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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)
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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

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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


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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
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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
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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)

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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
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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 !!!!
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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% chin synthesis egins lte 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  norml H is not effectively
trnsport O2, it is usully ssocite
with  -thlssemi synrome.
6. Brts 4 An abnormal Hb that is not effective in
O2 transport, found in -thlssemi.
H <11 mg/l
MCV (80100) MCV < 80 MCV > 100
1. T hlssemi
2. A OC
3. Iron eficiency
i

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

nemi
4. L e Poisoning
5. S iero lstic
nemi
isese
4. Drug inuce
1. M rrow filure
2. A plstic
Anemi
3. M yelofi rosis
4. C  mtstsis
5. A OC
6. R enl filure
2. All the
utoimmune
nemi
1. All the
hemolytic
nemi
Intrvsculr
Extrvsculr
1. S ickle Cell Disese
2. H emglu in C
Disese
3. G-6-P-D eficiency
4. T helssemi Mjor
5. P NH
Hereitry
Spherocytosis
Heme Synthesis (mitochonri)
Glycine + Succiny CoA
-Aminolevulic ci
Propho ilinogen
ALA ehyrse
Le (P )

ALA Synthse
Rte limite
B6 +
Siero lstic
Anemi
Uroporphyrinogen-III
Protoporphyrin IX (protoheme)
Heme
Uroporphyrinogen-I
synthse
Ferrocheltse Fe2+ Le (P )
Acute Intermittent
Porphyri
Iron Deficiency
Anemi
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Siero lstic Anemi Le Poisoning
cuse Symptoms
1. ecrese Vit B6 (m.c.) 1. L e L ine: in gums
2. isonizi therpy 2. CNS : E ncephpthy,
3. A ominl pin (le colic)
4. PNS: wrist n foot D rop
Dignosis:is: Dignosis:is:
Microcytic Anemi
Dignos Dignos
1. BM: ring siero lst
(most specific test)
An erythro lst contining
grnules of ferritin
1. loo le level > 10 g/l
2. increse free erythrocyte
protoporhyrin
2. L 3. sophilic stippling (remnnts of
RNA) :
Tretment Tretment
Pyrioxine succimer (PO), EDTA
Acute Intermittent Porphyri Porphyri Cutne Tr
Uroprophyrinogen-1 Synthse
eficiency

Uroprophyrinogen
ecr oxylse eficiency
Clinicl Feture Clinicl Feture
1. AD, vri le expression 1. Photosensitivity
2. cute  ominl pin 2. listeringg of skin
Microcytic Anemi
p
multiple lproscopies (scrs on
 omen)
3.psychotic chnges
4. increse ALA n PBG
(propho ilinogen)
5. no photosensitivity
6. Contrinicte: r iturte
Anemi of Chronic Disese (AOCD)
Definition L Tretment
1. Iron eing trppe in
one mrrow
mcrophges, cuses
in ility to use of iron in
stores.
1. serum ferritin
elevte
2. serum iron low
3. reticulocyte count
low lo
2. long term chronic
isese cuse ecrese
liver functions,
1. ecrese protein
synthesis
2. Trnsferrin low =
TIBC low
3. It cn e microcytic or
normocytic
reticuloenothelil
system
Anemi of Chronic Disese (AOCD)
Iron eficiency Anemi Iron eficiency Anemi
Cuse 1. ecrese intke or
Increse emn
elerly, chilren, pregnnt women
2. ecrese  sorption:
(ml sorption)
1) ecrese ci (Vc)
2) Dumping Synrome: ecrese
smll intestine trnsit time
3) fter gstrectomy
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. ecrese storge iron in
intestinl mucos, spleen,
n liver
Decrese ferritin
2. ecrese circulting iron Decrese serum iron
Increse TIBC
3. formtion of
microcytic/hypochromic
nemi
Decrese RBC size
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Iron eficiency Anemi
Symptoms 1. Generl Low energy stte, pllor of skin n nils,
2. others 1. Koilonychi: spooning of the fingernils
2. Pic
L H , MCV, Ht Decrese
RDW ecrese
Serum iron ecrese
Trnsferrin (TIBC) increse
ferritin ecrese ferritin ecrese
microscope microcyte
nisocytosis  norml size
poikilocytosis  norml shpe
Dignosis 1. epen on l
2. efinitive Dx: one mrrow
Tretment 1. iet
2. ferrous sulfte t lets
3. prenterl iron
4. loo trnsfusion: most effective
Terminology
1. H Hemoglo in F12-15 g/l,
M 13-16g/l
2. Ht (Hct) Hemtocrit % of RBC in the loo 40 --50%
3. MCV men cell (corpusculr) volume 80100
4. MCH men cell hemoglo in 25.435 pg/cell
5. MCHC men cell hemoglo in concentrtion 3136 g/l
6. RDW re cell istri ution with (A mesure
of the vrition in size of re loo
cells)

