L5 Heme Porphyrin metabolism and iron homeostasis
92 Questions
0 Views

Choose a study mode

Play Quiz
Study Flashcards
Spaced Repetition
Chat to Lesson

Podcast

Play an AI-generated podcast conversation about this lesson

Questions and Answers

What is primarily responsible for the impaired heme biosynthesis in sideroblastic anemia?

  • Increased iron stores
  • Genetic disorders of hemoglobin synthesis
  • Deficiency of pyridoxine (vitamin B6) (correct)
  • Excessive iron absorption

Which condition is NOT known to cause vitamin B6 deficiency?

  • Alcoholism
  • Hyperthyroidism (correct)
  • Chronic kidney disease
  • Chronic diarrhea

What is a characteristic feature of iron-deficiency anemia?

  • Macrocytic red blood cells
  • Sideroblastic red blood cells
  • Microcytic and hypochromic erythrocytes (correct)
  • Normocytic red blood cells

Which symptom is NOT typically associated with iron deficiency?

<p>Macrocytic anemia symptoms (B)</p> Signup and view all the answers

Which of the following is TRUE regarding the progression of iron deficiency?

<p>Iron stores diminish first, followed by circulating iron, then hemoglobin production (C)</p> Signup and view all the answers

What laboratory test is commonly used to assess iron deficiency?

<p>Total iron-binding capacity (TIBC) (B)</p> Signup and view all the answers

Which of the following symptoms is indicative of severe vitamin B6 deficiency?

<p>Glossitis (A)</p> Signup and view all the answers

Which factor does NOT contribute to iron deficiency?

<p>Iron supplementation (D)</p> Signup and view all the answers

Which of the following symptoms is least likely to be present in cases of moderate lead poisoning?

<p>Convulsions (D)</p> Signup and view all the answers

What is a primary effect of lead acting as a competitive inhibitor of Fe2+ in heme biosynthesis?

<p>Accumulation of protoporphyrin IX (PPIX) (D)</p> Signup and view all the answers

Which treatment option for lead poisoning is a chelator that helps remove lead from the body?

<p>Dimercaprol (C)</p> Signup and view all the answers

What type of anemia is caused by a deficiency of heme due to lead poisoning?

<p>Microcytic hypochromic anemia (D)</p> Signup and view all the answers

Porphyrias are primarily caused by deficiencies in which type of enzymes?

<p>Heme synthesizing enzymes (A)</p> Signup and view all the answers

Which of the following is a leading indicator of heavy metal poisoning?

<p>Increased urinary excretion of d-ALA (D)</p> Signup and view all the answers

Which of these conditions is NOT considered an acquired disorder of heme synthesis?

<p>Congenital porphyria (B)</p> Signup and view all the answers

How does the accumulation of porphyrinogens in the skin affect patients with certain porphyrias?

<p>It results in photosensitivity (D)</p> Signup and view all the answers

Which form of iron does ferrochelatase incorporate into protoporphyrin IX to produce heme?

<p>Fe2+ (C)</p> Signup and view all the answers

What is the primary site of heme biosynthesis in the body?

<p>Erythroid progenitor cells (A), Liver (B)</p> Signup and view all the answers

What is the consequence of high heme concentration on ALA synthase?

<p>Inhibits ALAS by negative feedback (C)</p> Signup and view all the answers

Which vitamin is essential for the function of ALA synthase (ALAS) in heme biosynthesis?

<p>Vitamin B6 (B)</p> Signup and view all the answers

Which isoform of ALA synthase is expressed in non-erythroid cells and responds to toxins?

<p>ALAS1 (A)</p> Signup and view all the answers

What genetic deficiency results in X-linked sideroblastic anemia?

<p>Deficiency of ALAS2 (B)</p> Signup and view all the answers

Which of the following is NOT a cause of acquired disorders in heme synthesis?

<p>X-linked deficiency (D)</p> Signup and view all the answers

What is the committed step for heme biosynthesis?

<p>Synthesis of d-aminolevulinic acid (B)</p> Signup and view all the answers

What is the primary role of hepcidin in regulating iron levels in the body?

<p>Decreases iron absorption by degrading ferroportin (B)</p> Signup and view all the answers

What condition is characterized by abnormal iron accumulation?

