y Thalamus y Thalamus

y Hypothalamus
y Subthalamic Nucleus
Epithalamus
y The ONLY nucleus with NO known
function
Thalamus
y ALL SENSORY information in and out of
the brain MUST stop here
y ALL information about the ARMS stay
LATERAL
y ALL information about the LEGS stay
MEDIAL
Hypothalamus
y Controls hunger
y Hunger center: lateral
y Satiety center: medial- 80% NE and 5HT (+)
y You can override via cortex stimulus FOOD
y Controls menstrual cycle
y Controls temperature
y Anterior: cools
y Posterior: warms
y Controls stress response (NE release)
230
4/29/2008
12
Stress Response
y Parasympathetic discharge always first
y Sympathetic discharge always second
y
y
y
y

Stress ulcers
Curlings ulcers
Cushings ulcers (triad: bradycardia, HTN, Inc. ICP)
IBS

Acetomenophen
y Works at the level of the hypothalamus
y First, it cools the body (+ anterior hypothalamus)
2nd it resists fever (blocks posterior hypothalamus) pothalamus) 2nd it resists
fever (blocks posterior h
y Oxidizes the liver (toxicity) by destroying bisulfur

groups
y Treat with n-acetylcystiene ( reducing agent);
y the four hour level is the most important factor
Subthalamic Nucleus
y Final relay station for coordinating
fine motor movements fine motor movements
y Lesion: Ballismus and Hemiballismus
Substantia Nigra
y Responsible for INITIATING movements
y Uses DOPAMINE for neurotransmitter
y Receives inhibitory signals from basal ganglia via ACH
or GABA
Parkinsons Disease
y Loss of DOPAMINE fibers from substantia nigra
to striatum (caudate and putamen)
y Unable to initiate activities Unable to initiate activities
y
y
y
y
y

Mask like facies

Bradykinesia
Shuffling gait
Pill rolling tremor
Autonomic dysfunction: Shy Dragger syndrome

231
4/29/2008
13
Parkinsons Disease, cont
y Treatment: L-dopa/ carbidopa
y 2nd line: Bromocryptine (dopamine agonist)
y Amantadine (Tx influenza A)- increase DA
release from nerve terminal
y Selegyline (MAO-B inhibitor)- prevent DA
breakdown
Movement disorder in middle-aged people
y
y
y
y

Huntingtons disease
90%
AD
Trinucleotide repeats

y
y
y
y
y

Wilsons disease
< 10%
AR
Ceruloplasmin def Trinucleotide repeats
Caudate nucleus involved

y Anticipation
y Decreased GABA fibers
y Treat with DA blockers
(they have too much DA)
Ceruloplasmin def
y Copper excess
y Lenticular nucleus
involved
y Kayser-Fleischer rings
y Liver involvement
y Treat with penicillamine
Internal Capsule
y ALL MOTOR fibers going in and out of the brain goes
through here
Blood d ly from he lenticulostriate i l i ies y Bl suppl comes f th l arteri
( smallest arteries in the brain)
y Lacunar hemorrhages: due to HTN
y Causes significant MOTOR deficits
Reticular Activating System (RAS)
y Maintain FOCUS on one item at a time
y Requires NE and Serotonin y Requires NE and Serotonin
y cAMP second messenger (sympathetic)
y Has a refractory period first thing in the
morning
Sleep cycles y BAT D
y Beta waves wide awake (eyes open)
y Alpha waves - Eyes close - awake not asleep
y Theta waves
y light waves stage 1 and 2. (Stage 2: K complex and sleep spindles)
y Delta waves Deep sleep big stage 4 all motor activities (teeth
griding, sleepwalking, enuresis).
y Night terrors occur
y Benzos, imipramine inhibts this fase
y
y
y
y
y

Beta waves - Rem sleep. Every 90 min. (REM latency) 5-7 x night
Parasympathetic. Most of the rest.
Dreams, penile/clitoral erection
NE, EtOH, Barbs, Age inhibts this
5-HT, Ach increase

Attention Deficit Disorder

y ADD or ADHD (Not focus).
y RAS not working
y Poor attention and focus y Poor attention and focus
y Restlessness
y Unable to sit long enough to complete a task
y Tx: methylphenidate (1st in children);

pemoline; dexadrine; adderal

232
4/29/2008
14
Mid-brain brain Mid
Corticospinal Tract
y Responsible for fine motor activity
y Has to inhibit extension so that smooth flexion can
occur
y
y
y
y

Spasticity- can not flex

Babinski extension of toes
Hyperreflexia
Clonus

Corticospinal Tract, cont

y Fibers originate from the frontal lobes,
the precentral gyri
y Fibers descend through the internal
capsule and CROSS at the medullary
pyramids
CST Pathology
y Atonic seizures: depolarization
goes across the frontal cortex
y B-12 deficiency
y ALS
Increased Intracranial Pressure
y First sign: papilledema (optic nerve)
y First symptom: headache
y Second sign: esotropia (CN VI paralysis)
abdusence
y Second symptom: diplopia or blurred vision
y Third sign: Sluggish pupils
233
4/29/2008
15
Decorticate Posturing If Herniation Continues

y Second sign of herniation:

DECORTICATE posturing
y Compression has occurred below CN y Compression has occurred below CN
III but above the red nucleus
y Red nucleus still makes the upper

extremities flex while the legs extend

y UNTIL
The Final Push
y Herniation goes beyond the red nucleus
y CST and Corticorubral and rubrospinal
tracts are all lost tracts are all lost
y All extremities will extend by default
y Medulla is pushed through the foramen
magnum.
y DECEREBRATE posturing
DECEREBRATE posturing
Dorsal Columns
y Vibratory sensation
y Two-point discrimination
y Position sense y Position sense
y (toe m0vement)
y Conscious proprioception
y (eyes closed knowing what he is doing)
y The only sensory pathway with four
synapses
Dorsal Columns, cont
y Gracilis: carries leg fibers; located
MEDIALLY MEDIALLY
y Cuneatus: carries arm fibers; located
LATTERLY
234
4/29/2008
16
Dorsal Columns, cont
y FIRST SYNAPSE: dorsal root ganglion
Fasciculus gracilis: ( lower extremities)
Fasciculus cuneatus: ( upper extremities)
y SECOND SYNAPSE: MEDULLA
y THIRD SYNAPSE: THALAMUS
y FOURTH SYNAPSE: parietal lobes
y ( postcentral gyri)- ALL SENSORY
Dorsal Column Pathology
y Syphilis
y Vitamin B-12 Def
y Brown-Sequard
Spinothalamic Tract
y Pain and Temperature
y (opposite all other lesions)

y The only pathway that CROSSES in the

spinal cord (only one)
y Fibers enter the spinal cord, ascend two
levels, then cross to opposite side via the
anterior white commisure
Spinothalamic Tract
y FIRST SYNAPSE: dorsal root ganglion
y SECOND SYNAPSE:thalamus y SECOND SYNAPSE: thalamus
y THIRD SYNAPSE: parietal lobes
y ( postcentral gyri)- Sensory
Spinothalamic Tract Pathology
y Syringomyelia
P
Spinocerebellar Pathway
y The only pathway in the spinal cord that crosses
twice ( equivalent to ipsilateral)
y
y
y
y
y
y

Responsible for depth perception

Signs of damage:
INTENTION TREMOR (during reach)
DYSMETRIA (heal to shin) or PRONATOR DRIFT
DYSDIODOKINESIS (rapid movement)
ROMBERG SIGN (loss of unconscious proprioception)