612%)
7. Reticulocyte immture RBC (1 y, norml 1.5%)
< 1%, poor one mrrow response
> 1%, goo one mrrow response
Bluish color (polychromsi) ue to
free ri osome RNA
Terminology
serum iron 100mg/l
Ferritin 1. physiologicl storge iron form
2. intestinl mucos, spleen, n liver
Hemosierin 1. egre ferritin + lysosoml e ris
2. Prussin lue positive
Trnsferrin A et glo ulin in loo serum tht com ines with n
trnsports iron.
Totl iron- ining
cpcity (TIBC):
1. mens trnsferrin level
2. Trnsferrin = TIBC = 300 mg/l
% sturtion of
trnsferrin
serum iron/TIBC = 1/3
Microcytic Anemi
Iron
eficiency
AOCD Thlssemi
minor
Siero lstic
nemi
serum
Iron
ecrese ecrese norml increse
serum ecrese increse norml increse
Go Bck
serum
ferritin
ecrese increse norml increse
TIBC increse ecrese norml ecrese
%
sturtion
ecrese ecrese norml increse
B12 Deficiency Anemi
Cuses
1. Dietry
eficiency
1. B12 in re met n fishe

2. B12 stores t oy for more thn 1 yer supply.


3. strict vegetrins, lcoholism
2. Decrese
 sorption
1. ecrese IF, gstrectomy or pernicious nemi
2. Pncretic insufficiency
3. intestinl ml sorption
. prsites: fish tpewormp iphyllo othriump ltum p y
. cteri: lin-loop synrome
c. Crohns isese
Sign n symptom
1. eefy tongue ue to generlize epithelil trophy
2. peripherl neuropthy
3. SCDSD: (Su cute com ine egenertion of the spinl cor)
ii. emyelintion of the posterior columns n lterl corticospinl trcts n
spinocere ellr trcts
iii. Urinry n fecl incontinence, impotence
iv. Dementi
B12 Deficiency Anemi
Dignosis
1. peripherl smer Mcro lstic nemi, hypersegmente
neutrophils
2. nti-IF: initil test sensitivity 50-80% , specificity 100%
3. serum homocysteine
increse
Due to folte or B12 eficiency
4. increse
methylmlonichylmlonic cii
only ue to B12 eficient
met c
5. Schilling test: over the 24 hours,  norml result shows t lest
10% of the orl intke rioctive vitmin B12 will
e in the urine.
i. B12 injection + riol elle B12 orlly
ii. B12 injection + riol elle B12 orlly + IF
Tretment Tretment
B12 orl
Or prenterl
After give B12, my evelop hypoklemi in 48
hrs, ecuse potssium rpily go into cells
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Folte Deficiency
Folte Deficiency
1. contin in green leves veget le
2. 3 month supply
Cuse y
1. cuse y te n tost life-style
2. Methotrexte
3Ph. ttoin i
Go Bck

3 Pheny
4. Pregnncy
L
1. serum homocysteine increse: ue to oth folte n B12 eficiency
Tretment
Folic ci
Autoimmune Hemolytic Anemi (AIHA)
Wrm AIHA Col AIHA
Mechnism The IgG ttch to  RBC,
leving their FC portion
sticking out. The FC is
recognize n gr e onto
y monocytes n
mcrophges in the spleen.

nti oies initite


complement lysis of
re loo cells
Anti oy 1. IgG to Rh type 1. IgM
2. IgA
Cuse 1. Methylop
2. Penicillin
1. Quiniine
coom s test + IgG, or IgG + C3 C3
Col gglutinin negtive positive
Tretment 1. steroi
2. splenectomy
3. tret cuses
4. Cyclophosphmie
1. Cyclophosphmie
2. Chlorm ucil
Normocytic Anemi
Intrvsculr (SH GTP) Extrvsculr Microngiopthic
Hemolytic Anemi
increse methemoglo in
(oxiize hemoglu in)
Rx; methylene lue
no methemoglo in 1. increse shictocytes
(frgmente RBC)
2. Helmet cell
mrkely ecrese ecrese
hptoglo in heptoglo in
1.
2.
3.
4.
5.

S ickle Cell Disese


H emglu in C Disese
G-6-P-D eficiency
T helssemi Mjor
P NH

Hereitry
spherocytosis
1. D IC
2. T TP
3. H US

4. P rosthetic Hert Vlve


5. H ELLP
Hereitry Spherocytosis
Definition 1. AD,
2. efect spectrin in RBC mem rne
Clinicl
feture
1. splenomegly
2. increse risk for cute plstic crisis with Provirus
B19 infection
L 1. increse spherocytes
2. normocytic hyperchronic
3. increse MCHC
4. increse osmotic frgility
Rx
Sickle Cell Disese Hemoglo
single nucleotie chnge in
vline (neutrl) to replce
ci (ciic) t 6 position
chin

in C Disese
coon csues
norml glutmic
of the -glo in

single nucleotie chnge in


coon cuses lysine ( sic) to
replce norml glutmic ci
(ciic) t 6 position of the glo in chin
Hemoglo in S Sign:
1. ecome less solu le uner ecresing
oxygengen concentrtionsrtions
1. splenomegly
Sickle Cell Disese
oxy concent
2. The eoxygente molecules form rigi
ros clle polymers into crystls tht istort
the re loo cells into  sickle shpe.
2. trget cell
3. These  normlly sickle-shpe cells re
oth rigi n sticky.
3. ro-shpe crystls in RBCs
Genitic types
1. heterozygous (AS): trit
loo urine n resistnce to mlri
2. Homozygous (SS):Sickle cell isese
Sickle Cell Disese
Affecting fctors 1. increse concentrtion (ehyrtion), mke it
worse
ecrese concentrtion mke it etter
2. Decrese pH ecrese oxygen ffinity: worse
3. increse H F: etter
Incresencrese RBC 1. Erythroirythroi hyperplsiperplsi I RBC
estruction cuse

