Blood Chemistry….

Cont’d

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Magnesium 1.4–1.8 mEq/L
Magnesium is primarily an intracellular electrolyte
Maintain a neutral charge within the cell with potassium and calcium
serves an important metabolic role in the phosphorylation of ATP
Hypomagnesemia
Primary cause …..malnourishment.
Toxemia(Preeclampsia) in pregnancy
Needs to be corrected before attempting to correct hypokalemia
or hypocalcemia.
Attempts to replace K+ or Ca2+ in patients with hypomagnesemia
will be ineffective until the low magnesium concentrations are
adequately addressed.
It may lead cardiac arrhythmia (Torsade De Points QT
prolongation)
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Magnesium 1.4–1.8mEq/L
Hypermagnesemia
Excessive ingestion of magnesium-containing antacids
In patients with reduced renal function.
 can slow conduction in the heart, prolong PT intervals, and
widen the QRS complex

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Phosphate: 2.6–4.5 mg/dL

The intracellular phosphate is the source of phosphate

for ATP, phospholipid synthesis and in the regulation of
nucleotide degradation.
The ECF concentration of phosphate is influenced by
 parathyroid hormone
intestinal phosphate absorption
 renal function
bone metabolism, and
 nutrition

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 Phosphate: 2.6–4.5 mg/dL
Hypophosphatemia is encountered by
 malnourished patients
patients who excessively use antacids (aluminum-containing antacids bind phosphorus in
the GI tract)
 chronic alcoholics, and
 septic patients
Clinical consequences of severe hypophosphatemia involve
nervous system dysfunction
muscle weakness
 rhabdomyolysis
cardiac irregularities
 dysfunction of leukocytes and erythrocytes.
 Hyperphosphatemia is most commonly caused by
renal insufficiency
increased vitamin D
hypoparathyroidism
advanced malignancies
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 Carbon Dioxide Content (22–28 mEq/L)
The CO2 content in the serum represents

the sum of HCO3 and dissolved CO2 in the serum.

The dissolved CO2 represents a relatively small component of

total CO2 content, making CO2 essentially a measure of the

bicarbonate concentration in serum.
• PCo2 (gas) not the same as serum CO2 content

• CO2 is a base with bicarbonate controlled by kidney

• PCO2 is acid and regulated by the lungs

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Carbon Dioxide Content (22–28 mEq/L)
Chloride and bicarbonate are the primary negatively
charged anions that offset the positively charged cations
Although several buffer systems (e.g., hemoglobin
[Hgb], phosphate, protein) participate in regulating pH
within physiological limits, the carbonic acid–
bicarbonate system is the most important.
 Most disturbances of acid–base balance result from
imbalances of the carbonic acid-bicarbonate system.

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 Chloride (95–105 mEq/L)
Chloride is the principal inorganic anion of the ECF
changes in chloride concentration are usually related to
sodium concentration in an effort to maintain a neutral charge.
The serum chloride concentration has no real diagnostic
significance
In fact, the only real reason for measuring the serum chloride
is to validate the serum sodium concentration.
The relationship between serum concentrations of sodium,
bicarbonate, and chloride is described by following Equation,
where R represents the anion gap:
Cl− + HCO3 − + R = Na+

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 Chloride (95–105 mEq/L)
As with bicarbonate, Cl- contributes to maintaining acid–base
balance.
A decreased serum in [Cl-] often accompanies metabolic alkalosis,
An increased serum in [Cl-] may be indicative of a hyperchloremic
metabolic acidosis.
 However, it can also be slightly decreased in acidosis if organic acids
or other acids are the primary cause of the acidosis.
 Hyperchloremia, in the absence of metabolic acidosis, is seldom
encountered because chloride retention is usually accompanied by
sodium and water retention.
Hypochloremia can result from
 excessive GI loss of chloride-rich fluid (e.g., vomiting, diarrhea, gastric
suctioning, intestinal fistulas)
significant diuresis.
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 Anion Gap (R)
The anion gap represents the contribution of unmeasured acids, such as
lactate, phosphates, sulfates, and proteins.
A patient’s anion gap is determined by subtracting the primary anions (Cl–
and HCO3 –) from the primary cation (Na+).
Some clinicians include potassium in this determination and subtract the
anions from both major cations (Na+ and K+).
A normal anion gap is typically 5 to 12 mEq/mL if potassium is not
incorporated in the calculation or less than 16 mEq/mL if potassium is
considered.
An elevated anion gap may be indicative of a metabolic acidosis caused by
an increase in lactic acids, ketoacids, salicylic acids, methanol, or ethylene
glycol.
A low anion gap may be the result of reduced concentrations of
unmeasured anions (e.g., hypoalbuminemia) or from systematic
underestimation of serum sodium (e.g., hyperviscosity of myeloma).
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ORGAN FUNCTION TESTS

