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HEMOGLOBIN
Major transport molecule for oxygen carries carbon dioxide from the tissues to the lungs for excretion Protein with two major components:
a. Four nonprotein heme groups each containing iron in the reduced ferrous form, which is the site of oxygen binding Globin portion consisting of four polypeptide chains
b.
Hemoglobin Structure
In the normal subject these chains can be of four types: - Alpha - Beta - Delta - Gamma In normal and abnormal hemoglobins (with the exception of hemoglobin H and Barts), two sets of identical polypeptide chains make up the globin. The structure of the globin chain, like all proteins, is genetically controlled.
Hemoglobin A This is the most common type of hemoglobin found normally in adults some diseases, such as severe forms of thalassemia, may cause hemoglobin A levels to be low and hemoglobin F levels to be high.
Hemoglobin Test
Screen for, diagnose, and measure the severity of anemia (low RBCs, hemoglobin and hematocrit) or polycythemia (high RBCs, hemoglobin and hematocrit) Monitor the response to treatment of anemia Help make decisions about blood transfusions or other treatments if the anemia is severe
Electrophoresis Process
is a blood test done to check the different types of hemoglobin in the blood. takes advantage of the fact that hemoglobin types have different electrical charges. an electrical current is passed through the hemoglobin in someone's blood sample, which causes the hemoglobin types to separate at different rates and form bands by comparing the pattern formed with that of a normal blood sample, doctors can see the types and quantities of hemoglobin present in the blood sample. Hemoglobin S and hemoglobin C are the most common types of abnormal hemoglobins that may be found by an electrophoresis test.
Hemoglobin electrophoresis Hemoglobin A1: 96.5%-98.5% of total hemoglobin or 0.96-0.985 mass fraction
Hemoglobin A2:
Hemoglobin F:
More than 400 different types of abnormal hemoglobin have been found, but the most common are: Hemoglobin S - This type of hemoglobin is present in sickle cell disease. Hemoglobin C - This type of hemoglobin does not carry oxygen well. Hemoglobin E - This type of hemoglobin is found in people of Southeast Asian descent. Hemoglobin D - This type of hemoglobin is present in a sickle cell disorder. Hemoglobin H (heavy hemoglobin) - This type of hemoglobin may be present in certain types of thalassemia.
Abnormalities in Hemoglobin
Structural defects in the hemoglobin molecule. Alterations in the gene for one of the two hemoglobin subunit chains, alpha (a) or beta (b), are called mutations. Sickle hemoglobin exemplifies this phenomenon. Diminished production of one of the two subunits of the hemoglobin molecule. Mutations that produce this condition are termed "thalassemias." Abnormal associations of otherwise normal subunits. A single subunit of the alpha chain (from the a-globin locus) and a single subunit from the b-globin locus combine to produce a normal hemoglobin dimer.
clogs capillaries and prevents blood flow, causing poor circulation and leading to higher risks for stroke, organ damage, and bacterial infections Normal red blood cells live about 120 days in the bloodstream and then die.
Sickle cells usually die after only about 10 to 20 days.
in its T-state, the additional valine residues bind to a hydrophobic area on other S-hemoglobin molecules
forming long, rod-like structures that cause red blood cells to become stiff and assume a sickle shape
This dangerous effect only occurs on hemoglobin in its deoxygenated state because oxygenated hemoglobin has the R conformation, which covers the hydrophobic patch that the extra valine binds to.
Inheritance
autosomal recessive condition: gene can be passed on from a parent carrying it to male and female children must be inherited from both the mother and the father, so that the child has two sickle cell genes
inheritance of just one sickle gene: sickle cell trait or the "carrier" state
does not cause sickle cell anemia do not have many symptoms of the disease and have normal hospitalization rates and life expectancies have one of the genes that cause sickle cell anemia can pass the sickle hemoglobin gene on to their children
basic problem: the sickle-shaped red blood cells tend to get stuck in narrow blood vessels, blocking the flow of blood
Hand-foot syndrome small blood vessels in hands or feet are blocked pain, swelling, fever, ulcerations may occur may be the first symptom of sickle cell anemia in infants.
Fatigue, paleness, rapid heart rate, and shortness of breath symptoms of anemia or a shortage of red blood cells Yellowing of skin and eyes signs of jaundice from the accumulation of bilirubin results from the rapid breakdown of red blood cells
Complications
Splenic Crisis
spleen becomes to large, scarred, or damaged due to an overload of sickle cells flowing into it cells clog the spleen and disrupts it usual function, which is to fight infections by filtering out abnormal red blood cells leads to the shrinkage of the spleen blood transfusion
Stroke
can happen when sickle cells flow into the brain and block blood vessels can result from bursting blood vessels. if death isnt the result of this complication, then a person may experience learning disabilities or paralysis.
