Professional Documents
Culture Documents
A. Iron metabolism
Excess Fe deposited in lysosomal membrane as Hemosiderin (pseudocrystalline complex) under LM as Prussian Blue Staining Dec. transferrin: 1)Collagen disease 4) RA
1)
2) RE cells 3) BM
2)
3)Malignancies (tumor, CA) Sideroblasts nucleated RBC w/ stored ferritin Siderocytes mature RBC w/ ferritin deficiency Fe stores are depleted; defects in Fe
- 1 mg required for each ml of RBC produced - 20-25 mg erythropoiesis (95% - recycled Fe salvaged from
normal RBC turn over & Hb catabolism)
5) Iron
- Cytochrome hemoprotein; resp. for electron transport - Myoglobin has 1 heme pigment, bind w/ O2 tightly; muscle
protein
1. Inappropriate oral intake Fe content in food - Infants too long on milk diet - Native pop. w/ marginal & poor diets - Older people w/ limited food intake (tea & toast) 2. Insufficient or defective absorption from intestine
transport = dec. transferrin (Rheumatic arthritis) mense) (inflammatory
after
4. Abnormal loss of Fe loss of circulating RBC (hemorrhage / Males: pathologic blood loss prime suspect (hemorrhoids occult carcinomas of bowel)
a. b.
protein)
B. Iron absorption Regulated by intestines just enough Fe to cover losses w/o excessive absorption Normal dietary intake = 10-20 mg/day (1 mg absorbed) Dietary Fe Fe+3 (Ferric) or Fe+2 (Ferrous) only absorbed Source of Fe+2 (heme) liver Source of Fe+3 (non-heme) eggs & ampalaya (veggies) Reduction by acid pH of stomach & reducing subst. in duodenum & jejunum, sometimes in stomach Inc. Fe absorption: 1)Vit. C 2)AA 3)sugars
Loss of Fe in men & menopausal women hemorrhoid & bleeding neoplasm Accompanying factors in Fe depletion: 1)Malaria 3) Kala-azar (L. donovani) 2)Trypanosomiasis 4) Other intestinal parasites Abnormal loss of Fe:
1) 2)
IDA
Mens
hemolysis)
Esophagealvarices
1) 3) 4) a.
2) Fatigued
6) Iron overload 1. Increased absorption Primary hemochromatosis genetically determined metabolic disorder
Dec. Fe absorption: 1)Antibiotics 2)Antacids 3)Oxalates 4) Phytates (cereal & veggie fiber) 5) Tannins from tea 6) Phosphates
once absorbed intestinal mucosal cells oxidize it ferric Fe temporarily stored as ferritin unabsorbed in bowel excreted severe ID inc. absorption to 30% to compensate for depletion Fe requirement pregnant & lactating women, children up to 2 yrs
b.
Hemosiderosis
moderate
deposited
1) 2)
Dietary Bantu, Africa cooking utensils, H2O & food Medicinal prolonged administration of medicine Fe
bound to specific Fe transport protein (Transferrin) plasma beta-globulin synthesized from liver transferrin attach to receptors of developing RBC membrane release free Fe into RBC (incorporate into heme in mitochondria) 10-20% of T Body Iron stored as ferritin
Hemoglobin
Formation in developing RBC in BM (except fetal life) 1 week formation occupy 1/3 of RBC (2/3 H2O)
2. 4. 1.
3. Translation mRNA leaves nucleus for ribosome in cytoplasm appropriate ribosome site Normal Hb variants: - identified by electrophoresis (also abnormal) Embryonic Hb (1st 3 months after conception)
Components:
1) 2) 3) 4) 1. 2.
4 molecules of nitrogenous subs. Protoporphyrin IX 4 iron atoms in Fe+2 state (heme w/ porphyrin) Globin protein component 2 sets of 2 different polypeptide 1 2,3 diphosphoglycerate (2,3-DPG) sometime resident in Produced in anaerobic glycolytic (Emden-Meyerhof) pathway generates energy for RBC Hb binds 2,3-DPG O2 affinity dec. Plasma level of 2,3-DPG dec Hb 2,3-DPG released Hb O2 affinity Adequate tissue oxygenation need adequate 2,3-DPG
chains center
a)
2. Fetal Hb (4 month of embryonic devt. birth) 80 Nb, <1 A 3. Adult Hb (1yr +) a. HbA, or HbA (22) 97% of Hb 20 Nb, 97A b. HbA2 (22) 2% of Hb - <0.5Nb, 2.5A
Hb derivatives: - Physiologic Hb OxyHb & reduced Hb readily converted to series of cmpds. By acids, alkalies, Oxidizing & reducing subs, heat & other agents
encourage Hb to release O2 to tissues Function: Carries CO2 reduced Hb Carries O2 oxiHb (1g Hb = 1.34 ml O2) O2 combining capacity of blood dir. Proportional to Hb, not RBC
1. 2. -
Hi to combine reversibly w/ O2 - Normal: 1.5% of Hb is Hi If - cyanosis & functional anemia Sulfhemoglobin (SHb) mix of oxidized, partially denatured Hb Hb oxidation S incorporated to heme rings green - Reduced back to Hb by erythrocyte enzyme sys. w/c form during oxidative hemolysis hemochrome Further oxi denaturation & pption of Hb as Heinz bodies Cant transport O2, but combine w/ CO2
Determination used to: 1. Screen for disease assoc. w/ anemia 2. Determine severity of anemia 3. Follow response to treatment for anemia
2. 3. 1. 2. 3. -
Age (Nb = 14-20 g/dL 1 yr adults old) Sex (female = 12-16 g/dL; male = 14-18 g/dL)
4. Pregnancy dilutional anemia Pathologic factors w/c affect Hb conc: Anemia () Pulmonary disease Dehydration ( value) 5. Hemorrhage 6. Leukemia () 7. Polycythemia ()
Carboxysulfhemoglobin - Cant be reduced to Hb, remains in cells until they break down - In patients having treatment w/ sulfonamides or aromatic amine drugs (phenacetin, acetanilid) * Hb S hemoglobin (sickle)
3.
