Clinical Chemistry 2 ➢ Stage 1- the tumor is localized in the organ/tissue that

it affects.
Tumor Markers and Vitamins ➢ Stage 2- invasion of primary tumor to epithelium and
blood vessel. Once it is in the blood vessel we can
assume that this tumor cells are already present in the
What is cancer? blood of an individual.
➢ Stage 3- migration of tumor into regional lymph nodes
➢ Cancer is the leading cause of mortality in developed or what we call as lymph node involvement.
country. Most of the Filipinos died bcs of cancer. ➢ Stage 4- the tumor invades other tissues/organs or
Before it is more of genetic cause but now it is more distant tissues and there is now metastasis- spreading
of the acquired cause (lifestyle, food, etc) of tumor cells to other areas of the body.
➢ Cancer can be detected and monitored using biological
markers known as tumor markers. What makes an ideal tumor marker?
➢ Cancer is a broad term that describe more than 200
• Tumor-specific
types of malignancy that could affect 50 tissue types
➢ Kung yung organ lang na yun yung nag p-produce ng
within the body of an individual.
marker, the better.
• Uncontrolled growth (tumorigenesis) of cells that
• Absent in healthy individuals
could develop into a solid mass or tumor and spread to
• Elevated at an early stage
other areas of the body (metastasis).
• Readily detectable in body fluids
• Caused: Genetic mutations
➢ There’s no tumor marker that fits the criteria. There
o Acquired or inherited
is no ideal tumor marker. Tumor marker + signs and
o Activation of oncogenes, Growth factor
symptoms + histology presented to the physician, we can
dysregulation, loss of tumor suppressor gene,
facilitate accurate diagnosis of what type is cancer the
mutation of cell cycle and DNA repair genes,
patient suffering from.
deactivation of adhesion molecules,
➢ Tumor markers could be produce directly by the
stimulation of angiogenesis genes,
tumor or that could be produce as the effect of tumor to
upregulation of proteases.
unhealthy host tissues.
➢ These mutations can lead to tumorigenesis or
metastasis.

1. Tumor size
Cancer severity
~ ♦ ~ Proliferation and/or
dedifferentiation
2. Histology
3. Regional lymph node involvement
4. Metastasis
5. Histologic assessment
➢ Solid tumors affect mainly the breast, lung and kidney
(not limited to these 3). Can be classified to stages, stage
.....-Elevation in
1-4, each stages correlate to the disease severity wherein it concentration
Markers
means that an increase stage could mean a significant (e.g .. HER2/neu,
PSA)
spread and severe systemic disease of the cancer.
Different types of serum tum01 ma,ker are used to detect cancer.
Cancer Staging and Progression HER2 and prostate-specifK antigen (PSA) reflect increased cellular proliferation.
Locah:ed Invasion of primary Migration of tumor Me1as1asisllllld Camnoembryonic antigen represents ded,fferentiation process of cancer. Current
p1imary l umo1 tulOOflhrough irloregc>nal ir,,,asionof1umor
epithelium and lymph nodes todistarittissaes
genomic and proteomks focus on collective changes in mahgMnt cells.
i'ltobloodvessels

Different serum tumor marker that are used to detect cancer:

➢ HER2/neu, PSA- reflect increased cellular

proliferation
➢ Carcinoembryonic antigen (CEA)- represents
differentiation process of cancer
➢ Current genomic and proteomics focus on collective
Slage l Stage II St, ge lll S!agelV

F IGURE 32.2 Generalized cancer staging and progression. Numerous factors changes in malignant cell.
are used in combination 10 define cancer stage; these include tumor size, extent
of invasion, lymph node involvement, metastasis, and histologic assessmems
(basis for the TNM staging system) . In this simplified diagram, stage is Types of tumor markers
presented as a fun ct ion of invasion and spreading regionally and to other tissues;
rhe primary tumor is nor shown.
1. Serum proteins
➢ Examples: beta 2 microglobulin and immunoglobulin
that are mostly used in therapy purposes.
 ... _ _
➢ Beta-2 microglobulin is a non-specific tumor marker
bcs it is present in the surface of all nucleated cells.
➢ Immunoglobulins are commonly used for hematologic
malignancy like leukemia.
2. Oncofetal antigens
- -·
~..WfN~

·--
-II<-
--
--
- _
- ....... _.
..
TA8l( 11-4 fHDOCltfN! TUMOlt MUl(fltS

--
...-
---fUIIOI m,

..
, .. , . . . MIW
"'"
,"'""'" C--....UTllTY

-- -- _- .. ·
,....., •.oc:,•~ 2...........
..........
➢ Known to be the first classes of tumor markers ~

discovered. It includes CEA and alpha-fetoprotein.