<p>Hemosiderosis (D)</p> Signup and view all the answers

In hereditary hemochromatosis (HH), what results from mutations in the HFE gene?

<p>Increased levels of iron absorption (A)</p> Signup and view all the answers

Which of the following could potentially lead to iron overload?

<p>Frequent blood transfusions (A)</p> Signup and view all the answers

What effect does high iron levels have on hepcidin production?

<p>Hepcidin production increases (C)</p> Signup and view all the answers

What clinical manifestation is associated with chronic hemochromatosis?

<p>Bronzed skin pigmentation and diabetes mellitus (C)</p> Signup and view all the answers

Which type of iron storage protein is partially denatured and stores excess iron?

<p>Hemosiderin (D)</p> Signup and view all the answers

What triggers the increased degradation of ferroportin?

<p>High levels of hepcidin (C)</p> Signup and view all the answers

What causes increased unconjugated bilirubin in the blood during hemolytic jaundice?

<p>Massive production of bilirubin due to hemolytic anemia (A)</p> Signup and view all the answers

In hepatocellular jaundice, which of the following findings is likely NOT present?

<p>Increased urobilinogen in urine (A)</p> Signup and view all the answers

Which genetic condition is associated with increased hemolytic activity leading to jaundice?

<p>Sickle cell anemia (B)</p> Signup and view all the answers

What is the most likely cause of dark urine in posthepatic jaundice?

<p>Backup of conjugated bilirubin in circulation (A)</p> Signup and view all the answers

Which of the following methods is used to diagnose hemolytic jaundice?

<p>Decreased plasma levels of haptoglobin (D)</p> Signup and view all the answers

What treatment is generally used for Gilbert’s Syndrome?

<p>Small doses of phenobarbital (C)</p> Signup and view all the answers

In which type of jaundice is there a major issue with conjugation of bilirubin in the liver?

<p>Hepatocellular jaundice (C)</p> Signup and view all the answers

Which of the following would likely increase due to hemolytic jaundice?

<p>Urobilinogen in blood (A)</p> Signup and view all the answers

What is the most significant contributing factor for the expression of porphyria cutanea tarda?

<p>Chronic alcoholism or liver damage (D)</p> Signup and view all the answers

Which enzyme is primarily responsible for the initial reaction of heme degradation?

<p>Heme oxygenase (A)</p> Signup and view all the answers

What is the primary route through which conjugated bilirubin is excreted from the body?

<p>Bile into the duodenum (B)</p> Signup and view all the answers

What percentage of urobilinogen is typically excreted in feces?

<p>80–90% (B)</p> Signup and view all the answers

How does prolonged exposure to sunlight affect patients with porphyria cutanea tarda?

<p>It exacerbates cutaneous photosensitivity (C)</p> Signup and view all the answers

Which of the following statements about bilirubin is accurate?

<p>Most cells in the body generate bilirubin (D)</p> Signup and view all the answers

What is a key characteristic of the feces due to urobilinogen?

<p>It has a brown-orange color from stercobilin (D)</p> Signup and view all the answers

What is the role of UDP-glucuronyl transferase in bilirubin metabolism?

<p>It conjugates bilirubin to make it water soluble (A)</p> Signup and view all the answers

What is the primary role of heme in the human body?

<p>Transport of oxygen (C)</p> Signup and view all the answers

Which symptom is commonly associated with iron deficiency anemia?

<p>Increased fatigue (C)</p> Signup and view all the answers

What is the metabolic consequence of lead poisoning?

<p>Inhibition of heme synthesis (C)</p> Signup and view all the answers

Which of the following best describes hemochromatosis?

<p>A condition of abnormal iron accumulation (C)</p> Signup and view all the answers

What is a typical indication of jaundice due to hemolytic conditions?

<p>Elevated levels of unconjugated bilirubin (B)</p> Signup and view all the answers

Which iron form is incorporated into protoporphyrin IX to form heme?

<p>Fe2+ ferrous (D)</p> Signup and view all the answers

What is the rate-limiting enzyme in heme biosynthesis?

<p>ALA synthase (C)</p> Signup and view all the answers

Which condition is associated with genetic deficiencies of ALAS2?

