Iron metabolism in neonates is a less known topic. tried to make it simple by few diagrams.hope this presentation would help you. In case you need any help mail at dockamalpaeds@yahoo.com
Iron homeostasis is tightly regulated in the body. Hepcidin acts as the master regulator of iron by inhibiting intestinal iron absorption and macrophage iron release. Disorders of iron overload occur when hepcidin production is insufficient, such as in hereditary hemochromatosis. The most common type is HFE hemochromatosis caused by mutations of the HFE gene. Treatment involves regular phlebotomy to reduce iron levels. Family screening is important given the hereditary nature of the disease.
This document discusses anemia in chronic kidney disease (CKD). It outlines the benefits of treating anemia, including improved quality of life and reduced cardiovascular risks. It then presents a case study of a 65-year-old CKD patient with diabetes and hypothyroidism. His lab results show hemoglobin of 8.4 g/dL, ferritin of 950 ng/mL, and TSAT of 15%. The document goes on to discuss factors contributing to anemia, methods of assessing iron status, iron replacement therapies including oral and parenteral options, ESA therapies, and guidelines around hemoglobin targets in CKD patients. Safety issues of iron treatment and limitations of ESA therapy are also reviewed.
Anemia of renal disease is common and is associated with significant morbidity and death. It is mainly caused by a decrease in erythropoietin production in the kidneys and can be partially corrected with erythropoiesis-stimulating agents (ESAs). However, randomized controlled trials have shown that using ESAs to target normal hemoglobin levels can be harmful, and have called into question any benefits of ESA treatment other than avoidance of transfusions.
Iron deficiency anaemia (for v year mbbs)mona aziz
Iron Deficiency Anaemia is a widespread problem globally. It affects toddlers, women of childbearing age, and school-aged children. Iron is essential for oxygen transport, cell metabolism, and immune function. Causes of iron deficiency include low dietary iron intake, blood loss, pregnancy/lactation, and malabsorption. Symptoms include pallor, fatigue, and behavioral changes. Laboratory findings show low iron stores, serum iron and transferrin saturation. Treatment involves iron supplementation orally or parenterally, and treating the underlying cause. Uncorrected iron deficiency can lead to developmental delays in children.
This document discusses iron refractory iron deficiency anemia (IRIDA). It defines key terms like anemia and iron deficiency. It describes normal iron metabolism and the role of transport proteins like DMT1 and ferroportin in intestinal iron absorption. Hepcidin regulates iron transport by binding to ferroportin and inducing its degradation. Mutations in ferroportin can cause iron overload by preventing its binding to hepcidin. The document also discusses rare conditions like atransferrinemia caused by near absence of plasma transferrin.
The pathogenesis of CKD-MBD is complex, involving disruptions in mineral homeostasis and hormone levels as kidney function declines. Key factors include hyperphosphatemia, decreased calcitriol levels, and hypocalcemia. This leads to elevated PTH levels as the parathyroid glands respond to low calcium and calcitriol. Over time, the parathyroid glands become resistant due to downregulation of receptors. Progressive CKD also impairs the kidneys' ability to regulate phosphate, exacerbating hyperphosphatemia and CKD-MBD.
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired hematopoietic stem cell disorder characterized by hemolytic anemia, bone marrow failure, and thrombosis. It results from a somatic mutation in the PIG-A gene, leading to a deficiency in glycosylphosphatidylinositol-anchored proteins on the surface of blood cells. This renders the cells susceptible to complement-mediated lysis, causing intravascular hemolysis. Diagnosis involves flow cytometry to detect the deficient proteins on red blood cells and granulocytes. Management focuses on treating anemia, thrombosis, and infections, with complement inhibitors now providing an effective targeted treatment option. PNH has a
Refractory anemia is a subtype of myelodysplastic syndrome characterized by non-responsiveness to conventional anemia treatment. It is defined by less than 5% blasts in the bone marrow and less than 1% in the peripheral blood. Refractory anemia involves dysplasia primarily affecting the erythroid lineage. Evaluation includes blood counts, peripheral smear, bone marrow biopsy and cytogenetic testing to confirm the diagnosis and guide prognosis. Management focuses on treating the anemia and related symptoms.
Iron homeostasis is tightly regulated in the body. Hepcidin acts as the master regulator of iron by inhibiting intestinal iron absorption and macrophage iron release. Disorders of iron overload occur when hepcidin production is insufficient, such as in hereditary hemochromatosis. The most common type is HFE hemochromatosis caused by mutations of the HFE gene. Treatment involves regular phlebotomy to reduce iron levels. Family screening is important given the hereditary nature of the disease.
This document discusses anemia in chronic kidney disease (CKD). It outlines the benefits of treating anemia, including improved quality of life and reduced cardiovascular risks. It then presents a case study of a 65-year-old CKD patient with diabetes and hypothyroidism. His lab results show hemoglobin of 8.4 g/dL, ferritin of 950 ng/mL, and TSAT of 15%. The document goes on to discuss factors contributing to anemia, methods of assessing iron status, iron replacement therapies including oral and parenteral options, ESA therapies, and guidelines around hemoglobin targets in CKD patients. Safety issues of iron treatment and limitations of ESA therapy are also reviewed.
Anemia of renal disease is common and is associated with significant morbidity and death. It is mainly caused by a decrease in erythropoietin production in the kidneys and can be partially corrected with erythropoiesis-stimulating agents (ESAs). However, randomized controlled trials have shown that using ESAs to target normal hemoglobin levels can be harmful, and have called into question any benefits of ESA treatment other than avoidance of transfusions.
Iron deficiency anaemia (for v year mbbs)mona aziz
Iron Deficiency Anaemia is a widespread problem globally. It affects toddlers, women of childbearing age, and school-aged children. Iron is essential for oxygen transport, cell metabolism, and immune function. Causes of iron deficiency include low dietary iron intake, blood loss, pregnancy/lactation, and malabsorption. Symptoms include pallor, fatigue, and behavioral changes. Laboratory findings show low iron stores, serum iron and transferrin saturation. Treatment involves iron supplementation orally or parenterally, and treating the underlying cause. Uncorrected iron deficiency can lead to developmental delays in children.
This document discusses iron refractory iron deficiency anemia (IRIDA). It defines key terms like anemia and iron deficiency. It describes normal iron metabolism and the role of transport proteins like DMT1 and ferroportin in intestinal iron absorption. Hepcidin regulates iron transport by binding to ferroportin and inducing its degradation. Mutations in ferroportin can cause iron overload by preventing its binding to hepcidin. The document also discusses rare conditions like atransferrinemia caused by near absence of plasma transferrin.
The pathogenesis of CKD-MBD is complex, involving disruptions in mineral homeostasis and hormone levels as kidney function declines. Key factors include hyperphosphatemia, decreased calcitriol levels, and hypocalcemia. This leads to elevated PTH levels as the parathyroid glands respond to low calcium and calcitriol. Over time, the parathyroid glands become resistant due to downregulation of receptors. Progressive CKD also impairs the kidneys' ability to regulate phosphate, exacerbating hyperphosphatemia and CKD-MBD.
