nephrology is the art of homeostasis n.
Download
Skip this Video
Loading SlideShow in 5 Seconds..
Nephrology is the art of homeostasis PowerPoint Presentation
Download Presentation
Nephrology is the art of homeostasis

Loading in 2 Seconds...

play fullscreen
1 / 128

Nephrology is the art of homeostasis - PowerPoint PPT Presentation


  • 70 Views
  • Uploaded on

Nephrology is the art of homeostasis. Its one thing balancing atoms in millimolar quantities. Its another balancing protons at nanomolar quantities. Introduction to acid-base physiology. Joel Topf, M.D. Assistant Professor of Medicine

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about 'Nephrology is the art of homeostasis' - hei


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
introduction to acid base physiology

Introduction to acid-base physiology

Joel Topf, M.D.

Assistant Professor of Medicine

Oakland University William Beaumont School of Medicine

http://www.pbfluids.com

getting acid base
Getting acid-base
  • Acid base physiology is the regulation of hydrogen ion concentration
  • A normal hydrogen concentration is 40 nmol/L
  • This is .00004 mmol/L

So

  • It is measured on a negative log scale called pH, normal is 7.4

Every change of 0.3 pH units represents a change in H+ by a factor of 2

40 nanomol/L = 0.00004 milimol/L

slide9

bicarbonate

bone

hemoglobin

that makes 4 possible disturbances
That makes 4 possible disturbances

HCO3–

CO2

HCO3–

CO2

HCO3–

CO2

HCO3–

CO2

pH ∝

pH ∝

pH ∝

pH ∝

each one gets a name
Each one gets a name

HCO3–

CO2

HCO3–

CO2

HCO3–

CO2

HCO3–

CO2

pH ∝

pH ∝

pH ∝

pH ∝

Metabolic alkalosis

Respiratory alkalosis

Metabolic acidosis

Respiratory acidosis

compensation is always in the same direction as the primary disorder
Compensation is always in the same direction as the primary disorder.

Primary

Compensation

Metabolic acidosis

HCO3

pCO2

Respiratory alkalosis

pCO2

HCO3

Respiratory acidosis

pCO2

HCO3

Metabolic alkalosis

HCO3

pCO2

compensation is always in the same direction as the primary disorder1

If all three variables move in the same direction the disorder is metabolic.

Compensation is always in the same direction as the primary disorder.

If they move in discordant directions it is respiratory

Primary

Compensation

Metabolic acidosis

HCO3

pCO2

pH

Respiratory alkalosis

pCO2

HCO3

pH

Respiratory acidosis

pCO2

HCO3

pH

Metabolic alkalosis

HCO3

pCO2

pH

determine the primary disorder
Determine the primary disorder

pH / pO2 / pCO2 / HCO3

  • Acidosis or alkalosis
    • If the pH is less than 7.4 it is acidosis
    • If the pH is greater than 7.4 it is alkalosis
  • Determine if it is respiratory or metabolic
    • If the pH, bicarbonate and pCO2 all move in the same direction (up or down) it is metabolic
    • If the pH, bicarbonate and pCO2 move in discordant directions (up and down) it is respiratory
determine the primary disorder1

7.2 / 78 / 25 / 16

7.2 / 78 / 25 / 16

pH / pO2 / pCO2 / HCO3

pH / pO2 / pCO2 / HCO3

Determine the primary disorder
  • Acidosis or alkalosis
    • If the pH is less than 7.4 it is acidosis
    • If the pH is greater than 7.4 it is alkalosis

Metabolic Acidosis

  • Acidosis or alkalosis
    • If the pH is less than 7.4 it is acidosis
    • If the pH is greater than 7.4 it is alkalosis
  • Determine if it is respiratory or metabolic
    • If the pH, bicarbonate and pCO2 all move in the same direction (up or down) it is metabolic
    • If the pH, bicarbonate and pCO2 move in discordant directions (up and down) it is respiratory
  • Determine if it is respiratory or metabolic
    • Ifthe pH, bicarbonate and pCO2 all move in the same direction (up or down) it is metabolic
    • If the pH, bicarbonate and pCO2 move in discordant directions (up and down) it is respiratory
determine the primary disorder2

