hemoglobin metabolism.pptx

8/14/2019 HEMOGLOBIN METABOLISM.pptx

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Functions of Blood

Blood performs a number of functions

dealing with:

Substance distribution

Regulation of blood levels of particular

substances

Body protection


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Blood Functions: Distribution

Blood transports:

Oxygen from the lungs and nutrients from the

digestive tract

Metabolic wastes from cells to the lungs and

kidneys for elimination

Hormones from endocrine glands to target

organs


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Blood Functions: Regulation

Blood maintains:

Appropriate body temperature by

absorbing and distributing heat to otherparts of the body

Normal pH in body tissues using buffer

systems

Adequate fluid volume in the circulatory

system


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Blood Functions: Protection

Blood prevents blood loss by:

Activating plasma proteins and platelets

Initiating clot formation when a vessel is broken

Blood prevents infection by: Synthesizing and utilizing antibodies

Activating complement proteins

Activating WBCs to defend the body against foreign

invaders


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Physical Characteristics of Blood Average volume of blood:

56 L for males; 45 L for females (Normovolemia)

Hypovolemia - low blood volume

Hypervolemia - high blood volume

Viscosity (thickness) - 4 - 5 (where water = 1)

The pH of blood is 7.357.45; x = 7.4

Osmolarity = 300 mOsm or 0.3 Osm This value reflects the concentration of solutes in the plasma

Salinity = 0.85%

Reflects the concentration of NaCl in the blood

Temperature is 38C, slightly higher than normalbody temperature

Blood accounts for approximately 8% of body weight


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Composition of Blood

Blood is the bodys only fluid tissue (a

connective tissue)

2 major components Liquid = plasma (55%)

Formed elements (45%)

Erythrocytes, or red blood cells (RBCs)

Leukocytes, or white blood cells (WBCs)

Platelets - fragments of megakaryocytes in

marrow


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Components of Whole Blood

Withdraw blood

and place in tube

1 2 Centrifuge

Plasma(55% of whole blood)

Formed

elements

Buffy coat:leukocyctes and

platelets

(


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Blood Plasma Blood plasma components:

Water = 90-92% Proteins = 6-8%

Albumins; maintain osmotic pressure of the blood

Globulins

Alpha and beta globulins are used for transport purposes

Gamma globulins are the immunoglobulins (IgG, IgA, etc)

Fibrinogen; a clotting protein

Organic nutrientsglucose, carbohydrates, aminoacids

Electrolytessodium, potassium, calcium,chloride, bicarbonate

Nonprotein nitrogenous substanceslactic acid,urea, creatinine

Respiratory gasesoxygen and carbon dioxide


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Plasma Protein

Plasma : Albumin, Globulin, Fibrinogenro.

Serum ; Albumin, Globulin

Electrophoretic separated plasma/serumprotein.


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Formed Elements Formed elements comprise 45% of

blood

Erythrocytes, leukocytes, and plateletsmake up the formed elements

Only WBCs are complete cells RBCs have no nuclei or organelles, and

platelets are just cell fragments

Most formed elements survive in thebloodstream for only a few days

Most blood cells do not divide but arerenewed by cells in bone marrow


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Stages of

Differentiation

of Blood Cells

Figure 17.9


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RBC

RBC is the most abundant cell in our body

Erythrocyte is the simplest cell in our body

The highest specific rate of glucose utilization of any cell

in the body (10 g/kg tissue/day : 2,5 for the whole body)

It has no sub-cellular organelleWithout nucleus its cannot divided, degraded after

120 days

Without mitochondriacannot produce energy (the

lowest rates of ATP synthesis of any cell in the body) without endoplasmic reticulum can not synthesis

protein and lipid

without lysosome can not produce digestive enzyme

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Hemoglobin

Hb is the oxygen carrier of RBC to bring O2from the lung to the extra pulmonary

tissues (reversible)

Mb, is found in muscle tissues, where itstore oxygen and use in exercise

Its consist of Heme and globin

Heme consist of Iron and protophorpyrine Oxygenation: Hb + O2 Hb O2

Oxidation: Fe++ of Hb Oxidi into Fe+++


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Heme group

Heme is the oxygen binding site of Hb andMb (myoglobin)

Heme contain protoporphyrin IX with

ferrous iron chelated in the centre. Protoporphyrin contain 4 mol of pyrole

rings, held together by methin (-CH=}

bridge, decorated with methyl (-CH3), finyl(-CH=CH2), and propionate (-CH2-CH2-COO-) side chain.


