Acid base disorders-RTA

Presenter: Denis Katatwire

Facilitator: Dr. Alfred Meremo
 Outline
i. Introduction
ii. Buffering/Compensatory mechanisms
iii. Acid-base disorders
iv. RTA
v. Diagnosis
vi. Treatment
 Introduction
•
To maintain homeostasis, the human body employs many phy
siological adaptations, among these is the acid-base balance. I
n the physiological state, the body pH ranges between 7.35 to
7.45, with ¬ Of 7.40
•
The overall acid-base balance of the body is maintained by co
ntrolling the H+ concentration of body fluids.
•
Precise H+ regulation is essential because the activities of alm
ost all body enzyme systems are influenced by H+ concentrati
on.
 Cont...
•
Therefore, changes in H+ concentarion alter virtually all cell an
d body functions. Most enzymes function only with narrow pH
ranges
•
Arterial blood gas measurement is the gold standard
investigation for diagnoses of acid-base disorders. This
measures
pH
•

HCO3- conc
•

PaCO2
•

PaO2
•

Normal values ranges:for pH is 7.35-7.45; HCO3- conc:, 21-27

•

mEq/L; PaCO2, 35 to 45 mmHg and PaO2, 75-100mmHg.

Buffering/Compensatory mechanisms
•
Maintaining pH in its normal range is ideal for many biological
processes/metabolism, due to the importance of sustaining a
pH level in the needed narrow range, the human body contain
s buffering/compensatory mechanisms which include:
I. Chemical acid-base buffer systems: acts immediately, combin
e with acid or base to prevent excessive changes in H+ concen
tration, It involve bicarbonate, phosphate and proteins
II. Respiratory system: regulates the removal of CO2/H2CO3 fro
m the extracellular fluid
III. Kidneys, which can excrete either acid or alkaline urine, ther
eby readjusting the extracellular fluid H+ conc toward normal
during acidosis or alkalosis.
 Rates of Correction
Respiratory mechanisms
Renal mechanisms
Chemical buffer system

Almost instantaneously

Minutes to hours
Hours to days
7
 BICARBONATE BUFFER SYSTEM
• This is the most important ECF buffer.
• The bicarbonate buffer system consists of a water solutio
n that contains two ingredients: Weak acid, H2CO3, and
Bicarbonate salt, such as NaHCO3.
a) Carbonic Acid: (H2CO3)
H2CO3 results from the reaction of CO2 with H2O.
CO2 + H2O = H2CO3
This reaction requires carbonic anhydrase
 Cont...
• This enzyme is abundant in the walls of the lung alveoli,
where CO2 is released, Also is present in the epithelial
cells of the renal tubules, where CO2 reacts with H2O to
form H2CO3.
• H2CO3 ionizes weakly to form small amounts of H+ and
HCO3–.
H2CO3 <===> H+ + HCO3
CO2 +H2O  H2CO3  H+ + HCO3-
• H+ increases the acidity or decreases the blood pH
 Cont...

b) Bicarbonate Sal
• Occurs predominantly as NaHCO3 in the ECF

NaHCO3 ionizes almost completely to form HCO3– and N
a+, as follows: NaHCO3  Na+ + HCO3-

Putting the entire system
-CO2 + H2OH2CO3  H+ + HCO3-
-HCO3- + Na+ → NaHCO3
-Because NaHCO3 is a base it will decrease the acidit
y.
 Cont...

• H+ from strong acid, is buffered by HCO3-

• H+ + HCO3-  H2CO3  H2O + ↑CO2
• Thus H+ from strong acid react with HCO3- to form a weak
acid: then dissociates to form CO2 and H2O
• ↑ CO2 stimulates respiratory center
Increase in ventilation... then Eliminates CO2
-KEY CONCEPT: As CO2 rises, there is more acid  r
espiratory acidosis
-KEY CONCEPT: As CO2 drops, there is less acid  r
espiratory alkalosis
 Cont...
• Addition of strong base e.g. NaOH is buffered by weak
acid H2CO3 leads to formation of weak base.
NaOH + H2CO3  NaHCO3 + H2O

• H2CO3 
i.More CO2 will be used to form H2CO3 to combine
with strong base, consequently
ii. CO2 + H2O  H2CO3  H+ + HCO3-
•  CO2 inhibits respiration.
•  HCO3- are excreted by kidneys.
 PHOSPHATE BUFFER SYSTEM
• Plays a major role in buffering renal tubular fluid and intrac
ellular fluids.
• The main elements of the phosphate buffer system are H2P
O4– and HPO42-
• HPO42- accepts H+ from strong acids to form weak acid H 2PO
4- and the  in pH is minimized
• HCl + Na2HPO4  NaCl + NaH2PO4
• Strong bases are converted to weak base by phosphoric aci
d H2PO4-
• Causing only a slight increase in pH
•NaOH + NaH2PO4  Na2HPO4 + H2O
 PROTEIN BUFFER SYSTEM
• Proteins are among the most plentiful buffers in the bod
y because of their high concentrations within the cells
• The proteins act as buffers and consume small amounts
of acid/base.
• ??Hb as a buffer
PROTEIN BUFFER SYSTEM
 RESPIRATORY MECHANISM
• Rapid and powerful buffer system with the respiratory
centres adjusting the rate and depth of breathing in
response to the change of pH, increasing ventilation in
response to acidosis and vice versa
• H+ + HCO3- ↔ H2CO3 ↔ CO2 + H20
↑alveolar ventilation(hyperventilation)
↓PCO2, ↓H2CO3, ↓[H+], ↑pH of ECF. And vice versa.