7.5 / 55 / 24 / 22

pH / pO2 / pCO2 / HCO3

Respiratory alkalosis

Determine the primary disorder
  • Respiratory acidosis
  • Metabolic acidosis
  • Respiratory alkalosis
  • Respiratory alkalosis
  • Respiratory acidosis
  • Metabolic acidosis
  • Respiratory alkalosis
  • Metabolic alkalosis
  • Respiratory acidosis
  • Metabolic acidosis
  • Respiratory alkalosis
  • Metabolic alkalosis
the direction of compensation is determined by the direction of the primary disorder

The direction of compensation is determined by the direction of the primary disorder

The magnitude of the compensation is determined by the magnitude of the primary disorder

empiric data
Empiric data

HCO3 = 15

pH = 7.32-7.38

pH = 7.3

pH = 7.37

CO2 = 30-26

why do we care
Why do we care?

HCO3 = 9

pH = 7.12

CO2 = 28

slide32

Determine the primary Acid-Base disorder

Metabolic acidosis

Metabolic alkalosis

Respiratory acidosis

Respiratory alkalosis

Determine if the compensation is appropriate

Winter’s formula

⅓ the Δ HCO3

1:10 acute3:10 chronic

2:10 acute4:10 chronic

To look for a second disease calculate what the compensation should be.

Compare it to the actual compensation

If they overlap, one disease, if they don’t 2 diseases

slide33
Metabolic acidosis: Winter’s Formula
      • 1.5 × HCO3 + 8 ± 2
  • Metabolic alkalosis:
      • pCO2 rises 0.7 per mmol rise in HCO3
  • Respiratory acidosis:
      • 1 or 3 mmol rise in HCO3 for 10 rise in pCO2
  • Respiratory alkalosis:
      • 2 or 4 mmol fall in HCO3 for 10 fall in pCO2
predicting pco 2 in metabolic acidosis
Predicting pCO2 in metabolic acidosis
  • In metabolic acidosis the expected pCO2 can be estimated from the HCO3

Expected pCO2 = (1.5 x HCO3) + 8 ± 2

  • If the pCO2 is higher than predicted then there is an addition respiratory acidosis
  • If the pCO2 is lower than predicted there is an additional respiratory alkalosis
predicting pco 2 in metabolic acidosis1

7.23 / 78 / 19 / 8

pH / pO2 / pCO2 / HCO3

Predicting pCO2 in metabolic acidosis
  • Example:
    • Expected pCO2 = (1.5 x HCO3) + 8 ±2
    • Expected pCO2 = 18-22
    • Actual pCO2 is 19, which is within the predicted range, indicating a simple metabolic acidosis
predicting pco 2 in metabolic acidosis2

7.15 / 112 / 34 / 12

pH / pO2 / pCO2 / HCO3

Predicting pCO2 in metabolic acidosis
  • Example:
    • Expected pCO2 = (1.5 x HCO3) + 8 ±2
    • Expected pCO2 = 24-28
    • Actual pCO2 is 34, which is above the predicted range, indicating an additional respiratory acidosis
respiratory disorders
Respiratory disorders
  • Metabolic compensation for respiratory acid-base disorders is slow.
  • So the predicted bicarbonate needs to be calculated for pre-compensation, called acute, and after compensation, called chronic.
    • Chronic compensation is complete so the pH will be closer to normal at the expense of increased alteration of serum bicarbonate.
why is metabolic compensation slow
Why is metabolic compensation slow?
  • The lungs ventilate 12 moles of acid per day as carbon dioxide
  • The kidneys excrete less than 0.1 mole of acid per day as ammonia, phosphate and free hydrogen ions
  • The high excretion capacity of the lungs relative to the kidneys means that metabolic disorders are rapidly compensated by the lungs while respiratory disorders take hours to days for compensation by the kidneys.
slide42

In metabolic acidosis, the increase in H+ comes with an associated anion and that anion can be just about anything.

defining the anion gap
Defining the anion gap

Cl + HCO3 + Anions = Na + Cations

Cl + HCO3 + Anions – Cations = Na

Anions – Cations = Na – (Cl + HCO3)

Define (Anions – Cations) as the anion gap

Other anions

Lactate–

Albumin

PO4–

IgA

Other cations

Anions Gap = Na – (Cl + HCO3)

K+, Ca++

Mg++, IgG

slide46

Anions Gap = Na – (Cl + HCO3)

Normal

anion

gap

Lactate–

Albumin

PO4–

IgA

K+, Ca++

Mg++, IgG

slide47

=

Normal anion gap

Increased anion gap

what is the anion

Or it is not chloride

It is either chloride

What is the anion?

