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Dana Daraghmeh 0100203Hala abutaleb 0100199Suha Jarad 0100215Haneen bargouth 0100200
Acid-base disorders (introduction)
pH of blood is maintained at 7.40 (range of 7.35-7.45).
acid–base status is usually
analyzed based on measurement of blood pH.
Buffering
Is the ability of weak acid & its corresponding anion (base) to resist change in pH of solution on addition of strong acid or base
•The principal extracellular buffer is carbonic acid/bicarbonate (H2CO3/HCO3–) system.
•Other physiologic buffers: plasma proteins, hemoglobin, & phosphates.
•In presence of carbonic anhydrase, carbonic acid, [H2CO3] is in equilibrium with carbon dioxide (CO2) gas.
Changes in ventilation → # in partial pressure of CO2 (PCO2) in blood → # carbonic acid level in blood.
Concentration of carbonic acid is directly proportional to amount of CO2 dissolved in blood [equal to product of PCO2 & its solubility in physiologic fluids, (PCO2 x 0.03)].
• → this term can be substituted into Henderson- Hasselbalch equation place of [H2CO3].
Normally, kidneys maintain serum bicarbonate at ~24 mEq/L (24 mmol/L), whereas lungs maintain PCO2 at ~40 mm Hg.
•→ normal physiologic pH is 7.4:
Ph = 6.1+log(24/(0.03*40)) = 7.4
Regulation of Acid–Base Homeostasis
3 mechanisms maintain acid–base balance:
1.extracellular buffering →
2.ventilatory regulation of carbon dioxide elimination →
3.renal regulation of H+ & bicarbonate excretion.
Acid–Base Disturbances
Acidemia: arterial blood pH <7.35 •Alkalemia: arterial blood pH >7.45. •Metabolic acid–base disorders: primary disturbance
is in plasma bicarbonate concentration. •Metabolic acidosis: ↓ plasma bicarbonate concentration. •Metabolic alkalosis: ↑ plasma bicarbonate
concentration. •Respiratory acid–base disorders: alterations in
alveolar ventilation → changes in PaCO2. •Respiratory acidosis: PaCO2 is ↑. •Respiratory alkalosis: PaCO2 is ↓.
Metabolic Acidosis
•can be defined as a low arterial pH (normal 7.40, with a range of 7.35-7.45) and a low serum bicarbonate concentration (normal 24 meq/L, with a range of 22-28 meq/L).
Serum anion gap (SAG), as defined below, can be used to infer whether organic or mineral acidosis is present.
Normal anion gap= 9
Common Causes of Metabolic Acidosis
1. ↑ Serum Anion Gap (SAG) •Lactic acidosis •Diabetic ketoacidosis •Renal failure (acute or chronic) •Methanol ingestion •Ethylene glycol ingestion •Salicylate over dosage•Starvation
2. Normal SAG/Hyperchloremic States•GI bicarbonate loss •Diarrhea •External pancreatic or small bowel drainage (fistula) •Ileostomy •Drugs •Cholestyramine (bile acid diarrhea) •Magnesium sulfate (diarrhea) •Calcium chloride (acidifying agent
Clinical Presentation of Metabolic Acidosis
General •Acute & mild - relatively asymptomatic. •Severe acidemia (pH <7.15-7.20): cardiovascular, respiratory, & CNS can be
affected.
Symptoms •Loss of appetite, N&V.
Signs •Cardiac: peripheral arteriolar dilatation → flushing, ↑HR, wide pulse pressure,
↑ CO can be seen initially • →↓ CO, BP, & liver & kidney blood flow. •↑ Vagally mediated bradycardia & heart block. •Cerebral: Obtundation or coma. •Metabolic: Insulin resistance; ↑ protein degradation; ↑ metabolic demands. •GI: N&V, loss of appetite.
Respiratory: dyspnea, hyperventilation with deep, rapid (Kussmaul) respirations in severe acidosis.
•In extremely severe acidosis (pH <6.8) respiratory center is depressed
•Chronic acidemia → bone demineralization with rickets in children & osteomalacia & osteopenia in adults.
Laboratory Tests •↓serum CO2. •Hyperglycemia & hyperkalemia are
common.