1 E hy
2. increse

iliru in

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Vso-occlusion
1. Hn-foot synrome (ctylitis) 1st sign of SD, in chilren
2. Vso-occusive (pinful) crisis Rx: 1. Self limiting, lst 2-7 ys
2. hyrtion: NS
3. Morphine for pin
4. keep wrm
5. Oxygen
3. Autosplenoectomy 1. Howell-Jolly oies in peripherl loo:
tff ller hhromtin ti
Sickle Cell Disese
remnnt o nuc c
2. increse infection of encpsulte
orgnisms, Rx: vccintions
4. Leg ulcers increse Slmonell osteomyelitis (leg pin)
5. Avsculr necrosis of the joints M.c. hip, 2n shouler
6. Pripism Emergencies, Rx: trnsfusion
7. Acute chest synrome Emergencies, Rx: trnsfusion
8. Aplstic crisis with infection of B19, Rx: folic ci
Tretment 1. Hyroxyure; increse H F
2. BM trnsplnttion
G-6 PD Deficiency
G-6 PD Deficiency
G-6 PD eficiency cuses ecrese glutthione peroxise
(ntioxint)
Clinicl Feture
1. X-link R
i. Africn Americn type:
ii. Meiterrnen type
2H. iinz oies: i iition ti ff hemoglo in l i 2 He
3. Bite cell: to et heinz oies y splenic mcrophges
Tretment

ox o h

Thlssemi Synrome
Definition: quntittive, not qulittive,  normlities of hemoglo in
1. -thlssemi 2. -thlssemi
1. ecrese -glo in chins ,
excess -chins
1. ecrese -glo in chins,
excess -chins
2. most commen in Asin popultion 2. most common in Meiterrnen
3. expression in prentlly n
postntllytntlly
expresse postntlly only
pos
-Thlssemi
Genetic
Norml

4 -chin (/)
Silent crrier 1. eletion 1 -chin
2. (-/),
-Thl trit
(minor)
eletion 2 -chin 1. Genotype: cis (--/) type
in Asin
2G. type: trns (- /- ) 2 Genot t ( / )
type in Africn-Americn
H H isese
(mjor)
1. eletion 3 -chin
2. (--/-)
1. increse H H,
2. forms Heinz oies
Hyrops fetlis 1. eletion 4 -chin,
2. lethl in utero (--/--)
increse rts H
-Thlssemi
Genetic 1. norml: 2 chins,
2. point muttions,
1. -Thl minor symptomtic, increse H A2 or H F
2. -Thl intermei  severe nemi, ut no trnsfusions neee
3. -Thl mjor
(Cooley Synrome)
1). norml t rith
2). evelop t  out 6 month s H F ecrese
3). severe hemolytic nemi
. increse iliru in, gllstones
. Congestion hert filure is most common cuse of
eth
4). Erythroi hyperplsi in BM: x-ry: crewcut skull ,
chipmunk fce
5). Peripherl in the loo: Numerous trget cells
Tretment 1. o not require specific tretment
2. -mjor: loo trnsfusions 1 or 2 / month:
SE: Hemochromtosis, tret with eferoxmine
3. splenectomy elimintes severe hemolytic nemi:
4. Bone mrrow trnsplnttion
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PNH
Proxysml Nocturnl Hemoglu inuri
ecrese glycosyl phosphtiyl inositol (GPI) linke proteins, especilly
ecy ccelerting fctor (DAF)
Function of DAF:
1. inhi it the ctivtion of the complement csce y reking own C3
convertse
2. ecrese O2, trigger complement pthwy
Symptomsmptoms n Complictiontion Sy n Complic
plstic nemi, leukemi, venous throm osis
Dignosis
1. Hms test (Aciosis in vitro)

2. sucrose lysis test (sugr wter test)


3. flow cytometry: CD55, CD59, much more sensitive n specific
Tretment
1. Glucocorticois
2. BM trnsplnttion
Summery
RBC shpes Diseses
Anisocytosis Iron eficiency nemi
Poikilocytosis Iron eficiency nemi
Shperocytes 1. hereitry spherocytosis
Trget cells Thlssemi, H C isese, Liver Disese
Bite cell G6PD eficiency
Terrop cells Myelofi rosis
Elliptocytes Hereitry elliptocytosis
Acnthocytes  etlipoproteinemi
Echinocytes ( urr cells) uremi
Schistocytes (Helmet cells) HUS, DIC, TTP
Rouleux Multiple myelom
Summery
RBC
inclusions
Diseses
Bsophilic
stipling
Cytoplsmic remnnt
RNA
Le poisoning
Howell-Jolly ell Joll Remnnts of nucler cler Iron eficiency nemi Ho
oies
Remnnts of n
chromtin
Iron eficienc nemi
Ring
siero lsts
Iron trppe
 normlly in
mitrochonri forming
 ring roun nucleus
Siero lstic nemi
Heinz- oies G6PD
Other types Anemi
1. Dimon-Blckfn Synrome:
congenitl pure RBCs nemi
2. Fnconi nemi (Constitutionl)
pencytopeni with  norml structures
243
10/13/2008