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Cardiac Biomarkers
1. Markers of Myonecrosis
Cardiac troponin (cTn)
Creatinine kinase MB (CK-MB)
Myoglobin
2. Markers of Inflammation
C-reactive protein (CRP)
Homocysteine
3. Markers of Hemodynamic stress
B-type natriuretic peptide (BNP)
N-terminal proBNP (NT proBNP)

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 A. Markers of myonecrosis
Proteins released from a recently necrotic myocytes into the blood (e.g. MI)
1. Cardiac troponins (cTn)
Troponins are proteins that regulate the calcium-mediated interaction of actin and
myosin within muscles.
There are two cardiac-specific troponins, cardiac troponin I (cTnI) and cardiac
troponin T (cTnT).
Whereas cTnT is present in cardiac and skeletal muscle cells, cTnI is present only in
cardiac muscles

Troponin I<0.12 ng/mL

Troponin T<0.01 ng/mL
Detected in the blood 2 to 4 hours after the onset of MI symptoms
Remains detectable for 5 to 10 days
Troponin I is the most sensitive & tissue-specific biomarkers

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A. Markers of myonecrosis
2. Creatine kinase (CK-MB)
Creatine kinase, formerly known as
References
creatine phosphokinase, catalyzes Men: 38–174 U/L
the transfer of high-energy Women: 26–140 U/L
phosphate groups in tissues that
consume large amounts of energy Isoenzymes
(e.g., skeletal muscle, myocardium, 1. MM (CK-3): 96%–100%
brain).
2. MB (CK-2): 0%–6%
Best alternative marker to cTn
Detected in the blood 2 to 4 hours 3. BB (CK-1): 0% or 0.00
after MI symptom onset
Peaks within 24 hours, and remains
detectable for 48 to 72 hours.
 Recurrent infarction 14
 A. Markers of myonecrosis
3. Serum myoglobin (5-7ng/ml)but less specific for myocardial
Myoglobin, a protein in heart and injury compared with CK-MB.
skeletal muscle cells, provides Used for early exclusion of
oxygen to working muscles. myocardial infarction
 If combined with a more specific
 When muscle is damaged, marker

myoglobin is released into the Generally, markers of

blood myonecrosis;
Released within 1 hour following 1. Aid in diagnosis of MI as the cause
of chest pain
onset of myonecrosis 2. Facilitate triage and risk stratification
A very early marker of 3. Allocate for specific therapeutic
myocardial infarction strategies

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 B. Markers of inflammation
C-reactive protein (CRP) [0–1.6 mg/dL]
a nonspecific, acute-phase reactant helpful in the diagnosis and
monitoring of inflammatory processes
 e.g., MI, rheumatoid arthritis and infections.
 CRP is produced by the liver in response to an inflammatory process.
CRP is similar to an older test, the erythrocyte sedimentation rate
(ESR), but it tends to be more sensitive than ESR and is also associated
with a more rapid and greater response to acute inflammation.
A more sensitive test for CRP is now available and is referred to as
high-sensitivity CRP (hs-CRP)
The hs-CRP test measures the same acute-phase reactant, but it is able
to detect much lower levels of CRP,
 making it useful for early detection of patients at risk of cardiovascular diseases.
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 B. Markers of inflammation
C-reactive protein (CRP)
Indicates risk of future vascular events
A. hs-CRP >3 mg/L -increased risk

B. Between 1 and 3 mg/L intermediate risk.

C. hs-CRP <1 mg/L - low risk.
Serum concentrations >10 mg/L
 Caused by an acute or chronic systemic illness.
A reasonable choice for risk stratification for additional prognostic
in ACS