235
4/29/2008
17
Spinocerebellar Pathway, cont
y This pathway does NOT reach the cortex
y Unconscious proprioception
y (donthave to thinkabout it) y (dont have to think about it)
y FIRST SYNAPSE: dorsal root ganglion
y SECOND SYNAPSE: thalamus
y THIRD SYNAPSE: cerebellum
Spinocerebellar Pathway Pathology
y Alcohol attacks the vermis (midline) of the cerebellum
while other diseases attack the hemispheres
y Fredriecks Ataxia-retinitis pigmentosa
y Ataxia Telangiectasia- spider vein all over your body
y Adrenoleukodystrophy- defective long chain FA
PONS

y Responsible for responding to the environment

y Contains the
y PNEUMOTACTIC (superior)inhibitory to the APNEUSTIC
(bottom) responds to pO2 dec., pCO2 inc.
y CNS area most sensitive to osmotic shifts
Pons Pathology
y Locked-in Syndrome
y Central Pontine Demyelinolysis y Central Pontine Demyelinolysis
Medulla
y Controls ALL basic functions
y Respiration of 8-10 ipm
Make sure you know the cranial nerves !
Midbrain 3,4
Medulla 9,10,11,12
Pons 5,6,7,8
236
4/29/2008
18
How Do I Figure
Out Any Lesion? Out Any Lesion?
You know its a spinal cord
lesion when
y Pain and temperature loss is opposite to
all other deficits
y Level of the lesion is two dermatomes above
where pain and temperature loss begins and on the
opposite side (Lesion L2- loss at L4)
You know its a CNS lesion
when
y UMN signs on one side of the body
y ( upper and lower extremities)
y Then the lesion is on the opposite side of the brain
y Use the cranial nerves to locate the level of the
lesion
THE END !
Too slow grasshopper !!!!
237

10/13/2008
1
Hematology
Hasenchecheg Qi MD., Ph.D. D Hasenchecheg Qi MD Ph
Red Blood Cell
Hemoglobin
1. A Hb is composed of:
1). four globins, proteins
pair of alpha (a2): located on chromosome 16
pair of beta (b2): located on chromosome 11.
2). four heme groups, with the iron compound which binds with the O2
2. Hb has 2 forms:
T (taut) low affinity for O2
R (relaxed) high affinity for O2
3. Function
1). In the lungs, each iron on Hb combines O2 reversibly.
2). Each Hb also has attached a single cysteine, which attracts nitric oxide (NO
).
3). The enriched Hb circulates to the tissues, where the NO dilates the small ca
pillaries,
allowing to deliver O2 to the tissues.
4). Then the O2- and NOfree Hb picks up CO2 and free NO and transports both back
to
the lungs, where they are exhaled as waste.
5). When RBC are destroyed
the hema (iron) is stored in the liver for the manufacture of new red blood cell
s.
Globins is converted into bile and stored in the gall bladder
Hemoglobin
1. Hb A 2 2 m.c.
2. H A2 2 2 2.5% ch
in synthesis egins l
te in the
thir trimester
n in
ults
3. H F 2 2 m.c. in the
fetus
small amounts in an adult, may be
abnormally elevated in certain forms
of anemia of anemia
4. Hb S sickle-cell
hemolobin
5. Hb H 4 An
norm
l H is not effectively
tr
nsport O2, it is usu
lly
ssoci
te
with
-th
l
ssemi
synrome.
6. B
rts 4 An abnormal Hb that is not effective in
O2 transport, found in -th
l
ssemi
.
H <11 mg/l
MCV (80100) MCV < 80 MCV > 100
1. T h
l
ssemi

2. A OC
3. Iron eficiency
i

1. B12 eficiency
2. Fol
te Deficiency
3. Alcoholic Liver
Reticulocyte
< 2.0 %Low > 2.0% high
Anemi

nemi
4. L e
 Poisoning
5. S iero l
stic

nemi

ise
se
4. Drug inuce
1. M
rrow f
ilure
2. A pl
stic
Anemi

3. M yelofi rosis
4. C
m
t
st
sis
5. A OC
6. R en
l f
ilure
2. All the

utoimmune

nemi

1. All the
hemolytic

nemi

Intr
v
scul
r
Extr
v
scul
r
1. S ickle Cell Dise
se
2. H em
glu in C
Dise
se
3. G-6-P-D eficiency
4. T hel
ssemi
M
jor
5. P NH
Hereit
ry
Spherocytosis
Heme Synthesis (mitochonri
)
Glycine + Succiny CoA
-Aminolevulic
ci
Propho ilinogen
ALA ehyr
se
Le
 (P )

ALA Synth
se
R
te limite
B6 +
Siero l
stic
Anemi

Uroporphyrinogen-III
Protoporphyrin IX (protoheme)
Heme
Uroporphyrinogen-I
synth
se
Ferrochel
t
se Fe2+ Le
 (P )
Acute Intermittent
Porphyri

Iron Deficiency
Anemi

238
10/13/2008
2
Siero l
stic Anemi
Le
 Poisoning
c
use Symptoms
1. ecre
se Vit B6 (m.c.) 1. L e
 L ine: in gums
2. isoni
zi ther
py 2. CNS : E nceph
p
thy,
3. A omin
l p
in (le
 colic)
4. PNS: wrist
n foot D rop
Di
gnosis:is: Di
gnosis:is:
Microcytic Anemi

Di
gnos Di
gnos
1. BM: ring siero l
st
(most specific test)
An erythro l
st cont
ining
gr
nules of ferritin
1. loo le
 level > 10 g/l
2. incre
se free erythrocyte
protoporhyrin
2. L
3.
sophilic stippling (remn
nts of
RNA) :
Tre
tment Tre
tment
Pyrioxine succimer (PO), EDTA
Acute Intermittent Porphyri
Porphyri
Cut
ne
T
r

Uroprophyrinogen-1 Synth
se
eficiency

Uroprophyrinogen
ec
r oxyl
se eficiency
Clinic
l Fe
ture Clinic
l Fe
ture
1. AD, v
ri
le expression 1. Photosensitivity
2.
cute
omin
l p
in 2. listeringg of skin
Microcytic Anemi

p
multiple l
p
roscopies (sc
rs on

omen)
3.psychotic ch
nges
4. incre
se ALA
n PBG
(propho ilinogen)
5. no photosensitivity
6. Contr
inic
te:
r itur
te
Anemi
of Chronic Dise
se (AOCD)
Definition L
Tre
tment
1. Iron eing tr
ppe in
one m
rrow
m
croph
ges, c
uses
in
ility to use of iron in
stores.
1. serum ferritin
elev
te
2. serum iron low
3. reticulocyte count
low lo
2. long term chronic
ise
se c
use ecre
se
liver functions,
1. ecre
se protein
synthesis
2. Tr
nsferrin low =
TIBC low
3. It c
n e microcytic or
normocytic
reticuloenotheli
l
system
Anemi
of Chronic Dise
se (AOCD)
Iron eficiency Anemi
Iron eficiency Anemi

C
use 1. ecre
se int
ke or
Incre
se em
n
elerly, chilren, pregn
nt women
2. ecre
se
sorption:
(m
l
sorption)
1) ecre
se
ci (Vc)
2) Dumping Synrome: ecre
se
sm
ll intestine tr
nsit time
3)
fter g
strectomy
3. chronic loo loss
(m.c.))
1) GI C
(m.c. in USA)