3. Hormones
4. Metabolites
➢ Hormones and metabolites are specific marker of
c...
11,-• --
.,....,.14.
-- P"'•t.:c ---
"wed
,,.-..,,g1o.o.a,,
...
.,..,oc,.....
"'"
"'"
"-
1-&hWilM

2..... unM
so......,_,
phtodUO,i'4(JM,aw'

p1-,.0MOC,lol!M.
pa......... ...
secreting tumor.
5. Receptors

_
➢ Useful in classifying tumors for therapy. Example: ➢ Endocrine tumor markers- they are the metabolites
ERPR- Estrogen Receptor Progesterone receptor and
they are known to be serologic markers that whenever
this ERPR yields positive for solid tumor
_
...
- ~-
➢ Metabolites – ends in 5-HIAA

c,n.-....,

- -......
.
..
(- ----
malignancies, we can tell what therapy could be given Hydr...,.........
""' 2•hr--
eMCIIIIOodtlftOl'l•
to the patient so that that will w effective ...,._
~,~·
(chemotherapy, surgery, etc)

--
MTCN IA
u.-.,.,

-
M.oa4«,l,ncllolllll0n tlftCIO'IM:to
6. Enzymes

--
--~ing

--
~OIMl(
➢ Enzymes are result of high metabolic demand of

--- --
PMalf¥Olld IA

--- -
proliferative cells. Enzymes are proteins that are

--
IIIIOMOI. . or 1

-- -- .................
confined in a cell so whenever that cell is diseased or .._
-- -
IA
dysfunctional, that’s the time that the enzyme
produces by that cell will go out of the cell and causes IA ...........
an increase in the serum and pag mataas that could !Mlllit.;ngor

indicate condition.
➢ For monitoring success of therapy.
➢ Except C peptide they are all hormones
TA8LE 11,2 ENZYME TUMOR MAlhC(RS ➢ Endocrine tumors includes hormones and metabolites

--
1\IMORMAIW
h-c

._,
fUMC» lYPl
,ro,sutt (.lnttf

Htrnoltologic
,.MU'HOO
.. --
SftCIIAH " ""-" uruTY
Pnm•~· (,ll'l(f!f ~
ttiN..-fflOMOI~.
Wrt0.ntnc:•
"ognos.tit incic:.,i1w;
➢
as type of tumor marker.
Metabolites commonly found in the urine.
Metanephrine you can use plasma.

.. - ➢ Acromegaly-a condition whrein there is an excess

NligNntift ~ttdno~

-
....... rl lVJIMl'MQlll(ffl

Lltetit#licW~ De'ltfl"iNtlon of ltwf production of growth hormone

~--
phot;phA-Ht ofbont.~tllul.¥ #ldboM~~
~•~.cionln

- -
O.UOMl(OtM. Nltyi:lont-ttlolitd,nd

Ntl#Ot11Pf'(i!fl<.
~IM.t~
_,.,.,_, RIA. IH(
h<•~
,..~~°'--
....... Adr•noc:ortk oC.roflk Muit..-y dnCWN ectopic IA ...... ~offfloPk

-··
ho<-..wn<) AC'THiWoduMt 1Uffl0f
~
~tMnkw Adi tnoll tWll'IOn IA StlvM Ot ""',..