1
Hemostsis
Bleeingg Disorer
Hsenchecheg Qi MD., Ph.D.
3:1 = M:E (myeloi to erythroi) rtio.
Bleeing
Hemostsis
Hemostsis
1. vsculr wll
injury
1. lee
2. trnsient
vsoconstriction
chnges loo flow cuse
tur ulence n stsis
Reynols num er = (imeter)
(velocity) (ensity)/viscosity
> 2000 = tur ulent flow
< 2000 = lminr flow
3. throm ogenic fctors 1. relese tissue fctor, ctivte
VIII ( tirinsic i ) VI (ext )
2. ctive fctor XII (intrinsic)
ue to expose su enothelil
collgen
3. relese vWF
2. trnsient clotting pltelet clotting leeing time 27 min
3. Seconry
clotting
Extrinsic Cogultion
fctor
PT: P rothrom in T ime 12sec
Intrinsic Cogultion
fctor
PTT: P rticl T hro oplstin
T ime 30sec
Ahesion
Aggregtionggregtion
1. pltelets
hesion
1. vWF heres
to su enothelil
collgen
2. Pltelets
here to vWF
y glycoprotein I
2. pltelets
ctivtion
1. pltelets
chnges shpe
n

egrnultion
Pltelets
A
2. synthesis of
TXA2
3. pltelets
ggregtion
1. ADP
clopiogrel,
Ticlopiine
2. TXA2
3. GpII /III
A cixim ,
Eptifi tie,
Tirofi n
ADP
Cogultion Fctors
Vitmin K
Glutmyl Cr oxylse
244
10/13/2008
2
Throm omoulin (trnsmem rne protein)
Throm in
(60 hrs)
Protein C
(Hlf life 14 hrs)s)
C-ctivte protein
+
(Hlf life 14 hr
Protein S
Inctivtes
Fctors V n VIII
+
Fctor V leien:
vrint of fctor V
Wfrin:
Trnsient eficiency
of protein C
Bleeing Disorer
Pltelet 150,000450,000/mm 3 leeing time: 27 min

1. Decrese Pltelet
ccount
2. A norml Pltelet
function
3. Von Wille rn
Disese (vWD)
AD/AR, vWF 1. leeing time prolong
2. ristocetin
ttri ute to Fctor 8
eficiency
3. PTT prolong
Rx: Desmopressin
cette (DDAVP)
4. Bernr-Soulier
Synrome
Gp I eficient Rx: Pltelet
5.Glnzmnn
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 isseminte
I ntrvsculr
C ogultion
1. nti-pltelet F ever
A nemi
T hromcytopeni
Dirrhe
Renl filure
1. D-imers
2. Increse BM
megkryocyte
2. Pltelet count
ecrese
3. cute form: chil
fter virl infection
R enl filure 3. Bleeing time increse
4. chronic: ult N europthyopthy 4. PT n PTTT increseese
Throm ocytopeni
4 chronic: ult
women 20-40 yo
N eur 4 PT n PT incr

Tretment Tretment Tretment Tretment


1. chil self limite in
6mo, or prenisone
plsmpheresis 1. ult:
plsmpheresis
1. supportive
2. ult
. prenisone
. IVIG, nti Rh (D): fst
c. splenoectomy,
Vccine
. pltelet trnsfusion
2. chil:
self limite
2. FFP
3. Cryoprecipitte
4. tret cuses
Throm ocytosis (rective) Essentil Throm ocythemi (ET)
Cuse Clinicl Fetures
1. Bleeing, hemolysis 1. Increse pltelet count
2. Inflmmtion 2. increse BT
3. Iron eficiency, Stress 3. increse BM megkryocytes
4. ttsplenectomy l t
Throm ocytosis
4 pos
5. Mlignncy
Disorer of Cogultion
von Wille rns Disese Hemophilli A Hemophilli B
vWF eficiency, VIII eficiency, IX eficiency,
AD/AR, XR, XR,
My hve VIII eficiency vWF norml
Clinicl Feture Clinicl Feture
1. Cutneous n mucosl leeing 1. joint n soft tissue leeing
2. Menorrhgi, 2. Hemrthrosis: m.c.
3. GI leeing 3. Intrcrnil leeing: 2n m.c.
Dignosis i Dignosis i Dignosis i Di Di Di
1. BT increse, my with increse PTT 1. PTT increse 1. PTT increse
Tretment Tretment Tretment
Do not give Aspirin/NSAIDs
1. DDAVP (esmopressin) 1. fctor VIII 1. fctor IX
2. Fctor VIII concentrtions,
give ll Pt with vWD fter mjor trum
or uring surgery
(reuce ristocetin-inuce pltelet
ggregtion)
2. FPP not recommene ecuse virus infections
Tretment of Acute hemrthrosis
1. Anlgesi, (Coeine)
2. Immo iliztion
3. Synovectomy (rthroscopic) or riosynovectomy
for severe n recurrent hemrthrosis

