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Download MBBS Biochemistry PPT 31 Acid Base Balance Lecture Notes

Download MBBS (Bachelor of Medicine, Bachelor of Surgery) 1st year (First Year) Biochemistry ppt lectures Topic 31 Acid Base Balance Notes. - biochemistry notes pdf, biochemistry mbbs 1st year notes pdf, biochemistry mbbs notes pdf, biochemistry lecture notes, paramedical biochemistry notes, medical biochemistry pdf, biochemistry lecture notes 2022 ppt, biochemistry pdf.

This post was last modified on 05 April 2022

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Content

? Buffer systems and its efficiency
? Requirement of maintenance of acid base

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balance

? Causes of acid base imbalances
? Regulation of acid base balance

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? Renal
? Respiratory

2
Case report 1

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? A patient with a history of chronic lung

disease has suffered from emphysema which

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has grown progressively worse over a period

of years. The patient experiences chronic

shortness of breath. Analysis of patient 's

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blood reveals the following PCO2=60 mmHg:

[HCO3] =34mM pH=7.38

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? What could be the diagnosis?

3

Case report 2

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? A man suffering from untreated diabetes

mel itus is admitted to the hospital. Glucose

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and acetoacetate are present in his urine and

he exhibits shal ow breathing. Analysis of his

blood indicates [HCO3-] =16 mM and

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PCO2=30

? The most likely pH of blood is

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4
Relationship of pH to hydrogen ion concentration

5

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Scheme demonstrating the relation between

pH and the ratio of bicarbonate concentration

to the concentration of dissolved CO2.

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6
? What is pH?

? Negative logarithm of H+ concentration in a solution

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? pH Scale:

? Ranges from 0 to 14

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? What is pKa?

? Negative logarithm of dissociation constant

? The pH at which an acid is half dissociated, existing as

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equal proportions of acid and conjugate base.

7

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What is buffer

? A buffer is a mixture of a weak acid and a salt of

its conjugate base that resists changes in pH

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when a strong acid or base is added

to the solution

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.

? Functions of a buffer depends on:

? pH

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? pK

? Salt to acid ratio

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8
? Does the dilution change the pH of a buffer?
? pH of a buffer solution is directly proportional

to the salt acid ratio. Dilution does not change

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the ratio

? Buffer efficiency:
? Maximum when the ratio of acid/base is

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within the range of 10:1 to 1:10

? Over a pH range is equal to pKa?1

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9

Requirement of maintenance of acid

base balance

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? For optimum function of biomolecules :

Enzymes, transport molecules, nucleic acid

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? To avoid disruption of structure and function

of cells

? Several serious health consequences: Acidosis,

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alkalosis

10
Buffer systems

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? 1. Bicarbonate/Carbonic acid buffer systems

? Extra cel ular buffer

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? pK=6.1

? cHCO3-/cdCO2= ?

? 2. Phosphate buffer

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? pK= 6.8

? cHPO4-/H2PO4-=

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? Intracel ular buffer

? 3. Plasma protein and Hemoglobin: Imidazole

group of histidine: pK=7.3

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11

Regulation of Acid-Base balance

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1. Respiratory mechanism

2. Renal mechanism

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Partial pressure of

oxygen and carbon di oxide

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Respiratory Response to Acid-Base

Perturbations

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? responds immediately to a change in acid -base

status

? several hours may be required for the response to

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become maximal

? in the early stage plasma pH decreases
? H+ ions equilibrate slowly across the blood -brain

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barrier, the pH in CSF remains nearly normal

? Stimulated peripheral chemoreceptor induces

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hyperventilation: Plasma pCO2 decreased

?

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? the PCO2 of the CSF decreases immediately

because CO2 equilibrates rapidly across the blood

?brain barrier, leading to a rise in pH of the CSF

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that inhibits the central chemoreceptor

? plasma bicarbonate gradual y fal s because of

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acidosis, bicarbonate concentration and pH in the

CSF wil also eventual y fall

? stimulation of respiration becomes maximal from

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both central and peripheral chemoreceptors.