....
ntwOffldoctnt l\lmon
........ -..
Cvltling', ~ .
c..._,_..,v ... ~ 1 1 1 ( , -. ......
---
Anticlur<t1k horPIOftt

--
Polt ttlor pillufl:M}' lumon IA ~of$1AOH
W>I<)
Chr°"'°9f,.._ A
ntufoblM1°""'- w dl'CM
......... ...... .................
Aid di dl"'9"0'" of

➢ IA- immunoassay h,/l'l'IC)t\,WNl (ittlli,ng

......
-··
·-
(.,ln(iff\ and MVobla,tom.9'
➢ EA-enzyme assay ll""""'• M<Htill9 t\lfflOH WS., IA

➢ RIA- radio immunoassay

➢ IHA- immunohistocytochemistry
➢ C peptide is not a hormone but rather whenever insulin
!AIU 31·3 SERUM PltOTtlH nt.lOR MARIC(RS
1\llolCIIIWlll
StnnM-f,1-

Stnn&"igt<-
1\llolCll lffl

"""""'dJia-
"""""'d)w-
ll(lH(IO

!11,fl

IA
--
s.n,,,
CIJNICAI UT1J1Y

~""'-
.............
-w,golJI-
~Nipt'AI<
➢
is produced by the body, pro-insulin is the first
substance present in the body and the pro-insulin is
converted into insulin. Once it is converted, it releases
C peptide.
Gastrine- hormone that can be use as tumor marker
""""""""°'
c,lffWI-
p1..... that detect presence of zolinger ellison syndrome (GIT

~,..,_..
~-, function).
~ KelldorJ<....,_ IA s.n.

.._ ......................._,.......,.._. cliiordffl

 ➢ Screening – involves biopsy indication, will undergo
TABLE 31-6 CARBOHYDRATI: AND CANCER ANTIGEN TUMOR MARKERS histotechniques
l\JMOltW. ER TUMOR TYPE METll00 SPEO £H ClJNICAL l/Tl/lY ➢ Diagnosis- high levels is indicative of disease
CA 19-9 Ga,tto,ntostiNI Un<ff lrnlnunoffloy Strom Monitoring
,nd ociono<Monom, pit1(1Htic:: uncer ➢ Prognosis- high levels associated with poor prognosis.
CA 1~3 MtWU
un<t<
brH<t ~ Strom •-tothtf~
and dotoct,ng
Receptor status used for indication of chemotherapy.
recurrtnet - Tumor marker concentration increases with tumor
CA2H9 Mtu.t• brust lrnmunoasloy s.«im
ore.,.,,,,. · thtf•PI'
- t~ng
ondde progression. The higher the level of the tumor, the
r«...-rtne~ more the possible it will metastasize. Increase
CA-12S o,,ri,nunc.tt Im~ s.«im "tO<ingtht<opy
concentration of tumor marker indicate presence
of malignancy and metastasis and this is
associated with poor prognosis.
➢ Monitoring treatment- monitor efficacy of
T OR MARKERS
chemotherapy, residual diseases after surgery. Tumor
Ill M£TMOD a.tnCAI. l/1lJTY
Estlogtn IKlptar IIHst<MICtf IHC Harmon, thlfapy
markers are routinely followed serially.
OI - Initially, there is an increase tumor marker at
ProgtsttfOIW
IKtptot
H«·lh>fll
81HstQIICtf

81HSl.~
g,wOllllestJNlttmon
IHC

IHC. 1&1.EUSA
8,cp,y

8'cply ---
HormoNJ lht,-apy

~nl
~llw,py
diagnosis. After therapy given to the patient and
bumaba na yung tumor marker then the therapy
given is effective.
➢ Detection of recurrence – increased associated with
EpodtnNlgrowdl Kud, ntdl, ov,n,n, IHC 8'oply Prognostx.,._

WS,\----11511.-• . .
fxto,rt«pCor CfMU!<MKtn relapse.

Laboratory considerations

➢ Receptor tumor markers are important for us to know • Two main consideration
what therapy should be given to the individual who o Wide concentration range of tumor markers
suffers from cancer. ▪ Vary in concentrations by orders of
magnitude
Alpha-fetoprotein and HCG o Variability in tumor concentration (lack of
harmonization and standardization)
▪ Using different assays for
Yo lk sac tumor Increased No measurement