Non-anion gap

anion gap

nagma
NAGMA

Chloride intoxicationDilutional acidosis

HCl intoxication

Chloride gas intoxication

Early renal failure

GI loss of HCO3

Diarrhea

Surgical drains

Fistulas

Ureterosigmoidostomy

Obstructed ureteroileostomy

Cholestyramine

  • Renal loss of HCO3
  • Renal tubular acidosis
    • Proximal
    • Distal
    • Hypoaldosteronism
slide51

pH = 5.5

Cl = 154 mmol/L

Plasma volume3 liters

Plasma Cl = 105

slide52

Increases in exogenous acid drive the reaction to the right, bicarbonate is consumed

Decreases in bicarbonate force the reaction to the left, replacing the bicarbonate and increasing H+

nagma1
NAGMA

Chloride intoxicationDilutional acidosis

HCl intoxication

Chloride gas intoxication

Early renal failure

GI loss of HCO3

Diarrhea

Surgical drains

Fistulas

Ureterosigmoidostomy

Obstructed ureteroileostomy

Cholestyramine

  • Renal loss of HCO3
  • Renal tubular acidosis
    • Proximal
    • Distal
    • Hypoaldosteronism
slide57

140 102

4.4 24

135 100

5.0 35

135 50

5.0 90

135 50

5.0 90

110 90

35 40

Plasma

Bile

Pancreas

Small intestines

Large intestines

slide59

Urine pH=5.5

Serum pH=7.4

100 fold difference

Ureterosigmoidostomy

Ureteroileostomy

nagma2
NAGMA

Chloride intoxicationDilutional acidosis

HCl intoxication

Chloride gas intoxication

Early renal failure

GI loss of HCO3

Diarrhea

Surgical drains

Fistulas

Ureterosigmoidostomy

Obstructed ureteroileostomy

Cholestyramine

  • Renal loss of HCO3
  • Renal tubular acidosis
    • Proximal
    • Distal
    • Hypoaldosteronism
renal causes of a non anion gap is called renal tubular acidosis rta
Renal causes of a non-anion gap is calledRenal Tubular Acidosis (RTA)
  • RTA is a failure of the kidney to
    • reabsorb all of the filtered bicarbonate
    • or synthesize new bicarbonate to replace bicarbonate lost to metabolism
daily acid load
Daily acid load
  • Protein metabolism consumes bicarbonate
    • 1 mmol/kg
    • 2 mmol/kg in children
    • 4 mmol/kg in infants
  • This bicarbonate must be replaced to maintain homeostasis
  • The kidney does this
normal bicarbonate handling
Normal bicarbonate handling
  • Normal plasma HCO3 concentration is 24 mmol/L
  • Normal GFR is 100 mL/min, or 0.1 L per minute
  • 1440 minutes in a day
  • 24 × 0.1 × 1440 =

3,456 mmol of bicarbonate are filtered a day (filtered load)

slide64

The kidney’s role in HCO3 handling is not excretory, it needs to synthesize new bicarbonate. All of the filtered bicarbonate must be reclaimedbefore the kidney can synthesize new HCO3 to compensate for the daily acid load

bicarbonate handling
The proximal tubule needs to reabsorb 3,456 mmol of bicarbonate that is filtered every day.

Proximal tubule

The kidney must synthesize 50-100 mmol per day of new HCO3 to replace HCO3 lost buffering the daily acid load.

Cortical collecting tubule

Bicarbonate handling

50-100 mmol/day

3456 mmol/day

bicarbonate handling1
The proximal tubule needs to reabsorb 3,456 mmol of bicarbonate that is filtered every day.

Proximal tubule

The kidney must synthesize 50-100 mmol per day of new HCO3 to replace HCO3 lost buffering the daily acid load.

