum of all buffer base HCO3-, Hb -, Pr - in blood (RBC & plasma) = 45- 55 mmol/L,BB,BB N - metabolic alkalosis BB N acidosis Change of CO2 ( ), CO2+H2O H+ + HCO3- ( ) Hbuf H+ + Buf ( ) ( weak acid) (non- HCO3- BB ) ( Inner regulation, NO change of total base ),5.5 Base Excess (BE),1 L of blood are measured under standard condition (= SB) : Amount of acid or base added to achieve a pH of 7.40 in vitro added acid - Base value in blood(PH 7.4): + (Plus ) ( metabolic alkalosis ) base - (PH + 3 metabolic alkalosis - 3 acidosis,5.6 AG in N & metabolic acidosis,Na+,HCO3-,3,Na+,Cl-,AG,Na+,Hco3-,AG,Cl-,Na +,AG,Cl-,N metabolic acidosis N AG AG,Hco3-,-UA,UC,UA-UC,negatively charged Proteins / Phosphate /Sulfate / Organic anions,Anion gap (AG),Difference between undetermined anion (UA) & undetermined cation (UC). Caculated by: AG = UA-UC = 23-11 OR AG = Na+ - ( Cl- + HCO3- ) = 140- ( 104+24 ) =12 B. Increased AG = accumulation of nonvolatile acids in body fluids C. Used as the differensiation of metabolic acidosis,Significance and Normal Values of Acid-Base Parameters,Significance and Normal Values of Acid-Base Parameters,Simple Acid-Base Disorders Changes in pH to values outside the 6.8- 7.8 range for more than a brief period are incompatible with life.,Types of acid-base disorders,The most frequently encountered clinical acid-base disorders occur as simple disorders. 4 fundamental types of acid-base disorders: A. Metabolic acidosis/metabolic alkalosis are characterized by primary disturbances of blood HCO3-; B. Respiratory acidosis, respiratory alkalosis by primarily PaCO2 alterations.,Types of acid-base disorders,( metabolic parameter ) PH = Pka + 1og HCO3- / H2CO3(20/1) ( Respiratory parameter ) (1) Definite & classification : classification A. By primarily: B. Compensation ( complete ?, incomplete ? ) HCO3- metabolic Alkalosis complete acidosis + compensation PH ( N ) compensated incomplete PH 7.45 H2CO3 respiratory acidosis compensation 7. 35 uncompensated Alkalosis,Clinical Histories metabolic D? Respiratory D ?,CO2CP SB、BB、BE (metabolic parameter ) PH HCO3- H2CO3 Respiratory parameter : 1) PCO2 2) A B - SB,Metabolic Acidosis 1. Concept ,Metabolic acidosis is defined as a primary decrease in plasma bicarbonate concentration HCO3- . 2. Cause & classfication Metabolic Acidosis is classified into 2 types: a. Normal AG b. High AG,(1) Metabolic acidosis characterized by AG,occurs either because : a. kidneys fail to excrete inorganic acids b. net accumulation of organic acids as follows:,cause : hypoxemia ( Zymolysis) live D ( obstruction in utilization of lactate ) lactic acidosis production trait : of acids ratio of lactate- / pyruvate - ketoacidosis : Cause : Diabetic,over-active decomposition of tissues ( Starvation ,fever, consumption Ds) trait: ketogenesis GFR : renal failure - nonvolatile acids Salicylates Salicylic acid,insulin TG,磷酯 TG FA 脂肪酰CoA(胞浆) 肉毒酰基转移酶 脂肪酰COA 氧化 ( 合成酶 ) ( 乙酰CoA羧化酶) 柠檬酸 乙酰CoA 丙二酰CoA (缩合) 草酰乙酸 酮戊二酸 脂肪酸 rate of ketogenes
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