Acid Base Physiology Renal

Front 1

Hydrogen Ion

Back 1

a proton freed of its electrons; exists in aqueous solutions as H3O+

Front 2

Acid

Back 2

proton donor, by donating a proton it dissociates into its conj base and a free proton

Front 3

Base

Back 3

Proton Acceptor, and by accepting the proton it becomes its conj acid

Front 4

What are the conjugat bases for the followin acids:
HCL, H2PO4-, NH4+, H2CO3

Back 4

Cl- + H+
HPO42- + H+
NH3 + H+
HCO3- + H+

Front 5

Measurement of Acidity

Back 5

pH = -log10[H+], Eq/L
[H+] = antilog(9-pH), nEq/L

range of pH compatable with life is ab 7.0-7.7


9 refers to nanoequivalents (i.e., 10-9 Eq)

Front 6

Law of Mass Action

Back 6

HA <------> A- + H+

At equilibrium:
[H+] [A-]
K’ = --------------
[HA]

The larger the K’ (and the lower the pK’), the stronger the acid, and vice versa.

any given rxn can be driven in either direction dep upon the conc of the products on either side of the reaction. Every rxn has an eq constant K.

Strong acid will have hi K, weak will have low K.

pKa- low if hi K
pKa hi if low K

Front 7

Buffers

Back 7

Weak acids or bases, when dissolved in water, undergo only partial dissociation--all species of the parent molecule are present.

These solutions can resist changes in acidity (provide buffering capacity).

Front 8

The Carbonic Acid- Bicarbinate Buffer System

Back 8

CO2dis + H2O carbonic anhydrase <--> H2CO3 <---> H+ + HCO3-

most imp buffer system
[H+] [HCO3-)
K’ = ----------------------
[H2CO3]

Henderson equation: comes from K eqation
24 PaCO2
[H+] = -----------------------
[HCO3-]

carbonic acid is a weak acid.

Front 9

non bicarb buffer systems

Back 9

are biologically crucial
are effective buffers because their pKs are near the pH of plasma (pH = 7.4)
include:
proteins (mainly hemoglobin)- has hi conc histidine which can serve as buffer bc it can donate and accept free H+.
phosphates
inorganic: major urinary buffers
organic: intracellular buffers
ammonium NH4+ NH3 + H+

Front 10

PaCO2 and CO2 balance

Back 10

15,000 mmol (300 L) CO2 produced by tissues daily
transported in a nongaseous form to minimize impact on acidity (since PaCO2 determines [H2CO3])

PaCO2 proportional to CO2 production and ind proportional to alveolar ventilation.

ventilation under control of central ([H+]) and peripheral chemoreceptors (PaCO2, PaO2) carotid bodies and aortic arch

Front 11

Transportation of CO2 from peripheral tissues to lungs

Back 11

CO2 in muscle cell diffuses out of cell into tissues down conc gradient. Some diffuses directly into plasma (sm amt). Some CO2 diffuses directly into RBCs taken up by Hb making carboxy Hb. Most of it combines with H2O catalyzed by carbonic anhydrase making carbonic acid, then dissociates into bicarb and free protons which are neutralized by Hb (histidine buffer). Bicarb that is left will diffuse out of plasma in exchange for Cl to maintain electrical neutrality. When CO2 and bicarb gets to lung reverse rxns occur. Free CO2 if liberated and ventilated off

Front 12

Sources of acid and alkali gain and losses

Back 12

Dietary intake (acid gain)
Metabolism / catabolism (acid gain)
Gastrointestinal H+ or HCO3- loss
Renal HCO3- filtration (potential loss) nearly 100% of bicarb is filtered
Renal HCO3- reabsorption and generation
Renal H+ secretion

Front 13

H+ load must be buffered

Back 13

plasma HCO3- ab 50%
plasma and interstitial proteins ab 1%
intracellular and bone proteins, phosphates, HCO3 and bone carbonate- up to 50%

Front 14

Renal Regulation of H+ balance

Back 14

The kidneys must:

conserve all existing HCO3-

generate new HCO3- to repay alkali deficit secondary to 1 mEq/kg/d of H+ input

Front 15

Proximal nephron and H+ balance

Back 15

reclaims ~ 90% of filtered HCO3-

generates NH3

generates “new” HCO3- via H+ secretion and NH4+ production

Front 16

How H+ ions get from blood stream to urin

Back 16

H+ can get from blood to prox tub epith cells fairly easily down an electrochemical gradient. To go from epith cells to lumen must go against pH and electrochem gradient. H+ must have an active transport process to get them into the urin.