• 2 times buffering capacity of total chemical buffers in the

ECF
 RENAL MECHANISM
• Long term control of acid base balance
• Mainly achieved through PCT(70-80%) and DCT(¬30%).
• PCT:extensive reabsorption of HCO3- and excretion of H+
(through ATPase and NA+/H+ exchanger. Failure of this
mechanism accounts for RTA type II
• DCT: this function through 2 types of cells:
i. Intercalated cells type A:which work in similar fashion as
the PCT cells, but has K+/H+ exchanger, works in acidotic
conditions. Failure of this mechanism accounts for RTA
type I
ii.Intercalated cells type B: reabsord H+ through Na+/H+,
H+/K+ exchangers and ATPas. works in alkalotic
conditions
 Removal of excess H+ in the tubular
lumen
•
The excess H+ in the tubular lumen primarily combine with
with NH3/HPO4 to form NH4+/H2P04
•
This enable removal of H+ through urinetherefore preventing
its detrimental effects on body cells
 Acid-base disorders
•
There are 4 main types of acid-base disorders:
i. Metabolic acidosis
ii. Respiratory acidosis
iii. Metabolic alkalosis
iv. Respiratory alkalosis
• Normal range is pCO2 in blood 35–45mmHg
• Normal range of HCO3- in blood is 24-32mmol/dl
Acid-base nomogram
 Metabolic acidosis
• = Low pH, Low HCO3−, Low PaCO2
• Results from 3 major causes:
i. Increased acid generation due,e.g,lactic acidosis/ketoacidosis
ii. Loss of bicarbonate e.g, due to diarrhea
iii. Diminished renal acid excretion due, e.g, RTA
 RTA
•
There are 4 types of RTA:
i. Proximal (Type II): ↓ proximal reabsorption of HCO3
•
1° (Fanconi’s syndrome) = ↓ proximal reabsorption of H
CO3, PO4, glc, amino acids
•
Acquired: paraprotein (MM, amyloidosis), metals (Pb, Cd,
Hg, Cu), ↓ vit D and PNH
•
Meds: acetazolamide, aminoglycosides, ifosfamide, cispl
atin, topiramate, tenofovir
 Cont...
ii. Distal (Type I): defective distal H+ secretion
•
1°, autoimmune (Sjögren’s, RA, SLE), hypercalciuria, meds
(ampho, Li, ifosfamide);
•
normally a/w ↓ K; if with ↑ K → sickle cell, obstruction, re
nal transplant
 Cont...
iii. Hypoaldo (Type IV): hypoaldo → ↑ K → ↓ NH3 synthesis →
↓ urine acid-carrying capacity
•
↓ renin: diabetic nephropathy, NSAIDs, chronic interstitial ne
phritis, calcineurin inh, HIV
•
↓ aldo production: 1° AI, ACEI/ARBs, heparin, severe illness, i
nherited (↓ 21-hydroxylase)
•
↓ response to aldosterone
•
meds: K-sparing diuretics, TMP-SMX, pentamidine, calcineurin
inhibitors
•
Tubulointerstitial disease: sickle cell, SLE, amyloid, DM
iv. Combined (Type III): rarely discussed or clinically relevant, als
o called juvenile RTA, has distal & proximal features, can be du
e to CA II deficiency
 Treatment of Metabolic acidosis
•
DKA: insulin, IVF, K repletion; AKA: dextrose, IVF, replete K, M
g, PO4
•
Lactic acidosis: treat underlying condition, avoid vasoconstrict
ors
•
Renal failure: hemodialysis
•
Methanol & ethylene glycol: fomepizole (20 mg/dL), vit. B1 &
B6 (ethylene glycol), folate (methanol), dialysis (if AKI, VS unst
able, vision Δ or >50 mg/dL)
•
Alkali therapy: if pH <7.1 or <7.2 and co-existing AKI...NaHCO3:
Three 50-mmol amps in 1 L D5W OR [desired-current HCO3] ×
wt (kg) × 0.4
•
Side effects: ↑ volume, ↑ Na, ↓ ICa, ↑ PaCO2 (& ∴ intracell
ular acidosis; ∴ must ensure adequate ventilation to blow off
CO2)
 METABOLIC ALKALOSIS
= High pH, Low HCO3−, Low PaCO2
Pathophysiology:
•
Saline-responsive etiologies require initiating event and maintenanc
e phase.
•
Initiating event:
i. Net HCO3− reabsorption (due to loss of volume, Cl-, and/or K+) or lo
ss of H+
ii. Loss of H+ (± Cl-) from GI tract, kidneys, or transcellular shift in hypo
kalemia
iii.Contraction alkalosis: loss of HCO3--poor fluid → extracellular fluid
“contracts” around fixed amount of HCO3- → ↑ HCO3- concentratio
n
iv.Exogenous alkali: iatrogenic HCO3- (with renal impairment), milk-alk
ali syndrome
v. Posthypercapnia: resp. acidosis → compensation with H+ excretion
and HCO3- retention; rapid correction of hypercapnia (eg, intubatio
n) → transient excess HCO3-
 Cont...
Maintenance phase
•
Volume depletion → ↑ ATII → ↑ PCT reabsorption of HCO3-
& ↑ aldosterone
•
Cl- depletion → ↓ Cl- uptake in macula densa → ↑ RAS & ↑ C
CD Cl-/HCO3-exchanger
•
Hypokalemia → transcellular K+/H+ exchange; intracellular aci
dosis → HCO3-reabsorption and ammoniagenesis & ↑ distal
H+-K+-ATPase activity → HCO3- retention
•
Hyperaldosteronism (1° or 2°) → ↑ CCD α-intercalated H+ sec
retion w/ HCO3-retention & Na+ reabsorption in principal cell
→ H+ secretion (for electrical neutrality)
 Workup
•
Check volume status and UCl
•
UCl <25 mEq/L → saline responsive
•
UCl >40 mEq/L → saline resistant (unless currently receiving di
uretics)
•
(UNa unreliable determinant of volume status in alkalemia →
↑ HCO3- excretion → ↑Na excretion; negatively charged HCO
3- w/ Na+ maintaining electrical neutrality)
•
If UCl >40 and volume replete, ✔ UK; UK < 20 laxative abuse; U
K >30, ✔ blood pressure
 Treatment of metabolic alkalosis
•
If saline responsive: resuscitate with Cl-rich solution (NS), repl
ete K, d/c diuretics.... cardiopulmonary disease precludes hydr
ation, can use KCl, acetazolamide, HCl
•
If NGT drainage that cannot be stopped: PPI or H2-blocker
•
Hyperaldosteronism: treat underlying condition, K-sparing diu
retic, resect adenoma if primary
 RESPIRATORY ACIDOSIS
= Low pH, High HCO3−, High PaCO2
Aetiologies:
i. ↑ CO2 production (↑ VCO2): fever, thyrotoxicosis, sepsis, steroids,
overfeeding (carbs)
ii. CNS depression (↓ RR and/or VT): sedatives (opiates, benzos, etc.),
CNS trauma, central sleep apnea, obesity hypoventilation, hypothyr
oidism
iii.Neuromuscular disorders (↓ VT): Guillain-Barré, poliomyelitis, ALS,
MS, paralytics,myasthenia gravis, muscular dystrophy, high spinal co
rd injury
iv.Chest wall (↓ VT): PTX, hemothorax, flail chest, kyphoscoliosis, anky
losing spondylitis
v. Upper airway (↓ VT): foreign body, laryngospasm, OSA, esophageal
intubation
vi.Lower airway (gas exchange) (↑ VD and/or ↓ VT): asthma, COPD, p
ulm edema, IPF, Often hypoxia → ↑ RR → resp. alk., but muscle fati
gue → resp. acid
vii.Post infusion of bicarbonate in acidemic Pt w/ limited ability to ↑
minute ventilation
 Rx
•
Rx depends on the cause
Severe pneumonia: Oxygen therapy+specific therapy
•