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Basic structure of Hb/heme


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Heme (cont-)

The porphyries ring system contain conjugated

double bonds. These are responsible for the

color of our blood (affected by the oxygenation

state) Oxygenated Hb is red, and deoxy-Hb is blue.

Therefore Oxygen deficiency or hypoxia can

be recognized as a blue discolorization of the

lips and other mucus membranethis is called

cyanosis.


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Heme Iron

The most important part of the heme group is itsiron.

Ionized iron can form coordinate bonds with theunpaired electron of oxygen or nitrogen atom.

In heme, the iron is bounds to nitrogen of 4pyrole rings

Both in Hb and Mb, the iron forms a fifth bondwith a nitrogen atom in a histidine side chain of

apoprotein . This histidine is called proximalhistidine.

A sixth coordinate bond can be form with mol O2


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Iron can exist in ferrous (Fe++) and ferricstate (Fe+++).

Ferric state is the oxidized form because it

can be formed from ferrous iron by aremoval of electron.

The heme iron of Hb and Mb is always in

ferrous state. Even during oxygen binding,it is not oxidized to the ferric form.

It becomes oxygenated but not oxidized


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RBC

RBCs circulate about 120 days before they

scavenged by phagocytic cells in the spleen and

other tissue.

RBCs have no nucleus there fore unable todivide and synthesized proteins. Also lack of

mitochondria they do not consume any of the

oxygen they transport.

They cover their energy needs by anaerobic

metabolism of glucose to lactic acid


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RBC-Hb

RBCs are bagsfilled with Hb with

concentration not less than 33%, dissolved

in cytoplasm.

Blood cells concentration of whole blood =

hematocrit.

Patient with an abnormally low Hb

concentration are said to have anemia.


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Hbs are tetrametric protein

The most importance difference between Hb

and Mb is the sub-unit structure.

Mb consist of single polypeptide with its heme

group.

Hb has four polypeptides each with its ownheme.

Human have several types of Hb : HbA, HbA2,

HbF (HbA has a2b2 polypeptide composition,

HbA2 has a2d2 elevated in beta thallasemia =

deficiency in beta globin biosynthesis). HbF

(a2g2 polypeptide composition)


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Structure of Hemoglobin

Figure 17.4


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SYNTHESIS HEMOGLOBIN

Its start from pro-erythroblast stadium and a bit

of reticulocyte stadium

Retikulocyte leaving bone marrow to blood

stream hemoglobin Suksinil-KoA (Krebs cycle) bind glysin pyrole.

4 pyrole condense to formed protoforfirin IX

Protoforfirin IX + Fe++

heme Heme + globin Hemoglobin


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Heme + long polypeptida (globin,

synthesizes in ribosome) hemoglobinchain (MW 16.000)

4 hemoglobin chain connect together to

formed hemoglobin


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Chain variation of Hb sub-unit depend on

aa array in polypeptide.

Chain type : , , gamma dan delta

Adult Hb : hemoglobin A (MW 64.458)

consisit of 2 and 2 chain combination.

4 atoms of iron Hb, @ connect to 1

molekul O2


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Chain abnormalities

Would changes physical properties Hb.

E.g : cycle cell anemia.

aa valine replace by glutamate in each ofbeta chain, if it is shine by O2low grade

formed long crystal 15 mikrometer in

erythrocyte, destroyed erythrocyte

membrane.


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Sintesis Hemoglobin


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MetHb

Is non funcional oxidized form of Hb

The heme iron of Hb bind molecular oxygen onlyin the ferrous state (Fe++). Its oxidation to theFerric forms result in met-Hb which is useless asan oxygen transporter.

Normally less than 1% of total Hb is in the formof Met-Hb, but oxidizing chemicals (aniline dyes,

aromatic nitrous compounds, inorganic andorganic nitrous compound) cause excessivemet-Hb formation.


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Defense mechanism

Fortunately the RBCs can defend itself againstexcessive met-Hb formation e.g

1. Erythrocyte reducing substances (ascorbic acid andglutathion).

2. The binding of heme to the apoprotein, creates aprotective environment for the iron. Heme hemin +hydroxyl ion hematin.

3. Met-Hb reductase reduce met-Hb back to Hb usingNADH as a reductant. Deficiency of this enzymeCongenital methemoglobinemia.