2) GYN leeing ( 2) GYN leeing

3) Hookworm (m.c. rest of the worl)
Sequence
event ue
to iron
eficiency:
1. ecre
se stor
ge iron in
intestin
l mucos
, spleen,

n liver
Decre
se ferritin
2. ecre
se circul
ting iron Decre
se serum iron
Incre
se TIBC
3. form
tion of
microcytic/hypochromic

nemi

Decre
se RBC size
239
10/13/2008
3
Iron eficiency Anemi

Symptoms 1. Gener
l Low energy st
te, p
llor of skin
n n
ils,
2. others 1. Koilonychi
: spooning of the fingern
ils
2. Pic

L
H , MCV, Ht Decre
se
RDW ecre
se
Serum iron ecre
se
Tr
nsferrin (TIBC) incre
se
ferritin ecre
se ferritin ecre
se
microscope microcyte

nisocytosis
norm
l size
poikilocytosis
norm
l sh
pe
Di
gnosis 1. epen on l

2. efinitive Dx: one m
rrow
Tre
tment 1. iet
2. ferrous sulf
te t
lets
3. p
renter
l iron
4. loo tr
nsfusion: most effective
Terminology
1. H Hemoglo in F12-15 g/l,
M 13-16g/l
2. Ht (Hct) Hem
tocrit % of RBC in the loo 40 --50%
3. MCV me
n cell (corpuscul
r) volume 80100
4. MCH me
n cell hemoglo in 25.435 pg/cell
5. MCHC me
n cell hemoglo in concentr
tion 3136 g/l
6. RDW re cell istri ution with (A me
sure
of the v
ri
tion in size of re loo
cells)

612%)
7. Reticulocyte imm
ture RBC (1 
y, norm
l 1.5%)
< 1%, poor one m
rrow response
> 1%, goo one m
rrow response
Bluish color (polychrom
si
) ue to
free ri osome RNA
Terminology
serum iron 100mg/l
Ferritin 1. physiologic
l stor
ge iron form
2. intestin
l mucos
, spleen,
n liver
Hemosierin 1. egr
e ferritin + lysosom
l e ris
2. Prussi
n lue positive
Tr
nsferrin A et
glo ulin in loo serum th
t com ines with
n
tr
nsports iron.
Tot
l iron- ining
c
p
city (TIBC):
1. me
ns tr
nsferrin level
2. Tr
nsferrin = TIBC = 300 mg/l
% s
tur
tion of
tr
nsferrin
serum iron/TIBC = 1/3
Microcytic Anemi

Iron
eficiency
AOCD Th
l
ssemi

minor
Siero l
stic

nemi

serum
Iron
ecre
se ecre
se norm
l incre
se
serum ecre
se incre
se norm
l incre
se
Go B
ck
serum
ferritin
ecre
se incre
se norm
l incre
se
TIBC incre
se ecre
se norm
l ecre
se
%
s
tur
tion
ecre
se ecre
se norm
l incre
se
B12 Deficiency Anemi

C
uses
1. Diet
ry
eficiency
1. B12 in re me
t
n fishe

2. B12 stores
t oy for more th
n 1 ye
r supply.

3. strict veget
ri
ns,
lcoholism
2. Decre
se

sorption
1. ecre
se IF, g
strectomy or pernicious
nemi

2. P
ncre
tic insufficiency
3. intestin
l m
l
sorption

. p
r
sites: fish t
pewormp iphyllo othriump l
tum p y
.
cteri
: lin-loop synrome
c. Crohns ise
se
Sign
n symptom
1. eefy tongue ue to gener
lize epitheli
l
trophy
2. peripher
l neurop
thy
3. SCDSD: (Su
cute com ine egener
tion of the spin
l cor)
ii. emyelin
tion of the posterior columns
n l
ter
l corticospin
l tr
cts
n
spinocere ell
r tr
cts
iii. Urin
ry
n fec
l incontinence, impotence
iv. Dementi

B12 Deficiency Anemi

Di
gnosis
1. peripher
l sme
r M
cro l
stic
nemi
, hypersegmente
neutrophils
2.
nti-IF: initi
l test sensitivity 50-80% , specificity 100%
3. serum homocysteine
incre
se
Due to fol
te or B12 eficiency
4. incre
se
methylm
lonichylm
lonic
cii
only ue to B12 eficient
met
c
5. Schilling test: over the 24 hours,
norm
l result shows
t le
st
10% of the or
l int
ke r
io
ctive vit
min B12 will
e in the urine.
i. B12 injection + r
iol
elle B12 or
lly
ii. B12 injection + r
iol
elle B12 or
lly + IF
Tre
tment Tre
tment
B12 or
l
Or p
renter
l
After give B12, m
y evelop hypok
lemi
in 48
hrs, ec
use pot
ssium r
pily go into cells
240
10/13/2008
4
Fol
te Deficiency
Fol
te Deficiency
1. cont
in in green le
ves veget
le
2. 3 month supply
C
use y
1. c
use y te

n to
st life-style
2. Methotrex
te
3Ph. ttoin i
Go B
ck

3 Pheny
4. Pregn
ncy
L

1. serum homocysteine incre
se: ue to oth fol
te
n B12 eficiency
Tre
tment
Folic
ci
Autoimmune Hemolytic Anemi
(AIHA)
W
rm AIHA Col AIHA
Mech
nism The IgG
tt
ch to
RBC,
le
ving their FC portion
sticking out. The FC is
recognize
n gr
e onto
y monocytes
n
m
croph
ges in the spleen.

nti oies initi
te

complement lysis of
re loo cells
Anti oy 1. IgG to Rh type 1. IgM
2. IgA
C
use 1. Methylop

2. Penicillin
1. Quiniine
coom s test + IgG, or IgG + C3 C3
Col
gglutinin neg
tive positive
Tre
tment 1. steroi
2. splenectomy
3. tre
t c
uses
4. Cyclophosph
mie
1. Cyclophosph
mie
2. Chlor
m ucil
Normocytic Anemi

Intr
v
scul
r (SH GTP) Extr
v
scul
r Micro
ngiop
thic
Hemolytic Anemi

incre
se methemoglo in
(oxiize hemoglu in)
Rx; methylene lue
no methemoglo in 1. incre
se shictocytes
(fr
gmente RBC)
2. Helmet cell
m
rkely ecre
se ecre
se
h
ptoglo in heptoglo in
1.
2.
3.
4.
5.