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Role of

RBC and

Hb

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Role of RBC and Hb

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Renal mechanisms in the regulation of

Acid-Base Balance

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? pH of plasma=

? 7.4

? PH of urine=

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? 6.0

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1. Na+-H+ exchange :

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2. Reclamation of HCO3-

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3. Renal production of Ammonia and

excretion of Ammonium ions

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4. Excretion of H+ as H2PO4-

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Conditions associated with abnormal acid base

status and abnormal electrolyte composition of

the blood

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? Metabolic acidosis
? Metabolic alkalosis
? Respiratory acidosis
? Respiratory alkalosis

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Simple depiction of the body as a two-vat system

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of acid and base

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Metabolic acidosis (Primary

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bicarbonate deficit)

? Decreased plasma HCO3-

? Ratio of cHCO 3- /cdCO 2 is decreased

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Causes

? 1. Production of organic acids that exceeds the

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elimination: Diabetic ketoacidosis

? 2. Reduced excretion of acids: Renal failure,

RTA

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? 3. Excessive loss of bicarbonate:

? Diarrhea (loss of duodenal fluid)

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25

? An alcoholic has come to you with a complaint

of severe vomiting. His blood test reveals pH

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7.42 and HCO3- 25 mmol/L,

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Simple depiction of normal gap, anion gap acidosis,

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and nonanion gap acidosis.

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Increase in anion gap

Methanol

Uremia

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Diabetic ketoacidosis

Paraldehyde

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Iron, Isoniazid, Ibuprofen

Lactic acidosis

Ethylene glycol, Ethanol

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Salicylates, starvation ketoacidosis

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? Methanol:

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? Metabolized by the liver to formaldehyde and

formic acid

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Alcohol

Serum Anion Serum Urine

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osmol Gap

acetone oxalate

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gap

Ethanol

+

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----

-----

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-----

Methanol +

+

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-----

-----

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Isopropanol +

---

+

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----

Ethylene

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+

+

-----

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+

glycol

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30
Osmol gap

? OSMg = OSMm - OSMc

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The diff erence between the actual osmolality (OSMm),

measure by freezing-point depression, and the calculated

osmolality (OSMc).

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? OSMc (mOsm/kg) = 2 Na (mmol/L)

+ glucose (mg/dL) /18

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+ urea (mg/dL) /2.8

? presence of unmeasured osmotically active substances:

Volatile alcohols: methanol, isopropanol , ethylene glycol

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31

Uremia or renal failure

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? (1) decreased ammonia formation,
? (2) decreased Na+-H+ exchange, and
? (3) decreased GFR.
? All result in decreased acid excretion.
? Acidosis usually develops if GFR falls below

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20 mL/min.

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Diabetic ketoacidosis

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? -hydroxybutyrate and 2-oxoglutarate

accumulate

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? decrease in HCO3- and a high anion gap
? Ketoacids also accumulate in states of

starvation and alcoholic malnutrition

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Paraldehyde toxicity

? after chronic paraldehyde ingestion

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? -hydroxybutyric acid
? Patients with paraldehyde toxicity have a

pungent, apple-like odor to their breath

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.

34
Isoniazid, Iron, or Ischemia (" Three I's")

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? accumulating organic acids with a predominance

of lactic acid

? production of toxic peroxides that act as

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mitochondrial poisons and interfere with normal

cel ular respiration

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? Ischemia results in anaerobic metabolism with

accumulation of organic (mainly lactic) acids.

