You are on page 1of 17

Laboratory medicine

Last updated: Nov 14, 2019


QBANK SESSION
CLINICAL SCIENCES
LEARNED

Summary
Laboratory medicine involves the analysis and evaluation of body fluids such as
blood, urine, or CSF, the results of which are important for the prevention, diagnosis,
and staging of diseases. Laboratory medicine plays an important role in daily clinical
practice; however, the evaluation of results should always take into account the
patient's medical history, as well as clinical and diagnostic findings. In addition to the
basics of laboratory medicine, this learning card covers important laboratory
parameters such as liver function tests and iron metabolism. Further parameters of
clinical relevance may be found in other learning cards and are listed in the section
“Overview of important laboratory values”. Current NBME laboratory reference values
can be found under “Tips & Links” below.
FEEDBACK

Overview of important laboratory values


Topics covered in this learning card
 Liver function tests
o Parameters of hepatocellular damage: AST, ALT, GLDH

o Parameters of cholestasis: γ-GT, ALP, bilirubin

o Parameters of hepatic synthesis: albumin, CHE, platelet count

 Kidney function tests


o Urea and uric acid

o Kidney function parameters

 Pancreatic parameters: amylase, pancreatic lipase, elastase

 Electrolytes: chloride, magnesium, phosphate

 Iron metabolism: iron, ferritin, transferrin

Laboratory values covered in other learning cards


 Heart
o Cardiac enzymes
o NT-proBNP (N-terminal pro-B-type brain natriuretic peptide)

 Thyroid parameters
o Hypothyroidism

o Hyperthyroidism

 Urinalysis
o Diagnostic evaluation of the kidney and urinary tract

 Inflammation
o Inflammatory markers

 Carbohydrate metabolism parameters: HbA1c, OGTT, C-
peptide, see “Diabetes mellitus”

 Lipids: See “Lipid disorders”

 Tumor markers

 Blood gas analysis


FEEDBACK

Inflammatory markers
Inflammatory markers are of great diagnostic value because their plasma
concentrations change in different ways depending on the underlying cause.

 Important inflammatory markers
o ↑ CRP

o ↑ Leukocytes (> 11,000/mm ) 3

o ↑ ESR

Erythrocyte sedimentation rate (ESR)


 Description
o The test measures the distance that erythrocytes have fallen
in a vertical tube of anticoagulated blood after one hour.
o Normal values: ♀ 0–20 mm/h and ♂ 0–15 mm/h

 Factors that increase ESR


o Elevated fibrinogen level (infection, inflammation,
malignancy) 
o Pregnancy (↑ fibrinogen)

o Old age

o Anemia, macrocytosis

o Multiple myeloma, Waldenstrom macroglobulinemia

o Autoimmune diseases (systemic lupus


erythematosus, rheumatoid arthritis, giant cell
arteritis, polymyalgia rheumatica, de Quervain thyroiditis)

 Factors that decrease ESR


o Extreme leukocytosis (e.g., in chronic lymphocytic leukemia)

o Polycythemia

o Sickle cell disease 

o Spherocytosis

o Microcytosis

o Hypofibrinogenemia 

o Hypogammaglobulinemia

Acute phase reaction


 The acute phase reaction is the initial response of the
organism to systemic or local disturbances (e.g., operation,
trauma, inflammation, infection, malignancy).

 It provides rapid protection for the host by destroying


pathogens and promoting the healing processes. Part of this
response is the release of more than 30 acute phase reactants,
which are produced in the liver.

 Acute phase reactants are mainly part of the alpha-


1 and alpha-2 zones in serum protein electrophoresis and
cause an increase in these zones during acute inflammation. 

Important acute phase reactants

 C-reactive protein (CRP): promotes opsonization of


pathogens
o Increases the capacity of macrophages to phagocytose

o High sensitivity for detecting inflammation


o In bacterial infections, especially marked increase

o Increases about 6–12 hours after the inflammatory process


begins
o Half-life of 24 hours

o Not specific to any disease or organ

 Ferritin: protein that stores and releases iron


o Serum ferritin levels increase in the case of an infection or
malignancy to reduce the amount of free iron available to
pathogens or tumor cells, respectively. 
o In contrast, some organisms (e.g., Pseudomonas) cause
serum ferritin levels to drop. 