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired hematopoietic stem cell disorder characterized by hemolytic anemia, bone marrow failure, and thrombosis. It results from a somatic mutation in the PIG-A gene, leading to a deficiency in glycosylphosphatidylinositol-anchored proteins on the surface of blood cells. This renders the cells susceptible to complement-mediated lysis, causing intravascular hemolysis. Diagnosis involves flow cytometry to detect the deficient proteins on red blood cells and granulocytes. Management focuses on treating anemia, thrombosis, and infections, with complement inhibitors now providing an effective targeted treatment option. PNH has a
Refractory anemia is a subtype of myelodysplastic syndrome characterized by non-responsiveness to conventional anemia treatment. It is defined by less than 5% blasts in the bone marrow and less than 1% in the peripheral blood. Refractory anemia involves dysplasia primarily affecting the erythroid lineage. Evaluation includes blood counts, peripheral smear, bone marrow biopsy and cytogenetic testing to confirm the diagnosis and guide prognosis. Management focuses on treating the anemia and related symptoms.
Thrombotic Microangiopathies are diverse group of disorders wherein thrombocytopenia, hemolytic anemia and organ dysfunction such as Kidney and brain occur . Major recent advances in this field have occurred which opens up oppurtunities to effectively manage its clinical challenges .
Anemia is a common complication of chronic kidney disease that can cause fatigue. While the kidneys normally produce erythropoietin to stimulate red blood cell production, CKD patients have relative erythropoietin deficiency. This leads to anemia which, if left untreated, can negatively impact quality of life and cardiovascular health. Erythropoiesis-stimulating agents and iron supplementation are used to treat anemia in CKD, though the appropriate hemoglobin target level remains an area of ongoing research and debate given risks identified with higher targets in some studies.
This document discusses the management of anemia in chronic kidney disease (CKD). It begins by defining anemia and its causes in CKD, which include reduced erythropoietin production and decreased red blood cell survival due to kidney failure. Left untreated, anemia in CKD can lead to deterioration in cardiac function, impaired cognition, and increased fatigue and mortality risk. The main therapeutic options for treating anemia in CKD are red blood cell transfusions, androgens, and erythropoiesis-stimulating agents (ESAs). ESAs such as epoetin alfa and darbepoetin alfa are now the standard treatment as they reduce transfusion needs and risks while helping to mobilize
This document discusses anaemia and its causes in chronic kidney disease (CKD). It defines anaemia and outlines how it is diagnosed based on haemoglobin levels. The main causes of anaemia in CKD are decreased erythropoietin production and iron deficiency. Iron supplementation using oral or intravenous iron is recommended to treat iron deficiency anaemia in CKD, along with erythropoiesis-stimulating agents (ESAs) like epoetin and darbepoetin to treat all anaemia. Guidelines on monitoring haemoglobin levels and initiating/maintaining ESA therapy are provided. Red blood cell transfusion is indicated when rapid correction of anaemia is needed or ESA therapy is ineffective.
Hyperphosphatemia in CKD patients; The Magnitude of The Problem - Prof. Alaa ...MNDU net
Hyperphosphatemia in CKD patients; The Magnitude of The Problem
Prof. Alaa Sabry - Professor of Nephrology
Mansoura Nephrology and Dialysis Unit (MNDU) Course
This document discusses iron metabolism and iron deficiency. It begins by outlining how iron is essential for many metabolic processes and exists in both ferric and ferrous states. It then discusses iron transport and storage in the body, as well as iron absorption, distribution, and regulation. The document also covers the causes, pathogenesis, morphology, diagnosis of iron deficiency and the role of hepcidin in various iron-related diseases.
Dr Abdullah Ansari
MBBS, MD Medicine
Aligarh Muslim University
Clinical case
Hemolytic Anemia
Intravascular vs extravascular hemolysis
Classification of hemolytic anemia
Approach to hemolysis
Patient history
Clinical features
Peripheral blood smear
Investigation
Treatment
Iron deficiency anemia develops when iron stores are too low to support normal red blood cell production. It can be caused by inadequate dietary iron, impaired iron absorption, bleeding, or loss of body iron. Diagnosis involves a complete blood count showing microcytic, hypochromic anemia and low serum iron and ferritin levels. Treatment primarily involves oral iron supplementation, while parenteral iron or blood transfusions are reserved for more severe cases. The underlying cause also needs to be addressed to prevent recurrence.
This document provides an overview of pancytopenia, including its definition, etiology, clinical presentation, diagnostic workup, and treatment approach. Pancytopenia is defined as a low hemoglobin, white blood cell count, and platelet count. It can be caused by primary bone marrow diseases or secondary to other conditions that impair bone marrow function. The diagnostic workup involves blood tests, peripheral smear examination, bone marrow aspiration and biopsy for cytogenetics and immunophenotyping to identify the underlying cause. Specific tests help diagnose conditions like Fanconi anemia, lymphoproloferative disorders, and paroxysmal nocturnal hemoglobinuria. Treatment is directed at managing the specific disease identified as the cause
This document discusses chronic kidney disease (CKD), anemia in CKD, and treatments for anemia in CKD. It defines CKD and its stages based on glomerular filtration rate and kidney damage. Anemia in CKD is defined based on hemoglobin levels. Causes of anemia in CKD include relative erythropoietin deficiency, iron deficiency, blood loss, shortened red blood cell lifespan, and the "uremic milieu." Iron therapy and erythropoiesis-stimulating agents (ESAs) are discussed as treatments for anemia in CKD, including criteria for starting therapy, drug options, dosing, monitoring, and dose adjustment.
Thalassemia is caused by defective production of the globin portion of hemoglobin, resulting in an imbalance of globin chain production. There are two main types: alpha thalassemia involves a defect in alpha chain synthesis, while beta thalassemia involves a defect in beta chain synthesis. Beta thalassemia major is the most severe form, causing severe anemia starting in infancy that requires lifelong blood transfusions and iron chelation therapy. Beta thalassemia intermedia is milder, while beta thalassemia minor causes few or no symptoms. Alpha thalassemia can range from the lethal hydrops fetalis form to asymptomatic alpha thalassemia trait. Diagnosis involves blood
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired hematopoietic stem cell disorder characterized by hemolytic anemia. It arises due to a somatic mutation in the PIGA gene, causing deficiency of glycosylphosphatidylinositol-anchored proteins (GPI-APs) like CD55 and CD59 on the surface of blood cells. This renders the cells highly sensitive to complement-mediated lysis. Diagnosis involves flow cytometry to detect GPI-AP deficiency and tests like Ham and sucrose hemolysis to demonstrate complement sensitivity of the red blood cells. PNH is associated with hemoglobinuria, thrombosis, and bone marrow failure. It requires differentiation
Primary hyperoxaluria and renal hypercalciuriaPrateek Laddha
This document discusses primary hyperoxaluria and renal hypercalciuria. It defines hyperoxaluria and describes the four main types: primary hyperoxaluria types I and II, enteric hyperoxaluria, dietary hyperoxaluria, and idiopathic/mild hyperoxaluria. It explains oxalate production, absorption, and excretion in the body. For primary hyperoxaluria, it covers the genetic defects, pathophysiology, clinical manifestations, prognosis, treatment including pyridoxine, orthophosphate, magnesium, and sometimes combined liver-kidney transplantation. The document provides details on evaluation, management, and treatment of the different types of hyperoxaluria.
Approach to a case of iron defciency anaemiaSachin Adukia
- Anaemia is defined as a reduction in haemoglobin, red blood cell count or haematocrit below normal levels. Iron-deficiency anaemia affects around 2 billion people worldwide including 20-40% of people in India.
- Iron-deficiency anaemia is classified based on the underlying cause such as reduced red blood cell production, increased red blood cell destruction, or loss of red blood cells.
- Diagnosis involves examination of symptoms, signs, and laboratory tests including a blood smear, iron studies, and bone marrow examination. Treatment involves oral or intravenous iron supplementation depending on the severity of the deficiency.