<p>Sideroblastic anemia (C)</p> Signup and view all the answers

What triggers the negative-feedback inhibition of ALA synthase (ALAS)?

<p>High heme concentration (D)</p> Signup and view all the answers

Which of the following is NOT a factor causing acquired disorders of heme synthesis?

<p>Genetic mutations (A)</p> Signup and view all the answers

Where does most heme synthesis take place in the body?

<p>Liver and bone marrow (D)</p> Signup and view all the answers

Which diagnostic marker is typically low in cases of hemolytic jaundice?

<p>Haptoglobin (C)</p> Signup and view all the answers

Which vitamin is required by ALA synthase (ALAS) for its activity?

<p>Pyridoxine (Vitamin B6) (D)</p> Signup and view all the answers

In hepatocellular jaundice, which component is likely to decrease in the urine?

<p>Urobilinogen (B)</p> Signup and view all the answers

What is a characteristic finding of posthepatic (obstructive) jaundice?

<p>Dark urine (A)</p> Signup and view all the answers

Which is an acquired disorder of heme synthesis?

<p>Lead poisoning (B)</p> Signup and view all the answers

Which condition is associated with a benign inability to conjugate bilirubin?

<p>Gilbert’s Syndrome (D)</p> Signup and view all the answers

What is the primary mechanism leading to pale stools in hepatocellular jaundice?

<p>Decreased conjugated bilirubin secretion (A)</p> Signup and view all the answers

Which environmental factor might contribute to hemolytic anemia?

<p>Viral infections (D)</p> Signup and view all the answers

Which treatment option is commonly used to stimulate bilirubin conjugation in Gilbert's Syndrome?

<p>Phenobarbital (C)</p> Signup and view all the answers

What is the function of hepcidin in iron homeostasis?

<p>Inhibits iron absorption by degrading ferroportin. (C)</p> Signup and view all the answers

Which condition is associated with abnormal accumulation of iron?

<p>Hemosiderosis (C)</p> Signup and view all the answers

Hereditary Hemochromatosis (HH) is primarily caused by mutations in which gene?

<p>HFE gene (C)</p> Signup and view all the answers

What happens to hepcidin levels when iron is detected to be low in the body?

<p>Hepcidin levels decrease. (A)</p> Signup and view all the answers

Which of the following may lead to iron overload?

<p>Frequent blood transfusions (C)</p> Signup and view all the answers

What effect does the degradation of ferroportin have on iron levels?

<p>Decreases iron levels in circulation. (D)</p> Signup and view all the answers

What is the consequence of high hepcidin levels due to high iron concentrations?

<p>Inhibition of ferroportin and reduced iron release. (C)</p> Signup and view all the answers

What skin condition may develop due to chronic hemochromatosis?

<p>Bronze pigmentation (C)</p> Signup and view all the answers

What enzyme deficiency is the cause of acute intermittent porphyria?

<p>Porphobilinogen deaminase (D)</p> Signup and view all the answers

Which of the following symptoms is commonly associated with acute intermittent porphyria episodes?

<p>Severe abdominal pain (B)</p> Signup and view all the answers

What condition can worsen the symptoms of acute intermittent porphyria?

<p>Drugs inducing cytochrome P-450 synthesis (C)</p> Signup and view all the answers

How does an acute attack of AIP lead to the accumulation of ALA and porphobilinogen?

<p>Decreased heme availability (A)</p> Signup and view all the answers

What color does urine typically darken to when exposed to air due to acute intermittent porphyria?

<p>Purple or port-wine color (C)</p> Signup and view all the answers

Which of the following treatments should be avoided in managing acute intermittent porphyria symptoms?

<p>Barbiturates (C)</p> Signup and view all the answers

What dietary recommendation is typically made for long-term management of acute intermittent porphyria?

<p>Carbohydrate-rich diet (C)</p> Signup and view all the answers

What effect does dieting have on attacks of porphyria?

<p>It worsens the condition (A)</p> Signup and view all the answers

What is the main consequence of pyridoxine deficiency?

<p>Sideroblastic anemia (A)</p> Signup and view all the answers

What symptom is commonly associated with iron deficiency?