Chorioca rcinoma No Increased Methods of detection

Embryona l ca Increased +!- • Immunoassays

➢ Considered as the most common method of measuring
Te ratoma No No tumor markers bcs the advantage of immunoassay over
others is that it is easy to perform and does not require
Seminoma Not elevated in pure +!-
tumors expensive materials and equipment, skill in performing IA.
o Tumor markers are detected using capture
and label antibodies
➢ Alpha-fetoprotein is an oncofetal antigen together
o Excessively high levels of tumor markers can
with CEA. It is commonly measured together with HCG.
result to antigen excess or hook effect
➢ AFP and HCG is commonly used for detecting
(disadvantage)
testicular cancer. This testicular cancer can be
o Interference by heterophile and antibodies
seminomatous or non-seminomatous. Non-seminomatous
(disadvantage)
includes embryonal ca, teratoma, choriocarcinoma and
➢ Common cause of heterophile
yolk sac
antibodies are your Human anti
tumor.
Tumor markers in Cancer Management mouse antibody (HAMA) and
Uses of tumor Human anti-animal antibody
..........

_ ~[§]
Monttot1ng OetecUon of

markers
TtNtnwnt Recurr-.nce
(HAAA)
➢ These heterophile antibodies could
.._......
UNdlorlndk:alion
either result to false positive or false
negative.

iI
"°""'
PSA
N'P"
--INA/VMA

P1lt
Ctwomogrll'W\A
112_
CA ,,s
CEA
lD
Hlf·2/MU
ER
.. CA, 25
CAHMI
CEA
N'P
hCG
PSA
CA , 5-3
CA,25
CEA
N'P
hCG
▪ Hook effect
• When analyte
concentrations exceed the

---
PSA
j ~--------------------~
"""'
PR SPE
analytical range
10
excessively, both the
 capture and label 4. HCG
antibodies can be 5. PSA
saturated, resulting in a
lack of sandwich
formation, which results in • AFP
a significant and decrease o Major fetal serum proteins
in signal. o Major carcinoembryonic protein
➢ Result to falsely low o Elevated in primary hepatocellular
measurement carcinoma (HCC) and germ cell tumors
➢ Perform dilution o Also elevated in pregnancy and many benign
technique liver diseases, testicular cancer
o Affected by icteric, lipemic and hemolyzed o High levels of AFP in HCC is correlated to
samples and antibody cross reactivity poor prognosis
(disadvantage) ➢ Decreased in level would only mean a
➢ Lipemic sample can be accepted whenever the prolonged survival rate for those with HCC.
individual is suffering from hyperproteinemia and
• CA-125
those that suffer from liver damage. o Mucin protein
• High performance liquid chromatography o Ovarian tumors at early stage
o Most widely used for detecting o The only clinically accepted serologic marker
catecholamines in plasma and urine for ovarian cancer
➢ This method is commonly used for detecting small o Correlate with ovarian cancer stage
molecules and endocrine metabolites. o Elevated also in: endometriosis, 1st trimester
➢ Based on detecting tumor markers based on their of pregnancy, during menstruation
physical characteristic either as to charge, size and ➢ HE4- human epididymis protein that can also
polarity. be used for ovarian CA diagnosis. Specific over
➢ Disadvantage is labor intensive and at the same time CA125 bcs HE4 is less frequently increased in case of
more experienced, more expensive and skill is non-malignant condition such as
required. endometriosis/myoma. Increase CA125 & HE4 is very
➢ Advantage is no linearity or hook effect, no lot to lot evident for ovarian CA.
antibody variation, no heterophile antibody that could
• CEA
react during measurement.
o Most widely used marker for colorectal
➢ HPLC – extraction of metabolite in a column either
cancer
liquid to liquid, liquid to solid, liquid to gas etc.
o Also elevated in lung, breast, and GI tumors
o For diagnosis: o Associated to cell adhesion
▪ Neuroblastoma (epi, norepi, dopa)
o May also be elevated due to impaired
▪ Pheochromocytoma
clearance
(metanephrines)
➢ Not all increase CEA could mean cancer
▪ Carcinoid tumors (5-HIAA)
➢ Not used for screening bcs it is sometimes
• Immunohistocytochemistry regarded for being not specific for colorectal cancer.
o Tumor markers directly within solid tissues o Used for colon cancer prognosis and to
o Like immunoassay, but specific cell type is monitor response to chemotherapy
determined
• HCG
o ER/PR for breast cancer
o Hormone normally secreted by the
• Enzyme detection trophoblasts of placenta to maintain the
o Enzymes are released from the cell when corpus luteum during pregnancy
cells are necrosed or underwent changes in o Elevated in trophoblastic tumors,
permeability. choriocarcinoma, ovarian and testicular
o Detection of elevated circulating enzyme tumors
cannot be used to identify specific tumor or o It is beta-HCG, not alpha- HCG or total HCG
site of tumor. that is sensitive and specific for aggressive
➢ Ex. PSA- prostate specific antigen for neoplasms
detecting prostate cancer. ➢ HCG has two types: Beta and alpha
Commonly requested tumor markers subunit. What is important in tumors are
the beta HCG- we have so called intact
1. AFP beta HCG and free beta HCG subunit.
2. CA-125 They are increase in malignancies and
3. CEA
 they are detecting multiple fragments of
Vitamins are organic molecules that are essential for normal
HCG. health and growth . They are required in trace amounts and must
➢ Common use of HCG is for detection of be obtained from the diet because they are not synthesized in the
gestational trophoblastic diseases or so body. Before vitamins were discovered, it was known that lime
juice prevented the disease scurvy in sailors and that cod liver oil
called hydatidiform mole.
could prevent rickets. In 1912, scientists found that, in addition to
➢ Total beta HCG detects both the intact carbohydrates, fats, and proteins, certain other factors called
and the free beta HCG. The beta HCG is vitamins must be obtained from the diet.
the subunit that is use in detecting
pregnancy. ➢ Lime juice has increased vitamin C on it and scurvy is
• PSA (Prostate Specific Antigen) actually a condition wherein there is decreased level of
o Serine proteases that regulates the viscosity vitamin C in the body.
of the seminal fluid ➢ Cod liver oil- has high level of vitamin D bcs rickets
o Aids in dissolving the cervical mucus cap to is a condition that is present whenever you have a
allow penetration of sperm decreased level of vitamin D.
o Two forms: Free (present in serum) and
Why are they good for us?
complexed form (has two types of protein:
Alpha-1-antichymotrypsin and alpha-2-
Greater need due to
macroglobulin) worse environment
➢ This tumor marker is measured by immunoassay and
detects both free PSA and the PSA bound to alpha-1
chymotrypsin but it cannot detect the PSA that is complex
with alpha-2 macroglobulin.
o Low free for correlates with malignancy
o Screening of prostate cancer from men >50
y/o Slower aging
o <4 ng/mL is normal
o Infection, irritation and benign prostatic
hyperplasia also have increased PSA levels.
➢ Patient with malignancy has decreased percentage of free
PSA. Fat SOiubie Water soluble

