B&B Renal: Acid-Base Disorders Flashcards
Acid-Base regulation
Renal Functions
- Reabsorb / generate bicarbonate
- Excrete H+
Types of acids
Acid Excretion
2 types of acids produced via metabolism
1. Volatile acids
2. Non-volatile acids
Volatile acids
Acid Excretion
CO2
* Combines w/ H2O to form carbonic acid (H2CO3)
* Eliminated by lungs (respiration)
Non-volatile acids
Acid Excretion
Derived from AAs, fatty acids, nucleic acids
* Non-volatile acids are buffered by bicarbonate
* Prevents changes in blood pH due to build up of acidic metabolic products
* Bicarbonate must be replenished by the kidneys
Bicarbonate reabsorption
Proximal Tubule
All filtered bicarbonate is reabsorbed in the kidneys
2. 1. Na+/H+ exchanger in apical membrane transports Na+ into cells & H+ into urine
2. H+ & HCO3- in urine form H2CO3
3. CA converts H2CO3 to CO2 & H2O
4. CO2 & H2O diffuse into cells
5. CA converts CO2 & H2O back to H2CO3
6. H2CO3 divides into H+ & HCO3-
7. NBC in BL membrane cotransports Na+ & HCO3- into blood
80% of bicarbonate reabsorption occurs in proximal tubule
Bicarbonate generation
Collecting Duct
Bicarbonate is generated in intercalated cells of CD to replace any that was used to buffer non-volatile acids
1. CO2 & H2O are combined to form H2CO3 by CA
2. H2CO3 divides into H+ & HCO3-
3. HCO3- is transported from cell into blood
4. H+ is pumped out of cell into urine by H+-ATPase; high urine [H+} has low pH, needs to be buffered
Urinary Buffers
H+ Excretion
- Titratable acids
- Ammonia
Titratable Acids
Urinary Buffers
Phosphate
* HPO4 is filtered by glomerulus
* Becomes H2PO4 in urine w/ addition of H+
* Picks up H+ produced in HCO3- generation
* H2PO4 is excreted in urine = excretion of H+
Ammonia
Urinary Buffers
- Limited supply of titratable acids
- Varies with dietary intake (especially PO4)
- Supply of ammonia is adaptable
- Kidneys generate more NH3 when H+ increases
- Synthesized from glutamine (Glu = 2 NH3)
- NH3 picks up H+ produced in HCO3- generation
- NH4+ is excreted in urine = excretion of H+
Renal Acid-Base
Summary
- Non-volatile acids in serum are buffered by HCO3-
- Prevents changes in blood pH
- Low HCO3- levels stimulate:
- PCT: HCO3- resorption
- CD: HCO3- generation & H+ excretion
- H+ in the urine is buffered by urinary buffers:
- Titratable acids: phosphate (HPO4-, H2PO4)
- Ammonia (NH3, NH4+)
Acid-Base Equilibrium
Acid-Base Principles
CO2 + H2O <–> HCO3- + H+
* H+: determines pH
* HCO3-: maintained by kidneys, metabolism
* Low HCO3- –> high H+ (low pH)
* High HCO3- –> low H+ (high pH)
* CO2: maintained by lungs
* Low CO2 –> low H+ (high pH)
* High CO2 –> high H+ (low pH)
Henderson-Hasselbalch Equation
Acid-Base Principles
pH = 6.1 + log [HCO3-] / (0.03 x pCO2)
Normal Values
Acid-Base Equilibrium
- Normal HCO3- = 26 mEq/L
- Normal pCO2 = 40 mm Hg
- Normal pH = 7.4
- Hyperventilation
- Kussmaul breathing
- Depression of myocardial contractility
- Decreased CO
- Cerebral vasodilation
- Increased cerebral blood flow (CBF)
- Increased intracranial pressure (ICP)
- CNS depression
- Due to high CO2 levels
- Hyperkalemia
- Shifts H+ into cells in exchange for K+
- Shift in Hgb dissociation curve
- Bohr effect
- Low pH leads to greater O2 dissociation
Symptoms
Acidosis
- Inhibition of respiratory drive
- Depression of myocardial contractility
- Cerebral vasoconstriction