Management of anemia in chronic kidney disease -Boushra Alsaoor
This document provides an overview of the management of anemia in chronic kidney disease. It defines anemia according to WHO criteria and notes that nearly 90% of CKD patients with a GFR below 30 mL/min have anemia. The main causes of anemia in CKD are decreased erythropoietin production and a shorter red blood cell lifespan. Treatment with erythropoiesis-stimulating agents or ESAs like epoetin and darbepoetin can help increase hemoglobin levels and improve outcomes. The goals of ESA therapy are to raise hemoglobin by 1-2 g/dL per month until it reaches 10-11.5 g/dL without exceeding 13 g/dL. Iron supplementation is
Dr Sarath Menon presents an approach to diagnosing and classifying hemolytic anemia. Hemolytic anemia results from increased red blood cell destruction and bone marrow compensation. It can be congenital/hereditary or acquired. Classification includes intracorpuscular defects like hemoglobinopathies and enzymopathies, and extracorpuscular factors like mechanical destruction, toxic agents, infections, and autoimmune causes. Diagnosis involves confirming hemolysis and determining the etiology through history, physical exam, peripheral smear, and ancillary lab tests. Common etiologies discussed in detail include sickle cell disease, thalassemia, G6PD deficiency, membrane defects like hereditary spherocytosis, and autoimmune
Jay B. Wish, MD, prepared anemia in CKD infographics for this CME activity titled "Addressing Unmet Needs in Managing Anemia in Chronic Kidney Disease: A Closer Look at the Clinical Potential of HIF-PH Inhibitors." For the full presentation, monograph, complete CME information, and to apply for credit, please visit us at http://bit.ly/2WdYNpK. CME credit will be available until June 12, 2020.
This document provides an overview of chronic kidney disease (CKD)-related anemia, including its definition, causes, effects, evaluation, and management. It defines the stages of CKD based on glomerular filtration rate and describes how anemia is defined for CKD patients based on hemoglobin levels. The main causes of anemia in CKD are identified as relative erythropoietin deficiency, iron deficiency, blood loss, shortened red blood cell lifespan, and inflammation. Evaluation involves testing hemoglobin, reticulocyte count, ferritin, transferrin saturation, and vitamins. Iron therapy is indicated based on ferritin and transferrin saturation levels, and intravenous iron is generally preferred for patients on dialysis
Anemia of prematurity is common in preterm infants less than 32 weeks gestation. It is caused by impaired erythropoietin production, blood loss from medical procedures, reduced red blood cell lifespan, and iron depletion. Symptoms include tachycardia, poor weight gain, and increased oxygen needs. Management includes iron supplementation, red blood cell transfusions based on hemoglobin levels and symptoms, and limiting blood sampling. While erythropoiesis stimulating agents may reduce transfusions, their routine use is not recommended due to risks of retinopathy of prematurity.
This document provides a classification and overview of hemolytic anemia. It discusses intracorpuscular defects like hereditary membrane defects (spherocytosis, elliptocytosis), enzyme defects (G6PD, pyruvate kinase), and hemoglobinopathies. Extracorpuscular defects include immune hemolytic anemia (autoimmune, alloimmune) and nonimmune causes. Evaluation of anemia involves hematological parameters. Thalassemias are classified based on affected globin chain (alpha, beta). Common hereditary spherocytosis causes premature RBC destruction and can be treated with splenectomy. G6PD deficiency results in drug-induced hemolysis.
Anemia of chronic disease, also known as anemia of inflammatory response, is a common type of anemia seen in patients with chronic illnesses like infections, immune disorders, or cancers. Recent research has found that the liver protein hepcidin, which regulates iron metabolism, plays a central role in causing this anemia by blocking the release of iron stores during inflammation. Hepcidin increases during inflammation and prevents the release of iron, leading to insufficient iron availability for red blood cell production. While locking up iron is beneficial in the short term for fighting infection, prolonged inflammation and iron sequestration can severely limit the bone marrow's ability to produce red blood cells. The ideal treatment is resolving the underlying chronic disease, but otherwise patients
This document discusses hepcidin, a peptide hormone that plays a central role in regulating iron metabolism. It is predominantly synthesized by hepatocytes and works by binding to ferroportin, a cellular iron exporter, causing its internalization and degradation. This decreases iron absorption from the diet and iron release from cells. The document reviews hepcidin's structure, kinetics, function, and regulation. It also discusses how hepcidin levels are altered in various iron disorders and inflammatory states. Reliable assays have been developed to measure hepcidin levels, showing promise for diagnosing iron disorders, though more research is needed before clinical use.
Thrombotic Microangiopathies are diverse group of disorders wherein thrombocytopenia, hemolytic anemia and organ dysfunction such as Kidney and brain occur . Major recent advances in this field have occurred which opens up oppurtunities to effectively manage its clinical challenges .
Anemia is a common complication of chronic kidney disease that can cause fatigue. While the kidneys normally produce erythropoietin to stimulate red blood cell production, CKD patients have relative erythropoietin deficiency. This leads to anemia which, if left untreated, can negatively impact quality of life and cardiovascular health. Erythropoiesis-stimulating agents and iron supplementation are used to treat anemia in CKD, though the appropriate hemoglobin target level remains an area of ongoing research and debate given risks identified with higher targets in some studies.
This document discusses the management of anemia in chronic kidney disease (CKD). It begins by defining anemia and its causes in CKD, which include reduced erythropoietin production and decreased red blood cell survival due to kidney failure. Left untreated, anemia in CKD can lead to deterioration in cardiac function, impaired cognition, and increased fatigue and mortality risk. The main therapeutic options for treating anemia in CKD are red blood cell transfusions, androgens, and erythropoiesis-stimulating agents (ESAs). ESAs such as epoetin alfa and darbepoetin alfa are now the standard treatment as they reduce transfusion needs and risks while helping to mobilize
This document discusses anaemia and its causes in chronic kidney disease (CKD). It defines anaemia and outlines how it is diagnosed based on haemoglobin levels. The main causes of anaemia in CKD are decreased erythropoietin production and iron deficiency. Iron supplementation using oral or intravenous iron is recommended to treat iron deficiency anaemia in CKD, along with erythropoiesis-stimulating agents (ESAs) like epoetin and darbepoetin to treat all anaemia. Guidelines on monitoring haemoglobin levels and initiating/maintaining ESA therapy are provided. Red blood cell transfusion is indicated when rapid correction of anaemia is needed or ESA therapy is ineffective.
Hyperphosphatemia in CKD patients; The Magnitude of The Problem - Prof. Alaa ...MNDU net
Hyperphosphatemia in CKD patients; The Magnitude of The Problem
Prof. Alaa Sabry - Professor of Nephrology
Mansoura Nephrology and Dialysis Unit (MNDU) Course
This document discusses iron metabolism and iron deficiency. It begins by outlining how iron is essential for many metabolic processes and exists in both ferric and ferrous states. It then discusses iron transport and storage in the body, as well as iron absorption, distribution, and regulation. The document also covers the causes, pathogenesis, morphology, diagnosis of iron deficiency and the role of hepcidin in various iron-related diseases.
Dr Abdullah Ansari
MBBS, MD Medicine
Aligarh Muslim University
Clinical case
Hemolytic Anemia
Intravascular vs extravascular hemolysis
Classification of hemolytic anemia
Approach to hemolysis
Patient history
Clinical features
Peripheral blood smear
Investigation
Treatment
Iron deficiency anemia develops when iron stores are too low to support normal red blood cell production. It can be caused by inadequate dietary iron, impaired iron absorption, bleeding, or loss of body iron. Diagnosis involves a complete blood count showing microcytic, hypochromic anemia and low serum iron and ferritin levels. Treatment primarily involves oral iron supplementation, while parenteral iron or blood transfusions are reserved for more severe cases. The underlying cause also needs to be addressed to prevent recurrence.