Vilamin A Non 11-compiex

Vitamins Vitamin 0 I

!
Vitamin E V,wnin C
Energy-releasJng ~
What are vitamins? Vitamin K
Thiamine (8 1) [Folk: acid (8.)
• Organic molecules with a wide variety of functions Rilollavin (B,J V,wnin 8 12
(cyn,oobalamil)
Niacin (B,l
• Co-factors for many enzymatic reactions Pyridoxlne (B,l
• Essential, supplied in the diet (some: bacterial Biolln (B,)
synthesis) PantoCheoic acid (B,J

• Two-distinct type:
o Fat soluble: Vitamin A,D,E,K Fat soluble vitamins
o Water soluble (vitamin B- complex, C)
➢ Vitamin deficiency- defined as inadequate intestinal
Are A, D, E, and K.
absorption and activity levels from the diet of those
vitamins
Soluble in lipids, but not in
➢ Vitamin insufficiency independency- related whenever aqueous solutions
we have inadequate absorption and at the same time
decrease intake of these vitamins in the body.
➢ Dietary deficiency- known as hypovitaminosis, abnormal Important in vision, bone
increase of metabolism of these vitamins requiring high formation, antioxidants, and
blood clotting
supply of one of those vitamins. Can also be caused by
inadequate intake and absorption of these vitamins in the Stored in the body
body.