COPD: Oxygen therapy with Cylinder/BIPAP machine

•

CNS Depression-Opiates/Benzo: Antidotes:

•

Naloxone+Flumezanil
Chest wall abnormalitis-pneumothorax: Chest tube +
•

mechanical ventilation
e.t.c
•
 RESPIRATORY ALKALOSIS
= High pH, Low HCO3−, Low PaCO2
Aetiologies:
i. Hypoxia → hyperventilation: pneumonia, CHF, PE, restrictive l
ung disease, anemia
ii. Primary hyperventilation: CNS stimulation, pain, anxiety, trau
ma, stroke, CNS infection, pontine tumors drugs: salicylates to
xicity (early), β-agonists, progesterone, methylxanthines, sepsi
s, hepatic failure, hyperthyroidism, fever
iii.Pseudorespiratory alkalosis: ↓ perfusion w/ preserved ventila
tion (eg, CPR, severe HoTN) → ↓ delivery of CO2 to lungs for e
xcretion; low PaCO2 but ↑ tissue CO2
 Rx
•
Slow breathing rate/Hold breath
•
Rule out K+/CA2+ derangement and Rx accordingly
•
Rx of other medical conditions: pneumonia, CHF, PE, restrictiv
e lung disease, anemia
 References
•
Harrison's Principles of Internal Medicine; 18Th Edition
•
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