- Decreased CBF
- Hypokalemia
- Shifts K+ into cells in exchange for H+
- Shit in Hgb dissociation curve
Symptoms
Alkalosis
Approach to Acid-Base Problems
Acid-Base Principles
- Check the pH
- Check HCO3- & pCO2
- Determine acid-base disorder
- Calculate anion gap (metabolic acidosis only)
- Check for mixed disorders
Step 1: Check the pH
Approach to Acid-Base Problems
pH < 7.4 = acidosis
pH > 7.4 = alkalosis
Step 2: Check HCO3- & pCO2
Approach to Acid-Base Problems
HCO3-: venipuncture; normal = 26 mEq/L
CO2: ABG; normal = 40 mm Hg
Step 3: Determine acid-base disorder
Approach to Acid-Base Problems
- Acidosis + low HCO3- = metabolic acidosis
- Acidosis + high pCO2 = respiratory acidosis
- Alkalosis + high HCO3- = metabolic alkalosis
- Alkalosis + low pCO2 = respiratory alkalosis
Compensatory Changes
Acid-Base Disorders
- Metabolic acidosis: pH < 7.4; low HCO3-
- Compensation: decrease pCO2
- Metabolic alkalosis: pH > 7.4; high HCO3-
- Compensation: increase pCO2
- Respiratory acidosis: pH < 7.4; high pCO2
- Compensation: increase HCO3-
- Respiratory alkalosis: pH > 7.4; low pCO2
- Compensation: decrease HCO3-
Respiratory Compensation
Acid-Base Disorders
Changes pCO2 to compensate for metabolic disorders
- Metabolic acidosis –> Hyperventilation
- Blows off CO2 –> pCO2 decreases
- Less H+ in blood –> pH rises
- Metabolic alkalosis –> Hypoventilation
- Retains CO2 –> pCO2 increases
- More H+ in blood –> pH falls
Metabolic Compensation
Acid-Base Disorders
Changes HCO3- to compensate for respiratory disorders
* Respiratory acidosis –> HCO3- resorption
* Bicarbonate is reabsorbed
* Excess H+ is filtered / secreted into nephron
* Urinary buffers are excreted = H+ is excreted
* Respiratory alkalosis –> HCO3- secretion
* Reverse of acidosis
Mixed Disorders
Acid-Base Disorders
- 2 concurrent acid-base disorders
- Metabolic acidosis & respiratory alkalosis / acidosis
- Metabolic acidosis & metabolic alkalosis
- 2 metabolic acidoses
- Determined expected compensatory response to assess for mixed disorders
- Expected HCO3- for respiratory disorder
- Expected CO2 for metabolic disorder
- Use renal formulas to determine expected response
- 2nd disorder is present if actual response does not equal expected response
- Body cannot compensate to normal pH
- If pH = 7.4 in context of acid-base disorder, mixed disorder is likely
- If actual (A) does not equal expected (X), determine abnormality
- CO2 > X: 2nd respiratory acidosis
- CO2 < X: 2nd respiratory alkalosis
- HCO3- < X: 2nd metabolic acidosis
- HCO3- > X: 2nd metabolic alkalosis
- Body cannot compensate to normal pH
Metabolic Acidosis Compensation
Mixed Acid-Base Disorders
Compensatory respiratory alkalosis
* Hyperventilation: decreased pCO2
* Winter’s formula: calculates expected pCO2
pCO2 = 1.5 x ([HCO3-]) + 8 =/-2
- If actual pCO2 does not equal expected, mixed disorder is present
Metabolic Alkalosis Compensation
Mixed Acid-Base Disorders
Compensatory respiratory alkalosis
* Hypoventilation: increased pCO2
Change in pCO2 = 0.7 x Change in [HCO3-]
* 0.7 mm Hg increase in pCO2 per 1.0 mEq/L increase in [HCO3-]
* If actual pCO2 does not equal expected, mixed disorder is present
Respiratory Acidosis Compensation
Mixed Disorders
Acute compensation
* Occurs in minutes
* Intracellular buffers (Hgb) raise [HCO3-]
* Small pH increase
