April 2018 Clinical Pathology fellowship program Renal Handling of acidbase status How does the kidney help to maintain a normal amount of both H and HCO 3 H secretion Reabsorption of HCO ID: 934331
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Slide1
Acid-Base Disorders & Blood Gas Analysis
April 2018
Clinical Pathology fellowship program
Slide2Renal Handling of acid-base status:
How does the kidney help to maintain a normal amount of both H
+ and HCO3- ?
H
+ secretion
Reabsorption of HCO
3
-
Aldosterone: exchange Na
+ for H+ &K+
The renal glomeruli filter H
+ and any acid anions presentThe Proximal tubules reclaim bicarb with high effectiveness (70-80%)The distal tubules and collecting ducts secretes H+ as NH4+Aldosterone acts on the cortical collecting duct to reabsorb Na+ in exchange for K+ and/or H+
Filtration of H+ and A-
Slide3Renal Tubular Acidosis (RTA)
In RTA, the kidneys inappropriately fail to excrete the amount of acid needed to maintain a normal
pH.The renal defect could occur at different points of the nephron.Glomerular damage loss of entire nephrons and reduction of the number of tubules available for excretion of
H+ and reabsorption of bicarb.
Slide4Types of Renal tubular acidosis
Type
Site of defect
Associated features
IDistal tubuleKidney stones, low K+
IIProximal tubule
Defective reabsorption of many other substancesIV
Distal tubuleAldosterone deficiency or resistance, high K+
Hyperchloremic
acidosis with hyperkalemia, similar to type IV RTA is seen in the majority of patients with mild to moderate chronic renal failure, even if due to glomerular disease.
Slide5ALKALOSIS
Causes:
increased excretion of acid: the most common mechanismdecreased excretion of base: a common contributor to alkalosis, but rarely the only cause. Also called: “Contraction alkalosis” or “ Chloride-responsive alkalosis”increase addition of alkali: the body does not naturally manufacture base as a metabolic end product, all cases are due to alkali administration i.e. exogenous alkali
Slide6Alkalosis due to increased excretion of acid
Places of losing acids from the body:
Stomach
Lung
KidneyThere is no common lab or clinical feature to this group of disorders (because acids secreted in each location differs)
Slide7Alkalosis due to increased excretion of acid from stomach
The single most common cause of alkalosis is
: excessive loss of
HCl (prolonged vomiting or nasogastric suction).Diagnosis:
Clinical history
Lab tests:
Serum electrolytes:
↑HCO3-↓Cl
-Na+: normal till dehydration occurs
Urine electrolytes: ↓ (undetectable)
Cl-Measurable urine Na+
↓ K+
Slide8Alkalosis due to increased excretion of acid from kidneys
Causes
:
increased serum mineralocorticoidsCushing syndrome
1ary hyper-aldosteronism2ndry
hyper-aldosteronism (e.g. dehydration volume depletion 2ndry
hyper-aldosteronism)Overtreatment with loop diuretics (e.g. furosemide)
the most common cause of iatrogenic metabolic alkalosis
Slide9continued….
Diagnosis of 1ary and 2ndry
hyperaldosteronism
: Serum electrolytes:
↓ Na+:
↑K+
Na+: high normal
↓ K+Urine electrolytes:
Differentiate between 1ary and 2ndry
hyperaldosteronism:Urine Cl-: Udetectable in hyperaldosteronism 2ndry to dehydration
Measurable in 1ary hyperoaldosteronism
Slide10Alkalosis due to increased excretion of acid from lungs = Respiratory Alkalosis
Causes of acute hyperventilation
(usually transient and self limited)
increased respiratory drive due to:
Hypoxemia
Salicylates
Psychogenic (including alcohol withdrawal)
Causes of chronic hyperventilation
(less common and often misdiagnosed)
Chronic hypoxemia due to impaired pulmonary gas exchange and decreased oxygenation due to:
Decreased alveolar ventilation
Impaired gas exchange.