<p>Cold or abnormal sensations in extremities (A)</p> Signup and view all the answers

What type of anemia is characterized by microcytic and hypochromic erythrocytes?

<p>Iron-deficiency anemia (A)</p> Signup and view all the answers

Which laboratory test is most indicative of iron deficiency?

<p>Low hemoglobin levels (B)</p> Signup and view all the answers

What condition can result from isoniazid therapy?

<p>Sideroblastic anemia (B)</p> Signup and view all the answers

What is a significant cause of iron deficiency anemia?

<p>Celiac disease (D)</p> Signup and view all the answers

What dietary factor can lead to iron deficiency?

<p>Dietary lack of iron (B)</p> Signup and view all the answers

Which of the following is NOT a symptom of vitamin B6 deficiency?

<p>Frequent headaches (B)</p> Signup and view all the answers

Flashcards

Protoporphyrin IX

A molecule that binds metals such as iron, forming heme and hemin.

Heme

A molecule containing ferrous iron (Fe2+). It is a component of hemoglobin and other proteins.

Hemin

A molecule containing ferric iron (Fe3+). It is a non-functional form of heme.

Heme biosynthesis

The process of synthesizing the molecule heme.

Signup and view all the flashcards

Ferrochelatase

An enzyme responsible for inserting ferrous iron into protoporphyrin IX to form heme.

Signup and view all the flashcards

ALA Synthase (ALAS)

The rate-limiting enzyme in heme biosynthesis. It requires vitamin B6.

Signup and view all the flashcards

X-linked sideroblastic anemia

A genetic deficiency of ALAS2, leading to a specific type of anemia.

Signup and view all the flashcards

Porphyrias

Disorders of heme synthesis, either acquired or congenital, that can lead to a variety of health problems.

Signup and view all the flashcards

Transferrin

A protein in the blood that carries iron (Fe3+) to cells.

Signup and view all the flashcards

Ferritin

A protein within cells that stores iron.

Signup and view all the flashcards

Hepcidin

A hormone that regulates iron levels in the body by controlling iron absorption and release.

Signup and view all the flashcards

Ferroportin

A protein on the surface of cells that transports iron out of cells.

Signup and view all the flashcards

Hemosiderosis

A condition characterized by an excessive accumulation of iron in the body.

Signup and view all the flashcards

Hereditary Hemochromatosis (HH)

An inherited disorder where excess iron builds up in the body due to a faulty gene (HFE).

Signup and view all the flashcards

HFE protein

A protein that helps control the production of hepcidin and reduces the binding of transferrin to its receptors.

Signup and view all the flashcards

Transferrin receptor uptake

The process where cells take up transferrin, which delivers iron to them.

Signup and view all the flashcards

Heme Synthesis

The process by which the body makes heme, a crucial component of hemoglobin.

Signup and view all the flashcards

ALA Synthase

This enzyme is the rate-limiting step in heme synthesis, which means its activity determines the overall speed of the process. It requires vitamin B6 (pyridoxine) for its function.

Signup and view all the flashcards

Sideroblastic Anemia

A type of anemia caused by insufficient production of heme. It's characterized by small, pale red blood cells (microcytic, hypochromic) and the presence of ringed sideroblasts.

Signup and view all the flashcards

Iron Deficiency

A condition where the body doesn't have enough iron. It's also a cause of microcytic, hypochromic anemia.

Signup and view all the flashcards

Iron Deficiency Stage 1: Diminished Iron Stores

The stage of iron deficiency where the body's iron stores are depleted, but the circulating iron level is still normal.

Signup and view all the flashcards

Iron Deficiency Stage 2: Decreased Circulating Iron

The stage of iron deficiency where the levels of circulating iron in the blood decrease.

Signup and view all the flashcards

Iron Deficiency Stage 3: Reduced Hemoglobin Production

The stage of iron deficiency where the production of hemoglobin is affected, leading to anemia.

Signup and view all the flashcards

Blood Tests for Iron Deficiency

These blood tests measure different aspects of iron metabolism and red blood cell health. They help diagnose iron deficiency anemia.

Signup and view all the flashcards

Lead poisoning and heme synthesis

A condition where the body's ability to produce heme is disrupted due to the inactivation of key enzymes in the heme synthesis pathway by lead.