This document provides an overview of pancytopenia, including its definition, etiology, clinical presentation, diagnostic workup, and treatment approach. Pancytopenia is defined as a low hemoglobin, white blood cell count, and platelet count. It can be caused by primary bone marrow diseases or secondary to other conditions that impair bone marrow function. The diagnostic workup involves blood tests, peripheral smear examination, bone marrow aspiration and biopsy for cytogenetics and immunophenotyping to identify the underlying cause. Specific tests help diagnose conditions like Fanconi anemia, lymphoproloferative disorders, and paroxysmal nocturnal hemoglobinuria. Treatment is directed at managing the specific disease identified as the cause
This document discusses chronic kidney disease (CKD), anemia in CKD, and treatments for anemia in CKD. It defines CKD and its stages based on glomerular filtration rate and kidney damage. Anemia in CKD is defined based on hemoglobin levels. Causes of anemia in CKD include relative erythropoietin deficiency, iron deficiency, blood loss, shortened red blood cell lifespan, and the "uremic milieu." Iron therapy and erythropoiesis-stimulating agents (ESAs) are discussed as treatments for anemia in CKD, including criteria for starting therapy, drug options, dosing, monitoring, and dose adjustment.
Thalassemia is caused by defective production of the globin portion of hemoglobin, resulting in an imbalance of globin chain production. There are two main types: alpha thalassemia involves a defect in alpha chain synthesis, while beta thalassemia involves a defect in beta chain synthesis. Beta thalassemia major is the most severe form, causing severe anemia starting in infancy that requires lifelong blood transfusions and iron chelation therapy. Beta thalassemia intermedia is milder, while beta thalassemia minor causes few or no symptoms. Alpha thalassemia can range from the lethal hydrops fetalis form to asymptomatic alpha thalassemia trait. Diagnosis involves blood
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired hematopoietic stem cell disorder characterized by hemolytic anemia. It arises due to a somatic mutation in the PIGA gene, causing deficiency of glycosylphosphatidylinositol-anchored proteins (GPI-APs) like CD55 and CD59 on the surface of blood cells. This renders the cells highly sensitive to complement-mediated lysis. Diagnosis involves flow cytometry to detect GPI-AP deficiency and tests like Ham and sucrose hemolysis to demonstrate complement sensitivity of the red blood cells. PNH is associated with hemoglobinuria, thrombosis, and bone marrow failure. It requires differentiation
Primary hyperoxaluria and renal hypercalciuriaPrateek Laddha
This document discusses primary hyperoxaluria and renal hypercalciuria. It defines hyperoxaluria and describes the four main types: primary hyperoxaluria types I and II, enteric hyperoxaluria, dietary hyperoxaluria, and idiopathic/mild hyperoxaluria. It explains oxalate production, absorption, and excretion in the body. For primary hyperoxaluria, it covers the genetic defects, pathophysiology, clinical manifestations, prognosis, treatment including pyridoxine, orthophosphate, magnesium, and sometimes combined liver-kidney transplantation. The document provides details on evaluation, management, and treatment of the different types of hyperoxaluria.
Approach to a case of iron defciency anaemiaSachin Adukia
- Anaemia is defined as a reduction in haemoglobin, red blood cell count or haematocrit below normal levels. Iron-deficiency anaemia affects around 2 billion people worldwide including 20-40% of people in India.
- Iron-deficiency anaemia is classified based on the underlying cause such as reduced red blood cell production, increased red blood cell destruction, or loss of red blood cells.
- Diagnosis involves examination of symptoms, signs, and laboratory tests including a blood smear, iron studies, and bone marrow examination. Treatment involves oral or intravenous iron supplementation depending on the severity of the deficiency.
Management of anemia in chronic kidney disease -Boushra Alsaoor
This document provides an overview of the management of anemia in chronic kidney disease. It defines anemia according to WHO criteria and notes that nearly 90% of CKD patients with a GFR below 30 mL/min have anemia. The main causes of anemia in CKD are decreased erythropoietin production and a shorter red blood cell lifespan. Treatment with erythropoiesis-stimulating agents or ESAs like epoetin and darbepoetin can help increase hemoglobin levels and improve outcomes. The goals of ESA therapy are to raise hemoglobin by 1-2 g/dL per month until it reaches 10-11.5 g/dL without exceeding 13 g/dL. Iron supplementation is
Dr Sarath Menon presents an approach to diagnosing and classifying hemolytic anemia. Hemolytic anemia results from increased red blood cell destruction and bone marrow compensation. It can be congenital/hereditary or acquired. Classification includes intracorpuscular defects like hemoglobinopathies and enzymopathies, and extracorpuscular factors like mechanical destruction, toxic agents, infections, and autoimmune causes. Diagnosis involves confirming hemolysis and determining the etiology through history, physical exam, peripheral smear, and ancillary lab tests. Common etiologies discussed in detail include sickle cell disease, thalassemia, G6PD deficiency, membrane defects like hereditary spherocytosis, and autoimmune
Jay B. Wish, MD, prepared anemia in CKD infographics for this CME activity titled "Addressing Unmet Needs in Managing Anemia in Chronic Kidney Disease: A Closer Look at the Clinical Potential of HIF-PH Inhibitors." For the full presentation, monograph, complete CME information, and to apply for credit, please visit us at http://bit.ly/2WdYNpK. CME credit will be available until June 12, 2020.
This document provides an overview of chronic kidney disease (CKD)-related anemia, including its definition, causes, effects, evaluation, and management. It defines the stages of CKD based on glomerular filtration rate and describes how anemia is defined for CKD patients based on hemoglobin levels. The main causes of anemia in CKD are identified as relative erythropoietin deficiency, iron deficiency, blood loss, shortened red blood cell lifespan, and inflammation. Evaluation involves testing hemoglobin, reticulocyte count, ferritin, transferrin saturation, and vitamins. Iron therapy is indicated based on ferritin and transferrin saturation levels, and intravenous iron is generally preferred for patients on dialysis
Anemia of prematurity is common in preterm infants less than 32 weeks gestation. It is caused by impaired erythropoietin production, blood loss from medical procedures, reduced red blood cell lifespan, and iron depletion. Symptoms include tachycardia, poor weight gain, and increased oxygen needs. Management includes iron supplementation, red blood cell transfusions based on hemoglobin levels and symptoms, and limiting blood sampling. While erythropoiesis stimulating agents may reduce transfusions, their routine use is not recommended due to risks of retinopathy of prematurity.
This document provides a classification and overview of hemolytic anemia. It discusses intracorpuscular defects like hereditary membrane defects (spherocytosis, elliptocytosis), enzyme defects (G6PD, pyruvate kinase), and hemoglobinopathies. Extracorpuscular defects include immune hemolytic anemia (autoimmune, alloimmune) and nonimmune causes. Evaluation of anemia involves hematological parameters. Thalassemias are classified based on affected globin chain (alpha, beta). Common hereditary spherocytosis causes premature RBC destruction and can be treated with splenectomy. G6PD deficiency results in drug-induced hemolysis.
