3. Hemoglobin copy
Page 1: Absorption of Iron From the Intestinal Tract
Overview of Iron Absorption
Iron is absorbed from all parts of the small intestine.
The liver secretes moderate amounts of apotransferrin into bile, which then reaches the duodenum.
Apotransferrin binds with free iron and iron compounds such as hemoglobin and myoglobin from meat, forming transferrin.
Transferrin binds to receptors on intestinal epithelial cells.
Via pinocytosis, transferrin, along with its iron, is absorbed into epithelial cells and released into blood as plasma transferrin.
Page 2: Slow Iron Absorption
Iron Absorption Rate
Iron absorption from the intestines is extremely slow (only a few milligrams per day).
This slow rate means that even large amounts of iron in food result in low absorption levels.
Page 3: Regulation of Iron Absorption
Iron Absorption Control
When iron stores are saturated, the absorption rate significantly decreases.
When iron stores are depleted, absorption rates may increase by five times normal.
Total body iron is primarily regulated by modifying the rate of absorption.
Page 4: Role of Hepcidin
Major Regulator
Hepcidin, a polypeptide hormone secreted by the liver, is the primary regulator of iron homeostasis.
It affects enterocytes and macrophages by causing the removal of ferroportin channels from their membranes.
Hepcidin inhibits intestinal iron absorption and release from storage, lowering plasma iron concentration.
This mechanism forms a negative feedback loop, with hepcidin production decreasing in iron deficiency and increasing with high iron intake.
Page 5: Iron Absorption Mechanism
Iron Transport in the Small Intestine
Ferric iron (Fe3+) must be converted to ferrous iron (Fe2+) for absorption.
The reduction occurs due to duodenal cytochrome b (Dcytb).
DMT1 (Divalent Metal Transporter 1) is responsible for transporting Fe2+ across the luminal membrane into enterocytes.
Iron can also be absorbed as heme via a heme transporter; the heme is converted to iron and biliverdin by heme oxygenase-1 (HO-1).
Most iron is shuttled across the membrane by ferroportin for transport into the bloodstream.
Page 6: Regulation of Iron Absorption Under Varied Conditions
Plasma Iron Levels Effect
Low plasma iron increases iron absorption; high or ineffective erythropoiesis raises hepcidin levels, decreasing absorption.
Diseases like hemochromatosis result from systemic inflammation, further complicating iron homeostasis.
Page 7: Destruction of Hemoglobin by Macrophages
Phagocytosis Process
RBCs burst and release hemoglobin, which is phagocytized by macrophages, especially in the liver, spleen, and bone marrow.
Iron is retrieved from hemoglobin and transported back into the bloodstream via transferrin for new RBC production or storage.
The porphyrin part of hemoglobin is converted to bilirubin for excretion.
Page 8: Intravascular Red Blood Cell Destruction
Causes of Intravascular Hemolysis
Destruction of RBCs occurs less frequently in circulation but involves cell membrane breach.
Factors contributing to this condition include rigidity of older RBC membranes and membrane defects leading to hemolysis.
Page 9: Hemoglobin Processing in the Liver
Hemoglobin Breakdown
Released Hb in plasma binds with haptoglobin.
The Hb-haptoglobin complex is transported to the liver where it is processed into iron and biliverdin by heme oxygenase.
Page 10: Ionic Breakdown Products from Hemoglobin
Further Breakdown of Heme
CO is released as a byproduct during heme cleavage by heme oxygenase.
Biliverdin is then converted to bilirubin, while heme in plasma binds to hemopexin until saturation, after which it binds to albumin to form methemalbumin.
Page 11: Extravascular Red Blood Cell Destruction
Macrophage Activity
Older RBCs are phagocytized by macrophages, a crucial process in recycling hemoglobin components.
Page 12: Changes in Red Blood Cells with Age
Decreased Deformability
Changes in red blood cell structure (e.g., spherocytosis, increase in internal viscosity) make them vulnerable to lysis in the spleen.
Page 13: Surface Alterations in Aging Red Blood Cells
Alterations in Chemical Composition
Antibody binding results in oxidation of membrane components, prompting macrophage-mediated ingestion of aged RBCs.
Breakdown of RBCs yields bilirubin, lipids, and proteins for recycling.
Page 14: Bilirubin Excretion Process
Pathway to Excretion
Bilirubin from RBC destruction is excreted into bile, converted to urobilinogen in the intestine, and further processed into stercobilin for fecal excretion.
Some urobilinogen is reabsorbed and excreted via urine.
Page 15: Overview of Erythrocyte Recycling
Lifecycle of Erythrocytes
Erythrocytes have a lifespan of about 120 days before being phagocytized by macrophages in the liver and spleen.
Components of hemoglobin are recycled: globin into amino acids, iron transported as Fe2+, and heme processed into bilirubin.
Page 16: Understanding Anemias
Definition and Causes
Anemia refers to a deficiency of hemoglobin in blood, arising from insufficient RBCs or hemoglobin content.
Page 17: Blood Loss Anemia
Mechanism of Blood Loss
Rapid hemorrhage leads to low RBC concentration although plasma fluid is quickly restored.
Chronic blood loss may hinder sufficient iron absorption for hemoglobin production, resulting in microcytic hypochromic anemia.
Page 18: Aplastic Anemia Causes
Bone Marrow Dysfunction
Aplastic anemia occurs due to lack of functioning bone marrow, often due to radiation, toxic chemicals, or autoimmune disorders.
Without treatment, severe aplastic anemia can be fatal.
Page 19: Megaloblastic Anemia Overview
Nutrient Deficiencies
Anemia can arise from deficiencies in vitamin B12, folic acid, and intrinsic factor, leading to slow reproduction in erythroblasts and the formation of oversized RBCs (megaloblasts).
Page 20: Consequences of Nutrient Poor Absorption
Impact on Erythrocyte Formation
Inadequate absorption of vitamins results in fragile RBC membranes and increased rupture, causing anemia.
Page 21: Hemolytic Anemia Description
RBC Fragility Issues
Fragile RBCs rupture in capillaries due to hereditary or acquired abnormalities, often resulting in serious anemia despite normal production rates.
Page 22: Sickle Cell Anemia Mechanism
Hemoglobin S Abnormalities
In sickle cell anemia, hemoglobin S precipitates at low oxygen levels, distorting RBC shape.
This leads to increased fragility and potential crises resulting in rapid anemia.
Page 23: Sickle Cell Disease Crisis Explanation
Crisis Progression
Vicious cycles in sickle cell disease exacerbate the condition, leading to rapid decreases in RBC counts and potential life-threatening outcomes.
Page 24: Erythroblastosis Fetalis Mechanism
Maternal Antibody Interaction
Rh-positive fetal RBCs are attacked by maternal Rh-negative antibodies, causing rapid RBC rupture and severe anemia at birth.
Page 25: Secondary Polycythemia Overview
Adaptation to Hypoxia
Secondary polycythemia arises in response to hypoxic conditions (e.g., high altitudes or oxygen delivery failure) resulting in increased RBC production.
Page 26: Polycythemia Vera Conditions
Pathological Condition
Polycythemia vera, a genetic disorder, causes uncontrolled RBC production leading to significantly increased RBC counts and elevated hematocrit levels.
Page 27: Effects of Polycythemia Vera
Impacts on Vascular System
Increased blood volume and viscosity can lead to vascular engorgement and increased risk of capillary obstruction.
Page 28: Erythropoietin Feedback Circuit Modulation
Regulatory Mechanisms
Various factors affecting oxygen delivery result in alterations in erythropoietin secretion and corresponding shifts in erythrocyte production.