H+ are secreted out of the cell into the urinary space. They combine with bicarb filtered thru the glom- to form carbonic acid and can dissociate into CO2 and H2O via carbonic anhydrase on the brush border membrane of the prox tub epith cell. H2O excreted in urine, CO2 diffuses back into cell (down conc grad) CO2 then combined with water to form Carbonic acid and dissoc partially into bicarb and protons, protons can be resecreted bicarb goes down conc gradient into blood.

H+ secretion occurs via an active process, no pump on apical side of tubular epith cell, they are exchanged for K, Na K ATP ase drives this exchange. Secondary active transport.

Bicarb diffuses out of cell with Na to maintain electrical nutrality.

Front 17

NH3 / NH4+ production

Back 17

proximal nephron also produces ammonia.

In the distal nephron:
NH3 neutralizes H+ in the tubular lumen
NH4+ in the tubular lumen allows excretion of H+ (secreted by the α-intercalated cells, via H+/K+ ATP-ase)
Generated HCO3- is transported into the blood

glutamine is brken down into ammonia plus glutamate, then ammonia travels to distal nephron where it titrates H+ ions present within urinary space via secretory process and by the H+ from the intercalated cells.

allows urinary tract to excrete H+ only having min impact on urinary pH. no ammonia would cause super acidic pH
bicarb is also produced from the breakdown of glutamine

Front 18

Distal Nephron and H+ balance

Back 18

reabsorbs any remaining HCO3- (approx the other 10 % prox tubule didnt get)

generates “new” HCO3- via H+ secretion and titration of urinary buffers (HPO43-, NH3)

Front 19

Blood Gas Measurements

Back 19

Arterial measurement usually necessary, especially regarding oxygenation / respiratory status. (venous gives us an idea of waste products dumped into blood stream) Arterial blood has been filtered etc

Compared to arterial measurements, venous blood gases have the following characteristics:
pH 0.02-0.04 units lower
PaCO2 6-8 mmHg higher
HCO3 1-2 mEq/L higher
PaO2 approximately 60 mmHg lower

Avoid excessive amounts of heparin (lowers PaCO2 by dilution). often hep in tubes to prevent clotting.- thnk of this if labs dont match up to clinical scenario

Keep specimen on ice (continued anaerobic glycolysis by RBCs and WBCs will lower pH at room temperature).

Front 20

Steps in the interpretation of acid-base disorders:

Back 20

Is the pH acidemic or alkalemic? This indicates the direction of the predominant acid-base disorder. normal ph is 7.4, pCO2 is 40 and bicarb is 24

Is the abnormal pH due to changes in the PaCO2 (respiratory component) or HCO3- (metabolic component)?
-if pH and bicarb move in same direction = metabolic process, if opp = resp process

Is appropriate compensation present? use rule of 7's

What is the anion gap?

Front 21

acidosis vs acidemia

Back 21

acidosis- process that if not compensated for will result in overall state of acidity

acidemia- refers to state of organism as a whole- or the blood stream. acidemic- lo pH blood stream

poss to have metaolic acidosis and resp alkalosis, may have acidemia

Front 22

Rule of 7's

Back 22

Place disorders in ABC order, then list- first formula is winter's doesnt follow rule

Disorder
Correct compensation ( 2)