Anemia of chronic disease, also known as anemia of inflammatory response, is a common type of anemia seen in patients with chronic illnesses like infections, immune disorders, or cancers. Recent research has found that the liver protein hepcidin, which regulates iron metabolism, plays a central role in causing this anemia by blocking the release of iron stores during inflammation. Hepcidin increases during inflammation and prevents the release of iron, leading to insufficient iron availability for red blood cell production. While locking up iron is beneficial in the short term for fighting infection, prolonged inflammation and iron sequestration can severely limit the bone marrow's ability to produce red blood cells. The ideal treatment is resolving the underlying chronic disease, but otherwise patients
This document discusses hepcidin, a peptide hormone that plays a central role in regulating iron metabolism. It is predominantly synthesized by hepatocytes and works by binding to ferroportin, a cellular iron exporter, causing its internalization and degradation. This decreases iron absorption from the diet and iron release from cells. The document reviews hepcidin's structure, kinetics, function, and regulation. It also discusses how hepcidin levels are altered in various iron disorders and inflammatory states. Reliable assays have been developed to measure hepcidin levels, showing promise for diagnosing iron disorders, though more research is needed before clinical use.
1. Iron overload, also known as hemochromatosis, occurs when the body absorbs more iron than it loses, causing excess iron to accumulate and damage organs. It is commonly caused by a genetic disorder or frequent blood transfusions.
2. Hepcidin regulates iron levels in the body. Iron overload results from low hepcidin leading to increased iron absorption in the gut and spleen.
3. Treatment involves regular phlebotomy to remove excess iron from the body. Phlebotomy can prevent organ damage if started early and allows patients to live normally once iron levels are normalized.
This document discusses iron absorption and iron deficiency anemia. It states that iron absorption primarily occurs in the duodenum and jejunum, and is regulated by both dietary intake and iron stores. Iron deficiency is the most common cause of anemia worldwide, especially impacting women and children. The key signs of iron deficiency anemia are a decreased hemoglobin level and red blood cell size.
Iron metabolism in the body involves several key processes:
1) Iron exists in the body bound to hemoglobin, myoglobin, enzymes, and cytochromes or stored as ferritin and hemosiderin.
2) Dietary non-heme iron is reduced and transported across the intestinal barrier by transporters before binding to transferrin in the bloodstream.
3) Transferrin transports iron through the bloodstream and delivers it to cells through endocytosis and release from endosomes.
4) Hepcidin regulates iron levels by inhibiting intestinal iron transport and macrophage recycling of iron.
precocious puberty is one of the grey areas for pediatricians and gyenecologists. this is an attempt to answer some of the questions the content is references taken from authorative textbooks
This document discusses iron deficiency anemia (IDA) in children. It begins by defining anemia and listing the WHO thresholds used to define anemia in different age groups. It then covers the etiological, morphological and pathophysiological classifications of anemia. Under the etiological classification, it describes anemias caused by blood loss, impaired red blood cell formation, and excessive red blood cell destruction. It also discusses the clinical features, laboratory diagnosis, treatment, complications and prevention of IDA in children.
El documento describe los conceptos de homeostasis y retroalimentación negativa. La homeostasis se refiere a la capacidad de los seres vivos de mantener constantes las propiedades internas a pesar de cambios externos, mediante mecanismos fisiológicos de control. Estos mecanismos actúan principalmente a través de retroalimentación negativa, donde los sensores detectan cambios y los efectores los corrigen devolviendo la variable al valor normal.
- Iron is an essential mineral found in the body, with 66% stored in hemoglobin and 4% in myoglobin. Small amounts are also bound to enzymes and stored in ferritin and hemosiderin.
- Daily iron requirements are 15-20 mg, though only 1 mg is normally absorbed. Requirements are increased during infancy, adolescence, pregnancy, and fetal development, placing additional demands on maternal iron stores.
- Iron absorption occurs via divalent metal transporter 1 and ferroportin, and is regulated by the peptide hormone hepcidin which controls ferroportin levels. Transferrin transports iron in the blood and transferrin receptors facilitate its uptake into cells.
1) Iron enters the body each day and is incorporated into hemoglobin in red blood cells or stored in ferritin. Iron is also transported in the blood bound to transferrin.
2) Ferritin stores iron inside its shell, while transferrin transports iron in the blood and is the only source of iron for hemoglobin.
3) Iron homeostasis is maintained through regulating iron absorption in the intestine and recycling iron from broken down red blood cells. Specialized proteins transport and regulate iron levels.
The document discusses iron metabolism in the human body. It notes that 1-2 mg of iron enters the body daily, mostly incorporated into hemoglobin in red blood cells. Iron is stored in ferritin and transported by transferrin. Iron is absorbed in the duodenum through transport proteins like DMT1 and exported by ferroportin. Tight regulation of absorption and storage maintains iron homeostasis, controlled by the hormone hepcidin in response to body iron levels. Diseases like hereditary hemochromatosis result from defects in this regulatory system.
This document discusses iron metabolism in the human body. It covers:
1) Molecules involved in iron transport including DMT1, ferroportin, transferrin receptors, hephaestin, transferrin, ferritin, and hepcidin.
2) Steps of iron absorption in the gut and transport through the body.
3) Utilization of iron in erythropoiesis to produce hemoglobin.
4) Disorders of iron metabolism like iron deficiency anemia, hemochromatosis, and atransferrinemia.
Hepcidin plays a central role in regulating iron metabolism. It is a peptide hormone produced by the liver that inhibits iron absorption in the intestine and iron release from macrophages and hepatocytes. By binding to the iron exporter ferroportin, hepcidin causes ferroportin to be internalized and degraded, thereby trapping iron inside cells and reducing serum iron levels. Hepcidin expression is regulated by factors like anemia, hypoxia, inflammation and iron levels to control dietary iron absorption and mobilization of iron stores. Diseases can result from hepcidin deficiency or excess, impacting iron absorption and availability.
This document discusses iron absorption, transport, storage, excretion, functions, deficiency, and toxicity in the human body. It notes that iron is an essential nutrient that is vital for oxygen transport and many enzyme systems. It is absorbed in the duodenum and jejunum and transported by transferrin in the bloodstream. Iron is stored in the liver bound to ferritin and hemosiderin. Deficiency can cause fatigue and anemia while toxicity is caused by excessive absorption leading to organ damage.
IRON METABOLISM & MICROCYTIC HYPOCHROMIC ANAEMIAS.pptxparisdepher
This document discusses microcytic hypochromic anemias, including iron deficiency anemia, anemia of chronic diseases, and thalassemias. It covers iron metabolism, the causes and symptoms of anemia, the development of different types of microcytic hypochromic anemia, and their laboratory diagnosis and treatment. Specifically, it outlines iron's role in the body, how the body regulates iron levels, the causes and signs of iron deficiency, and how excess iron can be toxic. It also discusses the adaptive responses to anemia and the diagnostic markers used to identify different types of microcytic hypochromic anemia.
IRON METABOLISM & MICROCYTIC HYPOCHROMIC ANAEMIAS.pptxparisdepher
Abigail was diagnosed with iron deficiency anaemia (IDA) at KNUST Hospital. On her follow up visit after 3 months of iron fersolate treatment, her iron profile results are expected to show:
1. Increased serum iron and transferrin saturation levels as the treatment replenishes her iron stores.
2. Normal serum ferritin levels as the treatment addresses the iron deficiency.
3. Potentially normal or increased sTFR-1 levels depending on whether her increased iron levels meet erythropoietic demand, since sTFR-1 reflects iron availability for red blood cell production.
The treatment is expected to correct the iron deficiency underlying Abigail's IDA
This document summarizes iron metabolism and the key proteins involved. It discusses that iron is stored in the body bound to ferritin and hemosiderin, and is transported by transferrin. Ferritin stores iron within a hollow protein shell, while hemosiderin aggregates from degraded ferritin. Transferrin transports iron in the bloodstream. Hepcidin regulates iron levels by decreasing ferroportin, the iron exporter. The document outlines the roles and structures of these iron-transport and storage proteins in maintaining iron homeostasis.
