Acid And Base 1 Flashcards
What are acids?
Acids are compounds that can donate a hydrogen ion to a solution/accepts electron
- Acidosis can be due to to addition of acid
- Alkalosis can be due to loss of acid
What are bases?
Bases are compounds that accept hydrogen ions/donates electrons
- Acidosis can be due to loss of a base
- Alkalosis can be due to gain of base
Contrast strong and weak acids
Strong acids tend to dissociate completely in solution
Weak acids tend to dissociaate to a limited extent (function as better buffers)
How is pH calculated?
The negative log of [H+]; at a plasma pH = 7.4, the [H+] = 35- 45nmol/L
Nite that the [H+] abd pH are inversely related, and pH is a logarithmic scale
What is the Henderson-Hassalbach equation?
pH= pKa+log[A-]/[HA]
What is a buffer?
Buffers consists of a weak acid (HA) and it’s conjugate base(A-)
Conjugate pair= acid and base that differ by the presence of a proton
What is the function of Buffers?
These resist a change in pH (minimize a pH change), on addition of small quantities of acid (H+) or base (OH-)
Buffers can reversibly bind to H+
When pH of the solution is equal to pKa,
[weak acid]= [conjugate base]
What does buffering capacity depend on?
pKa(dissociation constant): buffers in body fluids require pKa around 7.4
Concentration of buffer: higher the concentration of buffer, higher 8s the buffering capacity
Usually effective when pH is pKa +/-1
-example: aceitic acid-acetate buffer is effective at a pH range of 3.8-5.8 (pK=4.8)
What are the examples of body buffers?
H2CO3- NaHCO3^-(bicarbonate buffers) ok=6.1
NaH2PO4^- Na2HPO4^2- (phosphate buffer) pk=6.8
NH4^+Cl NH3 (ammonia buffer) pk=9.2
What are the implications of the Henderson’s-hassalbach equation?
If pKa for a weak acid is known, H-H equation used to calculate the ratio of weak acid to conjugate base at any pH
At a pH of 1 unit below pKa, the ratio of [acid]:[base]=10:1
At a ph of 1 Unit ab9ve pKa, the ratio of [acid]:[base]= 1:10
Describe drug ionization of acidic medicine
Uncharged forms (permanent forms) easily absorbed -Cross lipid bilayermembrane
- Acidic drugs (pK<7) present in uncharged form in stomach;
- Acidic drugs are better excretedin alkaline urine
HA A-
RCOOH RCOO-
Basic drugs (pK>7) better in intestine, basic drugs better excreted in acidic urine
BHB
RNH3+R-NH2
Describe the absorption of acidic drugs like aspirin
- Unchanged form (-COOH) in stomach(ph1.5), is absorbed in the stomach
- pK of aspirin (Acetyl salicylic acid)=3.5
HAA-
In stomach,[Uncharged form; COOH]» [Charged form; COO-] —Hence absorbed in stomach
In intestine(pH=7.5], [Uncharged form; COOH] «_space;[Charged form; COO-]
Calculate ratio of charged to uncharged forms in stomach and intestine
Describe absorption of basic drugs:morphine
Morphine (weak base) is charged in stomach (-NH3^+)
Uncharged form at intestinal pH (pH about 8), and mainly absorbed in intestine (pK morphine about 7.9)
(pH<7.9) R-NH3^+ R-NH2 (pH>7.9)(BH+B)
In stomach, [Charged form; -NH3^+]» [Uncharged form;NH2]
-Not as well absorbed in stomach
In intestine, [Unchsrged form;-NH2]>[Charged form;-NH3^+]
-Better absorbed in intestine (compared to stomach, [Uncharged form]> [Charged form] in intestine)
Explain the excretion of drugs
- To increase excretion, it is important to prevent its Reabsorption from tubule
- Adjust urine pH to ionize drug
- As a result, drug will be “trapped” in tubule
- Weak acids excreted better in alkaline urine (ionized at alkaline pH; R-COO-)
- Salicylate (aspirin) poisoning treated by alkaline zing urine
Weak bases excretedbetter in acidic urine (Ionized form at acidic pH; R-NH3@^+)
Calculate the ratios of acids and bases
Aspirin: pk is 3.5
At stomach pH of 1.5, the difference is: 3.5-1.5=2
COOH: COO-=100:1
In the intestine pH of 7.5, the difference is: 7.5-3.5=4
COOH:COO-= 1:10000(10^4)
Urine pH is 6.5. Calculate ratio
Calculate using the pK of morphine =8
Assume, stomach pH is 2 the difference is 8-2=6
NH3+:NH2=1000000:1(10^6:1)
Intestine pH is 8, the difference is: 8-8=0
NH3+:NH2= 1:1= equal concentration of charged and uncharged forms
Urine pH is 6 calculate ratio
Explain the acid base balance if the body
Plasma pH=7.4(+/-0.05); [H+] = 35-45 mmol/L
Note logarithmic relation and inverse relation between pH and [H+]
Intracellular enzymes and protein functions are pH dependent
Metabolism produces several acids (about 20,000 mmol/day)
Three systems to regulate [H+]:
- Buffers (first line)-immediate defense
- Respiratiry system (second line)- regulates PCO2
- Renal system (third line)-regulates HCO3- leveks
What are the examples of volatile acids ?
Carbon dioxide- major metabolic acid (15,000-20,000 mEq/day)
-handled by lungs
What are the nonvolatile acids?