S ickle Cell Dise
se

H em
glu in C Dise
se
G-6-P-D eficiency
T hel
ssemi
M
jor
P NH

Hereit
ry
spherocytosis
1. D IC
2. T TP
3. H US

4. P rosthetic He
rt V
lve

5. H ELLP
Hereit
ry Spherocytosis
Definition 1. AD,
2. efect spectrin in RBC mem r
ne
Clinic
l
fe
ture
1. splenomeg
ly
2. incre
se risk for
cute
pl
stic crisis with P
rovirus
B19 infection
L
1. incre
se spherocytes
2. normocytic hyperchronic
3. incre
se MCHC
4. incre
se osmotic fr
gility
Rx
Sickle Cell Di
sese Hemoglo
single nucleotie ch
nge in
v
line (neutr
l) to repl
ce

ci (
ciic)
t 6 position
ch
in

in C Dise
se
coon c
sues
norm
l glut
mic
of the -glo in

single nucleotie ch
nge in

coon c
uses lysine (
sic) to
repl
ce norm
l glut
mic
ci
(
ciic)
t 6 position of the glo in ch
in
Hemoglo in S Sign:
1. ecome less solu le uner ecre
sing
oxygengen concentr
tionsr
tions
1. splenomeg
ly
Sickle Cell Dise
se
oxy concent
2. The eoxygen
te molecules form rigi
ros c
lle polymers into cryst
ls th
t istort
the re loo cells into
sickle sh
pe.
2. t
rget cell
3. These
norm
lly sickle-sh
pe cells
re
oth rigi
n sticky.
3. ro-sh
pe cryst
ls in RBCs
Genitic types
1. heterozygous (AS): tr
it
loo urine
n resist
nce to m
l
ri

2. Homozygous (SS):Sickle cell ise
se
Sickle Cell Dise
se
Affecting f
ctors 1. incre
se concentr
tion (ehyr
tion), m
ke it
worse
ecre
se concentr
tion m
ke it etter
2. Decre
se pH ecre
se oxygen
ffinity: worse
3. incre
se H F: etter
Incre
sencre
se RBC 1. Erythroirythroi hyperpl
si
perpl
si
I RBC
estruction c
use

1 E hy
2. incre
se

iliru in

241
10/13/2008
5
V
so-occlusion
1. H
n-foot synrome (
ctylitis) 1st sign of SD, in chilren
2. V
so-occusive (p
inful) crisis Rx: 1. Self limiting, l
st 2-7 
ys
2. hyr
tion: NS
3. Morphine for p
in
4. keep w
rm
5. Oxygen
3. Autosplenoectomy 1. Howell-Jolly oies in peripher
l loo:
tff lle
r hhrom
tin ti
Sickle Cell Dise
se
remn
nt o nuc c
2. incre
se infection of enc
psul
te
org
nisms, Rx: v
ccin
tions
4. Leg ulcers incre
se S
lmonell
osteomyelitis (leg p
in)
5. Av
scul
r necrosis of the joints M.c. hip, 2n shouler
6. Pri
pism Emergencies, Rx: tr
nsfusion
7. Acute chest synrome Emergencies, Rx: tr
nsfusion
8. Apl
stic crisis with infection of B19, Rx: folic
ci
Tre
tment 1. Hyroxyure
; incre
se H F
2. BM tr
nspl
nt
tion
G-6 PD Deficiency
G-6 PD Deficiency
G-6 PD eficiency c
uses ecre
se glut
thione peroxi
se
(
ntioxi
nt)
Clinic
l Fe
ture
1. X-link R
i. Afric
n Americ
n type:
ii. Meiterr
ne
n type
2H. iinz oies: i ii
tion ti ff hemoglo in l i 2 He
3. Bite cell: to e
t heinz oies y splenic m
croph
ges
Tre
tment

ox o h

Th
l
ssemi
Synrome
Definition: qu
ntit
tive, not qu
lit
tive,
norm
lities of hemoglo in
1. -th
l
ssemi
2. -th
l
ssemi

1. ecre
se -glo in ch
ins ,
excess -ch
ins
1. ecre
se -glo in ch
ins,
excess -ch
ins
2. most commen in Asi
n popul
tion 2. most common in Meiterr
ne
n
3. expression in pren
t
lly
n
postn
t
llytn
t
lly
expresse postn
t
lly only
pos
-Th
l
ssemi

Genetic
Norm
l

4 -ch
in (/)
Silent c
rrier 1. eletion 1 -ch
in
2. (-/),
-Th
l tr
it
(minor)
eletion 2 -ch
in 1. Genotype: cis (--/) type
in Asi
n
2G. type: tr
ns (- /- ) 2 Genot t ( / )
type in Afric
n-Americ
n
H H ise
se
(m
jor)
1. eletion 3 -ch
in
2. (--/-)
1. incre
se H H,
2. forms Heinz oies
Hyrops fet
lis 1. eletion 4 -ch
in,
2. leth
l in utero (--/--)
incre
se
rts H
-Th
l
ssemi

Genetic 1. norm
l: 2 ch
ins,
2. point mut
tions,
1. -Th
l minor
symptom
tic, incre
se H A2 or H F
2. -Th
l intermei

severe
nemi
, ut no tr
nsfusions neee
3. -Th
l m
jor
(Cooley Synrome)
1). norm
l
t rith
2). evelop
t
out 6 month
s H F ecre
se
3). severe hemolytic
nemi


. incre
se iliru in, g
llstones
. Congestion he
rt f
ilure is most common c
use of
e
th
4). Erythroi hyperpl
si
in BM: x-r
y: crewcut skull ,
chipmunk f
ce
5). Peripher
l in the loo: Numerous t
rget cells
Tre
tment 1. o not require specific tre
tment
2. -m
jor: loo tr
nsfusions 1 or 2 / month:
SE: Hemochrom
tosis, tre
t with eferox
mine
3. splenectomy elimin
tes severe hemolytic
nemi
:
4. Bone m
rrow tr
nspl
nt
tion
242
10/13/2008
6
PNH
P
roxysm
l Nocturn
l Hemoglu inuri

ecre
se glycosyl phosph
tiyl inositol (GPI) linke proteins, especi
lly
ec
y
cceler
ting f
ctor (DAF)
Function of DAF:
1. inhi it the
ctiv
tion of the complement c
sc
e y re
king own C3
convert
se
2. ecre
se O2, trigger complement p
thw
y
Symptomsmptoms
n Complic
tion
tion Sy
n Complic

pl
stic
nemi
, leukemi
, venous throm osis
Di
gnosis
1. H
ms test (Aciosis in vitro)

2. sucrose lysis test (sug
r w
ter test)

3. flow cytometry: CD55, CD59, much more sensitive
n specific
Tre
tment
1. Glucocorticois
2. BM tr
nspl
nt
tion
Summery
RBC sh
pes Dise
ses
Anisocytosis Iron eficiency
nemi

Poikilocytosis Iron eficiency
nemi

Shperocytes 1. hereit
ry spherocytosis
T
rget cells Th
l
ssemi
, H C ise
se, Liver Dise
se
Bite cell G6PD eficiency
Te
rrop cells Myelofi rosis
Elliptocytes Hereit
ry elliptocytosis
Ac
nthocytes
et
lipoproteinemi

Echinocytes ( urr cells) uremi

Schistocytes (Helmet cells) HUS, DIC, TTP
Roule
ux Multiple myelom

Summery
RBC
inclusions
Dise
ses
B
sophilic
stipling
Cytopl
smic remn
nt
RNA
Le
 poisoning
Howell-Jolly ell Joll Remn
nts of nucle
r cle
r Iron eficiency
nemi
Ho
oies
Remn
nts of n
chrom
tin
Iron eficienc
nemi