1. Iron is an essential nutrient that is important for oxygen transport and cellular energy production. It must be tightly regulated as too little or too much can be toxic.
2. Iron is absorbed in the duodenum and transported through the blood bound to transferrin. Cells take up iron via transferrin receptors.
3. Laboratory tests can assess iron levels in the blood, transport and storage to diagnose iron deficiency or overload. These include serum iron, TIBC, ferritin and staining of tissues.
This document summarizes iron metabolism. It discusses daily iron requirements, absorption and transport of iron, iron storage, and regulation of iron levels. It also covers iron deficiency anemia and iron overload disorders like hemochromatosis. Iron is absorbed in the duodenum and transported bound to transferrin. It is stored primarily in the liver as ferritin or hemosiderin. Iron levels are regulated by the liver peptide hepcidin which controls intestinal iron absorption and macrophage iron recycling by degrading the iron exporter ferroportin.
Iron is an essential micronutrient, but both iron deficiency and excess can be harmful. Iron deficiency anemia affects 65-75% of people in India and can impact growth and development. The body tightly regulates iron levels through absorption in the duodenum, transport by transferrin, and storage in ferritin and hemosiderin. Hepcidin is the key regulator of iron absorption and release, inhibiting the iron exporter ferroportin. Disorders of iron metabolism include iron deficiency anemia, hemosiderosis, and hereditary hemochromatosis.
This document summarizes metal ion transport and storage in biological systems. It discusses the general properties of transport systems like ionophores, ion channels, and ion pumps. Specific mechanisms for transporting ions like sodium, potassium, iron, and calcium are described. Metal storage is achieved through proteins like ferritin and metallothionein. Problems associated with transporting and storing metal ions across membranes are also highlighted.
Iron is very important for Hemoglobin synthesis and avoidance for anemia so it is very important to understand to protect us from iron deficiency anemia & Iron overload
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Iron is the most abundant metal in the human body, with total body iron of around 3600 mg. It is stored in hemoglobin, myoglobin, ferritin and hemosiderin. Dietary iron intake is around 1.5-2 mg per day, with 10% absorption. Iron is essential for oxygen transport, electron transport, and cellular processes. Iron deficiency can cause anemia, while excess iron causes hemochromatosis. Iron levels are regulated by hepcidin which controls intestinal absorption and macrophage recycling. Genetic disorders like hemochromatosis and juvenile hemochromatosis can lead to iron overload if not treated by phlebotomy.
Iron is an essential trace element in the human body, with the total body content being 3-5 grams. It exists in both heme and non-heme forms, with heme iron making up 75% of total iron and being found in hemoglobin, myoglobin, and enzymes. Iron is absorbed in the duodenum in its ferrous form and transported bound to transferrin in plasma. It is either stored bound to ferritin or transported to tissues where it participates in oxygen transport and electron transport. Iron deficiency anemia is the most common nutritional deficiency globally, while iron overload can result in hemosiderosis or hemochromatosis.
1. Sideroblastic anemias are a group of refractory anemias characterized by ring sideroblasts in the bone marrow, which are iron-containing erythroblasts.
2. Hereditary sideroblastic anemias are rare, often manifesting in males in childhood or adolescence. They can be caused by mutations in genes involved in iron-sulfur cluster formation or heme synthesis.
3. Acquired sideroblastic anemias have various causes including drugs, toxins, myelodysplastic syndromes, and other hematological malignancies.
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Iron metabolism in neonates and role of hepcidin
1. Dr Kamal Arora
MD, DM
Neonataology
All India Institute of medical sciences
New Delhi
India
2. Overview
Iron – must needed micronutrient
• Iron and developing brain
Physiology
• Iron absorption
• Iron transport and recycling
Tests for iron measurement
• Ferritin
• Hepcidin
• Zinc protoporphyrin ,sTFR
Iron dosing
• AAP recommendations
3. Iron is an essential element for microbes, plants and higher
animals.
It plays a significant role in critical cellular functions in all
organ systems in all species.
It is required for early brain growth and function in humans
since it supports neuronal and glial energy metabolism,
neurotransmitter synthesis and myelination.
4. Iron deficiency during the fetal or postnatal periods
◦ Alter brain structure and cognitive functioning
◦ Lead to long-term cognitive and motor impairment
◦ Cannot be corrected by iron supplementation later
J.L.Beard et al, Iron and neural functions , Annals review nutrition 2003 , 23:41–58
5. Iron: A Critical Nutrient for the Developing Brain
• Controls oligodendrocyte production of myelin
Delta 9- Iron Deficiency=> Hypomyelination
desaturase
1. Delta 9-desaturase
•Oxidative phosphorylation , determine neuronal and glial energy status
2. Cytochromes
Iron Deficiency=> Impaired neuronal growth, differentiation, electrophysiology
Cytochromes
3. Tyrosine Hydroxylase
• Monamine neurotransmitter and receptor synthesis (dopamine, serotonin,
norepinephrine)
Tyrosine Iron Deficiency=> Altered neurotransmitter regulation
Hydroxylase
J.L.Beard et al, Iron and neural functions , Annals review nutrition 2003 , 23:41–58
6. Potent oxidant stressor
◦ Role in Fenton reaction to create reactive oxygen species
Iron overload associated with neurodegenerative disorders in
adults
◦ Hypoxic-ischemic reperfusion injury
◦ Parkinson’s, Alzheimer’s diseases
Fetus/premature infant at high risk for iron toxicity
◦ Underdeveloped anti-oxidant systems
◦ Low Total Iron Binding Capacity
8. Fetuses have 75mg of elemental iron per kilogram body weight during 3rd
trimester
◦ Term infant: 200 - 250mg
◦ 24 week (500g): 37.5 mg
Majority is in the RBCs (55mg/kg)
Liver storage pools are relatively large at term (12 mg/kg)
Non-storage tissues, including brain, heart, skeletal muscle account for
the rest (8 mg/kg)
Preterm
Small-for-gestational age
1. Lozoff B, Georgieff M. Iron deficiency and brain development. Semin Pediatr Neurol. 2006;13:158–165
2. Lozoff B, Beard J, Connor J, Felt B, Georgieff M, Schallert T.Long-lasting neural and behavioral effects of iron deficiency in
infancy. Nutr Rev. 2006;64:S34–S43
9. Section II
Iron – must needed micronutrient
• Iron and developing brain
√
Physiology
• Iron absorption
• Iron transport and recycling
Tests for iron measurement
• Ferritin
• Hepcidin
• Zinc protoporphyrin ,sTFR
Iron dosing
• AAP recommendations
10.
11. Absorption of Iron
DMT -1 with
Ferroreductase Intestinal lumen
Fe3+ --- Fe2+
Duodenum
Brush border epithelium
Apical membrane
Divalent metal transporter (nonspecific)
Ferritin
Fe, Cu, Zn, Mn, Mg,Pb
Heirarchy of binding (Fe is highest)
Basolateral membrane
Iron Deficiency => increases uptake of
Ferroportin
others (including Zn, Pb) channels
PLASMA
Apo-transferrin molecules
Transferrin molecules
12. Action of Hepcidin- iron excess
Intestinal lumen
DMT -1 with
Ferroreductase
Apical membrane
Ferritin
Basolateral membrane
Ferroportin
channels
H
PLASMA
H
H H
13. Action of Hepcidin- Iron deficiency
Intestinal lumen
DMT -1 with
Ferroreductase
Apical membrane
Ferritin
Basolateral membrane
Ferroportin
channels
PLASMA
15. Fate of iron in mitochondria+ Globin = Hemoglobin
Fe
Transferrin Fe 2+ Ferrous Protoporphyrin
(Heme)
106 umol
FC
<5 umol
Protoporphyrin Free Protoporphyrin
50 umol
Porphobilinogen
Absorbed through
ALA DMT -1 channel
Dehydrogenase Zn
Aminolevulinic acid
Zinc Protoporphyrin (ZnPP)
16. Iron is efficiently recycled from senescent red blood cells.
Erythrocytes are phagocytosed by macrophages in the
spleen, where they are lysed and the protein is degraded.