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 B. Markers of inflammation
Homocysteine (5–15 μmol/L)
An amino acid typically present in very small amount in all
cells of the body.
It is converted into other products quickly by vitamins B6,
B12 and folate
Increase in homocysteine is usually due to deficiencies in
folate, vitamin B6, and vitamin B12.
High level damages blood vessels, which may increase the
risk for cardiac disease
e.g. Coronary heart disease, stroke, blood clots…

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 C. Markers of hemodynamic stress
 Normal value:
Natriuretic peptides  BNP <100 pg/mL
Released from ventricular  NT-proBNP <400 pg/mL
myocytes when increased Elevated in patients with an acute
demands are placed on the coronary syndrome
myocardial tissue  Elevations in BNP….congestive
heart failure.
Sub types
 In an effort to reduce workload on
1. B-type natriuretic peptide the heart,
(BNP)  BNP counteracts the RAAS

2. N-terminal pro-brain  causes vasodilatory effects,

natriuretic protein (NT- along with natriuresis

(increased excretion of sodium)
proBNP)
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C. Markers of hemodynamic stress

Patients with some degree of CHF typically have BNP

levels greater than 100 ng/L.
BNP levels greater than 500 ng/L represent definite left
ventricular dysfunction, and further evaluation is warranted
to more fully characterize the extent of impaired cardiac
function
More recently, the N-terminal proBNP (NT-proBNP) is a
component of BNP being used in the clinical setting to a
greater extent.

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Liver function tests

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 Liver functions tests
· Have many applications in 3. Used to monitor the

patient care : progression of a

disease such as viral
1. Provide a noninvasive
or alcoholic hepatitis
method to screen for the
presence of liver disease 4. Reflect the severity of
liver disease,
2. Used to measure the safety/
[cirrhosis].
efficacy of treatments for
liver disease
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Liver diseases tests
· The liver contains thousands of enzymes.
 Elevation of an enzyme activity in the serum primarily
reflects release from damaged liver cells.

Elevation of serum enzyme tests can be grouped into

two categories:
 Enzymes that reflect generalized damage to hepatocytes

 Enzymes that reflect cholestasis

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Information obtained from liver
function analytes
 ALT (0-35 IU/L)
Alanine Aminotransferase (ALT)
Formerly called Serum glutamic-pyruvic Use
transaminase [SGPT] To identify liver
More specific for liver-related injuries inflammation and
or diseases necrosis
Location: Results >20 x ULN
® Microsomal portion of hepatic cells
usually indicate hepatic
Although ALT is relatively more abundant
injury
in hepatic tissue versus cardiac tissue than
AST, the liver still contains 3.5 times more Elevation lasting 6
AST than ALT. months or more indicate
 More specific to hepatic injury chronic or persistent
Low concentration hepatitis
 Kidney and skeletal muscle
 Concentration not significantly increase following
acute Myocardial Infraction(MI) (ULN=Upper limit of Normal)
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 ALT (0-35 IU/L)
® ALT to AST ratio

1. Alcoholic hepatitis AST exceeds ALT (ratio>2:1 in 92%

cases)

2. Acute /viral hepatitis ALT exceeds AST

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 AST (0– 35IU/L)
Asparate Aminotransferase (AST)
Formerly called Serum-glutamic
oxaloacetic transaminase (SGOT)
Released during acute liver injury
Increased in liver disease, but also
in heart attacks
Location:
 Hepatic cell mitochondria
 Heart and liver (high conc.)
 Epidermis of the skin, skeletal
muscle, pancreas, and kidney
Increased
 Ethanol
 Fulminant viral Hepatitis
 >95% of patients after an MI
o After 4-6hours of MI onset
o Peak 24-36hr
o Normalized 4-5days
 Moderately elevated in
 Intrahepatic cholestasis, post
hepatic jaundice, or cirrhosis
 AST and ALT
 Elevated about 100xULN in
parenchymal liver disease
 AST > ALT in cirrhosis
 4-5 ULN
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 AST (0– 35IU/L)
Used Could be falsely elevated
 Acetaminophen
To evaluate
 Levodopa
myocardial injury  Methyldopa
To diagnose and  Tolbutamide
assess the prognosis  Erythromycin
of liver disease  Diabetes
resulting from
hepatocellular injury.