➢ Not secreted in the body but rather stored

 Vitamin A
Vitamin A status: Retinal
• Vitamin A is obtained from meats and beta-carotenes
in plants measurement (HPLC)
• Beta carotenes (also known as pro-vitamin A) are Toxicity: Retinyl ester l(HPLC)
converted by liver enzymes to vitamin A (retinol)
➢ Retinol is being oxidized in the rods of the eye to retinol
forming rhodopsin that allows us dim light vision. Vitamin D
• Stored in the liver, transported in complexed to RBP
• Is synthesized in skin exposed to sunlight
and transthyretin
(cholecalciferol from 7-dehydrocholesterol)
• Vitamin A deficiency – can lead to nyctalopia or later
• Major forms: ergocalciferol and cholecalciferol
on total blindness.
➢ This vitamin is very important for skeleton and
-can be caused by malabsorption, impaired liver
mineral homeostasis.
function and protein malnutrition.
• Most active metabolite: 1,25 (OH)2 D3 or 1,25-
• Hypervitaminosis- ingested high doses of vitamin A,
dihydroxycholecalciferol (also known as Calcitriol)
can lead to liver damage
o Intestinal absorption of calcium and PO4
• RDA: 900 ug/male;700 ug/female
o Stimulates bone to increase mobilization of
calcium and PO4
o Proapoptic effect
• Requires bile for absorption in GIT, stored in liver
• Sources: irradiated food and commercially prepared
mild
• RDA: 15-20 ug/day
• Vitamin D deficiency
➢ Severe deficiency of vitamin D is very important for it
can result to failure to calcify cartilage at the growth
plate resulting to rickets in infants or that could result
to mineralization of bone matrix also known as
osteomalacia that is common in adult.
➢ Could due to hypoparathyroidism
• Elevated levels (toxic esp to children)
o Hyperthyroidism and hypophosphatemia and
Adult RDA: 1000 µg RE during pregnancy
Fat •soluble
o Leads to hypercalcemia and hypercalciuria
➢ Couldresult to irreversible renal and cardiac damage.
i-Carol<c-n<> • Two forms most commonly measured
(anuoxldanl) o 25 (OH) D3 - calcidiol
l o 1,25 (OH)2 D3- calcitriol
Re nol
(steroid hormon.---growth and dlfferenOatlon) o RIA or HPLC in conjunction with
competitive protein binding
Retln I Retinyl phOapt,ate
(visual cycle) (glyoopf"oteln synthesis)
...
Fifi.
Retlnoic acid
(stef'oid hormone-growth and differentiation)

7.3: Sunvnary or,,,. functions

d'll#amlnA ~
0
➢ Beta carotene is an antioxidant that acts on the retinol that ,..,.,rr- - bony
necklace
is important for growth and differentiation either into
retinal or into retinyl phosphate.
➢ Retinoic acid is the end product of this beta carotene
bigjoinls
whenever it is being converted or being acted upon by
bowed legs
certain enzymes.
UNLIGHT ISTHE BEST PREVENTION
AND TREATMENT OFRICKETS
 Vitamin E • No vitamin K assays
• PT and PTT – measure the activity of clotting factor
• Tocopherol (alpha tocopherol) – most potent isomer of
vitamin E
• An antioxidant in cells
• Prevent the oxidation of unsaturated fatty acids
Vitamin A1 Night blindness, growth retardation,
• Major function: protecting erythrocyte membrane abnormal taste response, dermatitis,
from oxidant stress recurrent infections
• Absorbed in jejunum, stored in the liver and tissues
Vitamin D Rickets(young)
with high lipid content, excreted in feces Osteomalacia (adults)
• Sources: Green vegetables, vegetable oil, egg yolk,
break, dairy products, peas, beans Vitamin E Mild hemolytic anemia
➢ Vitamin E is also a defense against potentially harmful Red blood ce ll fragility
Ata xia
oxidation that causes disease and aging process.
• Vitamin E deficiency: Vitamin K Hemorrhage
o Hemolytic anemia Post traumatic bleed ing
o RBC fragility
o Ataxia Water soluble vitamins
o Cause: fat malabsorption – could be a result
of a certain condition such as cystic fibrosis
or a-beta lipoproteinemia
➢ Also common if you have low intake of vegetable oil
or other unsaturated fats.
➢ High doses of vitamin E has no intake intoxication
known or no beneficial effect. The higher the level of
L ~
Soluble in aqueous
solutions