Met-Hbemia is treated with methylene blue whichreducing Fe+++Fe++


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Carbon monoxide (CO)

CO compete with oxygen for binding to theheme iron.

CO products of incomplete combustion ispresent in cigarette smoke, automobile exhaust

and others source. Even in a small amountformed in our body.

CO binds to Fe++ in Hb and Mb

Its 200 fold higher affinity for heme than O2

does. Therefore, even a low concentration of COis sufficient to displace O2 from its binding siteon the heme iron and cause a serious poisoning.


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CO cont-

Carbon monoxide binding is reversible: in

normally breathing patient with CO poisoning,

O2 gradually displaces CO , leading to slow

recovery in several hours. The interaction between CO and O2 at the heme

iron competitive antagonism

CO concentration of only 1/200thof the O2, is

sufficient to convert half of oxy-Hb to CO-Hb.

Hyperbaric oxygen is the treatment of choice.


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BPG is physiological important regulator of

oxygen binding to HB

2,3-Bisphosphoglycerate (BPG) is a smallorganic molecule that present in RBC.

Concentration 5 mM

Most BPG is noncovalently bond to Hb (one molBPG/mol Hb)

BPG binds only to the T conformation of Hb stabilization of T conformation, which have low

binding affinity The observed effect is a decreased oxygen-

binding affinity


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BPG

BPG concentration in RBC increases

during hypoxic condition, including lung

disease, severe anemia, and adaptation to

high altitude.

This increase affect oxygenations in the

lung capillaries, but enhances the

unloading of oxygen in the tissue.


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HbF has oxygen binding affinity higher

than HbA

In HbA BPG forms salt bonds to the amino terminal ofthe -chain and with the side chain of Lys and His in thechain.

In the (gama) chain of HbF His are replace with serine

residue that is not able to form salt bond. Therefore BPG binds less tightly to HbF than to HbA

reduces the effect of BPG on the oxygen affinity.

At physiologic BPG concentration, the P450 of HbF only20 torr compared with 26 torr for HbAfacilitate thetransfer of oxygen from the maternal blood to the fetalblood in the capillaries of placenta.


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Iron metabolism Iron exist in 3 formed:

functional iron ( Hb, mioglobin & some

enzymes),

store iron (feritin & hemosiderin) &

transport iron(transferin) Total iron : 4050 mg Fe/kg BW

65% Hb

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30% stored as feritin (liver)

4% mioglobin

1% heme

0,1% bind to protein transferin in blood plasma.


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Transport and store

Fe absorbed in all part of small intestine

blood plasma + apotransferintransferin

Sitoplasma, iron + apoferitin (MW

460.000)

feritin (store iron) Hemosiderin, insoluble Fe, formed when

more Fe absobed (more than bind by

apoferitin.


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Transferin bind tightly to membrane

receptor erythroblast cell of bone marrow. Transferin-Fe, pass the erythroblast by

endositosis, iron to mitochondria

Low transferin impaired transport of Feto eritroblassevere hipochromic

anemia

Fe excreted 1 mg/day trough feces.Menstrual woman lost about 2 mg/day,

lactating 1 mg/day


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In the intestine apotrasferin + free Fe

transferin receptor membrane intestine

epitheel cell by pinositosis. Iron absorbtion depend on body required for Fe:

Mechanism of iron absorbtion regulation:

Dietary regulator, stores regulator &erythropoetic regulator

Dietary regulator : kind of diet

Stores regulator: iron body store

Erythropoetic regulator : the rate of erytropoesis

The rate of absorption is so slow mgms/day.


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Absorbtion Fe, absorbed in brush borderof epithel vili small

intestine, specially duodenum & upper part ofjejunum

Divided to 3 phase : luminal, mukosal &corporeal

Luminal : in gaster and ready to absorbed indoeodenum.

Mucosal : absorption in small intestine.

Corporeal : transport Fe in sirculation, utilisation by

cell. And sore of Fe Liver secrete apotransferin to the bile

duodenum.


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Iron absorption depend on : Fe diet,

Iron from plan (non heme) absorb 1-7%

Heme iron (meat, fish absorp 25-30%),

with high bioavailility and easier to absorb.


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To increase non heme iron absorpion

need trigger factor such as ascorbic acid

(lemon,grape, guava, papaya and greenvegetable). Inhibite by tannat (tea), coffe

and cereal (phitate).