Vision
blood vessels have to have the ability to transport oxygen into the eyes small blood vessels become blocked by sickle cells thin layers of the retina become damaged Can lead to blindness
Gallstone
result of the release of hemoglobin from a dead red blood cell. may form in the gallbladder due to the overload of bilirubin. nausea, vomiting, sweating, and chills can also occur
Prenatal Diagnosis
Converts a single base paie from Glutamate to Valine -In the sixth position of Beta Globin Converts CCT-GAG-GAG to CCT-GVG-GAG MstII restriction enzyme recognizes CCT-GAG and not GVG
Prenatal Diagnosis
Southern Blot Technique -DNA Recognition -Applicable for Sickle-Cell Anemia Diagnosis
Digestion of Fetal DNA with MstII using beta Globin as the radioactive probe whether the restriction site present in both copies.
Absent
Homozygous for the sickle trait -Missing in one copy Heterozygous for the sickle trait -Missing in both copies
Treatment
Bone Marrow Transplantation -Decreases the concentration of the Sickle-Cell RBC Pain Management -Treated with Non-Steroidal Anti-Inflammatory Drugs, Ketorolax tromethamine or Analgesics
Carbon Monoxide
colourless, odourless poisonous gas and is a common yet preventable cause of death from poisoning worldwide
binds to the heme group of hemoglobin molecule at the same site as oxygen and forms carboxyhemoglobin
binding of carbon monoxide to haemoglobin is over 200 times as strong as the binding of O2 to haemoglobin. sometimes called the "Silent Killer"
Thus, at a concentration as small as 0.1%(Pco=0.5mmhg), CO will combine with half the available hemoglobin molecules and reduce the oxygen carrying capacity of the blood by 50%. Elevated blood levels of CO causes carbon monoxide poisoning, one sign of which Is a bright, cherry-red color of the lips and oral mucosa. Administering pure oxygen, which speeds up the separation of carbon monoxide from the hemoglobin, may rescue the person.
Produced by the incomplete burning of various fuels, including coal, wood, charcoal, oil, kerosene, propane, and natural gas. Products and equipment powered by internal combustion engines such as portable generators, cars, lawn mowers, and power washers also produce CO
Pulmonary Fibrosis
Immunohistochemical analysis of lung tissue from patients with various forms of interstitial lung disease reveals increased expression of HO-1, primarily in alveolar macrophages. Increased expression of HO-1 by adenoviral transfer has been shown to suppress lung fibrosis in a murine bleomycin model, and Inhaled CO has similar effects.
lack of oxygen results in organs starving of oxygen and suffering serious or even permanent damage
damage depends upon the levels of CO inhaled.
Percentage of COHb in the body can determine the type of symptoms or levels of damage that may be experienced
10-30%: headaches dizziness, fatigue and flu-type symptoms around 30-50%: nausea, vomiting, headaches and breathing difficulties over 50%, loss of consciousness, seizures, and convulsions, and at these levels the sufferer can quickly die
If breathed in at large enough levels, it can kill in just a few minutes. If breathed in at smaller levels but over a longer period of time, it can lead to death or permanent damage.
Diagnosis
Combines with the reduced Heme Iron of cytochrome oxidase, inhibiting mitochondrial electron transport, impairing normal energy regeneration resulting death of the organism Presents with Flu-like Viral Syndromes, depression, fatigue, chest pain and migraine Other conditions
respiratory distress syndrome, altitude sickness, lactic acidosis, diabetic ketoacidosis, mengitis methemoglobinemia or opioid or toxic alcohol poisoning
Treatment
Hyperbaric Oxygen Therapy
Pathophysiology
1Viral or Bacterial infections 2High altitude 3Emotional or Physical Stress 4Surgery 5Blood Loss
1Dehydration 2Increased hydrogen ion concentration (acidosis) 3Increased plasma osmolality 4Decreased Plasma volume 5Low body Tempreature
Hypoxia
Sickling episode
Cannot easily pass through capillaries or other small vessels and causes vascular occlusion
Hemostasis promotes a cycle of local hypoxia, deoxygenation of more erythrocytes and more sickling.
Amino acid glutamic acid replaced with hydrophobic amino acid valine at the sixth position
Association of two wild type alpha-globin subunits with two mutant beta-globin subunits forms hemoglobin S (Hbs)
CO Poisoning