Hypercogultion
1. XII eficiency Throm osis, no
2. XIII eficiency Rre,
new orn leeing from cut
um ilicl cor

leeing PTT prolong,

Norml 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. Fctor V leien Leien vrint of fctor V,
(Activte protein C
resistnce)
recurrent DVT
Rx: life-long nticogultion
(Wrfrin)
6. Protein C
Deficiency
Active Fctors V n VIII 1. erml vsculr throm osis
2. skin necrosis
7. Protein S
Deficiency
245
10/13/2008
3
Plsm: no cells from loo
Serum: no cogultion fctor from plsm.
inclue ll the ion n nti oies, immunoglo ulin.
Streptokinse
Urokinse
+
Alteplse (tPA)
Reteplse (rPA)
Anistreplse
Throm olytics
Anticogultion Meictions
Heprin LMWH Wrfrin
Low-Moleculr Weight Heprin VIt K ntgonist
Inhi it II n X Mostly inhi it X Inhi it II, VII, IX, X, n protein C n S
Hlf-lift time Hlf-lift time Hlf-lift time
1 hour 3-24 hours 4 ys
Aministrtion Aministrtion Aministrtion

1. therpeutic ose:
IV heprin, monitor PTT
1. su cutneously
PTT monitor not necessry
1. orlly: monitor PTT, Monitor INR (2-3)
2. prophylctic ose:
SC low-ose ose heprin, SC low heprin
PTT monitor not necessry
SE n Avntge SE n Avntge SE n Avntge
1. Bleeing 1. eser use out Pt 1. Hemorrhge
2. Heprin-inuce
throm ocytopeni (HIT)
2. no HIT or osteoporosis 2. skin necrosis ( ecrese protein C)
3. Osteoporosis 4. no osteoporosis 3. Tertogenic uring pregncy
4. Trnsient lopeci 5. more expensive
5. re oun hypercogul ility
/t epression of ATIII
SE Tretment SE Tretment
1. stop meiction, 2. Give PPF, 3. Wrferin over ose my lso give Vit K
246
10/13/2008
4
247
10/13/2008
1
Lymphom
&
Leukemi k i L
Hsenchecheg Qi M.D.; PH.D.
3:1 = M:E (myeloi to erythroi) rtio.
Lymphom
Precursor
B-Cell
Mture
B cell
ALL T-ALL
Precursor
T-Cell
Mture
T cell
Plsm Cell
Neoplsm
1. Multiple myelom
2. MGUSS (Monoclonl Gmmopthymmopthy

Non-Hogkin Disese HD
1. not infections
Not B-cell
Not T-cell
< 15 yer ol
Positive TT
Thymom
< 25 yers ol
2 MGU (Monoclonl G
unetermine significnce)
3. Wlenstrom mcroglo ulinemi
2. owl-eye
3. R-S cell
1.
2.
3.
4.

NS: m.c. Lcunr cell


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

1. L1
2. L2
3. L3
Acute Lympho lstic Leukemi
1. ATLL
2. MF n Sezry S.
Terminl Deoxynucleotie
trnsferse
Lymphom
Mture B cell
Non-Hogkin Disese HD
If > 65 yers ol
1. CLL: m.c.
chronic lymphocytic leukemi, or
smll lymphocytic lymphom
1. Folliculrulr 1. m.c.c. non-HDHD 18:
2. Hiry 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 chnnel
2. Diffuse lrge Bcell lymphom
1. EBV
2. HHV-8

cl-2:2: inhi itss

3. Smll noncleve
lymphom (Burkitt
lymphom)
1. strry-sky
2. t (8, 14)
8: c-myc
4. Mntle Cell
Lymphom
T (11, 14) 11:

cl-1 (cyclin D)

5. MALTom
(Mrginl zone
Lymphom)
Tret s H.pylori
2chloroeoxyenosine
Trtrte-resistnt ci
phosphtse
Leukemi
AML
CML
1. M0M4: myelo-, WBC
2. M3t: (1517),
BM lst <30%
MDS
ET P. ver
Myeloprolifertive Synrome
MF
BM lst > 30%
1. t (9, 22) 2 M3 t (15 17)
15: PML
17: retinoic ci receptor -gene
(RAR-)
3. M5: mono lsts
4. M6: erythro lsts
5. M7: megkryocytes
1. Dry tp
2. Terrop 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
Fts
Sugrs
Proteins
The min intrcellulr uffers
AMINO ACIDS
An Aci
Pk is less thn 7
A Bse
Pk is greter thn 7
263 251
2
An Aci

Dissocites erly
Likes to give up hyrogen ions (protons)
Pk is less thn 7
Strong ci: Pk 1 to 3
Wek ci: Pk 4 to 7

A Bse

Dissocites lter
Likes to ccept hyrogen ions (protons)
Pk greter thn 7
Wek se: Pk 7 to 9
Strong se: Pk greter thn 9

