Heme, Iron, Blood Plasma Flashcards
Name 2 types of congenital methemoglobinemia
Congenital - lack of NADH cyctochrome b5
Inherited hemoglobin M disease - mutation in heme pocket which stablizes ferric F3 iron.
Causes of acquired methemoglobinemia
Sulfa drugs (TMP), lidocaine, benzocaine, Dapsone
Treatment methemoglobinemia
reducing agents - methylene blue or ascorbic acid
Explain the Bohr effect
Increase in pH (decrease in CO2) hemoglobin affinity increases
An increase in temperature does what to hemoglobin’s oxygen binding affinity?
Decreases it
What is the role of bicarbonate in the transport of oxygen and CO2 between the lungs and tissues?
Tissues - CO2 converted to bicarb and H+ the H+ then binds the heme and release O2 to tissues
Lungs - H+ released from hemeglobin to bind to O2 - the H+ binds bicarbonate forming water and CO2 which is expired.
Most common deficiency in hereditery spherycytosis?
ankyrin
Symptoms of spheryocytosis?
splenomegaly, jaundice, secondary to hemolytic anemia. typically follows EBV or intense physical work
Treatment for spherocytosis?
- Give vaccines for HIB, PCV, meningcocal
- Remove spleen
- Folic acid supplement
Difference between oncotic and hydrostatic pressure?
Hydrostatic pressure created by beating of the heart
Oncotic pressure is based on the amount of proteins in the blood
List causes of ascites
Alcoholism (cirrhois), CHF, Kwashiorkor (lack of proteins)
Also some cancers where the tumors produce fluid
Treatment for Ascites
Periscentesis - give albumin if remove more than 5 L
What is genetic heredibility of G6PD
x-linked
If you have G6PD you are unable to reduce this cofactor
NADP+ to NADPH
List stressers of G6PD and what do they cause
Infection, Fava beans, drugs like antimalarials, Dapsone, and sulfa, Henna tattoos. Oxidative stress
Histologic findings for G6PD
Heinz bodies, bite cells and blister cells
Sx of G6PD
Dark urine, skin pallor, jaundice, hepatosplenamegaly, fever
What cofactor is required for Glutathione reductase to make glutathione
FAD
What pathway does G-PD enter into?
Pentose Phosphate Pathway
Why is selenium required in diet?
Allows conversion of H202 to H+ and H20
What type of anemia is associated with lead poisoning?
microcytic anemia
What enzymes does Pb2+ block in the heme synthesis pathway?
Delta- ALA - dehydratase and ferrochetalase
What is porphyria?
Inherited disorder of heme production
Name symptoms of acute porphyria
constipation, diarrhea, n/v, back, chest and neck pain, AMS, tachycardia
Diagnostic signs of acute porphyria
Increase in intermediates (porphobilinogen), increased ALA if lead poisoning
What defect in heme synthesis pathway is not a porphyria?
delta -ALA synthase deficiency (also Autosomal recessive)
Describe Cutena Tarda.
Hepatic URO-D deficiency, linked to Hep-C (acquired) - congenital is HFE C282Y homozygous
Symptoms of cutaneous porphyria
Deposits in the skin, scarring, hyperpigmention, hyper trichosis, bullous dermatosis
B6 deficiency manifests as this.
Microcytic hypochromatic anemia
What supplement is needed for a patient on Isoniazid?
B6 - pyridoxal phosphate
What populations are at high risk for B6 deficiency?
Pregnant people, alcoholics, diabetes, HIV+, seizure disorders
If a pt. presents with excess unconjugated bilirubin there is a problem with this reaction?
Glucorination in the liver
Bilirubin is converted to this form for excretion in the urine, stool
Urobilinogens, stercobilinogens
List significant lab findings for hemochromatosis
Increased serum Fe, ferritin, transferrin iron sat.
Decreased total iron binding capacity
List significant lab finding for iron deficiency anemia
Increased total iron binding capacity.
Decreased serum iron, ferritin and transferrin iron
What AOCD?
Anemia of chronic disease - too much stored iron, can’t access it.
Confirmation of hemochromatosis diagnosiss is done with these procedures/tests
Liver biopsy and T2star MRI
What is the mutation associated with Type I hereditary hemochromatosis?
Cysteine to Tyrosine substitution at 282, C282Y
Effect of C282Y mutation
Decreased hepciden and increased iron absorption
Triad of symptoms for hemachromatosis or iron overload
Diabetes, hepatomegaly, hyperpigmentation, leads to cirrhois, hepatocellular carcinoma and CHF
Treatment for hemochromatosis
Ferritin < 1000 mg/L - phelbotomy
Ferritin > 1000 mg/L - add liver biopsy - check for HCC
Causes of iron deficiency anemia
Blood loss, increased requirement, and decreased absorption
Symptoms of iron deficency anemia
Fatigue, irritability, pica, koilonychia (spooned nails), glossitis. kids - impaired psychomotor development
Treatment of iron deficency includes in this steps
Look for source of blood loss, rule out intervascular hemolysis. If negative supplement with Iron
Disease states associated with AOCD
Infectious - TB, Malignant - Hodgkins, NHL, Autoimmune - RA, trauma and heart disease
Release of what 2 immunologic factors results in increased hepcidin
IL6 and IL1B
Treatment of AOCD
Treat the underlying process and give EPO
Why is heme iron absorbed more readily than non-heme iron
Heme does not have to converted to be absorbed.
List 2 transporters for heme
Ferrous +2 - HPC1
(Ferric +3 converted to Ferrous) - DMT1
What enzyme converts ferric iron to ferrous iron?
Duodoenal cytochrome B reductase
List promotors of iron absorption
Ascorbic acid, citric acid, beta carotene, alcohol
Describe Sprue
Disorder of duodenum which inhibits absoprtion of iron (often called Celiac)