Cortical collecting tubule

Bicarbonate handling

50-100 mmol/day

3456 mmol/day

distal tubule completion of reabsorption and replacing bicarbonate lost to the daily acid load
Distal tubule, completion of reabsorption and replacing bicarbonate lost to the daily acid load.

3 step process:

Electrogenic movement

of sodium into the

tubular cells (eNaC)

H+ pumped into the

tubular lumen ATPase

Maintain the 1000 fold

concentration gradient

fate of excreted hydrogen ion
Fate of excreted hydrogen ion

The minimal urine pH is 4.5. This is a H+ concentration a 1000 times that of plasma.

But

It still is only 0.04 mmol/L

In order to excrete 50 mmol (to produce enough bicarb-onate to account for the daily acid load) one would need…

1,250 liters of urine.

fate of excreted hydrogen ion1
Fate of excreted hydrogen ion

Ammonium

Titratable acid

slide72

Excretion of the daily acid load as free hydrogen is limited by a minimum urinary pH of 4.5

    • Only 0.1% of the daily acid load is excreted this way
  • Titratable acid is urinary phosphate
    • Titratable acid carries a significant portion of the daily acid load
    • Limited by dietary phosphate
    • Does not respond to changes in the acid load
  • Ammonium carries the bulk of the daily acid load
    • In response to an acid load the kidney will increase production of ammonia (NH3) in order to accept additional protons to carry the load
3 steps in renal bicarbonate handling
3 steps in renal bicarbonate handling

3456 mmol/day

50-100 mmol/day

proximal rta type 2
Proximal RTA (Type 2)
  • The Tm is the maximum plasma concentration of any solute at which the proximal tubule is able to completely reabsorb the solute.
  • Beyond the Tm the substance will be incompletely reabsorbed and spill in the urine.
  • In Proximal RTA the Tm for bicarbonate is reduced from 26 to 15-20 mmol/L.

Na+

H2O

Amino Acids

HCO3

Glucose

proximal rta type 21
Proximal RTA (Type 2)

Damage to the proximal tubule decreases its Tm from 28 to somewhere in the mid-teens

Tm for HCO3 at 15

Serum HCO3 is > Tm so HCO3 spills into the urine

24 mmol/L

15 mmol/L

pH 8

proximal rta type 22
Proximal RTA (Type 2)

Serum HCO3then falls

When it falls to the Tm (15 mmol/L) the kidney appears to work normally

Homeostasis resumes but at a decreased HCO3

15 mmol/L

15 mmol/L

pH 5

proximal rta type 23
Proximal RTA (Type 2)

If the patient encounters an acid load, they synthesize new bicarbonate to return the serum HCO3 to altered Tm (15)

12 mmol/L

12 mmol/L

pH 5

proximal rta etiologies
Acquired

Acetylzolamide

Ifosfamide

Chronic hypocalcemia

Multiple myeloma

Cisplatin

Lead toxicity

Mercury poisoning

Streptozocin

Expired tetracycline

Genetic

Cystinosis

Galactosemia

Hereditary fructose intolerance

Wilson’s disease

Hyperparathyroidism

Chronic hypocapnia

Intracellular alkalosis

Proximal RTA: etiologies
proximal rta consequences
Proximal RTA: consequences
  • Loss of potassium (hypokalemia)
  • Bone disease
    • Bone buffering of the acidosis
  • Decreased growth
  • Not typically complicated by stones
distal rta type 1
Distal RTA (Type 1)

Failure can happen at any one of the three steps in urinary acidification

distal rta voltage dependent
Only variety of distal RTA which is hyperkalemic

Differentiate from type 4 by failure to respond to fludrocortisone.