* 1 mEq/L increase in [HCO3-] per 10 mm Hg increase in pCO2
* Change in [HCO3-] = Change in pCO2 / 10
Chronic compensation
* Occurs in days
* Renal generation of [HCO3-]
* Larger pH increase
* 3.5 mEq/L increase in [HCO3-] per 10 mm Hg increase in pCO2
* Change in [HCO3-] = 3.5 x (Change in pCO2 / 10)
Respiratory Alkalosis Compensation
Mixed Disorders
Acute compensation
* 2 mEq/L decrease in [HCO3-] per 10 mm Hg decrease in pCO2
* Change in [HCO3-] = 2 x (Change in pCO2 / 10)
Chronic compensation
* 4 mEq/L decrease in [HCO3-] per 10 mm Hg decrease in pCO2
* Change in [HCO3-] = 4 x (Change in pCO2 / 10)
Compensation Timeframe
Acid-Base Disorder
- Respiratory compensation to metabolic disorders
- Rapid: within minutes
- Change in respiratory rate
- Metabolic compensation to respiratory disorders
- Acute: cells; mild compensation in minutes
- Chronic: kidneys; compensation in days
Caused by hyperventilation
* Pain
* Early high altitude exposure
* Early aspirin overdose
Etiology
Respiratory Alkalosis
pH > 7.4; pCO2 < 40 m Hg
High Altitude
Respiratory Alkalosis
Lower atmospheric pressure –> lower pO2
* Hypoxia –> hyperventilation
* pCO2 decreases –> pH rises
* Respiratory alkalosis
* After 24-48 hours, kidneys will excrete HCO3-
* pH will fall back toward normal
* Ventilation rate will decrease
* Acetazolamide can augment HCO3- excretion
Acetazolamide: CA inhibitor; sometimes given to those at high altitudes
Aspirin Overdose
Acid-Base Disorder
2 acid-base disorders
* Shortly after ingestion: respiratory alkalosis
* Salicylates stimulate medulla
* Respiratory control center
* Hyperventilation –> pCO2 decreases
* pH rises
* Hours after ingestion: AG metabolic acidosis
* Salicylates decreases lipolysis, uncouple oxidative phosphorylation
* Inhibits TCA cycle
* Accumulation of pyruvate, lactate, ketoacids
* pH falls
Aspirin Overdose
Presentation
- pH: variable due to mixed disorder
- Can be acidotic, alkalotic, or normal
- Acidotic patient: actual pCO2 will be lower than expected compensatory pCO2
- pCO2: low due to hyperventilation
- HCO3-: low due to accumulation of acids
Caused by hypoventilation
* Lung disease
* COPD
* Pneumonia
* Asthma
* Narcotics
* Respiratory muscle weakness
* Myasthenia gravis
* ALS
* Guillain-Barre syndrome
* Muscular dystrophy
Etiology
Respiratory Acidosis
pH < 7.4; pCO2 > 40 mm Hg
Hypercapnia
Respiratory Acidosis
- Hypercapnia can affect CNS system
- Most patients with acute high pCO2 are agitated
- Some have depressed consciousness (CO2 narcosis)
- Altered mental status in patient with respiratory disease:
- Consider high pCO2
- Check ABG
- If pCO2 is high –> ventilation
- ECV contraction
- Hypokalemia
- Diuretics
- Vomiting
- Hyperaldosteronism
- Antacid use
Etiology
Metabolic Alkalosis
- Loss of H+ or gain of HCO3-
pH > 7.4; HCO3- > 26 mEq/L
Contraction Alkalosis
Respiratory Alkalosis
Low ECV –> RAAS activation
* Ang II stimulates Na+/H+ exchanger in PCT
* Increases Na+ resorption
* Increases H+ secretion
* H+ secretion increases HCO3- resorption in PCT
* Aldosterone increased H+ secretion in CD
Hypokalemia
Metabolic Alkalosis
K+ can exchange with H+ to shift in & out of cells
* Low serum K+ –> K+ shifts out –> H+ shifts in
* Hypokalemia –> alkalosis (vice versa)
Diuretics
Metabolic Alkalosis
Loop & TZ diuretics –> metabolic alkalosis
* Volume contraction
* Decreased Na+/H2O resorption