 Fibrinogen → coagulant → wound healing

 α1-Antitrypsin → protection from protease activity

 Serum amyloid A → recruits immune cells to inflammatory


sites

 Haptoglobin
o Antioxidative properties 

o Antimicrobial properties 

o Decreases in hemolysis 

 Procalcitonin: sensitive parameter for following the


progression of bacterial infections, especially for pneumonia,
and sepsis

 Interleukin-6 (IL-6)

 Negative acute phase reactants 

: The most notable are albumin, transferrin, and antithrombin.

To memorize the positive acute phase reactants, think More FFiSH in the C


(sea): More =
upregulation, F = Ferritin, Fi = Fibrinogen, S = Serum amyloid A, H = Haptoglobin, C 
= C-reactive protein.

References: [1][2][3][4][5][6][7][8]

FEEDBACK
Liver function tests
 Liver function tests can be divided into three categories
o Parameters of hepatocellular damage

o Parameters of cholestasis

o Parameters of hepatic synthesis

Parameters of hepatocellular damage


 Relevance
o Damage to hepatocytes results in the release of various
enzymes that are detectable in blood and provide some
indication of the severity of hepatic cell damage.

MAXIMIZE TABLETABLE QUIZ

Laboratory parameter Physiologic Characteristics Frequent


al function causes of
elevation

Transam Alanine  Enzy  Organ-  AST 


inases  aminotransfer me involv specificity and ALT: 
ase (ALT)  ed in all
o ALT is
in glucon types
specific to
eogenesis  of hepato
hepatic cells. 
and the cyte dam
generation o AST is age!
of urea  present in
 Only 
the liver, heart,
AST
muscle,
and erythrocyte o Muscle
s. dama
Aspartate  Enzy ge
aminotransfer me  Subcellular
ase (AST)  involved localization o Myocar
in amino dial
o ALT a
acid infarc
nd AST are
metabolis tion
both present in
m the hepatocyte 
cytoplasm.
o AST is
also present in
the mitochondri
a. 
o AST/A
Laboratory parameter Physiologic Characteristics Frequent
al function causes of
elevation

LT ratio
 The 
AST/ALT
ratio can be used
to estimate
whether hepatic
damage is mild
or severe
Glutamate  Enzy  Organ-  Seve
dehydrogenase (GLDH) me specificity: GLDH  re hepatiti
involved is liver-specific. s
in amino
 Subcellular  Toxi
acid
localization: GLD ns (such
metabolis
H is only present in as α-
m
the mitochondria.  amanitin)
 Hep
atocellula
r
carcinom
a, liver
metastase
s

MAXIMIZE TABLETABLE QUIZ

AST/ALT < 0.7 (up to 1) = ≥ 1 = "necrotic type"


ratio "inflammatory type"

Possible  Uncomplicated  Alcoholic hepatitis (AST/ALT


causes viral hepatitis ratio typically > 2)
 Minor fatty  Fulminant, necrotic hepatitis
liver disease
 (Decompensated) cirrhosis
 Extrahepatic cholestasis
 Hepatocellular carcinoma, liver
metastases
AST/ALT < 0.7 (up to 1) = ≥ 1 = "necrotic type"
ratio "inflammatory type"

 Differential diagnosis: muscle


damage

Parameters of cholestasis
MAXIMIZE TABLETABLE QUIZ

Laboratory Physiological Characterist Frequent causes of


parameter function ics elevation

γ-glutamyl  Membra  The m  Cholestasis (obstr


transpeptidase (γ- ne-bound enz ost uctive or
GT or GGT) yme sensitive nonobstructive)
of glutathione  parameter
 Alcohol use 
metabolism for
and amino diseases of
acid transport the liver an
d/or biliary
tract!
 Found
in many
tissues 

Alkaline  Enzyme  Found  Cholestasis (obstr


phosphatase (ALP) responsible in uctive or
for various iso nonobstructive) 
cleaving phos enzymes in
 Increased osteobl
phate groups numerous
ast activity 
off various tissues 
substances  Pregnancy (third
under alkaline trimester)
conditions

Biliru Direct  Bilirubin, which has been  Cholestasis (obst


bin (conjugat conjugated with glucuronic ructive >
ed) acid in the liver, is water- nonobstructive) 
bilirubin soluble and is excreted by
the gallbladder.