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 ALP (30–120 units/L)
Alkaline Phosphatase Elevated serum concentrations ALP
 Mild intrahepatic or extra hepatic biliary
Large group of isoenzymes
obstruction
 Roles in the transport of sugar
and phosphate
Markerof early bile duct
Originates: abnormalities
 Elevation of serum ALP level is a
 80% in liver and bones sensitive indicator of cholestasis
® Primarily produced here
 placenta, intestine
ALP secreted into bile
 Biliary ductile cells increase
synthesis

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 ALP (30–120 units/L)
Useful for
Diagnosing hepatobiliary and
bone disease
®Diagnosis, screening, and
follow-up of
o Cholestatic, hepatobiliary lesions
and osteoblastic bone diseases
 Seldom elevated
Mild cases of acute liver cell
damage
In cirrhosis, variable and depend on
the degree of hepatic
decompensation and obstruction
Markedly elevated
Paget disease of the bone,
® Osteogenic sarcoma,
osteoblastic cancer
metastatic to bone, and
conditions of pronounced
osteoblastic activity
® Hyperparathyroidism
Drug-induced cholestatic
jaundice
 Chlorpromazine or
sulfonamides
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 ALP (30–120 units/L)
Physiologic elevations
1. During rapid bone growth
 Infancy, early childhood, healing bone fractures
2. During pregnancy
 Placenta and foetal bones play a role.

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ALP (30–120 units/L)

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 Gamma-glutamyl transferase (GGT)
Normal: 0–70 units/L Parallels the increase of ALP
Found in the kidney, liver, in obstructive jaundice and
infiltrative liver disease
and pancreas
 More sensitive liver enzymes for
 Major clinical value is in the
identifying biliary obstruction
evaluation of hepatobiliary
and cholecystitis.
disease
Increased ALP in the presence
Role
of a normal GGT
 Regulates transport of amino
 More suggestive of muscular
acids across cell membranes by
catalyzing the transfer of a or bone-related issues.
glutamyl group from glutathione
to a free amino acid

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Gamma-glutamyl transferase (GGT)
GGT is a hepatic GGT is a sensitive indicator
microsomal enzyme of recent or chronic alcohol
Increase in response to exposure.
 GGT/ALT ratio > 2.5 is highly
 Microsomal enzyme induction
indicative of alcohol abuse
1. Alcohol  Abstinence may lead to the ratio
2. Drugs like to go down by 50% in 2 weeks
 Carbamazepine Increase in AST without GGT
 Phenobarbital is due to non-hepatic origin
Phenytoin

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Gamma-glutamyl transferase (GGT)
Increase Decrease
Hepatitis (acute and chronic)  Hypothyroidism
Cirrhosis (obstructive and Remain normal
familial) Bone disorders
Liver metastasis and
Bone growth
carcinoma
Pregnancy
Cholestasis (especially
Skeletal muscle disease
during or following
pregnancy) Strenuous exercise
Chronic alcoholic liver Renal failure
disease, alcoholism
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 LDH (<200IU)
Lactate Dehydrogenase Five isozymes
Present in Although most tissues
Heart, kidney, liver, and skeletal
contain all some tissues
muscle
Also abundant in erythrocytes have a predominance
and lung tissue Heart:
Diagnostic usefulness is  LDH1 and, to a lesser
somewhat limited. extent, LDH2
 Implies disease in many organ Skeletal muscle and liver
tissues
 Markedly elevated level >
LDH5
1000 IU/L is usually associated
with acute diseases

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 LDH (<200IU)
Lungs, RBCs, kidneys,
brain, and pancreas
LDH3 and LDH4
Identifying specific
isoenzymes can increase
the diagnostic usefulness
Example:
® Myocardial Infraction -
LDH1 and LDH2
Acute liver disease
 LDH4 and LDH5
Problem??
Isoenzyme patterns are
not necessarily typical of
all myocardial or liver
Hence, used less
frequently, as a
diagnostic tool
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Bilirubin
38
 Bilirubin
What is bilirubin?
o it is waste product of haemoglobin breakdown