* Hypokalemia
* Increased Na+ delivery to CD
* Increased Na+ resorption, K+ & H+ secretion
Bartter & Gitelman Syndromes
Metabolic Alkalosis
Congenital disorders
* Bartter syndrome
* Defective NKCC in TAL of Loop of Henle
* Similar to loop diuretic: non-functional NKCC
* Gitelman syndrome
* Defective NCC in distal tubule
* Similar to TZ diuretic: non-functional NCC
* Both cause hypokalemia & alkalosis
* Defective NKCC: no Na+ resorption in TAL
* Defective NCC: no Na+ resorption in DT
* Both increase Na+ delivery to CD
* Increase Na+ resorption, K+ & H+ secretion
NKCC: Na-K-Cl channel; NCC: Na/Cl cotransporter
Vomiting
Metabolic Alkalosis
- Loss of ECV –> contraction alkalosis
- Loss of HCl
- Results in increased HCl production
- HCO3- is generated during HCl production
- Loss of K+
- Low urine [Cl]
Urinary Chloride
Metabolic Alkalosis
Useful measurement in alkalosis of unknown cause
* Low (< 10-20) in vomiting
* Loss of Cl in gastric secretions
* High (>20) in many other causes of alkalosis
- Adrenal hyperplasia
- Adrenal adenoma (Conn’s syndrome)
Etiology
Hyperaldosteronism
Hyperaldosteronism
Metabolic Alkalosis
Aldosterone increases Na+ reabsorption, K+ & H+ secretion in CD
* Excess H+ & K+ secretion
* Results in alkalosis & hypokalemia
* Excess Na+ & H2O resorption
* Results in resistant HTN
Patient with resistant HTN & hypokalemia –> consider hyperaldosteronism
Aldosterone Escape
Hyperaldosteronism
Pts with hyperaldosteronism often do not have edema
* Excess Na+ & H2O –> HTN
* Compensatory mechanisms are activated
* ANP secretion
* Increased Na+ & free H2O excretion
* Result: diuresis –> normal volume status
* Urinary chloride will be elevated
Antacid Use
Metabolic Alkalosis
Milk-Alkali syndrome
* Excessive intake of:
* Calcium
* Alkali (base)
* Usually calcium carbonate and/or milk
* Often taken for dyspepsia
* Hypercalcemia –> results in volume contraction
* Inhibition of NKCC in TAL
* Blocks ADH-dependent H2O resorption in CD
* Volume contraction + alkali intake = alkalosis
Metabolic Alkalosis
Treatment
IV Fluid Administration
* Resolves most forms of metabolic alkalosis
* “Fluid responsive” forms of metabolic alkalosis
* Diuretic use
* Vomiting
* Contraction alkalosis
* Exceptions: hyperaldosteronism, hypokalemia
Chem 7
Acid-Base Disorders
- Na+: 140 mEq/L
- K+: 4.5 mEq/L
- Cl-: 100 mEq/L
- HCO3-: 24 mEq/L
- BUN: 15 mg/dL
- Creatinine: 1.2 mg/dL
- Glucose: 100 mg/dL
Anion Gap
Calculation
Anion Gap = Cations (+) - Anions (-)
* Cations (+): Na
* Anions (-): Cl & HCO3
* Cl- is often indicative of AG vs. non-AG metabolic acidosis
* High Cl- –> non-AG metabolic acidosis
* Normal / Low Cl –> AG metabolic acidosis
* Anion Gap: Na - (Cl + HCO3)
* Normal: < 12 (+/- 4)
140 - (100 + 26) = 13
Anion Gap
Metabolic Acidosis
- Results from unmeasured ions
- Cations: Ca2+, Mg2+, other minerals
- Anions: proteins (albumin), phosphates, sulfates
- Low anion gap
- Can be caused by hypoalbuminemia
- Negative albumin is primarily responsible for AG
- Also caused by multiple myeloma
- IgG is cationic (+)
- Repels other cations (e.g., Na+) out of plasma
- Draws anions (e.g,. Cl-) into plasma
- Lowers measured (+) ions / raises measured (-) ions
- Decreases anion gap
- IgG is cationic (+)
- Can be caused by hypoalbuminemia
Anion Gap
Significance
Anion gap divides metabolic acidosis causes into 2 groups