Indirect  Lipophilic catabolite  Disturbed


(unconju of heme. conjugation
gated) (intrahepatic)
bilirubin 
o Cholestasi
s (nonobstructive) 
Laboratory Physiological Characterist Frequent causes of
parameter function ics elevation

 Increased
accumulation
(prehepatic) 
o Hemolysi
s/large hematomas
o Ineffective 
erythropoiesis

Parameters of hepatic synthesis


 Relevance
o The liver is one of the most important organs of protein
synthesis.
o The synthesis capacity of the liver can be reduced by the
destruction of hepatocytes (e.g., liver cirrhosis) or a
deficiency of basic nutrients (e.g., in malnutrition).
o In addition to the parameters listed in the table below, which
provide an interpretation of the synthetic function of
the liver, coagulation factors can also be used.
o Vitamin K-dependent coagulation factors are particularly
relevant, as their function is also indirectly reflected in
the prothrombin time (PT, INR).

MAXIMIZE TABLETABLE QUIZ

Laboratory Physiological Charact Frequent Frequent causes of


parameter function eristics causes of decreased values
elevated
values

Albumin  Albumin   A  D  Decreased


makes up the lbumin  ehydrat synthetic capacity
majority is ion of
(60%) of exclusi the liver (e.g., liver
total plasma vely cirrhosis)
proteins. It has produc
 Loss
two main ed in
of proteins (e.g., n
functions: the liv
ephrotic
er.
o M
Laboratory Physiological Charact Frequent Frequent causes of
parameter function eristics causes of decreased values
elevated
values

aintenance syndrome)
of colloid
 Malnutrition
osmotic
pressure
o T
ransport
protein fo
r
degradatio
n products
and
enzymes
(such
as indirect
bilirubin)

Cholinestera  Nonspeci  In  In  Decreased


se (CHE)  fic cholinester volved creased synthesis capacity
ase, which in the synthes of
cleaves breakd is the liver (e.g., liver
various own capacit cirrhosis)
choline esters of mus y of
 Occupational
and cle the live
or
demonstrates relaxa r
accidental organop
similarities nts
 Di hosphate pesticide
to acetylcholin
abetes exposure
esterase of
mellitu
nerve cells
s, coro
nary
artery
disease 

FEEDBACK

Kidney function tests


Parameters of renal function
 Relevance
o The kidney values listed here include substances that allow
for indirect measurement of the glomerular filtration
rate (GFR).
o These parameters are usually measured in blood. 

MAXIMIZE TABLETABLE QUIZ

Laborato Physiological function Characteristics Frequent causes of


ry elevation
paramete
r

Creatinin  Creatinine is a  The creati  Acute or


e constantly nine value is chronic renal failure
accumulating product susceptible to o See
of creatine catabolis interference. 
“Creatinine
m with an unknown
clearance”
biological function. 

Cystatin  Cystatin  Low  Acute or chronic


C C inhibits cysteine pr susceptibility renal failure 
oteinases and is to interference 
 Glucocorticoid ad
formed in the
ministration
majority of nucleated
cells.  Hyperthyroidism

Other common renal substances


 Relevance: Urea and uric acid are largely dependent on renal
excretion; however, they provide an inaccurate assessment of
renal function.