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 Bilirubin
RBC destruction Iron
Protein Urine
HEME 1-4mg of urobilinogen
excreted in the urine per day
Unconjugated bilirubin
Systemic circulation
A small portion of urobilinogen formed
Liver reaches the circulation and is excreted
Unconjugated bilirubin is conjugated through the kidney into the urine
with glucuronic acid by the action of
glucuronyl transferase to form conjugated bilirubin Enterohepatic circulation
20% of urobilnogen formed in the GI
tract will be absorbed and recirculated to
Intestine the liver and reexcreted in the feces
Conjugated bilirubin is reduced by
bacteria in the GI tract to urobilinogen

Feces
50-250mg of urobilinogen
excreted per day
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 Bilirubin (total)-0.1-1mg/dl
Sum total of 2. Unconjugated
(indirect) bilirubin
1. Conjugated (direct)
Circulates freely in the
 Conjugated with
blood until it reaches the
glucuronide transferase
liver
and then excreted into
the bile

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 Bilirubin (total)-0.1-1mg/dl
Elevated in
1. Hepatocellular jaundice
from injury or disease of the
parenchymal cells of the
liver caused by :
 Viral hepatitis
 Cirrhosis
 Drug
reactions:
(chlorpromazine)
2. Obstructive jaundice
 Obstruction of the common
bile or hepatic ducts due to
stones or neoplasms
3. Haemolytic jaundice
 Overproduction of high levels
of unconjugated bilirubin
 After many units of blood
transfusions,
 Pernicious anaemia
 Sickle cell anaemia
 Transfusion reaction
 Erythroblastosis fetalis
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Bilirubin (total)-0.1-1mg/dl
® Erythroblastosis fetalis
• RH- mother antibodies
• RH+ new born
• Hemolytic disease of new born

by
ba
d
ce
di
un
Ja

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Bilirubin (direct)-0-0.2mg/dl
Transferred to the  Elevated :
• Cancer of the head of the
blood pancreas
 Mechanism?

Serum concentration
increased in many liver
disease
Begin to appear in urine if
 Concentration exceeds 0.2 to
0.4 mg/dL

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 Bilirubin (indirect)
Characterized by  Tend to be elevated
 Neonatal jaundice
1. Water insoluble
 Hemolytic anaemia due
2. Highly bound to serum
to a large hematoma
albumin
 Trauma in the presence
Both factors account for
of a large hematoma
its lack of excretion in  Haemorrhagic

the urine pulmonary infarcts

45
 Albumin (3.3 – 4.8g/dL)
Produced entirely by the liver 3. Loss
 Role  Haemorrhage, exudates,
 About 80% to serum colloid nephrotic syndrome or
osmotic pressure intestinal (GI) loss, severe
Decreased infections/inflammation,
1. A lack of essential amino severe burns/skin disease
acids from Low serum albumin lead to:
 Malnutrition or
 Transudation of ECF
malabsorption,
alcoholism
 Peripheral oedema, ascites, and
pulmonary oedema
2. Impaired albumin  Can affect concentration of drugs;
synthesis phenytoin, salicylates, and calcium
 Cushing’s disease, thyrotoxicosis

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 Albumin (3.3 – 4.8g/dL)
 Interfering conditions
Albumin is decreased in:
1. Pregnancy
 Last trimester, owing to increased plasma volume
2. IV fluids
3. Rapid hydration, over hydration

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 Albumin (3.3 – 4.8g/dL)

 Albumin is the first one to decrease

during acute liver illness??

® Remains normal in acute illness

(t ½ = 20 days)

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 Miscellaneous Tests
Amylase (35–120 units/)
• Breaks starch into glucose
• Produced by salivary gland and • Increased:
pancreas
• Tests for Pancreatic Diseases
• Mostly used in diagnosis of
acute pancreatic disease
• Rise in 2-6 hrs; peaks 12-30
hrs; returns to normal 3-5
days
• acute pancreatitis,
pancreatic duct obstruction,
alcohol ingestion, renal
disease, cholecystitis, peptic
ulcers, intestinal
obstruction,
• Decreased: Liver damage,
pancreatic destruction
(pancreatitis, cystic fibrosis)
 Miscellaneous Tests
Lipase (< 160 IU/L)
• Aids fat digestion

• Has a longer half-life (t ½ = 7-14 hrs vs. 2 hrs for

Amylase)

• Specific to pancreatic diseases

• Lags behind amylase in peak and getting normal

• ↑ acute pancreatitis, elevated for longer period

than amylase.