Signup and view all the flashcards

Microcytic Hypochromic Anemia

A type of anemia characterized by small, pale red blood cells, often caused by a deficiency in heme production.

Signup and view all the flashcards

ALA and PPIX accumulation

A buildup of d-Aminolevulinate (ALA) and protoporphyrin IX (PPIX) in the body due to lead inhibition of enzymes involved in heme synthesis.

Signup and view all the flashcards

Chelator

A compound that binds to lead and facilitates its removal from the body, reducing lead toxicity.

Signup and view all the flashcards

Photosensitivity

Increased sensitivity to sunlight, often a symptom of porphyrias due to the accumulation of porphyrinogens in the skin.

Signup and view all the flashcards

Hepatic and Erythropoietic Porphyrias

A group of disorders that primarily affect the liver and red blood cell production, resulting from deficiencies in heme synthesis.

Signup and view all the flashcards

Neurological complications of Porphyrias

Toxic effects of accumulated intermediate metabolites in the heme synthesis pathway, often associated with nervous system pathology.

Signup and view all the flashcards

Porphyria Cutanea Tarda

A common porphyria primarily affecting older men, especially during summer months.

Signup and view all the flashcards

Heme Degradation

Degradation of heme from red blood cells (RBCs) and other heme-containing proteins by the liver and spleen.

Signup and view all the flashcards

Biliverdin

The green pigment formed during heme degradation, produced by heme oxygenase.

Signup and view all the flashcards

Bilirubin

The orange pigment formed by reduction of biliverdin, the final product of heme degradation.

Signup and view all the flashcards

UDP-Glucuronyl Transferase

The enzyme responsible for converting bilirubin to water-soluble conjugated bilirubin in the liver.

Signup and view all the flashcards

Urobilinogen

The breakdown product of conjugated bilirubin in the intestines, responsible for the characteristic color of feces.

Signup and view all the flashcards

Bilirubin Excretion

The major route of excretion of bilirubin, involving its conversion to conjugated bilirubin and transport through the bile.

Signup and view all the flashcards

Enterohepatic Circulation

The circulation of substances between the intestines and the liver.

Signup and view all the flashcards

What is hyperbilirubinemia?

Jaundice happens when there's too much bilirubin in the blood, due to a problem with how much bilirubin is made and how fast it's removed.

Signup and view all the flashcards

What is hemolytic jaundice?

Hemolytic jaundice is when the breakdown of red blood cells (hemolysis) is too fast, causing a buildup of bilirubin. The liver can't process it all.

Signup and view all the flashcards

What are some causes of hemolytic jaundice?

Hemolytic jaundice can be caused by genetic factors like sickle cell anemia or thalassemia, or by infections, drugs, or other environmental factors.

Signup and view all the flashcards

How is hemolytic jaundice diagnosed?

Hemolytic jaundice is diagnosed by looking at haptoglobin levels. Haptoglobin binds to free hemoglobin, so low levels indicate more hemolysis.

Signup and view all the flashcards

What is hepatocellular jaundice?

Hepatocellular jaundice happens when the liver itself is not working properly, causing a buildup of bilirubin the body can't process. This can be due to liver damage or disease.

Signup and view all the flashcards

How do you diagnose hepatocellular jaundice?

Hepatocellular jaundice often involves other liver problems, so looking at liver function tests (ALT, AST) is helpful.

Signup and view all the flashcards

What is Gilbert's Syndrome?

Gilbert's Syndrome is a mild, inherited condition where the liver can't conjugate bilirubin as well. This leads to a buildup of unconjugated bilirubin.

Signup and view all the flashcards

What is posthepatic jaundice?

Posthepatic jaundice (obstructive jaundice) happens when the bile duct is blocked, preventing the liver from releasing its bilirubin. This leads to a backup of bilirubin.

Signup and view all the flashcards

What are the signs and symptoms of B6 deficiency anemia?

A deficiency in vitamin B6 (pyridoxine) can lead to a specific type of anemia, characterized by impaired heme synthesis and insufficient production of red blood cells.

Signup and view all the flashcards

How does lead poisoning affect heme synthesis?