Metabolic acidosis
pCO2 = 1.5 x HCO3 + 8

Metabolic alkalosis
 10 HCO3 =  _6__ pCO2

Respiratory acidosis, acute
 10 pCO2 =  _1__ HCO3

Respiratory acidosis, chronic 10 pCO2 =  _3.5 HCO3

Respiratory alkalosis, acute
 10 pCO2 =  _2__ HCO3

Respiratory alkalosis, chronic 10 pCO2 =  _5__ HCO3

Front 23

Calculation of Anion Gap

Back 23

Cations = Na+, K+ (measured)
Ca2+, Mg2+, NH4+, proteins+ (unmeasured)

Anions = Cl-, HCO3- (measured)
SO42-, PO43-, alb-, organic acids- (unmeasured)


SO: Na - (CL and HCO3)

Front 24

Differential Dx of Metabolic Acidosis

Back 24

metabolic acidosis is only acid base disorder that can lead to incr anion gap

Elevated anion gap (MUDPILES): >12
Methanol-formic acid
Uremia
Diabetic ketoacidosis
Paraldehyde, propylene glycol
Iron, isoniazid, inhalants, idiopathic
Lactic acidosis
Ethylene glycol
Salicylates

Normal anion gap:
Loss of bicarbonate (GI)
-Diarrhea, ileal loop bladder
Loss of bicarbonate or failure of acid secretion (renal)
-Renal tubular acidosis, adrenal insufficiency, carbonic anhydrase inhibitors
Addition of hydrochloric acid
-E.g., ammonium chloride, arginine-HCl, lysine-HCl

Front 25

Systemic effects of Metabolic Acidosis

Back 25

Cardiovascular
Hypotension, arrhythmia
Pulmonary
Hyperventilation, reduced O2 delivery
Gastrointestinal
Hypomotility, decreased absorption
Renal
Na+, K+ wasting; uric acid retention
Metabolic
Protein catabolism; altered catecholamine, aldosterone, PTH, vitamin D production and response

Front 26

Salicylate toxicity

Back 26

only drug toxicity that causes metabolic acidosis and resp alkalosis, not compensatory- mixed disorder

Front 27

95% of all metabolic acidoses will have

Back 27

increased anion gap. 5% will be normal and most of those will be from diarrhea

Front 28

Correction of metabolic acidosis

Back 28

Goals: ph>7.2 and bicarb >12

Calculate HCO3 deficit or H+ surplus: (measured bicarb from art bg)
(HCO3 desired - HCO3 measured) x .5 x body weight kg

administrate alkali to titrate one hal of H+ surplus over 6-12 hrs and the remainder over the next 12 -24 hrs (usu given IV NAHCO3)

Can give up to 150 mEq of NaHCO3 per liter of D5W (5% dextrose in water solution)

Front 29

Metabolic Alkalosis (factors which lead to initiation and maintenance):

Back 29

net loss of hydrogen ions (H+) via GI tract (e.g., vomiting, nasogastric drainage) or kidney (e.g., hyperaldosteronism)

alkali loading (usually requires concomitant renal insufficiency; otherwise would need  1000 mEq HCO3-/day in normal individuals)

volume contraction with disproportionate loss of chloride (e.g., diuretics) losing Cl so resorbing bicarb

increased HCO3- absorption by the kidney:
sodium avidity coupled with diminished availability of chloride
mineralocorticoid excess

will not see-idiopathic chloride-resistant alkalosis (usually seen with severe potassium depletion)

Front 30

Metabolic Alkalosis: Chloride responsive

Back 30

(Urine Cl- < 25 mEq/L)
Gastric fluid losses (vomiting, NG suction)
Diuretic therapy (post-chronic use)- cl deficient from diuretics and body is trying to compensate after being taken off
Post-hypercapneic state- resp acidosis, kidneys retaining bicarb to compensate, then you ventilate them and they no longer have resp acidosis, you are left with metabolic alkalosis.
Low chloride intake (rare)
Stool losses (rare)
Congenital chloridorrhea, villous adenoma

non renal problem bc low cholride, kidneys trying to dump bicarb

Front 31

Metabolic Alkalosis: Chloride Resistant

Back 31

Urine Cl- > 40 mEq/L)
Primary hyperaldosteronism- Na is resorbed and Cl is too
Bartter’s syndrome-defect in Na K CL channel in thick ascending limb (same as loop diur)
Gitelman’s syndrome- defect in same ion channel in distal tubule (same as thiazide diuretics)
Cushing’s syndrome
Renal failure (with bicarbonate loading)
Idiopathic