Used as cofactors by
vitamin E, the better. However, infants with chronic many enzymes
cholestasis that could result to vitamin E deficiency could
also have neurologic function loss.
• RDA: 15 mg/d for males and females Not stored in the body
• Measurement of alpha tocopherol thru HPLC methods

Vitamin K

• German word: Koagulation ➢ Excreted in the body, readily excreted in the

• Essential for synthesis of zymogens for blood clotting
(factor 2,7,9,10, protein C and S)
• Dietary vitamin K is absorb in ileum (colon)
o Sources: green fruits and vegetables,
tomatoes, soy, beef liver, yolks, wheat, pork,
liver
• 50% vitamin K- intestinal bacteria
• AI: 120 ug/d for males and 90 ug/d for females
• Vitamin K deficiency
o Cause
▪ Antibiotic therapy
➢ Also acts on the normal flora present in our intestine
that also produces in our intestine, so it is possible na
mamatay yung mga bacteria nay un resulting to
vitamin K deficiency
▪ Vitamin K antagonists (warfarin-
coumadin) – drugs that acts on
vitamin K so decreasing also the
level of vitamin K in the body.
o Leads to hemorrhagic episodes – increase
bleeding tendency in an individual with the
decrease/deficiency of vitamin K.
• Large doses of vitamin K
o Hyperbilirubinemia (newborns)
urine so they are less likely to accumulate to toxic
levels in the body.
Thiamine (Vitamin B1)
• First B vitamin identified
• TPP cPArt of the coenzyme thiamine pyrophosphate
(TPP)
• Coenzyme is required by enzymes in the
decarboxylation of alpha-keto carboxylic acids.
• Absorbed in the intestine, excreted in urine.
• Chronic deficiency: beriberi
o Cause: Chronic alcoholism – known cause of
TPP
➢ Other cause could be decreased intake of vitamin B1,
impaired absorption or there’s an increase release of
this Vitamin B1.
➢ Dry and Wet beriberi.
Signs and symptoms:
-wrist and foot drop
-emaclation
-loss of reflexes in knees and feet
-wernicke’s syndrome
-edema
 THIAMINE DEFICIENCY (Beriberi!
DRYIEIIMtEltl
Common •wty mlntlfest.Uons

Vitamin B6 (pyridoxine) Is
important for maintaining
healthy brain function,
the fonnatlon of red blood
cells, the breakdown of
protein and the synthesis
of antibodies In support
of the Immune system
Adult RDA: 2 m
Water•

Niacin (Vitamin B3)

• Dietary tryptophan to niacin

• Generic name for nicotinic acid and nicotinamide
• Part of the coenzyme nicotinamide adenine
Riboflavin (Vitamin B2) dinucleotide (NAD) and NADP
• Absorbed in the intestine and excreted in urine
• Made of the sugar alcohol ribitol and flavin
(metabolites)
• Part of the coenzymes flavin adenine dinucleotide
• Deficiency: Pellagra, dermatitis, muscle fatigue,
(FAD) and flavin mononucleotide (FMN) – very
diarrhea and loss of appetite
important in many redox reaction in the body
o Result of alcoholism
• Absorbed in the small intestine and excreted in urine
• Sources: meats, rice and whole grains
• Deficiency: other nutritional deficiency, alcoholism
and chronic diarrhea and malabsorption

promote healthy growth and

tissue repair, and helps release
energy from carbohydrates

ROA: 1.7 "'i

Water•solwle
!!--,,....--Healthy red blood
cell productton

Pyridoxine (Vitamin B6)

• 3 forms: Pyridoxine, pyridoxal and pyridoxamine

➢ Pyridoxine- form present in plants
➢ Pyridoxal and pyridoxamine- form present in
animals
➢ Example of beriberi: glove and stocking lesion
• Absorbed in the intestine and excreted in urine
➢ Casal’s necklace wherein an individual suffering from
(metabolites)
pellagra could also suffer from dementia
• Sources: meat, poultry, fish, potatoes, vegetables,
➢ Principal causes of pellagra could be chronic
dairy products
alcoholism and corn and molasses diet- could result to
• Needed for amino acids and protein metabolism
deficiency of tryptophan and niacin.
• Deficiency: hyperhomocysteinemia
• High doses: peripheral neuropathy Panthothenic acid (Vitamin B5)