Obstructive uropathy

Sickle cell anemia

Lupus

Triameterene

Amiloride

Distal RTA: Voltage dependent
distal rta h secretion
Called classic distal RTA

Most common cause of distal RTA

Congenital

Lithium

Multiple myeloma

Lupus

Pyelonephritis

Sickle cell anemia

Sjögren’s syndrome

Toluene (Glue sniffing)

Wilson’s disease

Distal RTA: H+ Secretion
distal rta consequences
Distal RTA: consequences
  • Bones
    • Chronic metabolic acidosis results in bone buffering.
      • Bicarbonate
      • Phosphate
      • Calcium
  • Kidney stones
    • Calcium phosphate stones
      • Due to hypercalciuria
      • Increased urine pH
      • Decreased urinary citrate

Well Mr. Osborne, it may not be kidney stones after all.

type 4 rta hypoaldosteronism
Type 4 RTA: Hypoaldosteronism
  • Chronic hyperkalemia of any etiology decreases ammonia- genesis
  • Without ammonia to convert to ammonium total acid excretion is modest
slide91

Acidosis stimulates NH3 production

  • NH3 is needed to excrete the H+ in the urine
  • Alkalosis suppresses NH3 production
intracellular alkalosis decreases intrarenal ammonia production

With increases in serum potassium, potassium shifts inside the cells

Intracellular alkalosis decreases intrarenal ammonia production

Intracellular

alkalosis

To maintain electroneutrality, H+ moves out of the cells

hypoaldosteronism type 4
Hypoaldosteronism: Type 4
  • Chronic hyperkalemia decreases ammoniagenesis
  • Without ammonia acid excretion is modest
  • Urinary acidification is intact
  • Acidosis is typically mild without significant bone or stone disease
  • Primary problem is high potassium
the anion gap acidosis
Uremia (mild)

Ingestions

Methanol

Ethylene glycol

Ketoacidosis

DKA

Starvation

Alcoholic

Sepsis

L-Lactic acidosis

Salicylate intoxication

Ischemia

Cyanide intoxication

Nitroprusside

Malignancy

Metformin

Liver failure

Thiamine deficiency

D-Lactic acidosis

Pyroglutamic acidosis

The anion gap acidosis
goldmark
GOLDMARK
  • G Glycols
  • O Oxoproline: pyroglutamic acidosis
  • L L-lactic acidosis
  • D D-Lactic acidosis
  • M Methanol
  • A Aspirin
  • R Renal failure
  • K Ketoacidosis

AN Mehta, JB Emmett , M Emmett, Lancet, 372, 9642, p 892, 2008

lactic acidosis1
Lactic acidosis
  • Type A
    • Tissue hypoxia
      • Shock
        • Septic
        • Hemorrhagic
        • Neurogenic
        • Cardiogenic
      • Respiratory failure
      • Anemia
      • CO poisoning
  • Type B
    • Mitochondria failure
      • Cyanide
      • Malignancy
      • Medications
        • Anti-HIV
        • Metformin
        • Aspirin
      • Thiamine deficiency
diabetic ketoacidosis
Diabetic ketoacidosis
  • Type 1 diabetes
  • No ability to produce insulin
  • Without exogenous insulin patients are dependent on ketones for energy
  • So despite blood sugars 4-10x normal, patients act as if they are hypoglycemic
slide110

Aspirin

Causes type B lactic acidosis

Stimulates respiration so it also causes respiratory alkalosis

addition of bicarbonate
Addition of bicarbonate
  • One ampule of Na Bicarbonate is 50 mmol of HCO3
  • One 325 mg pill is 4 mmol of HCO3
  • One tsp of baking soda is 60 mmol of HCO3
contraction alkalosis
Contraction alkalosis
  • Volume deficiency increases the kidneys excretion of hydrogen ions
  • Enhanced sodium reabsorption in the proximal tubule increases reclaiming filtered bicarbonate
  • Increased angiotensin increases AT2 which stimulates aldosterone
  • Aldosterone increases intercalated cell hydrogen secretion, increasing synthesis of new bicarbonate
excess mineralcorticoid activity
Excess mineralcorticoid activity
  • Secondary hyperaldosteronism
  • Primary hyperaldosteronism
  • Cushing’s syndrome
  • Congenital adrenal hyperplasia
  • Hyperreninism (renal artery stenosis)
  • Licorice
metabolic alkalosis can be divided into chloride responsive and chloride resistant categories
Metabolic alkalosis can be divided into chloride responsive and chloride resistant categories

Saline responsive patients have a low urine chloride (less than 20 mmol/L)

Saline resistant patients have high urine chloride (greater than 20 mmol/L)