Compensation
Primary means to compensate for metabolic acidosis: ↑ CO2 excretion by ↑ RR (stimulation of respiratory center by changes in cerebral bicarbonate concentration & pH) →↓PaCO2
•For every 1-mEq/L (1 mmol/L) ↓ in bicarbonate concentration below the average of 24, PaCO2 ↓by ~1-1.5 mm Hg from normal value of 40
•E.g., with plasma bicarbonate of 16 mEq/L there should be arterial PCO2 of 28-32 mm Hg
Response to acid load: if serum bicarbonate concentration ↓ to 12 mEq/L [12 mmol/L],
predicted pH would be:
Ph=6.1+log(12/(0.03*40))=7.1
But: normal respiratory response to acid load is hyperventilation → if PCO2 ↓ to ~ 26 mm Hg, change in pH would be less:
Ph= 6.1+log(12/(0.03*26))=7.29
Case 1 :
Metabolic acidosis
Chief Complaint“I just feel so weak all the time.” HPI
Sue Rider is a 67-year-old woman with progressively declining renal function, due to hypertension, who is being seen in the nephrology clinic for management of fatigue, dyspnea, somnolence, and lethargy. She further reports that over the past few months she has experienced a decrease in appetite and occasionally feels nauseated without vomiting. She reports frequent nonadherence to her antihypertensive regimen “when I feel good.” She also reports no history of diarrhea.
PMH• HTN• Declining renal function due to HTN• Seasonal allergic rhinitisSH• She is a retired schoolteacher who lives with her
husband of 38 years and has three grown children. She denies alcohol use. There is no history of tobacco habituation or recreational drug use.
FH• History of CAD in her mother’s familyROS• As per HPI
Meds
• Amlodipine 5 mg po daily
• Lisinopril 20 mg po daily
• Metolazone 2.5 mg po daily, taken intermittently for lower extremity edema (reports that she has not taken any for the past few months)
ALL
• NKDA
Physical ExaminationGen• Pleasant African-American woman in NAD
VS
• BP 145/85 mm Hg, P 78 bpm, RR 22, T 37.2°C; Wt 75 kg, Ht 5′4″
HEENT• No hemorrhages or exudates on funduscopic examinationNeck/Lymph Nodes• JVP was 5 cm; carotid pulses were 2+ bilaterally; no thyromegaly or
lymphadenopathyLungs• CTA and PCV• Unable to palpate PMI; regular rate and rhythm; normal S1 and S2; no murmursAbd• Obese, soft, nontender; normoactive bowel sounds; no organomegalyMS/Ext• Minimal sternal and quadriceps tendernessNeuro• No focal cranial nerve deficits; strength 5/5 in all extremities. DTRs are 1+
brachioradialis, 2+ biceps, 2+ quadriceps, 1+ ankle jerks, toes downgoing bilaterally.
Na 132 mEq/L(135-145)
Hgb 12.2 g/dl(12-15)
AST 13 IU/L
(10-40)K 4.4 mEq/L(3.5-5)
Hct 37%(36-44)
ALT 7 IU/L(7-56)
Cl 98 mEq/L(95-105)
Plt 225 × 103/mm3
(150-450)
Alk phos 113 IU/L
(25-200)
CO2 16 mEq/L
(23-33)
WBC 7.6 × 103/mm3
(4.5-11)
GGT 14 IU/L(0-30)
BUN 37 mg/dL
(7-20)
Ca 7.4 mg/dL(8.6-10.3)
T. bili 0.4 mg/dL(0.3-1.9)
SCr 2.9 mg/dL
(0.6-1.1)
Mg 2.2 mg/dL(1.7-2.2)
Alb 3.6 g/dL(3.2-5)
Glu 89 mg/dL(60-110)
Phos 4.3 mg/(2.4-4.1)
Normal albumin
ABG on RA Normal levels • pH 7.28 (7.35-7.45)• PaCO2 34 mm Hg (35-45)• PaO2 106 mm Hg (80-100)• bicarbonate 15.5 mEq/L (22-26)
UA• SG (specific gravity ) 1.025; pH 5.0
KUB• No nephrocalcinosis
Assessment
• Acidosis• CKD• Hypertension• Hyponatremia• Hypocalcemia
a. Identify the type of acidosis (metabolic vs. respiratory) this patient exhibits, calculate the anion gap, and identify the
potential causes.Identify the type of acidosis:
A metabolic acidosis is present when there is a primary decrease in the concentration of bicarbonate. The normal compensatory
change is a decrease in pCO2 of 1-1.5 mm Hg for every 1 mEq/L fall in bicarbonate
In the presence of respiratory acidosis, there would be a primary increase in the pCO2 concentration. The expected compensatory change is an increase in bicarbonate of 1 or 3.5 mEq/L for acute
or chronic conditions, respectively, for every 10 mm Hg rise in pCO2.