Slide11Mechanisms of Impaired gas exchange
Due to interstitial damage in the lungs or shunting of blood
Shunting of blood (chronic right to left) occurs in pulmonary hypertension, congenital heart disease, functional shunts in cirrhosis
sCO2 exchange is much more efficient than O2, that is why when hyperventilation takes place to try to maintain normal oxygen delivery, there will be respiratory alkalosis
Causes of Impaired gas exchange
Interstitial lung diseases (CHF, interstitial fibrosis in diseases such as
sarcoidosis
)
continued….
Slide12Alkalosis due to increased addition of base
This is a very rare form of alkalosis
The history of exogenous administration of alkali is important in its diagnosis
Etiology:administration of HCO3- (abuse of antacids)
administration of citrate (in blood transfusion, massive transfusion of >10 units/day)patients with inability of the liver to metabolize citrate (neonates, liver disease)
Slide13Alkalosis due to decreased excretion of base
Other nomenclature
:
Contraction alkalosis (because chloride insufficiency usually occurs in contraction “decrease” of the intravascular volume)
Chloride-responsive alkalosis: because the alkalosis will respond to administration of adequate amounts of chlorideMechanism:
Normally in the distal renal tubules, Na+ can be absorbed only with the simultaneous absorption of an anion (first choice is Cl
-)If
Cl- is insufficient in the tubules, the major remaining anions is HCO3- decrease excretion of HCO3-
will result in alkalosis
Slide14Alkalosis due to decreased excretion of base,
continued…
Etiology
:
Dehydration
Overtreatment with diuretics
Diagnosis
:
Urinary electrolytes:
Undetectable
Cl- (in all patients)
Undetectable Na+ (in most patients)Evidence of decreased intravascular volume (in most patients):
Clinical exam
Increase BUN
Slide15Case
A70-yr-old man was admitted to the emergency room. He gave a history of dyspepsia and epigastric pain existing for many years. He had never sought medical attention for this. One week prior to admission, he had started to vomit, and had since vomited frequently, being unable to keep down any food. He was clinically dehydrated and had marked epigastric tenderness, but no sign of abdominal rigidity. Analysis of an arterial blood specimen gave the following results:
Describe this patient’s acid-base status. What might have caused the various abnormalities? Why is the Serum K+
so low? (Lecture Notes, 8th ed, p 47, case 3.1)
Serum
ResultsRef
rangeCommentUrea (
mM)17.32.5-6.6Na+
(mM)131135-145
K+ (mM)2.23.6-5
Creatinine (µM)25060-120
Blood gas analysis
ResultsRef rangeComment
H
+
(
nM
)
2637-45pCO2 (kPa)6.2
4.5-6
HCO3-+ (
mM
)
44
21-29
p
O2
9.5
12-15
Slide16Case, continued..
The patient has metabolic alkalosis due to loss of acid by the stomach (persistent vomiting, the vomit being likely to consist almost entirely of gastric contents, as he is not eating). Possible cause in his age: carcinoma of the stomach, or chronic peptic ulcer with associated scarring and fibrosis
obstruction of gastric outflow.
Causes of hypokalemia in this patient: 1- vomiting (gastric juice [K+] is ~ 10 mM) 2- Alkalosis K+
gets from ECF into the cells. 3- Dehydration 2ndry hyperaldosteronism
Na+ and water retention and K+
excretion (Na+ is avidly retained by the kidneys in exchange for (H
+ and K+) which will be excreted although the patient has alkalosis and hypokalaemic
, his urine is acid and contains large amounts of K+
Serum
Results
Ref rangeCommentUrea (mM)17.32.5-6.6Impairment of renal functionNa+ (mM)131
135-145K+ (
mM
)
2.2
3.6-5
Several reasons (see above)
Creatinine (µM)25060-120
Impairment
of renal function
Blood
gas analysis
Results
Ref
range
Comment
H
+
(
nM
)
26
37-45
Alkalosis
p
CO2
(
kPa
)
6.2
4.5-6
HCO
3
-
(
mM
)
44
21-29
Metabolic
p
O2
9.5
12-15
Slide17Evaluation of Oxygen Delivery
Oxygen delivery is critical for normal functioning of all organs
No food for weeks possible
No Water for days: possibleNo O2 for 5 minx -> irreversible damage and death of brain cells
However, O2 is poorly soluble in the bloodTherefore, our body needs an O
2 transport system (hemoglobin: contains ferrous (Fe2+ ))
Only hemoglobin is able to combine with oxygen and transport it to tissues.