* Acidosis from primary loss of HCO3-
* Body compensates with retention of Cl-
* AG = Na - (Cl + HCO3)
* Low HCO3-
* High Cl-
* Normal anion gap
* Acidosis from primary retention of acid (i.e., ketoacids, lactic acids)
* HCO3- is consumed as buffer for non-volatile acids
* HCO3- falls without compensatory rise in Cl-
* Rise in unmeasured acids to compensate for fall in HCO3-
* AG = Na - (Cl + HCO3)
* Low HCO3-
* Normal Cl-
* Increased anion gap
Secondary Respiratory Acid-Base Disorder
Metabolic Acidosis
Winter’s Formula
pCO2 = 1.5 x [HCO3-] + (8 +/- 2)
* Acidosis –> compensatory respiratory alkalosis
* Hyperventilation –> decreased pCO2
* WF calculates expected compensatory pCO2
* 2nd respiratory disorder if actual is not equal to expected
* Check WF for all metabolic acidoses
Secondary Metabolic Acid-Base Disorder
Metabolic Acidosis
Delta Ratio (DD)
* Used to evaluate potential 2nd metabolic acid-base disorder
* Applies only to AG metabolic acidoses
* Increase in AG should be consistent w/ decrease in HCO3-
* Change in AG: AG - 12
* Change in HCO3-: 24 - [HCO3-]
* DD = Change in AG / Change in HCO3-
* DD 1-2 = normal
* DD <1 = secondary non-AG metabolic acidosis
* HCO3- is too low
* DD >2 = secondary or preexisting metabolic alkalosis
* HCO3- is too high
- Diarrhea
- Addison’s disease
- Acetazolamide use
- Spironolactone use
- Saline infusion
- Hyperalimentation
- Renal tubular acidosis (RTA)
Etiology
Non-AG Metabolic Acidosis
Diarrhea
Non-AG Metabolic Acidosis
HCO3- is lost in stool
* Low HCO3- –> acidosis
* Compensatory Cl- retention –> no AG
Acetazolamide
Non-AG Metabolic Acidosis
Blocks formation & resorption of HCO3- in PCT
* Acetazolamide = CA inhibitor
* Low HCO3- –> acidosis
* Compensatory Cl- retention –> no AG
Addison’s disease
Non-AG Metabolic Acidosis
Loss of aldosterone effects (hypoaldosteronism)
* Decreased H+ secretion in CD
* Increased serum H+ –> acidosis
Spironolactone
Non-AG Metabolic Acidosis
Loss of aldosterone effects
- Spironolactone = aldosterone receptor blocker
- Decreased H+ excretion in CD
- Increased H+ –> acidosis
Saline Infusion
Non-AG Metabolic Acidosis
Suppresses RAAS activity
* Decreased aldosterone –> reduced H+ secretion in CD
* Increased serum H+ –> acidosis
Hyperalimentation
Non-AG Metabolic Acidosis
Metabolism of nutrients creates HCL
* Increase serum H+ –> acidosis
- Methanol
- Uremia
- Diabetic ketoacidosis (DKA)
- Propylene glycol
- Iron tablets / Isoniazid (INH)
- Lactic acidosis
- Ethylene glycol
- Salicylates (aspirin)
Etiology
AG Metabolic Acidosis
Mnemonic: MUDPILES
Methanol
AG Metabolic Acidosis
- Metabolized to formic acid
- Neurotoxic: visual loss, coma
- Found in antifreeze, de-icing solutions, windshield wiper fluid, solvents, cleaners, fuels, industrial products
- Suspected ingestion: accidental, suicide, alcoholic
- Confusion (may appear inebriated)
- Visual symptoms
- High AG metabolic acidosis
Presentation
Methanol Toxicity
Methanol Toxicity
Treatment
Inhibit alcohol dehydrogenase
* Blocks bioactivation of parent alcohol to toxic metabolite
* Fomepizole
* Ethanol
Ethylene Glycol
AG Metabolic Acidosis
- Metabolized to glycolate & oxalate
- Both are nephrotoxic (slow excretion)
- Glycolate: toxic to renal tubules
- Oxalate: precipitates calcium oxalate crystals in tubules
- Found in antifreeze, solvents, cleaners, etc.