The released iron can either be stored in the macrophage
or sent back into circulation bound to plasma transferrin
17. Section III
Iron – must needed micronutrient
• Iron and developing brain
Physiology
• Iron absorption
• Iron transport and recycling
Tests for iron measurement
√
• Ferritin
• Hepcidin
• Zinc protoporphyrin
• sTFR
Iron dosing
• AAP recommendations
18.
19. Direct
•Bone marrow aspiration and biopsy
•Hemoglobin
•Serum ferritin
•Free erythrocyte protoporphyrin
Indirect
•Zinc protoporphyrin
•Total iron binding capacity (TIBC)
•Transferrin receptor concentration
•Transferrin saturation
•Hepcidin
Each test identifies iron availability at a different point in iron metabolism.
20. Bone marrow aspiration and biopsy
◦ Prussian blue staining of marrow hemosiderin to semi-
quantitatively grade the amount of macrophage storage iron.
Disadvantage
Invasive
Not possible in newborns
21. Indirect Measures
Advantages
Less invasive Lack of sensitivity or specificity or
both.
Easy to perform on
peripheral blood. Affected by other factors such as:
◦ Concurrent infection
◦ Inflammation
◦ Maternal chorioamnionitis
◦ Liver disease
22.
23. Most useful laboratory measure of iron status
Universally available and well-standardized measurement that
offers important advantages over bone-marrow examination for
identifying iron deficiency
A valuable feature of the measurement is that the concentration
is directly proportional to body iron stores in healthy individuals;
1 mg/L serum ferritin corresponds to 8–10 mg or 120 ug storage
iron/kg body weight
24. Numerous studies have demonstrated its
superiority over other iron-related measurements
for identifying IDA.
25. A well-known limitation of the serum ferritin is the
elevation in values that occurs independently of iron status in
patients with acute or chronic inflammation, malignancy, or
liver disease.
26. S. Author, Study Study group(s) Outcome
No. year population
1. Mukhopadhy Mother Group 1: Cord ferritin –low in SGA group.
ay K et al infant pair : Term AGA (n=50) 68 vs141(p=0.0007)
2010 ≥37 weeks Group 2: Proportion of infants with low
Birth Term SGA (n=50) cord ferritin more in SGA
weight≥ Primary outcome-cord ferritin (p=0.05)
1500 gm Secondary outcome –infants with No correlation in maternal and
(n=126) 1.low cord ferritin (< 40ug/l) neonatal cord iron parameters
2. Serum iron and TIBC Serum ferritin levels were same
3. Serum ferritin at 28 days in both groups (p=0.16)
4. Correlation b/w maternal and
neonatal iron indices
2. Olivares et Birth weight: Group 1: At birth, preterm SGA infants
al,1992 1500 to 2500 Preterm AGA (n=29) have low iron stores as compared
grams; Group 2: to preterm AGA and term SGA
gestation: 33 Preterm SGA (n=17) infants: 55% preterm SGA group
- 40 weeks Group-3: had abnormally low cord serum
Term SGA (n=38) ferritin <60mcg/l as compared to
(SGA was defined as per the 20% and 9% in the preterm AGA
curves by Thomson ) and term SGA groups
(a sub-group of the study were respectively.
given iron supplements from 2 Preterm SGA<Preterm
months of age) AGA<Term SGA
27. 3 Haga P et al, Birth weight: Group 1: At birth, preterm SGA
1980 600-2000 Preterm AGA (n=24) infants have low iron
grams Group 2: stores as compared to
Preterm SGA (n=8) preterm AGA and term
Group 3: AGA infants
Term AGA (n=22) Term SGA infants were
not included in the study
4 Karaduman Group 1: Iron stores (as measured
D et al, 2001 Term SGA (n=21) by serum ferritin) are
low in term SGA infants
Group 2: as compared to term
Term AGA (n=19) AGA infants
5. Scott PH et Total no. Group 1 At birth, plasma levels of
al,1975 infants-106 PT SGA/AGA transferrin and iron in
Group 2 the SGA infants were
T-SGA/AGA similar to those in the
AGA group
6. Dr Bijan 34 SGA Late preterm and term No difference in SGA
Saha 30 AGA Group 1 :SGA and AGA group
(unpublished) Group 2: AGA
28.
29. Structure of cellular transferrin receptor
C terminal
671 AA residues
Disulphide
bond 61 AA residues
N terminal
2 identical subunits Molecular mass –
95000 daltons (each)
Erythrocyte precursor cell, placental cell
30. A soluble form of the transferrin receptor was first identified in serum
in 1986 by Japanese
Controls flow of transferrin iron inside the cell
Serum levels represent the total mass of tissue receptor
Serum receptor levels rises significantly with tissue iron deficiency.
Quantitative measure of iron deficiency and distinguishes from the
iron deficiency of chronic disease
31. Highest no. of these receptors -
◦ Rapidly dividing cells
◦ Haemoglobin synthesis tissues
◦ Placenta
◦ Total absence in patients with aplastic anaemia
Iron replete cells – less no of receptors- protects
from excess iron
32. The only determinant of the sTfR other than the erythroid
precursor mass is tissue iron deficiency which increases the
sTfR in proportion to the severity of the iron deficit
33. Several commercial assays are now available,
Wider application of sTfR measurements has been limited to
date by the marked differences in normal values reported
with different assays
34.
35. Hepcidin
Urinary Antimicrobial Peptide Synthesized in the Liver
•25 aminoacid peptide (from clevage
of a 84 aminoacid propeptide)
•Defensin-like (family of natural
antimicrobial peptides involved in
innate immunity)
HEP (atic) CIDIN (antimicrobial)
Park CH, J Biol Chem 2001; 276:7806-10
38. Production stimulated by increased plasma iron
and tissue stores.
Negative feedback - hepcidin decreases release of
iron into plasma (from macrophages and
enterocytes).
Fe-Tf increases hepcidin mRNA production (dose
dependent relationship).
42. GENETICALLY DETERMINED IRON OVERLOAD SYNDROMES
(HEMOCHROMATOSIS)
OMIM classification
Gene chr. Remarks
Type 1: “classical HFE 6p21.3 90%, only Caucasians
Type 2: ”juvenile” 2a. HJV 1q21 = penetrance M and F
2b. Hepcidin 19q13.1
Type 3: TfR2 7q22 similar to “classical”
Type 4: Ferroportin 2q32 dominant
43.
44. Hepcidin studies in newborns
S. Author, Study Intervention Outcome
No. year population
1. Ervasti Mari Pregnant mothers Mothers sample and newborn Maternal prohepcidin > cord
et al,2009(25) and newborns cord blood. (325ug/L vs. 235 ug/L not
Gestation: 37 – Main outcome : maternal and cord significant)
42 weeks serum prohepcidin , transferrin
(n =193 pairs) receptors, serum ferritin Correlation b/w maternal
and cord prohepcidin –very
significant spearmans
coefficient=0.600
Prohepcidin levels did not
correlate with iron status in
mothers or newborns.