degradation bilirubin 0.5 (CO) in blood & in hemolytic anemia - Hb combines w/ CO 210x greater than affinity for O2 (even if conc. In air is extremely low [0.102 to 0.04%)
4. Destruction of BM Location of Hb during Function & Degradation: In developing RBC (prorubricyte after RBC is released in circulation) RBC destruction remnants captured by phagocytic cells of RES (mostly spleen & liver, also BM) Iron & globin chain AA recycled for Hb synthesis Biliverdin degraded & excreted
A. 1. 2. 3.
Build up typical symptoms of toxic appear >40% saturated blood acute CO poisoning death
- Cant bind O2 Hemoglobinometry measure conc. Of Hb in blood circulation Specific gravity method drops of blood fall into 16 small bottles Drop falls in few sec. - sp.gr. than CuSO4 Drop rises in few sec. - sp.gr. than CuSO4 Drop of blood suspended for 15 sec then fall same sp. Gr as w/ CuSO4 soln of inc. Sp. Gr (results):
Heme production & structure requires formation of protoporphyrin IX & Fe Heme synthesis steps enzymatically directed; in erythroid precursors - Remnants of heme production: Free Erythrocyte Protoporphyrin (FEP) excess porphyrin in mitochondria complexed to Zn
CuSO4 Bottle labe;s: Hb values Adv: fast, simple, inexpensive Disadv: inaccurate Used by blood banks screening test for blood donors Female 1.053 (normal in soln.) = 12.5 g% Hb - abnormal globulin Oxygen method Hb combines w/ & liberates fixed quantity of
a.
Globin chain production simple, nonconjugated proteins w/ AA only - (alpha), (Beta), (gamma), (delta), (epsilon), (zeta?) Greek
O2 blood hemolyzed w/ Saponin O2 collected & measured in Van Slyke apparatus b. CO method C. Colorimetric method
a.
Direct
matching
methods
(Tallqvists
proc.,
Dares
proc.,
Spencers proc) - Blood color compared w/ colored standards w/ known Hb quantities - Adv: fast, simple, convenient; Spencers proc is accurate - Used at bedside by physician
b.
acid hematin (brown-colored soln. formed by adding 1/10 N HCl) compare w/ standard - Venous blood (EDTA or double oxalate) or capillary blood
c.
blue-green soln (alkali hematin) measure w/ colorimeter or compared w/ standard - Adv: accurate - Disadv: not accurately measure Hb of infant
d.
OxyHb depth of resulting color measured w/ photoelectric colorimeter - Adv: fast, accurate
e. -
Disadv: Cu traces in diluting fluid can convert Hb MetHb value Cyanmethemoglobin method blood + FerriCN Hb Fe+2
Fe+3 form metHb + KCN stable pigment cyanmetHb - Conv. Time = 3 mins Absorbance dir. Prop. to amt. of Hb present (SHb not meas. Completely) Drabkins soln. (orig) NaHCO3 (1g) KCN (0.05 g) K3Fe(CN)6 (0.20g) Dist. H2O (1,000 ml) (new) anhydrous KH3PO4 KCN K. ferricyanide non-ionic detergent (Sterox S.E) or Triton x100 - Vol. of O2 corrected for temp. & pressure; Hb determined by: Vol. of O2 per 100 ml = gms. Of Hb per 100 ml 1.34 - Abnormal:
1. 2. 3. 4.
- globulin false add 0.1 g K2CO3 to 1L test soln. absorbance add 0.02 ml patients plasma to 6ml of cyanmetHb. HbC, HbS, Hbn abno turbidity (5 cyanmetHB: 5 Turbidity - WBC (+30,000) bacterial infection H2O); 1:2 dilution centrifuge cyanmetHb & read supernatant - Adv: none - Disad: time consuming, technique expensive equipment, inaccurate - Formerly used to calibrate instruments for determining Hb conc.
D. -
(0.34%) - 1 g or 1000 mg Hb = 3.4 mg Fe Method of Wong blood + conc. H2SO4 w/ K persulfate Fe detached from Hb proteins ppt. w/ Tungstic filter off Fe contect of filtrate determined by colorimeter & Hb value calculated by: mg Fe/100 ml = gms. Hb per 100 ml 3.4