Pk 4 to 9
Cn e  wek ci or  wek
se
Three Esy Wors Tht re Hr
To Unerstn

Dissocite: to lose  hyrogen (proton)


Solu le: chrge or polr
Biovil le: neutrl
Dissocition
Dissocition
To Lose A Hyrogen
264 252
3
Solu le Solu le
Chrge Or Polr
Solu le
Wter Solu le
Biovil le
Biovil le
Neutrl
Biovil le
Ft Solu le
265 253
4
AMINO ACIDS As n ci issocites
It gins  negtive chrge
It gins solu ility
It loses iovil ility
As  se issocites
It loses its positive chrge
It loses solu ility
It gins iovil ility
Henerson-Hssel ck Eqution
Henerson-Hssel ck Eqution ACIDS

IF you wnt to  sor more


A more Aci
IF you ont wnt to  sor it
A se

266 254
5

Bse

IF you wnt to  sor more


A more se
IF you ont wnt to  sor it
A ci

Acis you nee to know


Aspirin
Br iturtes
Myoglo in
TCAs
Bses you nee to know
Amphetmines
The min ci use in
meicine
NH4CL
The min se use in
meicine
HCO3
Now we look t the ISOELECTRIC
POINT
267 255
6
Isoelectric Point
NO NET chrge on the molecule
Also clle  zwitterion
Will NOT migrte towrs noe or
cthoe
Cthoe
Where CATIONS go: the
negtive electroe
Anoe
Where ANIONS go: the positive
electroe
268 256
7
To further ctegorize the
mino cis
Glycine

Smllest mino ci


NO chirl cr on
Inhi itory neurotrnsmitter for the spinl
cor
PHE, TRP, TYR
Aromtic mino cis
Recognize y chymotrypsin
LYS, ARG
Bsic mino cis
Hve  positive chrge
Recognize y trypsin
Asp, Glu
Aciic mino cis
269 257
8
Asp
The only excittory mino ci in the
( NMDA pthwy)
Cys, Met
Contin sulphur
Mke isulphie ons
Asprgine, Glutmine
Involve in N- ons
Serine, Threonine, Tyrosine
Involve in O- ons
Leu, Iso, Vl
Brnche chin mino cis
Tyr
Use to mke ctecholmines
Use to mke melnin
270 258
9
Trp
Use to mke serotonin
Ketogenic Amino Acis

rin

Lysine
Arginine
Both glucogenic n ketogenic
P
I
T
T

HE
SO
HR
RP

Glucogenic Amino Acis


ALL OTHERS
Essentil Amino Acis
You get them ONLY from the iet
NO cycle in YOUR oy cn mke these
A eficiency will ALWAYS le to 
isese
Deficiencies put the oy into  strvtion
stte
Essentil Amino Acis
271 259
10
How oes the oy utilize energy
uring strvtion?
Energy Utiliztion
(1)
(2)
(3)
(4)
(5)

plsm glucose: lsts 2 to 4 hours


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

Not les
PHE use to mke TYR
TYR ecomes essentil if PHE is eficient
MET use to mke CYS
CYS ecomes essentil if MET is eficient
Phenylketonuri
Phenyllnine hyroxylse is eficient
Un le to mke tyrosine
Un le to mke DA n NE n EPI
Un le to mke melnin without tyrosine
Blone hir; lue eyes; fir skin
Phenylcette n phenylpyruvte uil
up
Musty oor
PKU

Must screen ll new orns t 48 hours


Must voi sprtme (nutrisweet)
Pregnnt mother must e on restricte iet
especilly uring first 8 weeks while rin
is eveloping
Rin ow colore wheel on foo proucts
woul wrn these ptients ginst
sprtme
New orn Screening
PKU ( Guthrie test)
Hypothyroiism (TSH)
CAH
Biotinise ef
Glctosemi
272 260
11
Al inism
Tyrosinse eficiency
Preispose to skin cncer
Vitiligo
Autoimmune nti oies ginst
melnocytes
Loss of pigmenttion
Preispose to skin cncer
Alcptonuri (ochronosis)
Homogentisic ci oxise eficiency
Tyrosine uils up
Urine turns lck when expose to ir
Mple Syrup Urine Disese
Involves rnche chin mino cis
Defective renl trnsport of these mino
cis
LEUCINE
ISOLEUCINE
VALINE
Cystinuri
Defective renl trnsport of mino cis
Hexgonl, envelope shpe, or coffin li
shpe crystls 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
Primry
Seconry
Tertiry
Qurternry
Protein Structure

Primry
Seconry
Tertiry
Qurternry

Primry Structure
The mino ci sequence
Involves peptie ons
Restriction enzymes re use to sequence
proteins
Peptie Bon Peptie Bon
Plnr
Restricte mo ility
R-groups re in trns-configurtion
274 262
2
Sequencing
Before we unerstn the
present
We nee first visit the pst!
The history of sequencing

Aci hyrolysis
Gel electrophoresis
Ninhyrin rection
Emns egretion
Restriction peptises