Front 32

Systemic Effects of Metabolic Alkalosis

Back 32

Cardiovascular
Hypotension, arrhythmia
Pulmonary
Hypoventilation
Central Nervous System
Obtundation, delirium, decreased seizure threshold
Neuromuscular
Tetany
Metabolic
Hypokalemia, hypophosphatemia, decreased ionized calcium, increased anaerobic glycolysis and lactic acid production, leftward shift of oxyhemoglobin curve

Front 33

Management of Metabolic Alkalosis

Back 33

Goals: pH <7.6, bicarb < 45

Chloride-responsive alkalosis:
prevention: Cl- and K+ supplements
H2-antagonists, proton pump inhibitors antiemetics

correction: NaCl, KCl administration acetazolamide
acidifying-agents (e.g., HCl--rarely used)

Chloride-resistant alkalosis:
treat underlying defect (primary hyperaldosteronism, Cushing’s syndrome, etc.)
ancillary measures: Na+ restriction, large amounts of K+ supplementation

Front 34

Diff Dx of Resp Acidosis

Back 34

anything causing hypoventilation

Acute
Airway obstruction (aspiration, bronchospasm, laryngospasm, obstructive sleep apnea)
Circulatory collapse (cardiac arrest, pulmonary embolism)
CNS depression (medications, anesthesia, stroke, central sleep apnea)
Ventilatory restriction (pneumothorax, pneumonia)
Iatrogenic (mechanical ventilation, bronchoscopy)

Chronic
Airway obstruction (chronic obstructive pulmonary disease)
CNS depression (medications, stroke, central sleep apnea, brain tumor, obesity-hypoventilation syndrome)
Neuromuscular impairment (muscular dystrophy, multiple sclerosis, amyotrophic lateral sclerosis, poliomyelitis)
Ventilatory restriction (kyphoscoliosis, hydrothorax, interstitial fibrosis, morbid obesity)

Front 35

Systemic Effects of Resp Acidosis

Back 35

Cardiovascular
Hypertension, arrhythmia
Central Nervous System
Increased cerebral blood flow and intracranial pressure
Obtundation, confusion
Seizures
Metabolic
Altered catecholamine production and response, increased renin and aldosterone production, increased renal sodium excretion

Front 36

Management of Respiratory Acidosis

Back 36

Acute respiratory acidosis:
Treat underlying cause.
Treat hypoxemia.
HCO3- usually not needed, though may improve bronchodilatory and cardiovascular response to epinephrine (can actually worsen pCO2, however).
Usually takes PaCO2  100 mmHg to produce pH <7.10.


Chronic respiratory acidosis:
treatment of chronic obstructive pulmonary disease (COPD)
Look for complicating metabolic alkalosis.
Rapid reduction of PaCO2 may produce life-threatening alkalemia (seizures, arrhythmias).
Remember: Whenever PaCO2  HCO3-, pH will be > 7.60.

Front 37

Clinical manifestations of Respiratory Alkalosis

Back 37

Acute hypocapnia:
paresthesias of extremities
chest tightness
circumoral numbness
lightheadedness, seizures
cardiovascular: pulse, SVR, CO,  BP,  cerebral blood flow

Chronic hypocapnia:
usually asymptomatic
cardiovascular:  BP, cerebral blood flow returns to normal,  renal blood flow
 ECF volume (by 10-25%)   hematocrit

Front 38

Management of Resp Alkalosis

Back 38

Rarely life-threatening; usually a diagnostic, not a treatment problem
Exclude metabolic acidosis and/or hypoxemia before using paper bag in anxiety-hyperventilation syndrome.
Consider respiratory alkalosis when arrhythmias occur in mechanically-ventilated patients.