➢ Panthothenic means everywhere

• Converted to 4-phosphopanthetheine that bounds to
either serum acyl carrier or coenzyme A
• Needed for energy production as well as glucose and
cholesterol synthesis
• Sources: whole grains, vegetables, eggs, liver, heart,
yeast, mushroom
Biotin
• Serve as coenzyme for enzyme that transport carboxyl
units in tissue and plays an integral role in
gluconeogenesis, lipogenesis, and fatty acid synthesis
• Deficiency:
o Ingestion of large amounts of avidin
o Noted in patients receiving long term PN and
infants with genetic defects of carboxylase
and biotinidase enzymes
Ascorbic acid (Vitamin C)
• Important for formation and stabilization of collagen,
hormone synthesis, infection resistance, cure of cuts.
• Increases absorption of certain minerals such as iron
(absorbed in the upper small intestine)
• Source: fruits and vegetables
➢ Guava among all the fruits has the highest level of
vitamin C
• Hypovitaminosis: Scurvy
➢ Could result to hemorrhagic disorders,
bleeding/swollen gums, anemia and impaired wound
healing
• Hypervitaminosis: addiction to vitamic C, diarrhea
• Assay: 2,4 dinitrophenylhydrazine
Cobalamin (Vitamin B12)
• Coenzyme for enzymatic reaction necessary for
hematopoiesis and fatty acid metabolism
• Absorption happens in the ileum (intrinsic factor-
parietal cells of that stomach produces that intrinsic
factor)
• Large group of cobalt containing compounds
• Source: animal products (meat, egg, milk)
➢ In animals there’s this intestinal microbial synthesis of
cobalamin.
➢ 3 forms of cobalamin:
hydroxocobalamin,
methyl cobalamin and deoxy denosyl cobalamin??? –
the active cofactors/form of cobalamin and they are
very important cofactor for many enzymatic reactions.
• Deficiency of vitamin B12
o Pernicious anemia (megaloblastic anemia) –
bcs of lack of intrinsic factor. Intrinsic factor
is important so that cobalamin can be
absorbed in the intestine.
o Neurologic disorder
➢ Could result if you are a strict vegetarian
➢ Infected with fish tapeworm known as
Diphyllobothrium latum
➢ Due to dietary deficiency bcs of malabsorption

V1t•mln 812 is
tmport#lt
~.al>Ottwn,UW
'°'

--·
form•Uon of red
b&oodc.tb,.,,ct

Vltamtn C promotes
lhNlthyl~
SY1tem, helpsWOI.W'lds
---
---·
---
of

--
t,_ cent, ..

hHI, maintains
COMKtfve tissue
Folate
andatdsln~
""'°'1)lionofln>n
• Serves as coenzyme in various one carbon transfer
reactions
• Dietary folate is absorbed in the jejunum
• Source: Green and leafy vegetables, fruits, organ
meats and yeast
• Folate deficiency: megaloblastic anemia, alcoholism,
malabsorption syndrome, carcinoma, liver disease
A deficiency of vitamin C
may lead to a condition • Phenytoin (dilantin) – drug that interferes with folate
T"''-'t.-i.Jllw..._,called scurvy, characterized absorption, decrease folate of an individual
by weakness , anemia,
bruising, bleeding gums ➢ Large dose of this vitamin is also synthesized by
and loose teeth the bacteria present in the intestine.
➢ Increase requirement of folate is true in case of
pregnancy and lactation. Increase of folate in
 pregnant women could reduce incidence of fetal
neural tube defect.

Vitamin Name

Vitamin B1 Infa nts: dyspnea, cyanosis, diarrhea, vomiting

Adu lts: Be riberi, Wernicke· Korsakoff syndrome
Vitamin B2 Angula r stomatitis, dermatitis, photophobi a, ne urologic
changes
Vitamin B6 Infant s: irritability, seizures, anemia, vomiting,
weakness
Adu lts: Facial seborrhea
Niacin Pellagra

Folic acid Megaloblastic anemia

Vitamin B12 Megaloblastic anemia, neurologic abnormalitie s

Vitamin C First, vague aches and pain

Long te rm, Scurvy