Aci Hyrolysis

Dentures the protein


Does NOT ctully sequence the protein
Turns sprgine into sprtte (ciic
form) n glutmine into glutmte (ciic
form)
Gel electrophoresis
Uses grose gel to seprte proteins y
size first, chrge secon
Smller proteins migrte further
Lrger proteins sty closer to the strt site
Does NOT sequence the proteins
Gel Electrophoresis
275 263
3
Ninhyrin Rection
Rects with ll mino cis creting 
purple color
Proline rection cretes  yellow color
Goo ONLY for counting prolines
Emns egretion
Uses phenylIsoThioCynte (PITC)
Rects with ANY mino ci strting on
the mino terminl
Amino cis re ientifie y
spectrophotometry (light trnsmission)
Proceure is ccurte ONLY up to 100
mino cis
Restriction Peptises
Restricte y wht mino cis they cn
recognize
Use to ctully sequence proteins
Restriction Peptises
Trypsin: cuts to the right of LYS n ARG
Chymotrypsin: cuts to the right of the
romtic mino cis, PHE, TRP, TYR
Elstse: cuts to the right of GLY, ALA,
SER
CNBr: cuts to the right of MET
Aminopeptise: cuts to the right of the
mino terminl mino ci
Restriction Peptises, cont

Cr oxypeptise: cuts to the left of ny


mino ci on the cr oxyl terminl
Mercptoethnol: reks up isulfie ons
An Exmple
276 264
4
Seconry structure
Alph helix
Bet plete sheet
Alph helix
Bet plete sheet Serum proteins
Functionl
Acute phse rectnts
Too mny proteins in your plsm
Elevte ESR or CRP
Inictes nonspecific inflmmtion
Flsely high ESR: nemi
Flsely low ESR: sickle cell nemi;
polycythemi
Acute phse rectnts cuse y IL-6
TOO mny cute phse
proteins
Les to AMYLOIDOSIS
277 265
5
AMYLOIDOSIS
Primry: utosoml ominnt
Mssive intrcere rl hemorrhge in  young
person with no prior h/o HTN
Seconry: ue to ny chronic
inflmmtory isese
Congo re stin
Apple green irefringence
Seconry Amyloiosis
AA: chronic inflmmtory isese
AB: Alzhiemers isese
AB-2: Chronic renl filure
AE n AF: MEN-II
AL: Multiple myelom
Tertiry Structure

3-D structure
Most importnt fctor is hyropho ic n
hyrophilic interctions
Covlent ons now form
Qurternry Structure
Two or more proteins re intercting
Coopertivity
Allosterism: refers to enzymes
Allosteric enzyme mens the slowest enzyme;
mens rte-limiting enzyme; mens the
kinetic curve is sigmoilly shpe
Hemoglo in
The first qurternry protein
iscovere
Hemoglo in
Type A: 2 lph 2

et chins

Type A-2: 2 lph 2 elt chins


Type F: 2 lph 2 gmm chins
278 266
6
Hemoglo in F

Foun in the fetus


Disppers y 6 months of ge
Hs  low ffinity for 2,3, DPG
Hs  high ffinity for oxygen

Hemoglo in F
Erythropoiesis
Begins: in yolk sc t 4 months gesttion
6 mo gesttion: moves into the liver,
spleen, n flt ones
8 mo gesttion: moves into the long ones
1 yer of ge: liver, spleen, n flt ones
close
If you lose the long ones fter 1 yer, the
spleen cn reopen cusing mssive
splenomegly
Heme Synthesis
Iron eficiency nemi
Most common cuse of microcytic
hypochromic nemi
In chilren: Mcc is inequte intke
In young ults: Mcc is still inequte

intke
20 to 40: IBD
> ge 40: mucsl leeing
Tx: ferrous sulphte
Le Poisoning
Le inhi its elt ALA ehyrtse s
well s ferrochetolse
Mcc: eting peeling pint from ol
uilings
Clssic clue: sophilic stippling; elevte
FEP (free erythrocyte protoporphrins)
279 267
7
Heme Synthesis Le levels to know
Norml: < 10
If  ove 10: notify PHD; tret with succimer
If  ove 30: notify PHD; hospitlize; o 
C-EDTA chllenge; tret with
penicillmine n imercprol (BAL) if
urinry le is high
If  ove 50: o s  ove; skip EDTA
chllenge
Drug inuce lupus
Antihistone nti oies
Hyrlzine
INH
Procinmie
Penicillmine
Phenytoin
Ethusuximie
Le use to e the most
common cuse of mentl
retrtion
But NOT ANY MORE!
Mentl retrtion
Fetl lcohol synrome
Frgile X synrome
Downs synrome
Porphyris
A group of enzyme eficiencies
Synthesize too mny porphyrin rings or
inequte met olism re the pro lems
Porphyrin rings in the urine mke it re
Two types re most importnt
280 268

8
Acute Intermittent Porphyri
Enzyme ificiency
A uil up of porhyrin rings
Porphyrin rings re eposite in viscerl
orgns n roun nerves
Recurrent severe  ominl pin n
neuropthy
Tx:
Erythrocytic Protoporphyri n
Porphyri Cutne Tr
Enzyme ificiency
Porphyrin rings re eposite unerneth
the skin
Light rects with the rings cusing 
relese of het which les to urns
Mcc of eth: skin infections
Tx: protect them from light
Opites
CNS epressnts
Muscle relxnts
Anlgesics
Receptors:
Mu ( CNS)
Kpp: Spinl cor
Opites