MAXIMIZE TABLETABLE QUIZ

Labora Physiological Characteristic Frequent Frequent causes of


tory function s causes of decreased values
parame elevation
ter

Urea  Catabol  Assess  Sever  Malnutrition


ite ment of the e renal
of proteins  metabolic failure 
state is
 Cata
possible.
bolic state
s
 Dehy
Labora Physiological Characteristic Frequent Frequent causes of
tory function s causes of decreased values
parame elevation
ter

dration

Uric  Catabol  Trigger  Renal  Treatment


acid ite s gout  excretion  with allopurinol 
of purines ( disorders  or uricosuric
 Hyperu
component medication
ricosuria ca  Increa
of DNA)
n lead sed cell
to uric acid death (e.g.,
nephropath in tumor
y.  lysis
syndrome
)
 Lesch
-Nyhan sy
ndrome

FEEDBACK

Pancreatic parameters
 Relevance
o Pancreatic lipase and amylase are important primarily in the
diagnosis of pancreatitis.
o Elastase is a parameter of pancreatic exocrine function and is
usually determined from several consecutive stool samples
(also in serum during acute pancreatitis).

MAXIMIZE TABLETABLE QUIZ

Laboratory Physiolog Characteristics Frequent Frequent


parameter ical causes of causes of
function elevation decreased
values

Pancreatic  En  Pancreas-  Ac  Severe


lipase zyme in specific enzyme ute limitation of
volved pancrea exocrine
in the titis  pancreaticfu
digestio nction, e.g.,
 Re
n
nal o C
of fat in
Laboratory Physiolog Characteristics Frequent Frequent
parameter ical causes of causes of
function elevation decreased
values

the smal failure  ystic


l fibrosis
intestin o C
e. 
hronic
pancreat
itis

Amylase  En  Not specific to  Ac  Severe


zyme in the pancreas-  ute limitation of
volved pancrea exocrine
in the titis  pancreaticfu
digestio nction e.g.,
 Infl
n
ammatio o C
of carb
n of ystic
ohydra
the saliv fibrosis
tes in
ary
the smal o C
glands (
l hronic
e.g., mu
intestin pancreat
mps)
e.  itis
 Re
nal
failure 

Elas In  Ela  Pancreas-  Ac  Reduce


tase ser stase br specific enzyme ute d levels
um eaks pancrea of elastase in
 Most
down el titis serum are
commonly used
astin  not
parameter for
diagnosticall
assessing exocrine 
y relevant. 
pancreatic functio

In  Ele  Reduce
sto vated d in mild
ol levels limitations
of elasta of
se in exocrine pan
stool creatic functi
samples on, e.g., in:
are not o C
of
ystic
diagnost
Laboratory Physiolog Characteristics Frequent Frequent
parameter ical causes of causes of
function elevation decreased
values

ic fibrosis
relevanc o C
e. 
hronic
pancreat
itis

FEEDBACK

Electrolytes
 Relevance
o Electrolytes are chemical compounds that separate into ions
in aqueous solutions.
o May be differentiated into cations (positively charged) and
anions (negatively charged).
o The most important electrolytes are sodium,
potassium, chloride, magnesium, phosphate,
and bicarbonate ions. 
o The electrolytes that most commonly cause pathological
changes (and are therefore standard in analysis)
are sodium, potassium, and calcium, which are discussed
in detail in other learning cards (see “ Disorders of sodium
balance”, “Disorders of potassium balance”, “Disorders of
calcium balance”).

Chloride, magnesium, phosphate
MAXIMIZE TABLETABLE QUIZ

Labor Physiol Frequent Frequent causes Consequences of a


atory ogical causes of of decreased shift
para functio elevation values
meter n

Chlori  C  Renal  Loss, e.g.,  Hyperchlorem


de hlorid tubular via: ia
e is acidosis  o Vo o Decreas
an
 Chlorid miting e
anion
e overload of bicarbonate w
Labor Physiol Frequent Frequent causes Consequences of a
atory ogical causes of of decreased shift
para functio elevation values
meter n

and is  Bromid o Diu ith metabolic


the e retics acidosis 
main intoxication 
 Metabolic  Hypochloremi
count
acidosis  a
erpart
of the o Increase
positi of bicarbonate w
vely ith metabolic
charg alkalosis 
ed
o General
sodiu
weakness
m. 