- Suspected ingestion: accidental, suicide, alcoholic
- Sx of acute renal failure: flank pain, oliguria, anorexia
- High AG metabolic acidosis
Presentation
Ethylene Glycol Toxicity
Ethylene Glycol Toxicity
Treatment
Inhibit alcohol dehydrogenase
* Blocks bioactivation of parent alcohol to toxic metabolite
* Fomepizole (Antizol)
* Ethanol
Propylene Glycol
AG Metabolic Acidosis
- Metabolized to pyruvic acid, acetic acid, lactic acid
- High AG metabolic acidosis from lactate
- Many adverse effects:
- Hemolysis
- Seizure, coma, multisystem organ failure
- Main clinical feature of overdose: CNS depression
- No visual symptoms or nephrotoxicity
- Found in antifreeze
- Used as solvent for IV benzodiazepines
Uremia
AG Metabolic Acidosis
- Early kidney disease –> non-AG metabolic acidosis
- Loss of tubule function: impaired Na+/H+ exchanger
- Reduced H+ excretion
- increased HCO3- excretion
- Cl- retention to balance charge –> normal AG
- Loss of tubule function: impaired Na+/H+ exchanger
- Advanced kidney disease –> AG metabolic acidosis
- Kidneys cannot excrete organic acids: phosphates, sulfates
- Retention of non-volatile acids –> AG
Diabetic Ketoacidosis (DKA)
AG Metabolic Acidosis
- Usually occurs in type 1 diabetics
- Insulin requirements rise but cannot be met
* Often triggered by infection - Fatty acid metabolism –> production of ketone bodies
- Beta-hydroxybutyrate, acetoacetate
- Accumulation of ketones –> AG acidosis
- Polyuria, polydipsia
- Abdominal symptoms: pain, nausea, vomiting
- Kussmaul respirations: deep, rapid breathing
- High AG metabolic acidosis
Presentation
DKA
Glycosuria: increased urine [glucose] causes osmotic diuresis
DKA
Treatment
- Insulin –> lower serum glucose
- IV fluids –> hydration
- Potassium –> correct hypokalemia
Lactic Acidosis
AG Metabolic Acidosis
- Low tissue oxygen delivery
- Pyruvate converted to lactate (anaerobic respiration)
- High serum lactate (>4.0 mmol/L) –> lactic acidosis
- Lactate = unmeasured anion –> AG metabolic acidosis
- Shock (decreased tissue perfusion)
- Ischemic bowel
- Metformin therapy (especially with renal failure)
- Seizures
- Exercise
Etiology
Lactic Acidosis
AG Metabolic Acidosis
Iron
AG Metabolic Acidosis
- Acute iron poisioning
- Initial GI phase:
- Abdominal pain
- Direct toxic effects on GI tract
- Later (24 hours):
- Cardiovascular toxicity: shock, tachycardia, hypotension
- Coagulopathy: inhibition of thrombin formation / activity
- Hepatotoxicity: worsening coagulopathy
- Acute lung injury
- Weeks later: bowel obstruction
- Scarring at gastric outlet where iron accumulates
- AG metabolic acidosis
- From ferric irons = unmeasured anions
- Also hypotension –> hypoperfusion –> lactic acidosis
Isoniazid (INH)
AG Metabolic Acidosis
- TB antibiotic
- Acute overdose causes seizures (status epilepticus)
- Seizures cause lactic acidosis = AG metabolic acidosis
Renal Tubular Acidosis (RTA)
Non-AG Metabolic Acidosis
Rare disorders of nephron ion channels
* All cause non-AG metabolic acidosis
* Often present with low HCO3- or abnormal K+
* Many patients are asymptomatic
Type 1 (Distal) RTA
Non-AG Metabolic Acidosis
Distal nephron cannot acidify urine
* Impaired H+ excretion -> acidosis; alkaline urine
* Alkaline urine –> precipitates kidney stones
* Urine should be acidic in metabolic acidosis as kidneys try to remove excess H+ from serum
* Bilateral kidney stones = suggestive of type 1 RTA
* Acidosis
* Stimulates Ca2+ resorption from bone
* Bone demineralization –> Rickets; growth failure
* Suppresses Ca2+ resorption in kidneys
* Results in elevated urine [Ca2+]
* Impaired K+ resorption –> hypokalemia
* Impaired H+ secretion causes buildup of negative charge
* Negative charge holds K+ in the urine
* Results in increased K+ excretion
- Labs
- HCO3-: very low (< 10 mEq/L)
- Urine pH: high (pH > 5.5)
- Urine Ca2+: elevated