Heroin
Methone
Morphine
Meperiine
Coone
Oxycoone
Coiene
Dextromethorphn

Loperimie
Diphenoxylte
Fentnyl
Pentzocine

Hemoglo inopthies
Hemoglo in S isese
Hemoglo in C isese
Hemoglo in S isese
Autosoml recessive
High prevlence in Afric ( nturl
selection)
Su stitution of vline for glutmte t
position 6 of et chin

Hypoxi cuses cells to sickle leing to


vso-occlusion
281 269
9
Vso-occlusive crises
CVA
PULMONARY INFARCTION
SPLENIC SEQUESTRATION
PRIAPISM
Tx: exchnge trnsfusion; oxygen
Aplstic crisis
Complete one mrrow suppression
Alwys check the reticulocyte count
Mcc: prvovirus B-19
A Few Points to Remem er
Functionl spleni y ge 6 ue to
infrcts
Suscepti le to encpsulte orgnisms
Give pneumovx nytime fter ge 2
Infections re mcc reson for crises
Hyroxyure increses HgF, ecresing
chnce for hypoxi
Use opites for pin
Trnsfuse when nemic n symptomtic
Hemoglo in C isese
Autosoml recessive
Su stitution of LYS for GLU t position 6
of et chin
NO sickling occurs since oth mino cis
re hyrophilic
Thllesemis
Represent gene eletions
Autosoml recessive
Common in Meiterinin people
Minor: t lest one gene remining
Mjor: no genes remining
Hemoglo ins
282 270
10
Alph Thlessemi Bseline l s
RBC Mss: 3.5 to 4.5 million
Hemoglo in/Hemtocrit: 15/45%

Alph Minor

One gene missing


Asymptomtic ( HG 12) 75%
Two genes missing
IF seentry: symptomtic
IF ctive: symptomtic (HG 7.5) 50%
Three genes missing
Symptomtic in ALL (HG 4 to 5)

Alph Thlessemi Mjor

NO genes remining
Un le to mke ny hemoglo in t ll
Hyrops Fetlis
Hemoglo in Brt ( 4 gmm chins)
Hemoglo in H ( 4 et chins)

Bet Thlessemi: 2 genes


Bet minor (Hg 7.5)
One gene missing
If seentry:
symptomtic
If ctive: symptomtic
Increse Hg A-2 n
Hg F
Ineffective
erythropoiesis
Bet mjor
Both genes missing
A le to mke only Hg
A-2 n Hg F
Asymptomtic until 6
months of ge
Trnsfusion epenent
Bloo Trnsfusions

Done ONLY when ptient is symptomtic


One unit of PRBC s
Rises Hg y 1 to 2 grms ( 3 to 6 HCT)
Delivers 3.4 grms of iron

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Iron Overlo
Hemosierosis: one mrrow is
overwhelme y iron
Hemochromtosis: iron overlo hs
involve other orgns
Skin: ronze pigmenttion
Liver: ronze cirrhosis
Pncres: ronze i etes
Hert: restrictive criomyopthy

Hemochromtosis
Primry
Autosoml recessive
Too much iron
 sorption from
uoenum
HLA A3 on
chromosome 6
Seconry
Too mny trnsfusions
Mcc of eth in first 10
yers: trnsfusion
relte infections
Mcc of eth fter 10
yers: CHF
Trnsfusion Relte INFECTIONS Trnsfusion relte infections
HIV Bcteril infections
Heptitis B Mlri
Hepitis C B esiosis
Heptitis D Syphilis
EBV
CMV
Hemorrhgic viruses
Hemoglo in Sturtion Curve
COLLAGEN
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More thn  qurternry
structure
Its  TRIPLE HELIX
4 Types of collgen

Type
Type
Type
Type

1:
2:
3:
4:

S
C
A
B

kin
onnective tissue
rteries
sement mem rne

To synthesize collgen
Glycine: every thir mino ci
Lysine
Proline
OH-Proline
OH-Lysine
Protein synthesis for pckging
Protein synthesis for pckging Protein synthesis for pckging

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Protein synthesis for pckging Who mkes collgen?
Fi ro lsts: simple scrring
Myofi ro lsts: if you nee woun
contrction
When collgen synthesis goes
wrong
DESMOPLASIA
COLLAGENOUS REACTION
SURROUNDING A TUMOR
KELOID
TOO MUCH COLLAGEN
DEPOSITION
COLLAGEN PROFILE
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ALL YOU NEED NOW IS A CLUE
Collgen iseses
Ehlers Dnlos
Mrfns
homocystienuri
Scurvy
Osteogenesis imperfect
Minkys kinky hir synrome
Seconry collgen iseses

Ankylosing sponylitis
Frgile X synrome
Syphilis
Tkysus isese

Collgen Vsculr Diseses


CREST
Scleroerm
Progressive systemic
sclerosis
Rheumtoi rthritis
Feltys synrome
Becets synrome
Sjogrens synrome