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Fe deficiency

Deficient of Fe Fe deficiency anemia

Caused by : bleeding, worm investation

(ankylostomum duodenale ), intake Fe

reduce, Fe absorption block etc

Hypochromic microcytic anemia.

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Erythrocyte degradation

Eryenzymes NADPH

Function of NADPH :

- maintain membrane fragility.

- maintain ion transport through membrane

- maintain Fe of Hb cell in the form of Fe++

- Protect oxidation of protein in Ery.


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Hemoglobin Degradation

Ery cell lysis/fagocyte by macrophageheme and globin.

Heme ring open free irontransport to

the blood by transferinbiliverdinreductionbilirubinplasma.

Bilirubin + albumin, reabsorb to the theliverconjugated to glucoronic acid(biliirubin glucoronate 80% and bil sulfate10% and with another substance 10%.


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Bil secreted to bile canaliculi (active

transport)intestine.

of conjugated bil.urobilinogen (easierto solute in water. Some reabsorbs by

mucosa to the blood.

Excretion to by liver and renal.

Urobilinogen urine oxidized by air

urobilin

On feses urobilinogenstercobilin.


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Life Cycleof Red

Blood Cells


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INTRODUCTION


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INTRODUCTION

- Hemolytic anemia : a shortened

RBC survival result of increasedRBC destruction

- Congenital Hemolytic Anemias

- Result from mutationsinfluence the function of RBCproteins

- Three categories :

1. Membran defect2. Enzymatic defect

3. Hemoglobin defect


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GENERAL DIAGNOSTIC

A. History and physical examination

1. - Chronicity of the problem

- Ethnic, racial background

- Family history

- Medical conditions

- New medication

2. - Jaundice

- Splenomegaly


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B. Laboratory

1. reticulocyte index respon BM

2. LDH, unconjugated bilirubin,

or absent of haptoglobin

3. RBC morphology abnormal( important clue underlying

diseases )

4. Blood smear rarelypathognomonic

CATEGORY CONGENITAL HEMOLYTIC ANEMIAS


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CATEGORY CONGENITAL HEMOLYTIC ANEMIAS

Membrane defect

A. - autosomal dominantinheritance

- marked heterogenecity in

underlyingmutations

- marked clinicalheterogeneity

- generally mild

- splenectomy is curative

- intrinsic defect

- extravascular hemolysis

B. - hereditary spherocytosis(HS)

- hereditary elliptocytosis

(HE)

- hereditarypyropoikilocytosis

- hereditary stomatocytosis

- hereditary acanthocytosis

- hereditary xerocytosis

Enzymatic defect

G6PD- X linked

- >> Africa

- self limited hemolysisby stress,infection or drug

- intrinsic & extrinsicdefect

- extravasculer &intravasculerhemolysis

Pyrovat kinase- autosomal recessive

disorder- chronic hemolysis

Hemoglobin defect

Thalasemias- quantitative defect

- globin chainimbalance ( / )

Sickle cell ds- qualitative defect- amino acid

substitutionstability Hb

HS HE


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HS

- abnormalities RBC structural

protein (Spectrin,Ankyrin,Band)

mediate vertical interactions- clinical presentation :

a. Jaundice

b. Formation of pigment

gallstones

c. Mild to moderate

splenomegaly

d. Leg ulcer

- Laboratory

- peripheral blood smear

spherocytes

- anemia polychromasia- osmotic fragility test

- Treatment

- severe anemia

splenectomy

- abnormalities RBC Structural

protein (Spectrin)mediatehorisontal interactions

- clinical presentation :

a. Jaundice

b. Formation of pigment

gallstones

c. Mild to moderate

splenomegaly

d. Leg ulcer

- Laboratory

- peripheral blood smear

elliptocytosis

- anemia

- osmotic fragility normal

or abnormal

- Treatment

- severe anemia

splenectomy

HE


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Spherocytosis Elliptocytosis


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G6PD Deficiency PK Deficiency

X linked inheritance

Pathophysiology :

- acute hemolysis RBC is

exposed to oxidant stress,

infection, drugs (page 53)

- Glutathion stores oxidative

damage to RBC component

- Heinzs bodies(+)