Slide18Blood hemoglobin conditions
Normally*, blood hemoglobin exists in one of four conditions:
Oxyhemoglobin (O2Hb): Hemoglobin reversibly bound to O2
Deoxhemoglobin (HHb; reduced Hb
): Hemoglobin not bound to O2 but capable of forming a bond when O2 is availableCarboxyhemoglobin (COHb
): Hemoglobin bound to CO. The bond is reversible but is 200 times as strong as the bond between O2 and Hb
Methemoglobin (MetHb): is
Hb UNABLE to bind O2 because iron is in an oxidized rather than reduced state i.e. Hb molecules with ferric (Fe
3+) rather than Fe2+ . . Fe
3+ can be reduced by the enzyme methemoglobin reductase (found in RBC)* However, COHb, and
MetHb are considered dyshemoglobins.
Slide19Evaluation of Oxygen Delivery
Total hemoglobin:
98% Oxy/ and Deoxy-hemoglobin
The remaining is carboxy-hemoglobin (hemoglobin with CO)Advantages of oxygen binding to hemoglobin: although O2 is barely soluble in blood, hemoglobin has a high oxygen affinity
much greater amount of oxygen is extracted from air more O2 is available to tissuesoxygen’s relatively tight binding to hemoglobin prevents all of the oxygen from being released at once (oxygen will still be available for tissues far away from the lungs)
Slide20The oxygen dissociation curve
The
sigmoidal shape ensures that the delivery of oxygen to tissue is more closely related to the degree of saturation of hemoglobin than to the pO2What are the parameters affecting the dissociation of O2 from hemoglobin?
pO2The type of hemoglobin present (hemoglobin F has a higher affinity for oxygen than does HbA)2,3- BPG (a glycolytic product) is essential for normal oxygen delivery (its level falls in stored blood, this is a major concern in blood banking.
pHpCO2Temperature
Slide21The oxygen dissociation curve
Factors favoring the O
2 delivery to tissues i.e. decreasing the oxygen binding to hemoglobin Shift to the right
(it is the right way to get more oxygen to tissue)
pCO2 H+ (i.e. low pH)
Temperature 2,3-BPG
Certain rare hemoglobin variants
2,3 BPG
Factors decreasing the O
2 delivery to tissues i.e. increasing the oxygen binding to hemoglobin
Shift to the left (Oxygen is
left bound to hemoglobin)
pCO2
H
+
(i.e. high
pH)
Temperature
2,3-BPG
Certain rare hemoglobin variants
Slide22Is shift to the right always beneficial?
Not always
In fetal hemoglobin, hemoglobin F has a very high affinity to O2 the baby can extract oxygen from the mother’s circulation
Slide23Possible causes of tissue hypoxia
At the
lung: hypoxic hypoxiaAt the blood:
Anemia (reduced # RBCs or Hb)Carbon monoxide: left-shifted O2-Hb curve and decreased carrying capacityHypoxemiaAbnormal hemoglobin (thalassemia)
Perfusion-related (stagnant hypoxia)
Tissue
level
Metabolic disorders
Poisons
Cyanide: inhibits oxidative phosphorylation
Dinitrophenol
: uncouples oxidative phosphorylationCarbon monoxide (cytochrome binding): prevents electron transfer to oxygen
Slide24How to assess the O2
composition of a blood sample?