35

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Lactic acidosis

? Derived mainly from muscle cells and erythrocytes
? end product of anaerobic metabolism and is normally

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metabolized by the liver

? An increase in the concentration of lactate to >3 mmol/L with

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the associated increase in H+ is considered lactic acidosis

? caused by severe tissue hypoxia is seen in

(1) severe anemia, (2) shock, (3) cardiac arrest, and (4)

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pulmonary insufficiency

? Treatment: origin of lactate (e.g., seizure, hypoxic

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tissue) is rectified : rapidly metabolized to CO2, which then

is eliminated

36

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Ethylene glycol

? metabolized primarily to glycolic and oxalic acid s
? lead s to an acidosis with high anion and osmolal

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gaps

? Precipitation of calcium oxalate and hippurate

crystals in the urinary tract may lead to acute renal

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failure

? Patients develop a variety of neurologic symptoms

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that may lead to coma

37

Salicylate Intoxication

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? blood salicylate concentrations above 30 mg/L
=acidosis develops
? Salicylate, itself an unmeasured anion
? Alters peripheral metabolism, leading to the

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production of various organic acids

? stimulates the respiratory center to increase

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the rate and depth of respiration

? mixed respiratory alkalosis and metabolic acidosis.

38

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Normal anion gap acidosis

? Difference between high and normal anion gap acidosis

? high anion gap acidosis= bicarbonate

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is consumed from buffering excess H+

? normal anion gap acidosis= loss of bicarbonate-rich

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fluid from the kidney or the gastrointestinal tract :

more Cl- ions are reabsorbed with Na+ or

K+ to maintain electrical neutrality so that

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hyperchloremia ensues

39

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? Normal anion gap acidosis is divided

into (1) hypokalemic, (2) normokalemic, and

(3) hyperkalemic acidosis

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40
? Normal anion gap acidosis with Hypokalemia:
? Gastrointestinal loss
? RTA

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Gastrointestinal loss

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? Diarrhea may cause acidosis as a result of loss

of (1) Na+, (2) K+, and (3)HCO3-

? water, K+, an HCO- 3 in the intestine are not

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reabsorbed ,

? The resulting hyperchloremia is due to

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replacement of lost bicarbonate with Cl-

? a hypokalemic, normal anion gap metabolic

acidosis develops

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42
Renal tubular acidosis, Type I and I

? Loss of bicarbonate due to decreased tubular

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secretion of H+ = distal or type I R TA

? Decreased reabsorption of HCO3-= Proximal or

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type I RTA

? proximal and distal RTAs may be differentiated by

measurement of urine pH after administration of

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acid :

? proximal R TA, urine pH becomes <5.5, whereas

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in distal RTA, the distal tubules are compromised

and urine pH is >5.5

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? Hyperkalemic normal Anion gap Acidosis: RTA type IV

? (1) Failure of the kidneys to synthesize renin,

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(2) Failure of the renal cortex to secrete aldosterone,

and

(3) renal tubular resistance to aldosterone.

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? inhibits Na+ reabsorption, and both K+ an H+ are thus

abnormal y retained .

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? decreased renal ammonia formation and therefore

decreased elimination of H+.

44

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Normal Anion Gap

GI fluid loss

Severe diarrhoea

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Hypokalemia

Pancreatitis

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K+ variable

Renal tubular acidosis

Proximal (type I ) R TA

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Urine pH <5.5 , K+ normal or low

Distal (typeI) R TA

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Urine pH >5.5 with hypokalemia

Type IV R TA

Urine pH < 5.5 with hyperkalemia

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Compensation

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? Primary compensation: respiratory system

? Stimulation of RS (Kussmaul respiration )

(1) the elimination of carbonic acid as CO2,

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(2) a decrease in PCO2 (hypocapnia), and

(3) ultimately a decrease in cdCO2.