Hemolysis extravasculer commonly Hemolysis intravasculer severe

oxidant

Diagnosis measurement of

enzyme

Autosomal recessive disorder

Pathophysiology :- In the glycolytic pathway

convertphosphoenolpyruvate topyruvateaccumulation of

2-3 dyphosphoglycerate extremely severe hemolytic anemiaintense reticulocytosis,

splenomegaly Diagnosis

measurement ofenzyme

Treatment : Splenectomy


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Drugs That Provoke Hemolytic Episodes in

individuals deficient in G6PD

- Acetanilid - Sulfacetamide

- Methylene blue - Sulfamethoxasole

- Nalidixic acid - Sulfanilamide

- Napthalene (Mothballs) - Sulfapyridine

- Niridazole - Thiazolsulfone

- Nitrofurantoin - Toluidine blue

- Pamaquine - trinitrotoluene

- Pentaquine

- Phenylhydrazine- Primaquine

Th l i Si kl C ll di


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Thalassemias Sickle Cell disease

mutation in codon 6 of the -

globin chain Three genotype : SS, SC or

Sickle--thalassemia

Clinical Features :

- sickle cell trait

- sickle cell anemia

- sickle--thalassemia- hemoglobin SC

Cinical presentation

- periodic episodes of

acute vasculer occlusion

(painful crisis)

Howell-Jolly bodiesTreatment : supportive (hydration,

pain medication)

a globin chain imbalace

Mutation partially or

completely a globin

chain imbalance ratio dan

globin chain

The most common type :

- Beta ()- Alpha ()

- Combination with Hb abnormal

(HbE)

Clinicaly :

- Thalassemia major- Thalassemia intermedia

- Thalasemia

minor / thalassemia trait

Treatment ~ clinicaly


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Thalassemia Sickle cell disease


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Change in Globin Chain Production


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22 = 97 %(Hb A)

2

2

(Hb F)< 1 % 2 24 (Hb Bart`s)

224(Hb H)

2 2 (Hb A2) 2-3 % 2 24 ?

2 2 (Hb F)

2 2 (Hb A2)

224

Normal - Thal - Thal
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2. Extra vascular hemolytic

occur extra vascular by macrophage

phagositosis specialy in the spleen and other

RES. This is the most frequent of HE, followedby jaundice and splenomegaly. Unconyugated

hyper bilirubinemia is typically present


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Immune-mediated hemolytic disorder:

a. auto immune hemolytic anemias: is agroups of disorder that are the result of

antibody or complement binding to specificantigen on the RBC membrane, whichleads to RBC life spand.

This disorder can be primary (idiophatic)or secondary (underlying disease, drug)


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Anti-erythrocyte antibody can be devided into 3catagories:

a. IgG warm auto antibodies bound to RBC butfailed to agglutinate RBCs

b. Cold agglutinin almost are of the IgM subtypeand clump RBC at cold temperature.

c. Donat-Landsteiner (IgG) antibodies binds to

RBC membrane in the cold and activatehemolytic complement cascade when the RBCwarmed to 37C

Causes of Acquired Hemolytic Anemias


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Immunohemolytic

Transfusion of incompatible blood

Hemolytic disease of the newborn

Warm-antibody autoimmune hemolytic anemiaCold-antibody autoimmune hemolytic anemia

Traumatic and microangiopathic

Prosthetic valves and other cardiovascular abnormalities

Hemolytic uremic syndrome

Thrombotic thrombocytopenic purpura

Disseminated intravascular coagulation

Immunologic phenomena (e.g., graft rejection, immune complex formation)Cancer

Infectious agents

Protozoa (e.g., malaria, toxoplasmosis, leishmaniasis, trypanosomiasis)

Bacteria (e.g., bartonellosis, Clostridia, cholera, typhoid fever)

Chemicals, drugs, and venoms

Physical agents BurnsHypophosphatemia

Paroxysmal nocturnal hemoglobinuria

Spur cell anemia (liver disease)

Vitamin E deficiency in newborns

Drug induced immune hemolytic anemia


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Drug-induced immune hemolytic anemia.

Hapten mechanism Clinically, the DAT is positive for IgG, and hemolysis

occurs only when the offending drug (e.g., penicillin) is present.

Immune complex mechanism .This is the most common mechanism for drug-

induced (e.g., quinidine, phenacetin) immune hemolytic anemias. The DAT is

positive for complement (C3) only.

Autoantibody mechanism. The DAT is positive for IgG. As many as 20% of

patients treated with methyldopa have a positive DAT, but fewer than 1 % ofthese patients demonstrate hemolysis.