50-100 mEq/day
-handled by kidneys
Inorganic acids
-Sulfric acid(H2SO4) formed by sulfur containing amino acid metabolism
-Phosphoric acid (H3PO4) formed by metabolism of phospholipids
Organic acids
-Ketone bodies (acetoacetic acid, 3-hydroxybutyric acid)
-Lactic acid (glycolysis under anaerobic conditions)
How is plasma pH 34-45 mmol/L maintained despite addition of volatile and nonvolatile acids?
pH maintenance: Buffers, respiratory system and kidneys
- On a mixed diet, production of acids (Sulfric, hydrochloric and phosphoric ) as a result of protein metabolism
- Acids buffered by chemical buffer bases, ECF HCO3-
- Respiratory system disposes off CO2
- Kidneys eliminate H+ (combined with urinary buffers) and anions (sulfate/phosphate) in urine. They add new HCO3^- to ECF to replace HCO3^- consumed in buffering strong acids. They reabsorb filtered HCO3^-
Explain the defenses against changes in proton concentration
Three primary systems to regulate H+:
1. Buffering systems (ECF and ICF):
IMMEDIATELY combine with acid/base to prevent large changes in [H+]
- Respiratory response:
Within minutes to eliminate CO2(H2CO3) - Renal response
Slowest-hours/days to eliminate excess acid/base
MOST powerful regulatory system
Explain body buffers as the first line of defense
Plasma pH is 7.35-7.45 and intracellular pH is about 7.1
Buffers minimize change in pH (does NOT prevent it) on addition of small quantity of acid or base
Major body buffer systems
- Bicarbonate-carbonic acid buffer (ECF buffer)
- Hemoglobin - due to histidine residues
- Phosphate buffer (ICF buffer and renal tubular buffer)
- Proteins(ICF and plasma)-due to histidine residues
- Ammonia buffer (renal tubule)
Explain the mechanism of bicarbonate buffer
- CO2 + water forms carbonic acid (H2CO3)
- Weak acid (H2CO3) and conjugate base (HCO3^-)
- pKa bicarbonate buffer is 6.1 (close to plasma pH of 7.4)
- High concentration in ECF
- Carbonic anhydrase has different isoforms in RBC, renal tubule, parietal cells in stomaach
Whaat is the impact of the bicarbonate buffer?
- Addition of H+, forms H2CO3–> CO2 that is lost via lungs
- In clinical setting, applying H-H equation for bicarbonate buffer
- pKa of bicarbonate buffer is 6.1
Plasma pH of 7.4, ratio of [Base]/[Acid] is 20:1
Normal [HCO3^-]=22-26 mEq/L(24 mEq/L)
Arterial PaCO2= 38-42 mmHg. (40mmHg)
What is the ratio of bicarbonate buffer?
Plasma pH of 7.4, ratio of [Base]/[Acid] (24:1.2)=20.1
How are bicarbonate and. PaCO2 levels regulated?
Bicarbonate levels-renal system
PaCO2 levels -respiratory system
Bicarbonate levels and PCO2 levels independently regulated by two different systems (open system)
Assess acid-base status: measure blood pH, PaCO2 and HCO3^-
What is the central message of the H-H equation?
Plasma pH= simple function of the HCO3^-: aPaCO2 ratio
Increased (HCO3^-: aPCO2)= alkalosi; could be due to HCO3^- increase or PCO2 decrease
Decreased (HCO3^-:aPCO2)= acidosis; could be due to HCO3^- decreased or PCO2 increase
Explain the handling of volatile acid CO2
Daily CO2 production about 15,000- 20,000 mEq/day
CO2 lost via the lungs (volatile acid)
Respiratory system regulates PaCO2 (acid component) of bicarbonate buffer system
- CO2 produced by carbohydrate, fat and amino acid metabolism
- Hemoglobin (non-bicarbonate buffers) buffers and accepts H+ formed during CO2 transport from tissues
- About 75% of CO2 transported as HCO3^-
- HCO3^- in venous blood higher than in arterial blood
Carbonic anhydrase is rich in RBC
How is CO2 transported from tissues to lungs?
- Oxygen dissociates from hemoglobin to form deoxyhemoglobin
- CO2 diffuses from tissues into blood
- Formation of carbonic acid in presence of carbonic anhydrase
- Carbonic acid (weak acid) dissociation
- Hydrogen ions formed buffered by hemoglobin (histidine)
Describe CO2 in the lungs
- Oxygen diffuses from alveoli into RBC and binds to Hb to form OxyHb
- H+ released from histidine residues from Hb
- H+ associate with HCO3^- to form carbonic acid (H2CO3^-)
- CO2 formed from carbonic acid by carbonic anhydrase
- CO2 diffuses into the alveoli and is lost by expiration
What are functions of chemoreceptors in regulating CO2 and pH?
Chemoreceptors: increased PaCO2–> increases proton concentration which stimulates respiratory center increasing respiration -hyperventilation
Control centers respond by increasing /decreasing ventilation to keep PaCO2 near 40 mmHg(-ve feedback controller)
What leads to respiratory acid base disorders?
- When CO2 production= CO2 loss via expiration, arterial PaCO2 is maintained constant
- Disorders which decrease rate of ventilation result in CO2 accumulation (respiratory acidosis) and increase in PaCO2
Increased CO2 + H2O H2CO increased H+ + HCO3^-
Disorders wh8ch increase rate of ventilation result in washout of CO2 (respiratory alkalosis ) and a fall in PaCO2
Decreaded CO2 + H2O H2CO3 decreased H+ + HCO3^-
What is the role of Respiratory center in pH in regulation?
-Respiratiry center responds to changes in pH
When blood pH falls(metabolic acidosis), stimulates respiratory center—> increased rate and depth of respiration (hyperventilation). Increased CO2 washout, lowers PaCO2(compensatory response)
When blood pH increases (metabolic alkalosis), inhibits respiratory center—> decrease in respiratory rate (hypoventilation). Increased CO2 retention, increases PaCO2 (compensatory response)
Respiratory system regulates PaCO2 (ac8d) components of bicarbonate buffer