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? Secondary compensation : by Kidney: takes 2-3 days

? increased excretion of acid and preservation of base by

an increase (1) rate of Na+-H+ exchange, (2) ammonia

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formation, and (3) reabsorption of bicarbonate

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Decrease in Anion Gap

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Laboratory error

1.Increase in unmeasured cations

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2.Lithium intoxication

3.Increased immunoglobulin

4.Monoclonal gammopathies

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5.Nephrotic syndrome

6.Hyperlipidemia

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47

Metabolic alkalosis

? (1) excess base is added to the system,

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? (2) base elimination is decreased ,

? or (3) acid -rich fluids are lost

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? Al lead to a primary bicarbonate excess

? alter the cHCO-3 / cdCO2

patient wil hypoventilate to raise PCO2

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? achieving a PCO2 =55 mm Hg

? Above pH 7.55, tetany may develop:

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? cause of the tetany is a decrease concentration of

ionized calcium due to increase binding of calcium ions

by albumin as H+ ions decrease

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? metabolic alkalosis all into
? (1) Cl- responsive,
? (2) Cl- resistant, and

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? (3) exogenous base categories

49

1. Cl- Responsive Metabolic Alkalosis

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? Occur as a result of hypovolemia
? contraction alkalosis
? Hypovolemia wil result in
? (1) increase reabsorption of Na+,

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? (2) increase HCO- 3 absorption and
? (3) excretion of K+ and H+.
? Urine Cl- wil be less than 10 mmol/L, as both the

available Cl- an HCO3 - are reabsorbed with Na+

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? Common causes of contraction alkalosis

include

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? prolonged vomiting or

? nasogastric suction and

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? the use of certain diuretics

? Treatment consists of replacing BW with

? (1) water, (2) NaCl tablets, or

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? (3) saline in fusion.

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2. Cl- Resistant Metabolic Alkalosis

? far less common than Cl- responsive MA
? Associated with:
? (1) primary hyper aldosteronism,

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? (2) Cushing syndrome, or
? (3) Bartter syndrome, or with excess addition

of exogenous base.

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? urine Cl- will be greater than 20 mmol/L.

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adrenocortical excess

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? K+ an H+ are "wasted " by the kidneys
? increased Na+ reabsorption stimulated by

elevated aldosterone or cortisol

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? hypokalemia often further contributes to the

alkalosis

? stimulates NH3 production and thus renal H+

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excretion as NH 4+

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3. Exogenous Base

? include (1) citrate toxicity following massive

blood transfusion,

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(2) aggressive intravenous therapy with

bicarbonate solutions, and

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? (3) ingestion of large quantities of antacids

(Milk alkali syndrome)

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Conditions leading to Metabolic Alkalosis
Chloride responsive (Urine Cl- < 10 mmol/L)

Contraction alkalosis (Hypovolemia)

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Prolonged vomiting

Upper duodenal obstruction

Dehydration

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Chloride resistant (Urine Cl- > 10 mmol/L)

Mineralocorticoid Excess

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Primary hyperaldosteronism

Bilateral adrenal hyperplasia

Secondary hyperaldosteronism

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Glucocorticoid excess

Primary adrenal adenoma

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Pituitary adenoma secreting ACTH

Exogenous cortisol therapy

Bartter syndrome (defective renal Cl- absorption )

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Exogenous base

Bicarbonate containing iv fluid therapy

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Massive blood transfusion ( Sodium citrate overload)

Milk Alkali syndrome

55

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Compensatory Mechanisms in

Metabolic Alkalosis

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? both respiratory compensation and , if

physiological y possible, renal compensation

? Respiratory compensation:

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? Th e increase in pH depresses the respiratory

center,

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? causing retention of carbon dioxide

? increase in cH2CO3 and cdCO2

? ratio of cHCO- 3 / cdCO2, which was

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original y increased , approaches its normal value

56
Renal compensation

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? The kidneys respond to the state of alkalosis

by

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? decrease
(1) Na+-H+ exchange,
(2) formation of ammonia,
and (3) reclamation of bicarbonate
? This response is blunted in conditions of

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hypokalemia and hypovolemia.