Ring
siero l
sts
Iron tr
ppe

norm
lly in
mitrochonri
forming

ring
roun nucleus
Siero l
stic
nemi

Heinz- oies G6PD
Other types Anemi

1. Di
mon-Bl
ckf
n Synrome:
congenit
l pure RBCs
nemi

2. F
nconi
nemi
(Constitution
l)
pencytopeni
with
norm
l structures
243
10/13/2008

1
Hemost
sis
Bleeingg Disorer
H
senchecheg Qi MD., Ph.D.
3:1 = M:E (myeloi to erythroi) r
tio.
Bleeing
Hemost
sis
Hemost
sis
1. v
scul
r w
ll
injury
1. lee
2. tr
nsient
v
soconstriction
ch
nges loo flow c
use
tur ulence
n st
sis
Reynols num er = (i
meter)
(velocity) (ensity)/viscosity
> 2000 = tur ulent flow
< 2000 = l
min
r flow
3. throm ogenic f
ctors 1. rele
se tissue f
ctor,
ctiv
te
VIII ( tirinsic i ) VI (ext )
2.
ctive f
ctor XII (intrinsic)
ue to expose su enotheli
l
coll
gen
3. rele
se vWF
2. tr
nsient clotting pl
telet clotting leeing time 27 min
3. Secon
ry
clotting
Extrinsic Co
gul
tion
f
ctor
PT: P rothrom in T ime 12sec
Intrinsic Co
gul
tion
f
ctor
PTT: P
rtic
l T hro opl
stin
T ime 30sec
Ahesion
Aggreg
tionggreg
tion
1. pl
telets

hesion
1. vWF
heres
to su enotheli
l
coll
gen
2. Pl
telets

here to vWF
y glycoprotein I
2. pl
telets

ctiv
tion
1. pl
telets
ch
nges sh
pe

n

egr
nul
tion
Pl
telets
A
2. synthesis of
TXA2
3. pl
telets

ggreg
tion
1. ADP
clopiogrel,
Ticlopiine
2. TXA2
3. GpII /III

A cixim
,
Eptifi
tie,
Tirofi
n
ADP
Co
gul
tion F
ctors
Vit
min K
Glut
myl C
r oxyl
se
244
10/13/2008
2
Throm omoulin (tr
nsmem r
ne protein)
Throm in
(60 hrs)
Protein C
(H
lf life 14 hrs)s)
C-
ctiv
te protein
+
(H
lf life 14 hr
Protein S
In
ctiv
tes
F
ctors V

n VIII

+
F
ctor V leien:
v
ri
nt of f
ctor V
W
f
rin:
Tr
nsient eficiency
of protein C
Bleeing Disorer
Pl
telet 150,000450,000/mm 3 leeing time: 27 min

1. Decre
se Pl
telet

ccount
2. A norm
l Pl
telet
function
3. Von Wille r
n
Dise
se (vWD)
AD/AR, vWF 1. leeing time prolong
2. ristocetin

ttri ute to F
ctor 8
eficiency
3. PTT prolong
Rx: Desmopressin

cet
te (DDAVP)
4. Bern
r-Soulier
Synrome
Gp I eficient Rx: Pl
telet
5.Gl
nzm
nn
Throm
stheni

Gp II /III
eficient Rx:
I mmune
T hrom ocytopeni

P urpur

T hrom otic
T hrom osytopeni

P urpur

H emolytic
U remic
S ynrome
D issemin
te
I ntr
v
scul
r
C o
gul
tion
1.
nti-pl
telet F ever
A nemi

T hromcytopeni

Di
rrhe

Ren
l f
ilure
1. D-imers
2. Incre
se BM
meg
k
ryocyte
2. Pl
telet count
ecre
se
3.
cute form: chil

fter vir
l infection
R en
l f
ilure 3. Bleeing time incre
se
4. chronic:
ult N europ
thyop
thy 4. PT
n PTTT incre
see
se
Throm ocytopeni

4 chronic:
ult
women 20-40 yo
N eur 4 PT
n PT incr

Tre
tment Tre
tment Tre
tment Tre
tment

1. chil self limite in
6mo, or prenisone
pl
sm
pheresis 1.
ult:
pl
sm
pheresis
1. supportive
2.
ult

. prenisone
. IVIG,
nti Rh (D): f
st
c. splenoectomy,
V
ccine
. pl
telet tr
nsfusion
2. chil:
self limite
2. FFP
3. Cryoprecipit
te
4. tre
t c
uses
Throm ocytosis (re
ctive) Essenti
l Throm ocythemi
(ET)
C
use Clinic
l Fe
tures
1. Bleeing, hemolysis 1. Incre
se pl
telet count
2. Infl
mm
tion 2. incre
se BT
3. Iron eficiency, Stress 3. incre
se BM meg
k
ryocytes
4. ttsplenectomy l t
Throm ocytosis
4 pos
5. M
lign
ncy
Disorer of Co
gul
tion
von Wille r
ns Dise
se Hemophilli
A Hemophilli
B
vWF eficiency, VIII eficiency, IX eficiency,
AD/AR, XR, XR,
M
y h
ve VIII eficiency vWF norm
l
Clinic
l Fe
ture Clinic
l Fe
ture
1. Cut
neous
n mucos
l leeing 1. joint
n soft tissue leeing
2. Menorrh
gi
, 2. Hem
rthrosis: m.c.
3. GI leeing 3. Intr
cr
ni
l leeing: 2n m.c.
Di
gnosis i Di
gnosis i Di
gnosis i Di Di Di
1. BT incre
se, m
y with incre
se PTT 1. PTT incre
se 1. PTT incre
se
Tre
tment Tre
tment Tre
tment
Do not give Aspirin/NSAIDs
1. DDAVP (esmopressin) 1. f
ctor VIII 1. f
ctor IX
2. F
ctor VIII concentr
tions,
give
ll Pt with vWD
fter m
jor tr
um

or uring surgery
(reuce ristocetin-inuce pl
telet

ggreg
tion)
2. FPP not recommene ec
use virus infections
Tre
tment of Acute hem
rthrosis
1. An
lgesi
, (Coeine)
2. Immo iliz
tion
3. Synovectomy (
rthroscopic) or r
iosynovectomy
for severe
n recurrent hem
rthrosis

Hyperco
gul
tion
1. XII eficiency Throm osis, no
2. XIII eficiency R
re,
new orn leeing from cut
um ilic
l cor

leeing PTT prolong,

Norm
l PT
n PTT

Dx. Clot solu ility test in 5M
ure
, positive
3. Antithrom in (AT)
III eficiency
Throm osis PTT prolong
4. Antiphospholipi

nti oyi oy Synromeynrome
Throm osis
Recurrent
ortion
PTT prolong

nt S
5. F
ctor V leien Leien v
ri
nt of f
ctor V,
(Activ
te protein C
resist
nce)
recurrent DVT
Rx: life-
long
ntico
gul
tion
(W
rf
rin)
6. Protein C
Deficiency
Active F
ctors V

n VIII
1. erm
l v
scul
r throm osis
2. skin necrosis
7. Protein S
Deficiency
245
10/13/2008
3
Pl
sm
: no cells from loo
Serum: no co
gul
tion f
ctor from pl
sm
.
inclue
ll the ion
n
nti oies, immunoglo ulin.
Streptokin
se
Urokin
se
+
Altepl
se (tPA)
Retepl
se (rPA)
Anistrepl
se
Throm olytics
Antico
gul
tion Meic
tions
Hep
rin LMWH W
rf
rin
Low-Molecul
r Weight Hep
rin VIt K
nt
gonist
Inhi it II

n X
Mostly inhi it X
Inhi it II, VII, IX, X,
n protein C
n S
H
lf-lift time H
lf-lift time H
lf-lift time
1 hour 3-24 hours 4 
ys
Aministr
tion Aministr
tion Aministr
tion