- Symptoms
- Adults: chronic kidney stones; Rickets
- Children: growth failure
Clinical Features
Type I (Distal) RTA
Diagnosis established if alkaline urine (pH > 5.5) w/ metabolic acidosis
Associated with autoimmune diseases
* Sjögren’s syndrome
* Rheumatoid arthritis
Etiology
Type 1 (Distal) RTA
Associated with amphotericin B use
Etiology
Type 1 (Distal) RTA
- Patient with Sjögren’s disease / rheumatoid arthritis
- Recurrent bilateral kidney stones
- Serum: very low [HCO3-] < 10 mEq/L; hypokalemia
- Urine: high pH > 5.5; UAG = +
- Ammonia challenge: pH remains high
Presentation
Type I (Distal) RTA
Type I (Distal) RTA
Treatment
Sodium bicarbonate
Urine Anion Gap (UAG)
Non-AG Metabolic Acidosis
Measurement used to distinguish types of RTA
* In acidosis, high [NH4] is excreted –> removes H+
* NH4+ cannot be measured directly
* UAG: Na + K - Cl –> estimates [NH4]
* NH4+ excreted in urine draws Cl- with it
* UAG becomes negative when acid is being excreted
* Increased urine H+ = increased NH4+ = increased Cl-
Type II RTA
UAG
UAG = (-)
* Functional CD intercalated cells –> H+ secretion is intact
* Acidosis –> increased excretion of NH4+ & Cl-
* Urine [Cl-] increases
Type I RTA
UAG
UAG = (+)
* Defective CD intercalated cells: impaired H+ secretion
* Excretion of NH4+ & Cl- does not increase despite acidosis
* Normal urine [Cl-]
Ammonia Challenge
RTA
Administer NH4Cl to patient
* Acid load should lower pH
* Distal RTA: urine pH remains >5.3
Type II (Proximal) RTA
Non-AG Metabolic Acidosis
Defect in proximal tubule HCO3- resorption
Type II (Proximal) RTA
Non-AG Metabolic Acidosis
Defect in proximal tubule HCO3- resorption
* Urine pH < 5.5
* Initially, pH may be high due to excess HCO3- excretion
* Once acidosis develops, distal tubule secretes H+
* Increased H+ excretion –> acidic urine
* Increased NH4+ & Cl- excretion –> (-) UAG
* Hypokalemia
* Loss of HCO3- resorption –> osmotic diuresis
* Volume contraction –> RAAS activation
* Aldosterone –> increased K+ secretion in CD
* Increased K+ excretion –> hypokalemia
- Labs
- HCO3-: low to normal (12-20 mEq/L)
- Symptoms
- No kidney stones
Clinical Features
Type II (Proximal) RTA
Associated with Fanconi’s syndrome
Etiology
Type II (Proximal) RTA
Fanconi’s syndrome: generalized proximal tubule failure
- Asymptomatic: routine blood work
- Mild weakness
- Serum: mildly reduced [HCO3] = 10-20 mEq/L; hypokalemia
- Urine: low pH < 5.5
Presentation
Type II (Proximal) RTA
Type II (Proximal) RTA
Treatment
Sodium bicarbonate
Type IV RTA
Non-AG Metabolic Acidosis
Loss of aldosterone effects on collecting ducts
* Impaired K+ secretion by prinicipal cells -> increased K+ retention
* Only RTA with hyperkalemia
* Impaired H+ excretion–> acidosis
* Impaired H+ secretion by intercalated cells
* Impaired NH3 secretion
* Hyperkalemia causes rise in pH of PCT cells
* K+ shifts into cells, H+ shifts out of cells
* High pH inhibits NH3 synthesis in PCT cells
* Decreased NH4 excretion = decreased H+ excretion
* Urine pH usually remains low (pH < 5.4)
* Distinguishes Type IV RTA from Type I RTA (high pH)
Hypoaldosteronism
1. Aldosterone deficiency
2. Aldosterone resistance
Etiology
Type IV RTA
Hypoaldosteronism
1. Aldosterone deficiency
2. Aldosterone resistance
Etiology
Type IV RTA
Decreased Aldosterone
Etiology
- Diabetic renal disease: decreased renin release –> impaired RAAS
- ACEi / ARB: disrupted RAAS –> impaired aldosterone production
- NSAIDs: impaired aldosterone production
- Adrenal insufficiency: impaired aldosterone production
Aldosterone Resistance
Etiology
- K+-sparing diuretics: block aldosterone receptors
- TMP / SMX (antibiotic): blocks aldosterone
- Diabetic patient with renal insufficiency
- Unexplained hyperkalemia
Presentation
Type IV RTA
Type IV RTA
Treatment
Fludrocortisone
Mineralocorticoid: effects similar to aldosterone