57

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Respiratory acidosis

? occurs only through decreased elimination of CO2

? increase in PCO2 (hypercapnia) an dCO2

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? decrease in the cHCO3 - / cdCO2 ratio (e.g., the ratio may be

28:1.7 [16:1] or a pH of 7.30 )

? conditions may be divided into those caused by factors that

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? directly depress the respiratory center
? mechanical obstruction of the airways

? Chronic obstructive pulmonary disease (COPD) is the most

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common cause

58
Conditions leading to Respiratory Acidosis

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Factors that directly depress the respiratory centre

Drugs such as narcotics

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CNS trauma, tumor

Infections of the CNS

Comatose states

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Conditions that affect the Respiratory apparatus

COPD (most common)

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Severe pulmonary fibrosis

Disease of the upper airway e,g laryngospasm, tumor

Impair lung motion due to pleural effusion

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ARDS

Others Abdominal distension as in peritontitis and ascites

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Extreme obesity

Sleep disorder, sleep apnea

59

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Compensatory mechanism

? Immediately via buffers

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? Over time via kidneys

? Excess carbonic acid present in blood is bufferd

by the hemoglobin and protein

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? Buffering of CO2 causes a slight rise in cHCO3-

? immediate post hypercapnic state appear as a

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metabolic alkalosis

60
Response of Kidney for respiratory

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acidosis

? similarly to the way that they responds to metabolic acidosis
? Increase in
(1) Na+-H+ exchange,

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(2) ammonia formation,

and(3) reclamation of bicarbonate
? Partially compensated= the plasma pH is returned about half

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way toward normal

Not effective before 6 to 12 hours and is not optimal until 2

to 3 days.

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COPD= full renal compensation

? COPD with superimposed metabolic alkalosis due to

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prolonged diuretics

61

Respiratory response for respiratory

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acidosis

? stimulates the respiratory center
? Increase pulmonary rate and depth of respiration,

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provided that the primary defect is not in the

respiratory center

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? Elimination of carbon dioxide through the lungs

results in a decrease in c CO2;

62

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Respiratory Alkalosis

? decrease in PCO2 (hypocapnia) and the resulting

primary defcit in cdCO2

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? increased rate and /or depth of respiration

? excess elimination of acid via the respiratory route

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? increase in the cHCO3-/ cdCO2 ratio.

? shifts the normal equilibrium of the

bicarbonate/carbonic acid buffer system

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? reducing the hydrogen ion concentration and

increasing the pH

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? Also results in a decrease in cHCO3-

63

? causes of respiratory alkalosis have been

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classified as

? those with a direct stimulatory effect on the

respiratory center

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? and those due to effects on the pulmonary

system.

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64
Factors causing respiratory Alkalosis

Nonpulmonary stimulation of respiratory center

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Anxiety, hysteria

Febrile state

Metabolic encephalopathy

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CNS infection

Cerebrovascular accident

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Hypoxia

Drugs and agents such salicylates, cathecholamines

Pulmonary disorder

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Pnemonia

pulmonary emboli

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Interstitial lung disease

CHF

Respiratory compensation after correction of metabolic acidosis

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Others Ventilation induced hyperventilation

65

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Compensatory mechanisms for

respiratory alkalosis

? respond in two stages

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? 1st stage: erythrocyte and tissue buffers

provide H+ ions that consume a small amount

of HCO3-

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? 2nd stage: in prolonged respiratory alkalosis:

renal compensation as metabolic alkalosis

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ABG parameters in various conditions

of acid-base imbalance

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Imbalance

Stage

pH

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HCO3

pCO2

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Metabolic

Uncompensated

<7.3

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Low

Normal

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acidosis

Compensated

Approx 7.35

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Low

Low

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Respiratory Uncompensated

<7.3

Normal

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High

acidosis

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Compensated

Approx 7.35

High

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High

Metabolic

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Uncompensated

>7.5

High

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Normal

alkalosis

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Compensated

Approx 7.45

High

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High

Respiratory Uncompensated

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>7.5

Normal

Low

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alkalosis

Compensated

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Approx 7.45

Low

Low

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67

Summary

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? According to Broensted and Lowry: An acid is defined as a substance , ion

or molecule that yields H+ in sollution and base is an ion , molecule or

substance that can combine with H+ ions.