1. ther
peutic ose:
IV hep
rin, monitor PTT
1. su cut
neously
PTT monitor not necess
ry
1. or
lly: monitor PTT, Monitor INR (2-3)
2. prophyl
ctic ose:
SC low-ose ose hep
rin, SC low hep
rin
PTT monitor not necess
ry
SE
n Av
nt
ge SE
n Av
nt
ge SE
n Av
nt
ge
1. Bleeing 1. e
ser use out Pt 1. Hemorrh
ge
2. Hep
rin-inuce
throm ocytopeni
(HIT)
2. no HIT or osteoporosis 2. skin necrosis ( ecre
se protein C)
3. Osteoporosis 4. no osteoporosis 3. Ter
togenic uring pregn
cy
4. Tr
nsient
lopeci
5. more expensive
5. re oun hyperco
gul
ility
/t epression of ATIII
SE Tre
tment SE Tre
tment
1. stop meic
tion, 2. Give PPF, 3. W
rferin over ose m
y
lso give Vit K
246
10/13/2008
4
247
10/13/2008
1
Lymphom

&
Leukemi
k i L
H
senchecheg Qi M.D.; PH.D.
3:1 = M:E (myeloi to erythroi) r
tio.
Lymphom

Precursor
B-Cell
M
ture
B cell
ALL T-ALL
Precursor
T-Cell
M
ture
T cell
Pl
sm
Cell
Neopl
sm

1. Multiple myelom

2. MGUSS (Monoclon
l G
mmop
thy
mmop
thy

Non-Hogkin Dise
se HD
1. not infections
Not B-cell
Not T-cell
< 15 ye
r ol
Positive TT
Thymom

< 25 ye
rs ol
2 MGU (Monoclon
l G
unetermine signific
nce)
3. W
lenstrom m
croglo ulinemi

2. owl-eye
3. R-S cell
1.
2.
3.
4.

NS: m.c. L
cun
r cell

LP: popcorn cell
LD: most RS cell
Mixe: eosinophils, IL-5

1. L1
2. L2
3. L3
Acute Lympho l
stic Leukemi

1. ATLL
2. MF
n Sez
ry S.
Termin
l Deoxynucleotie
tr
nsfer
se
Lymphom

M
ture B cell
Non-Hogkin Dise
se HD
If > 65 ye
rs ol
1. CLL: m.c.
chronic lymphocytic leukemi
, or
sm
ll lymphocytic lymphom

1. Follicul
rul
r 1. m.c.c. non-HDHD 18:
2. H
iry cell leukkemi

Dx: TRAP +
Rx: 2CDA
1. Follic
Lymphom

1. m. non
2. t (14, 18)
18: cl inhi it

poptosis y locking the

x ch
nnel
2. Diffuse l
rge Bcell lymphom

1. EBV
2. HHV-8

cl-2:2: inhi itss

3. S
mll noncle
ve
lymphom
(Burkitt
lymphom
)
1. st
rry-sky
2. t (8, 14)
8: c-myc
4. M
ntle Cell
Lymphom

T (11, 14) 11:

cl-1 (cyclin D)

5. MALTom

(M
rgin
l zone
Lymphom
)
Tre
t
s H.pylori
2chloroeoxy
enosine
T
rtr
te-resist
nt
ci
phosph
t
se
Leukemi

AML
CML
1. M0M4: myelo-, WBC
2. M3t: (1517),
BM l
st <30%
MDS
ET P. ver

Myeloprolifer
tive Synrome
MF
BM l
st > 30%
1. t (9, 22) 2 M3 t (15 17)
15: PML
17: retinoic
ci receptor -gene
(RAR-)
3. M5: mono l
sts
4. M6: erythro l
sts
5. M7: meg
k
ryocytes
1. Dry t
p
2. Te
rrop RBC
1 t (9 22)
9: c-
l
22: cr
2. LAP low
248

Biochemistry:
Week Three
261 249
262 250
1
BIOCHEMISTRY
AMINO ACIDS
Three sources of energy
Proteins
F
ts
Sug
rs
Proteins
The m
in intr
cellul
r uffers
AMINO ACIDS
An Aci
Pk
is less th
n 7
A B
se
Pk
is gre
ter th
n 7
263 251
2
An Aci

Dissoci
tes e
rly
Likes to give up hyrogen ions (protons)
Pk
is less th
n 7
Strong
ci: Pk
1 to 3
We
k
ci: Pk
4 to 7

A B
se

Dissoci
tes l
ter
Likes to
ccept hyrogen ions (protons)
Pk
gre
ter th
n 7
We
k
se: Pk
7 to 9
Strong
se: Pk
gre
ter th
n 9

Pk
4 to 9
C
n e
we
k
ci or
we
k

se
Three E
sy Wors Th
t
re H
r
To Unerst
n

Dissoci
te: to lose
hyrogen (proton)

Solu le: ch
rge or pol
r
Bio
v
il
le: neutr
l
Dissoci
tion
Dissoci
tion
To Lose A Hyrogen
264 252
3
Solu le Solu le
Ch
rge Or Pol
r
Solu le
W
ter Solu le
Bio
v
il
le
Bio
v
il
le
Neutr
l
Bio
v
il
le
F
t Solu le
265 253
4
AMINO ACIDS As
n
ci issoci
tes
It g
ins
neg
tive ch
rge
It g
ins solu ility
It loses io
v
il
ility
As

se issoci
tes
It loses its positive ch
rge
It loses solu ility
It g
ins io
v
il
ility
Henerson-H
ssel
ck Equ
tion
Henerson-H
ssel
ck Equ
tion ACIDS

IF you w
nt to
sor more

A more Aci
IF you ont w
nt to
sor it
A
se

266 254
5

B
se

IF you w
nt to
sor more

A more
se
IF you ont w
nt to
sor it
A
ci

Acis you nee to know

Aspirin
B
r itur
tes
Myoglo in
TCAs
B
ses you nee to know
Amphet
mines
The m
in
ci use in
meicine
NH4CL
The m
in
se use in
meicine
HCO3
Now we look
t the ISOELECTRIC
POINT
267 255
6
Isoelectric Point
NO NET ch
rge on the molecule
Also c
lle
zwitterion
Will NOT migr
te tow
rs
noe or
c
thoe
C
thoe
Where CATIONS go: the
neg
tive electroe
Anoe
Where ANIONS go: the positive
electroe
268 256
7
To further c
tegorize the

mino
cis
Glycine

Sm
llest
mino
ci

NO chir
l c
r on
Inhi itory neurotr
nsmitter for the spin
l
cor
PHE, TRP, TYR
Arom
tic
mino
cis
Recognize y chymotrypsin
LYS, ARG
B
sic
mino
cis
H
ve
positive ch
rge
Recognize y trypsin
Asp, Glu
Aciic
mino
cis
269 257
8
Asp
The only excit
tory
mino
ci in the
( NMDA p
thw
y)
Cys, Met
Cont
in sulphur
M
ke isulphie ons
Asp
r
gine, Glut
mine
Involve in N- ons
Serine, Threonine, Tyrosine
Involve in O- ons
Leu, Iso, V
l
Br
nche ch
in
mino
cis
Tyr
Use to m
ke c
techol
mines
Use to m
ke mel
nin
270 258
9
Trp
Use to m
ke serotonin
Ketogenic Amino Acis

r
in

Lysine
Arginine
Both glucogenic
n ketogenic
P
I
T
T

HE
SO
HR
RP

Glucogenic Amino Acis

ALL OTHERS
Essenti
l Amino Acis
You get them ONLY from the iet
NO cycle in YOUR oy c
n m
ke these
A eficiency will ALWAYS le
 to

ise
se
Deficiencies put the oy into
st
rv
tion
st
te
Essenti
l Amino Acis
271 259
10
How oes the oy utilize energy
uring st
rv
tion?
Energy Utiliz
tion
(1)
(2)
(3)
(4)
(5)

pl
sm
glucose: l
sts 2 to 4 hours

liver glycogen: l
sts 24 to 28 hours
proteolysis for gluconeogenesis
lipolysis
ketogenesis