• Based on the arterial pCO2 and plasma bicarbonate levels, this patient is classified as exhibiting a metabolic acidosis.
Calculate the anion gap:Anion gap = Na - (Cl + HCO3) = 132 mEq/L - (98 mEq/L
+ 16 mEq/L) = 18
Identify the potential causes of acidosis:• The presence of an elevated anion gap may be due to
ingestions (e.g., salicylates, methanol, ethylene glycol). Other causes include lactic acidosis, ketoacidosis, and renal failure. Based on the relatively mild and chronic nature of the acidosis and the patient’s medical history, the most likely cause of
her acidosis is her CKD.• The elevated anion gap rules out diarrhea, RTA, upper
GI fistulae, and total parenteral nutrition (TPN) fluids as the primary cause of the disorder
1.b. What medical conditions present in this patient are either untreated or inadequately treated?
• Metabolic acidosis.
• Hypertension.
• Electrolyte abnormalities (hyponatremia, hypocalcemia).
• Stage 4 CKD.
1.c. What information obtained from the patient’s symptoms, physical examination, and laboratory analysis indicates the presence of a chronic metabolic acidosis due to CKD?
• Symptoms: Somnolence, lethargy, nausea, and decrease in appetite.
• Physical examination findings: Diminished deep tendon reflexes.
• Laboratory values: Systemic pH 7.28; reduced serum bicarbonate, calcium, and sodium concentrations; urine pH 5.0.
1.d. What are the proposed mechanisms of metabolic acidosis in patients with CKD?
• Impaired bicarbonate generation and subsequently decreased hydrogen excretion are the main mechanisms leading to metabolic acidosis in patients withCKD. Increased endogenous hydrogen ion production is not thought to be a major factor, as it has been found to be normal or reduced in studies of acid-base dynamics in patients with CKD. However, this relatively normal production of hydrogen ions has been shown to significantly exceed daily acid excretion. This is due to a decrease in renal bicarbonate generation and possibly a decrease in bicarbonate absorption. Bicarbonate generation is impaired due to decreased glutamine metabolism in proximal renal tubular cells.The decrease in glutamine uptake and metabolism leads to a dependence on titratable acid excretion for the production of bicarbonate.
•when SAG normal: In some patients, a component of their metabolic
acidosis may be due to renal tubular defects leading to impaired bicarbonate absorption. This renal bicarbonate wasting may produce a nonelevated anion gap metabolic acidosis. Although these patients are capable of achieving a urine pH of <5.5, it occurs at a lower serum bicarbonate level than in patients with normal renal function. This mechanism of metabolic acidosis may be associated with hyperparathyroidism, salt wasting, or osmotic diuresis
1.e. What are the complications associated with prolonged acidosis in patients with CKD?
• Chronic metabolic acidosis is associated with disorders of several different organ systems. Patients with CKD and acidosis may experience accelerated development of metabolic bone disease through direct suppression of bone formation, altered parathyroid hormone and vitamin D metabolism, and increased bone resorption
• Acidosis in patients with CKD is also associated with anorexia and muscle wasting, as well as a decrease in albumin synthesis
• Patients with acidosis may also experience a more rapid decline in renal function. Metabolically, acidosis is associated with impaired glucose metabolism, growth hormone function, and thyroid function
• Although controversial, there are also data indicating that acidosis causes a general state of inflammation that may increase coronary artery disease and the risk of mortality in patients with CKD.
2. What are the pharmacotherapeutic goals for this patient?
1. Reduction the degree of acidosis by increasing the level of bicarbonate
2.Maintaine blood pressure within recommended range <140/<90
3.Correction the levels of electrolytes (Na and Ca )
3/4 What treatment alternatives are available to achieve the desired therapeutic outcomes and the optimal plane?