2. Amarilyo G et Gestation >35 Group 1: AGA (n=20) Hemoglobin and
al, 2010(26) weeks Group 2: SGA (n=20) prohepcidin – same
(All neonates- apgar >7 at 1 min
Cord pH->7.25) EPO and Erythrocyte
Measured progenitors –higher in SGA
1. Hemoglobin infants
2. Prohepcidin,
3. EPO,
4. Erythrocyte Progenitors
(CD71/CD45)
45. Ferritin and hepcidin in various conditions
Disease Serum iron Hepcidin Ferritin
1. Iron deficiency Low Low Low
2. Transfusional iron High High High
Overload
3. Anaemia of Low (?) High/normal High
Inflammation
4. Hereditary High Low or absent High
Hemochromatosis
46.
47. Zn
Zinc protoporphyrin (ZnPP) - normal metabolite that is formed in
trace amounts during heme biosynthesis
Final reaction in the biosynthetic pathway of heme is the
chelation of iron with protoporphyrin
During periods of iron insufficiency or impaired iron utilization,
zinc becomes an alternative metal substrate for ferrochelatase,
leading to increased ZnPP formation.
48. ZnPP is found in blood in healthy individuals at a
ratio of nearly 50 ZnPP molecules per 1 x 106
heme molecules .
49. Simple and reliable measurement of IDA.
Advantage of this well established assay is the ability to measure
the ratio ZPP/haem directly on a drop of blood using a dedicated
portable instrument called a haematofluorimeter.
The ZPP is ideally suited to screening for IDA in field surveys of iron
status or in paediatric and obstetrical clinics where uncomplicated
iron deficiency is the major cause of IDA.
50. 1. The ZPP is not widely used in large clinical laboratories,
partly because of the difficulty in automating the
assay.
2. Zinc protoporphyrin levels can be elevated :
Lead poisoning
Sickle cell anemia
Sideroblastic anemia
Anemia of chronic disease
51. The sensitivity and specificity of ZnPP/H in preterm and term
infants, have not been clearly determined.
A normal range for ZnPP/H of preterm infants has been proposed,
but the sample size was small.
Juul SE et al ; Zinc protoporphyrin/heme as an indicator of iron status in NICU patients. J Pediatr. 2003;142:273–278
52.
53. Current AAP dosing recommendations appear appropriate
for preterms in NICU
◦ 2-4 mg/kg/day enteral iron
4mg/kg if <30 weeks
2-3 mg/kg if >30 weeks
◦ 6 mg/kg/day if on rhEpo
Post-discharge recommendations (2.25 mg/kg/d) appear
low and should be increased to 3.3 mg/kg/d
Consider monitoring ferritin at birth, at discharge and at
follow-up (along with hemoglobin & indices)
54. Term AGA 1 mg/kg daily
Term SGA 2 mg/kg daily
Preterm >30 w 2 mg/kg daily
Preterm <30 w 4 mg/kg daily
Preterm on rhEpo 6 mg/kg daily
Preterm; ferritin <35 +2 mg/kg daily
55. AAP recommends hemoglobin screening at 12 months
of age
◦ Earlier screening for premies, SGAs
◦ sTfR, ZnPP, MCV might screen pre-anemia
sTfR, ZnPP not available everywhere, lacking standards for < 12
month olds
Pre-anemic screening
◦ Ferritin is a good pre-anemic screen
But, infant cannot have acute illness (acute phase reactant)
◦ NHANES and CDC testing sTfR/Heme ratio
◦ Hepcidin
56. Hepcidin is an iron-regulatory hormone that maintains plasma
iron levels and iron stores within normal range
Hepcidin regulates the entry of iron into plasma from duodenal
enterocytes, from macrophages (and from hepatocytes)
Hepcidin acts by binding the receptor/iron channel ferroportin
and causing its degradation
Hepcidin is regulated by iron, erythropoiesis and inflammation
Excess hepcidin causes the hypoferremia and anemia of
inflammation
Hepcidin deficiency, or resistance to hepcidin, cause
hemochromatosis
Editor's Notes
The uptake of iron by the enterocyte is an important regulatory step in body iron content. Iron can be absorbed into the enterocyte as heme iron or nonheme iron (both ferrous and ferric forms). Heme iron is soluble in the duodenum and is absorbed as an intact metalloproteinvia heme carrier protein 1 (HCP-1) (Fig. 2A). Ferrous iron is then released from heme via heme oxygenase. (5) Unbound iron is absorbed into the enterocyte in the ferrous or ferric form. In the duodenum, nonheme iron is converted to the ferrous (II) form by ascorbic acid and duodenal cytochrome B (DcytB) on the surface of the brush border (Fig. 2B). (6) Ferrous iron then binds to divalent metal transporter-1 (DMT1) and is transferred into the enterocyte.Iron available to gut is ferric form (Fe3+) and is absorbed as Ferrous form (Fe2+) by the enterocytes. This is facilitated by enzymatic reduction (ferrireductase) present in brush border epithelium.DMT is a non specific transporter of divalent ions. It has highest affinity with iron , after that which ever is in excess in diet. This forms the basis of one of the tests of iron deficiency which is known as Zn protoporphyrin. So if there is iron deficiency , it will lead to increase in ZnPP. Also if a child is iron deficient , he is at risk of lead poisoning.
Binds ferroportin, complex internalised and degraded.Resultant decrease in efflux of iron from cells to plasma
Binds ferroportin, complex internalised and degraded.Resultant decrease in efflux of iron from cells to plasma
In the balanced state, 1 to 2 mg of iron enters and leaves the body each day. Dietary iron is absorbed by duodenal enterocytes. It circulates in plasma bound to transferrin. Most of the iron in the body is incorporated into hemoglobin in erythroid precursors and mature red cells. Approximately 10 to 15 percent is presentin muscle fibers (in myoglobin) and other tissues (in enzymes and cytochromes). Iron is stored in parenchymal cells of the liver and reticuloendothelial macrophages. These macrophages provide most of the usable iron by degrading hemoglobin in senescent erythrocytes and reloading ferric iron onto transferrin for delivery to cells. Iron-laden transferrin (Fe2-Tf) binds to transferrin receptors (TfR) on the surface of erythroid precursors. These complexes localize toclathrin-coated pits, which invaginate to form specialized endosomes.2A proton pump decreases the pH within the endosomes,leading to conformational changes in proteins that result in the release of iron from transferrin. The iron transporter DMT1 moves ironacross the endosomal membrane, to enter the cytoplasm.3Meanwhile, transferrin (Apo-Tf) and transferrin receptor are recycled tothe cell surface, where each can be used for further cycles of iron binding and iron uptake. In erythroid cells, most iron moves intomitochondria, where it is incorporated into protoporphyrin to make heme. In nonerythroid cells, iron is stored as ferritin and hemosiderin.Tissue UptakeFor iron uptake in most tissues, transferrin binds totransferrin receptors on the surface of the cell, and thetransferrin receptor–transferrin complex is endocytosed.Protons are pumped into the endosome, lowering thepH and releasing iron from the transferrin. The free ironis released into the cell for use, and the transferrin isreleased back into the bloodstream. The number oftransferrin receptors expressed on the cell surface is regulatedby intracellular iron concentrations. In a low-ironstate, expression of the transferrin receptor is increasedand expression of ferritin is reduced. Conversely, whenthe intracellular iron concentration is high, expression ofthe transferrin receptor is reduced while expression offerritin is increased. (5)
2 identical bilobedstructrure which has an intracellular small portion and a large extracellular portion