Not
les
PHE use to m
ke TYR
TYR ecomes essenti
l if PHE is eficient
MET use to m
ke CYS
CYS ecomes essenti
l if MET is eficient
Phenylketonuri

Phenyl
l
nine hyroxyl
se is eficient
Un
le to m
ke tyrosine
Un
le to m
ke DA
n NE
n EPI
Un
le to m
ke mel
nin without tyrosine
Blone h
ir; lue eyes; f
ir skin
Phenyl
cet
te
n phenylpyruv
te uil
up
Musty oor
PKU

 Must screen
ll new orns
t 48 hours

Must
voi
sp
rt
me (nutrisweet)
Pregn
nt mother must e on restricte iet
especi
lly uring first 8 weeks while r
in
is eveloping
R
in ow colore wheel on foo proucts
woul w
rn these p
tients
g
inst

sp
rt
me
New orn Screening
PKU ( Guthrie test)
Hypothyroiism (TSH)
CAH
Biotini
se ef
G
l
ctosemi

272 260
11
Al inism
Tyrosin
se eficiency
Preispose to skin c
ncer
Vitiligo
Autoimmune
nti oies
g
inst
mel
nocytes
Loss of pigment
tion
Preispose to skin c
ncer
Alc
ptonuri
(ochronosis)
Homogentisic
ci oxi
se eficiency
Tyrosine uils up
Urine turns l
ck when expose to
ir
M
ple Syrup Urine Dise
se
Involves r
nche ch
in
mino
cis
Defective ren
l tr
nsport of these
mino

cis
LEUCINE
ISOLEUCINE
VALINE
Cystinuri

Defective ren
l tr
nsport of
mino
cis
Hex
gon
l, envelope sh
pe, or coffin li
sh
pe cryst
ls in the urine
C YSTIENE
O RNITHINE
L YSINE
A RGININE
THE END

TO BE CONTINUED
273 261
1
Protein Structure

n Function
Putting the Amino Acis
Together
Protein Structure
Prim
ry
Secon
ry
Terti
ry
Qu
rtern
ry
Protein Structure

Prim
ry
Secon
ry
Terti
ry
Qu
rtern
ry

Prim
ry Structure
The
mino
ci sequence
Involves peptie ons
Restriction enzymes
re use to sequence
proteins
Peptie Bon Peptie Bon
Pl
n
r
Restricte mo ility
R-groups
re in tr
ns-configur
tion
274 262
2
Sequencing
Before we unerst
n the
present
We nee first visit the p
st!
The history of sequencing

Aci hyrolysis
Gel electrophoresis
Ninhyrin re
ction
Em
ns egre
tion
Restriction pepti
ses

Aci Hyrolysis

 Den
tures the protein

Does NOT
ctu
lly sequence the protein
Turns
sp
r
gine into
sp
rt
te (
ciic
form)
n glut
mine into glut
m
te (
ciic
form)
Gel electrophoresis
Uses
g
rose gel to sep
r
te proteins y
size first, ch
rge secon
Sm
ller proteins migr
te further
L
rger proteins st
y closer to the st
rt site
Does NOT sequence the proteins
Gel Electrophoresis
275 263
3
Ninhyrin Re
ction
Re
cts with
ll
mino
cis cre
ting

purple color
Proline re
ction cre
tes
yellow color
Goo ONLY for counting prolines
Em
ns egre
tion
Uses phenylIsoThioCy
n
te (PITC)
Re
cts with ANY
mino
ci st
rting on
the
mino termin
l
Amino
cis
re ientifie y
spectrophotometry (light tr
nsmission)
Proceure is
ccur
te ONLY up to 100

mino
cis
Restriction Pepti
ses
Restricte y wh
t
mino
cis they c
n
recognize
Use to
ctu
lly sequence proteins
Restriction Pepti
ses
Trypsin: cuts to the right of LYS
n ARG
Chymotrypsin: cuts to the right of the

rom
tic
mino
cis, PHE, TRP, TYR
El
st
se: cuts to the right of GLY, ALA,
SER
CNBr: cuts to the right of MET
Aminopepti
se: cuts to the right of the

mino termin
l
mino
ci
Restriction Pepti
ses, cont

 C
r oxypepti
se: cuts to the left of
ny

mino
ci on the c
r oxyl termin
l
Merc
ptoeth
nol: re
ks up isulfie ons
An Ex
mple
276 264
4
Secon
ry structure
Alph
helix
Bet
ple
te sheet
Alph
helix
Bet
ple
te sheet Serum proteins
Function
l
Acute ph
se re
ct
nts
Too m
ny proteins in your pl
sm

Elev
te ESR or CRP
Inic
tes nonspecific infl
mm
tion
F
lsely high ESR:
nemi

F
lsely low ESR: sickle cell
nemi
;
polycythemi

Acute ph
se re
ct
nts c
use y IL-6
TOO m
ny
cute ph
se
proteins
Le
s to AMYLOIDOSIS
277 265
5
AMYLOIDOSIS
Prim
ry:
utosom
l omin
nt
M
ssive intr
cere r
l hemorrh
ge in
young
person with no prior h/o HTN
Secon
ry: ue to
ny chronic
infl
mm
tory ise
se
Congo re st
in
Apple green irefringence
Secon
ry Amyloiosis
AA: chronic infl
mm
tory ise
se
AB: Alzhiemers ise
se
AB-2: Chronic ren
l f
ilure
AE
n AF: MEN-II
AL: Multiple myelom

Terti
ry Structure

 3-D structure
Most import
nt f
ctor is hyropho ic
n
hyrophilic inter
ctions
Cov
lent ons now form
Qu
rtern
ry Structure
Two or more proteins
re inter
cting
Cooper
tivity
Allosterism: refers to enzymes
Allosteric enzyme me
ns the slowest enzyme;
me
ns r
te-limiting enzyme; me
ns the
kinetic curve is sigmoi
lly sh
pe
Hemoglo in
The first qu
rtern
ry protein
iscovere
Hemoglo in
Type A: 2
lph
2

et
ch
ins

Type A-2: 2
lph
2 elt
ch
ins

Type F: 2
lph
2 g
mm
ch
ins
278 266
6
Hemoglo in F

Foun in the fetus

Dis
ppe
rs y 6 months of
ge
H
s
low
ffinity for 2,3, DPG
H
s
high
ffinity for oxygen

Hemoglo in F
Erythropoiesis
Begins: in yolk s
c
t 4 months gest
tion
6 mo gest
tion: moves into the liver,
spleen,
n fl
t ones
8 mo gest
tion: moves into the long ones
1 ye
r of
ge: liver, spleen,
n fl
t ones
close
If you lose the long ones
fter 1 ye
r, the
spleen c
n reopen c
using m
ssive
splenomeg
ly
Heme Synthesis
Iron eficiency
nemi

Most common c
use of microcytic
hypochromic
nemi

In chilren: Mcc is in
equ
te int
ke
In young
ults: Mcc is still in
equ
te

int
ke
20 to 40: IBD
>
ge 40: muc
s
l leeing
Tx: ferrous sulph
te
Le
 Poisoning
Le
 inhi its elt
ALA ehyr
t
se
s
well
s ferrochetol
se
Mcc: e
ting peeling p
int from ol
uilings
Cl
ssic clue:
sophilic stippling; elev
te
FEP (free erythrocyte protoporphrins)
279 267
7
Heme Synthesis Le
 levels to know
Norm
l: < 10
If
ove 10: notify PHD; tre
t with succimer
If
ove 30: notify PHD; hospit
lize; o