Immunogenic drug-RBC complex mechanism

Non-immune protein adsorption mechanism.Proteins (e.g., drugs) may non-

specifically attach to the RBC membrane without causing RBC destruction.Examples include cephalosporins (primarily first generation), albumin, and

immunoglobulins (e.g., IVIG).


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NONIMMUNE HEMOLYTIC ANEMIAS

The nonimmune hemolytic anemias are generally the

result of extrinsic factors or effects on otherwise normal

RBCs. Many physical, chemical, and infectious causes

make up the differential diagnosis for the nonimmune

hemolytic anemias.

Fragmentation hemolysis


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Fragmentation hemolysisFragmentation hemolysis occurs when mechanical trauma or shear stress disrupts the physical integrity

of the RBC membrane.

Etiology

a.Damaged microvasculature with the resulting disorder commonly referredto as microangiopathic hemolytic anemia,

b.Arteriovenous malformations (e.g., arteriovenous shunts)

c.Cardiac abnormalities (e.g., prosthetic heart valves)

d.Drugs (e.g., cyclosporine, cancer chemotherapy agents, ticlopidine, clopi-

dogrel, cocaine)

Clinical presentationof fragmentation hemolysis. Except in cases of extremei ntravascularfragmentation, these patients typically demonstrate the same clinical findings associated with

extravascular hemolysis. These findings include pallor, jaundice, and a loss of a feeling of well-being.

Laboratory evaluation of fragmentation hemolysis

Laboratory findings are similar to those for extravascular hemolysis; some

intravascular hemolysis findings may be present.Diagnosis depends on examination of the peripheral

blood smear, which reveals fragmented RBCs (i.e., schistocytes, helmet cells, microspherocytes) and

polychromatophilia.

Treatment of fragmentation hemolysis

a.Therapy is directed at the underlying condition.

b.Ironand folic acid supplementation and RBC transfusions are administered as necessary.


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Hypersplenism

Hypersplenism is a functional state of hyperactivity of the spleen, includingits cellular sequestration activity. For this reason, hypersplenism can lead

to a decrease in the life span of RBCs, leukocytes, and platelets. Spleno-

megaly is an anatomic term for enlargement of the spleen. All of the

activities of the spleen are accentuated in a large spleen; therefore,

hypersplenism is often associated with splenomegaly. Anemia in these

patients is the result of increased RBC destruction and splenicsequestration.

Treatment of hypersplenism

a.Therapy is directed at the underlying cause of the splenomegaly or hyper

splenism.b.Anemia and pancytopenia are not usually severe; if they are severe, sple

nectomy typically leads to improvements in the blood counts.

Causes of Hypersplenism


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Vascular congestion

Right heart failure

Hepatic vein thrombosis (Budd-Chiari syndrome)

Cirrhosis

Portal vein obstructionSplenic vein thrombosis

Infection

Bacterial endocarditis

Tuberculosis

Parasites

Viruses

Fungi

Inflammatory diseases

Systemic lupus erythematosus

Rheumatoid arthritis

Hemolytic anemias

Congenital (thalassemias, hereditary spherocytosis)

Acquired (autoimmune)

Neoplasms

Lymphomas

Hairy cell leukemia

Chronic lymphocytic leukemiaMyeloproliferative disorders Storage disorders Caucher disease

Mucopolysaccharidoses

Benign structural abnormalities

Cysts

Hamartomas

Other

Amyloidosis

Sarcoidosis

Infection


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Direct parasitization (e.g., malaria, babesiosis, bartonellosis) can result from an organism infecting

the RBC, which leads to intravascular or extravascular hemolysis, or attaching to the RBC

membrane, which leads to RBC destruction.

Immune mechanisms, such as Mycoplasma pneumoniae, Epstein-Barr virus (mononucleosis), are

discussed earlier in the text (see III.C.2.b.).

Induction of hypersplenism can occur as a sequela of some infections (e.g.,malaria,

schistosomiasis) by immune-mediated and non-immune-mediated mechanisms.

Altered RBC surface topology (e.g., Haemophilus influenzae) caused by interactions between the

microorganism and the RBC surface can lead to hemolysis.

Release of toxins and enzymes by a microorganism (e.g., Clostridium, Escherichia coli 0192) can

cause direct damage to the RBC membrane, which leads to shortened RBC survival.

Other causes of nonimmune hemolytic anemias.

Liver disease

Severe burns (heat denaturation)

Copper deficiency (Wilson disease)

Drug-induced oxidative damage


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hemoglobin metabolism.pptx

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