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? Human body produces volatile acids( Carbonic acid) and nonvolatile acid (

Sulfuric acid and lactic acid).

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? Buffers are the solution that resist the change in pH on addition of acid or

base.

? The pH of blood is maintained in a narrow range around 7.35-7.45 by

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extracellular and intracellular buffering.

? The carbonic-biocarbonate system is the major buffering system.
? The partial pressure of CO2 in blood is 40 mmHg

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? The pCO2 is regulated by respiratory system.
? The phosphate buffer system (Na2HPO4/NaH2PO4) operates in the cell

and contributes to only about 1% of the plasma buffering capacity.

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68
Summary contd

? Histidine is the most effective amino acid that helps proteins to

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work as buffer. Albumin has 16 and Hemoglobin has 38 histidine

residues.

? Kidneys play a very important role in the regulation of extracel ular

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pH through reabsorption of bicarbonate and secretion of H+,

synthesis and excretion of ammonia.

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? The clinical disorder associated with accumulation of acids in the

tissue and plasma is known as acidosis whereas the build up of

alkali in the body is known as alkalosis.

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? The respiratory acidosis is seen in cases of pulmonary diseases such

as COPD.

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? Metabolic alkalosis occurs as a result of net gain of HCO3- or loss of

nonvolatile acid

? Assessment of the acid-base imbalance is done by estimation of the

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arterial blood pH , cHCO3- and pCO2 along with electrolytes

69

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MCQ 1

? A 64 years old man who develops acute renal failure

while recovering from myocardial infarction. Blood

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chemistry reveals Na+140 meq/L , K=4 meq/L , Cl- 115

meq/L , Co2 =5 meq/L , pH 7.12 , paCO2=13 mm Hg

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, HCo3-=4 meq/L

? A. His anion gap of 14 indicates metabolic acidosis

? B. His anion gap of 20 conclusive of respiratory acidosis

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? C. His anion gap of 22 strongly suggestive of metabolic

alkalosis

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? D. His anion gap of 21 indicative of high anion gap

metabolic acidosis

70

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MCQ2

? A 48 year old man with bronchiectasis presents to the

hospital emergency room with 3 days of increasing

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cough, sputum and dyspnea.About 1 month ago his

blood analysis report showed pH 7,38, paO2 55 mmHg,

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HCO3- 32 meq/L. His current vital signs are BP117/65,

pulse 123/min, temp 100oF,. His current ABG in the

emergency room pH 7.28, paCO2 70 mmHg, paO2 50 ,

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HCO3- 23 meq/L. Which of the following best

characterizes the acid base status of this patient?

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? A. Compensated metabolic acidosis

? B. Compensated metabolic alkalosis

? C. Uncompensated metabolic acidosis

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? D. Uncompensated respiratory acidosis

71

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MCQ3

? A 50 year old chronic alcoholics brought to the

emergency room in semiconscious state. BP was

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100/50 and Heart rate 120/min, Resp rate 35/min,

temp 104oFBlood chemistry: Na+= 150 meq/L, K+2.5

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meq/L, Cl- 107 meq/L, HCO3- 10 meq/L, pH 7.2,pCO2

=25 mmHg, Alcohol 40 mmol/L (0), Osmolality 370

mOsm/L (280-295), glucose 50 mg/dl, BUN 50 mg/dl

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(5-22)What is the acid base status?

? A. Metabolic acidosis

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? B. Metabolic acidosis with resp compensation

? C. Metabolic alkalosis

? D. Metabolic alkalosis with resp comp

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72
MCQ4

? Which of the following is most appropriate for a

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17 year old female suffering from IDDM with the

following blood chemistry report:

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? pH 7.2, pO2 108 mmHg, pCo2 12 mmHg, HCO3- 5

meq/L

? A. Metabolic acidosis with resp compensation

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? B . Metabolic alkalosis with respiratory

compensation

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? C. Metabolic acidosis

? D. Metabolic alakalosis

73

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