Magn  M  Renal f  Congenital   Hypermagnese


esium agnes ailure  magnesium depl mia 
ium i etion in the
 Rhabd o Muscle
s intestine
omyolysis  weakness
a calc or kidney
ium  Magnes o Somnol
 Secondary
antag ium administ ence to coma
deficiency, for
onist  ration e.g.,
example: o ↑ PR
that for pre-
o Pol interval
norm eclampsia
ally yuria  Hypomagnese
serve mia
o Mal
s to
nutrition o Tetany
preve
nt the o La o Prematu
intrac xative re ventricular
ellula abuse contraction
r
o ↑ QT
accu
interval in ECG
mulat
ion of
calciu
m. 

Phosp  P  Renal  Malabsorpt  Hyperphospha


hate hosph failure ion or malnutriti temia
ate is on
 Hypop o Formati
an
arathyroidi  Chronic al on of a
impor
sm  cohol abuse  compound with
tant
calcium 
Labor Physiol Frequent Frequent causes Consequences of a
atory ogical causes of of decreased shift
para functio elevation values
meter n

sourc  Vitami  Diuretics   Hypophosphat


e of n emia
 Vitamin
energ D intoxicati
D deficiency  o Weakn
y in on 
the ess
form and paresthesia
of ad s
enosi o Hemoly
ne sis and thromboc
tripho ytopenia
sphat
o Insulin
e. 
resistance
o Osteom
alacia
o Uncons
ciousness
to coma

FEEDBACK

Iron metabolism
 Relevance
o Iron metabolism is closely associated with the formation of
blood and the disease state of anemia.
o In addition to the parameters listed here,
hematological parameters such as hemoglobin, MCV,
or MCH are important in assessing iron metabolism and
identifying causes of anemia.
o Iron deficiency is discussed in detail in a separate learning
card (see “Iron deficiency”).

MAXIMIZE TABLETABLE QUIZ


Iron studies

Labora Physiologic Characteristics Frequent Frequent


tory al function causes of causes of
parame elevation decreased
ter values

Serum  Cent  Iron levels  Iron  Iron


iron  ral trace are subject to overload, deficiency,
element i significant daily e.g., via: e.g., via:
nvolved fluctuation.  o H o H
in hemat
emochro emorrhag
opoiesis.
matosis e
o R o M
epeated bl alnutrition
ood o I
transfusio
ncreased
ns
demand
 Iron (e.g.,
toxicity  in pregna
ncy)
 Impaired
distribution of
ion, for
example:
o A
nemia of
chronic
disease 

Ferritin  Prot  Ferritin is  Acute  Iron


ein the parameter of phase deficiency (b
complex choice in reaction asically
that is determining iro conclusive in
 Anemia
responsib n deficiency.  suspected
of chronic
le cases!)
 Acute disease
for iron
phase protein  Nephroti
storage.  Iron
c syndrome
overload, e.g.
, via:
o H
emochro
matosis
o R
epeated bl
Iron studies

Labora Physiologic Characteristics Frequent Frequent


tory al function causes of causes of
parame elevation decreased
ter values

ood
transfusio
ns

Transfe  Tra  Transferrin  Iron  Acute


rrin* nsport pr saturation (TfS) deficiency phase
otein can be reaction
 Pregnan
for iron  calculated from
cy  Iron
both transferrin 
overload e.g.,
and iron values. 
via:
o A
o H
high TfS val
emochro
ue is an
matosis
indication
of iron o R
overload epeated bl
o A ood
transfusio
low TfS valu
ns
e
indicates iro  Nephroti
n deficiency. c syndrome
 Anti-acute 
phase protein 

*There are two additional forms of transferrin that may be used for diagnosis:
 Beta-2 transferrin (for the detection of a CSF leak in skull fractures)
 Carbohydrate-deficient transferrin (laboratory marker used to detect
chronic alcoholism)

A decrease in ferritin with a reduced hemoglobin concentration is essentially


evidence of iron deficiency anemia!

An elevated ferritin level does not exclude iron deficiency anemia. Concurrent


chronic inflammation can increase ferritin levels

You might also like