Parameter
How
to measureComment
pO2Arterial blood gas analysisDone
as a part of full acid-base assessmentRef range: 12-15 kPa
Valuable to assess the efficiency of O2 therapy when high pO2 value is foundAbove a pO2 of 10.5kPa, Hb is almost fully saturated with O2
[
Hb]CBCRoutinely done, and widely available
% O2 saturationOximeter
(and other tools)within the lab or a pulse oximeter at the bedside(attached to the patient’s finger or earlobe)http://www.amperordirect.com/pc/help-pulse-oximerter/z-what-is-oxygen-saturation.html
Slide25Methods for measuring oxygen saturation level
Pulse
Oximeter: A pulse oximeter is a device intended for the non-invasive measurement of arterial blood O2 saturation and pulse rate. Typically it uses two LEDs (light-emitting diodes) generating red and infrared lights through a translucent part of the body. Bone, tissue, pigmentation, and venous vessels normally absorb a constant amount of light over time.
OHb and HHb have significantly different absorption pattern. The arteriolar bed normally pulsates and absorbs variable amounts of light during systole and diastole, as blood volume increases and decreases. The ratio of light absorbed at systole and diastole is translated into an oxygen saturation measurement.
CO-oximeter: A CO-oximeter is a device for detecting hypoxia and works similar to a pulse oximeter. CO-oximeter
measures absorption at several wavelengths to distinguish OHb from COHb and determine the
OHb saturation even when the patient has carbon monoxide poisoning.
Slide26Continued …
Capnometer:
A capnometer is an instrument for monitoring breathing rate and adequacy of ventilation. It attaches to the endotracheal tube and measure the CO2 content in the inspired and expired air. It uses an IR light to measure the amount of light absorbed by CO2 during breathing. It detects changes in [CO2] in patients who are hemodynamically stable, but not critically ill.
Arterial blood gas (ABG) analysis: This is a blood test using samples extracted from an artery. The test determines the pH of the blood, the partial pressure of CO2 and O2, and the bicarb. level. Many blood gas analyzers will also report concentrations of lactate, hemoglobin, several electrolytes, oxy-hemoglobin, carboxyhemoglobin
and methemoglobin. The ABG analysis determines gas exchange levels in the blood
Slide27Carbon dioxide is carried in the
blood in three forms
Dissolved
As bicarbonate
3. As
carbamino
compounds
Slide28CO
2
+ H
2
O H
2
CO
3
C.A.
H
2
CO
3
H
+
+ HCO
3
-
Formation of bicarbonate
Slide29Hb.NH2 + CO2
Hb.NH.COOH
Formation of carbamino compounds
Slide30Take-Home Message
Arterial blood
specimen is needed for acid-base state assessment blood gas analysis. This specimen needs to be carried on ice, and to be analysed soon after collectionRespiratory
acidosis is common in chronic obstructive airways disease. Both the pCO2 and the HCO3- are raised, while the pH is low due to high [H+]. Compensatory renal HCO3- retention tends to return [H+] towards normal, but it takes few days to be maximum.Respiratory alkalosis is usually transient and due to
overbreathing, or occasionally artificial ventilation. Both the pCO2 and the HCO3- are reduced, while the pH is high due to low [H+].
Slide31Take-Home Message
Metabolic acidosis
is due to acid overproduction (e.g. DKA), failure to excrete acid (e.g. renal disease), or loss of base (in this case there is increase Cl- together with the decrease HCO3- in blood).pH is low (due to high [H+]), and HCO3- is low, and there is often a compensatory reduction of in pCO2 due to overbreathing
(Resp compensation starts quickly and it take 12 hours to maximize).Metabolic alkalosis: is most often due to loss of gastric acid (e.g. pyloric stenosis and frequent vomiting). The pH is high (due to low [H+]), and the HCO3- is raised.Respiratory insufficiency is said to be present when pO2 is < 8
kPa. In Type I, the pCO2 is normal or low, whereas in type II it is raised.