C
-EDTA ch
llenge; tre
t with
penicill
mine
n imerc
prol (BAL) if
urin
ry le
 is high
If
ove 50: o
s
ove; skip EDTA
ch
llenge
Drug inuce lupus
Antihistone
nti oies
Hyr
l
zine
INH
Proc
in
mie
Penicill
mine
Phenytoin
Ethusuximie
Le
 use to e the most
common c
use of ment
l
ret
r
tion
But NOT ANY MORE!
Ment
l ret
r
tion
Fet
l
lcohol synrome
Fr
gile X synrome
Downs synrome
Porphyri
s
A group of enzyme eficiencies
Synthesize too m
ny porphyrin rings or
in
equ
te met
olism
re the pro lems
Porphyrin rings in the urine m
ke it re
Two types
re most import
nt
280 268

8
Acute Intermittent Porphyri

Enzyme ificiency
A uil up of porhyrin rings
Porphyrin rings
re eposite in viscer
l
org
ns
n
roun nerves
Recurrent severe
omin
l p
in
n
neurop
thy
Tx:
Erythrocytic Protoporphyri

n
Porphyri
Cut
ne
T
r

Enzyme ificiency
Porphyrin rings
re eposite unerne
th
the skin
Light re
cts with the rings c
using

rele
se of he
t which le
s to urns
Mcc of e
th: skin infections
Tx: protect them from light
Opi
tes
CNS epress
nts
Muscle rel
x
nts
An
lgesics
Receptors:
Mu ( CNS)
K
pp
: Spin
l cor
Opi
tes

Heroin
Meth
one
Morphine
Meperiine
Coone
Oxycoone
Coiene
Dextromethorph
n

Loperimie
Diphenoxyl
te
Fent
nyl
Pent
zocine

Hemoglo inop
thies
Hemoglo in S ise
se
Hemoglo in C ise
se
Hemoglo in S ise
se
Autosom
l recessive
High prev
lence in Afric
( n
tur
l
selection)
Su stitution of v
line for glut
m
te
t
position 6 of et
ch
in

 Hypoxi
c
uses cells to sickle le
ing to

v
so-occlusion
281 269
9
V
so-occlusive crises
CVA
PULMONARY INFARCTION
SPLENIC SEQUESTRATION
PRIAPISM
Tx: exch
nge tr
nsfusion; oxygen
Apl
stic crisis
Complete one m
rrow suppression
Alw
ys check the reticulocyte count
Mcc: p
rvovirus B-19
A Few Points to Remem er
Function
l
spleni
y
ge 6 ue to
inf
rcts
Suscepti le to enc
psul
te org
nisms
Give pneumov
x
nytime
fter
ge 2
Infections
re mcc re
son for crises
Hyroxyure
incre
ses HgF, ecre
sing
ch
nce for hypoxi

Use opi
tes for p
in
Tr
nsfuse when
nemic
n symptom
tic
Hemoglo in C ise
se
Autosom
l recessive
Su stitution of LYS for GLU
t position 6
of et
ch
in
NO sickling occurs since oth
mino
cis

re hyrophilic
Th
llesemi
s
Represent gene eletions
Autosom
l recessive
Common in Meiter
ini
n people
Minor:
t le
st one gene rem
ining
M
jor: no genes rem
ining
Hemoglo ins
282 270
10
Alph
Th
lessemi
B
seline l
s
RBC M
ss: 3.5 to 4.5 million
Hemoglo in/Hem
tocrit: 15/45%

Alph
Minor

One gene missing

Asymptom
tic ( HG 12) 75%
Two genes missing
IF seent
ry:
symptom
tic
IF
ctive: symptom
tic (HG 7.5) 50%
Three genes missing
Symptom
tic in ALL (HG 4 to 5)

Alph
Th
lessemi
M
jor

NO genes rem
ining
Un
le to m
ke
ny hemoglo in
t
ll
Hyrops Fet
lis
Hemoglo in B
rt ( 4 g
mm
ch
ins)
Hemoglo in H ( 4 et
ch
ins)

Bet
Th
lessemi
: 2 genes

Bet
minor (Hg 7.5)
One gene missing
If seent
ry:

symptom
tic
If
ctive: symptom
tic
Incre
se Hg A-2
n
Hg F
Ineffective
erythropoiesis
Bet
m
jor
Both genes missing
A le to m
ke only Hg
A-2
n Hg F
Asymptom
tic until 6
months of
ge
Tr
nsfusion epenent
Bloo Tr
nsfusions

Done ONLY when p
tient is symptom
tic

One unit of PRBC s
R
ises Hg y 1 to 2 gr
ms ( 3 to 6 HCT)
Delivers 3.4 gr
ms of iron

283 271
11
Iron Overlo

Hemosierosis: one m
rrow is
overwhelme y iron
Hemochrom
tosis: iron overlo
 h
s
involve other org
ns
Skin: ronze pigment
tion
Liver: ronze cirrhosis
P
ncre
s: ronze i
etes
He
rt: restrictive c
riomyop
thy

Hemochrom
tosis
Prim
ry
Autosom
l recessive
Too much iron

sorption from
uoenum
HLA A3 on
chromosome 6
Secon
ry
Too m
ny tr
nsfusions
Mcc of e
th in first 10
ye
rs: tr
nsfusion
rel
te infections
Mcc of e
th
fter 10
ye
rs: CHF
Tr
nsfusion Rel
te INFECTIONS Tr
nsfusion rel
te infections
HIV B
cteri
l infections
Hep
titis B M
l
ri

Hep
itis C B
esiosis
Hep
titis D Syphilis
EBV
CMV
Hemorrh
gic viruses
Hemoglo in S
tur
tion Curve
COLLAGEN
284 272
12
More th
n
qu
rtern
ry
structure
Its
TRIPLE HELIX
4 Types of coll
gen

Type
Type
Type
Type

1:
2:
3:
4:

S
C
A
B

kin
onnective tissue
rteries

sement mem r
ne

To synthesize coll
gen
Glycine: every thir
mino
ci
Lysine
Proline
OH-Proline
OH-Lysine
Protein synthesis for p
ck
ging
Protein synthesis for p
ck
ging Protein synthesis for p
ck
ging

285 273
13
Protein synthesis for p
ck
ging Who m
kes coll
gen?
Fi ro l
sts: simple sc
rring
Myofi ro l
sts: if you nee woun
contr
ction
When coll
gen synthesis goes
wrong
DESMOPLASIA
COLLAGENOUS REACTION
SURROUNDING A TUMOR
KELOID
TOO MUCH COLLAGEN
DEPOSITION
COLLAGEN PROFILE
286 274
14
ALL YOU NEED NOW IS A CLUE
Coll
gen ise
ses
Ehlers D
nlos
M
rf
ns
homocystienuri

Scurvy
Osteogenesis imperfect

Minkys kinky h
ir synrome
Secon
ry coll
gen ise
ses

Ankylosing sponylitis
Fr
gile X synrome
Syphilis
T
k
y
sus ise
se

Coll
gen V
scul
r Dise
ses

CREST
Scleroerm

Progressive systemic
sclerosis
Rheum
toi
rthritis
Feltys synrome
Becets synrome
Sjogrens synrome