1.metabolic acidosis
Na bicarbonate Na and or K citrate and
Citric acid
Metabolized in the liver To bicarbonate
NaHco3(650 mg)(oral tablet)
Provide (8 mEq of Bicarbonate)
1.Bicitra (Na citrate and citric acid) (1mEQ for 1ml solution)2.Polycitra(K citrate and Na citrate and citric acid(2mEq for 1ml )
3.Polycitra K(K citrate and citric acid)(2mEq for 1 ml)
(all of them oral solutions)
Optimal plane for metabolic acidosis
If NaHco3 used the dose will be:1.dose = 0.5*weight*(24-serum bicarbonate)
=0.5*75*(24-15.5) = 319 mEQ Or 2. dose = 1 mEq /Kg/day = 1*75= 75 mEq /day 1 tablet give 8mEq??????? 75 mEqSo we need 9-10 tablets per day for around 4 days
• If bicitra solution used:
Every 1ml solution give 1mEq bicarnonate
when we need daily 75 mEq bicarbonate and so we need 75 ml solution bicitra
Better choice due to hyponatremia and to prevent the risk of flatulance and bloating that maybe result from NaHco3
• polycitra(k containing) not recommended here because it
may cause hyperkalemia • protien restriction up to 0.6-0.8 g/kg/day
Na containg it may cause Edema
So the patient may need loop diuretic
2. Hypertension :
Increasing the dose of amlodipine up to
10 mg daily and continue on lisinopril 20mg daily and also we can add loop
Diuretic like furosemide 20 mg
3.Hyponatremia :Initially we should make an assessement for
the patient’s:1. volume status 2. electrolytes in the urine 3. serum osmolaity To know if we need to give Na supplement
or water restriction or mineralocoricodesHere bicitra provide intially 75 mEq Na
per day is enough for mid hyponatremia
4. Hypocalcemia :
Thiazide diuretics Dercreas elemination
Of Ca but hereNot very effective
In ckd patient Because crcl<30
-Calcium carbonate 1250 mg Tablet (500 mg
Elemental ca )twice dayNot exceed 1500mg/day
-increas Calcium intake
Give vitamin DAccording to NKF guideline as
A prophylaxis from bone diseases
5. Outline a clinical and laboratory monitoring plan to assess the patient’s response to the pharmacotherapeutic regimen you recommended.
1. Serum osmolality , renin and aldosteron to know the cause of hyponatremia
2. Electrolyetes ( Na, k, p ,Ca,bicarbonate ) after 2 weeks
3.Blood pressure after 2 weeks4.Monitor metabolic acidosis status every 4 months 5. Spot urine/creatine ratio if we want to change her
antihypertensive drugs6.Physical exam at each visit to determine the oedema
status7. Side effects like (diarrhea ,constipation, Nand V)8.Symptoms of acidosis like (lethargy ,loss of
appetite )
Patient Education6. How should the patient be counseled about the drug
therapy to treat chronic metabolic acidosis?
Bicitra : 1.used to increase Hco3-
2. may cause side effects like( GI upset, diarrhea,swelling ,high blood pressure and weight gain)
3.diluted with glass of water and taken after meal at bed time
Ca carbonate : 1.used to prevent renal osteodestrophy
2. may cause side effect like (GI upset and constipation)
3. not taken with meal because the absorption will decrease
Follow-Up Case Questions1. How might the patient’s buffer therapy requirement change if
she is started on sevelamer to prevent dietary phosphorus absorption?•Sevelamer hydrochloride (a noncalcium-containing, nonaluminum-
containingphosphate binder for patients with CKD) is associated with reduced serum bicarbonate concentration due to hydrochloric acid release in the gut and the binding of short-chain fatty acids in the large intestine. Therefore, the patient’s dose of alkaline buffer may need to be titrated up to maintain the bicarbonate concentration within the desired range.
2. What clinical and laboratory parameters should be monitored to assess the adequacy of the patient’s ACE inhibitor dosing to slow the progression of her CKD?
In addition to monitoring her blood pressure, with a goal of <140/<90 mm Hg, the patient should also have her urinary protein monitored routinely. If her spot urine protein-to--creatinine ratio is >500-1,000 mg/g, then adjustment of her therapy to achieve a lower blood pressure goal should be considered.
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