Lead poisoning disrupts the delicate balance of heme biosynthesis by inhibiting specific enzymes involved in the pathway, causing a buildup of harmful intermediates.

Signup and view all the flashcards

What causes iron deficiency anemia?

Iron deficiency anemia is a common type of anemia caused by a lack of iron, essential for building hemoglobin, the oxygen-carrying molecule in red blood cells.

Signup and view all the flashcards

How are iron levels regulated in the body?

The iron levels are carefully regulated in the body through a complex interplay of absorption, transport, and storage mechanisms. This intricate balance ensures enough iron is available for vital bodily functions.

Signup and view all the flashcards

What is jaundice, and how does it relate to bilirubin?

Bilirubin, the yellow pigment produced during heme breakdown, needs to be effectively processed and eliminated from the body. When this process is disrupted, it can lead to a condition called jaundice.

Signup and view all the flashcards

What is Jaundice?

Jaundice is a condition where bilirubin levels in the blood are too high, causing a yellowish tint to the skin and whites of the eyes.

Signup and view all the flashcards

Hemolytic Jaundice

Hemolytic jaundice occurs when the body destroys red blood cells faster than normal, producing excess bilirubin which the liver cannot process.

Signup and view all the flashcards

Causes of Hemolytic Jaundice

Hemolytic jaundice can result from genetic conditions like sickle cell anemia, thalassemia, or hereditary spherocytosis, as well as infections, drugs, or toxic exposures.

Signup and view all the flashcards

Hepatocellular Jaundice

Hepatocellular jaundice occurs when the liver is damaged or diseased and cannot properly process bilirubin.

Signup and view all the flashcards

Gilbert's Syndrome

Gilbert's Syndrome is a mild, inherited condition where the liver has reduced ability to conjugate bilirubin, leading to increased unconjugated bilirubin levels.

Signup and view all the flashcards

Posthepatic Jaundice

Posthepatic jaundice (also called obstructive jaundice) occurs when the bile ducts are blocked, preventing bilirubin from being excreted, leading to a buildup in the body.

Signup and view all the flashcards

Haptoglobin in Hemolytic Jaundice

Low haptoglobin levels indicate increased hemolysis, suggesting hemolytic jaundice.

Signup and view all the flashcards

Liver Function Tests (ALT, AST) in Hepatocellular Jaundice

Liver function tests (ALT, AST) can reveal problems with the liver that may contribute to hepatocellular jaundice.

Signup and view all the flashcards

What are sideroblastic anemias?

A type/group of anemias that share a common feature of impaired heme biosynthesis, resulting in small, pale red blood cells (microcytic, hypochromic) and the presence of ringed sideroblasts.

Signup and view all the flashcards

What is ALA synthase?

An enzyme that requires pyridoxine (vitamin B6) for its function and acts as the rate-limiting enzyme in heme biosynthesis. Its deficiency can lead to sideroblastic anemia.

Signup and view all the flashcards

What is pyridoxine (vitamin B6) deficiency?

A deficiency of pyridoxine (vitamin B6), a critical cofactor for ALA synthase. Can be caused by factors like isoniazid therapy or malabsorption.

Signup and view all the flashcards

What is iron deficiency?

A condition characterized by a lack of iron in the body. It's one of the leading causes of microcytic, hypochromic anemia.

Signup and view all the flashcards

Describe the stages of iron deficiency

Iron stores are depleted first, followed by a decrease in circulating iron, and finally, a reduction in hemoglobin production.

Signup and view all the flashcards

How do you diagnose iron deficiency?

Blood tests used to diagnose iron deficiency include measurements of hemoglobin, hematocrit, iron, ferritin, total iron-binding capacity (TIBC), and transferrin saturation.

Signup and view all the flashcards

How are red blood cells affected by iron deficiency anemia?

Characterized by microcytic and hypochromic erythrocytes due to insufficient heme production.

Signup and view all the flashcards

What are the causes of iron deficiency?

Various causes include dietary lack, impaired absorption, blood loss, and increased requirements during growth, pregnancy, or lactation.

Signup and view all the flashcards

What is Hepcidin?

Hepcidin is a hormone primarily produced by the liver that tightly regulates iron levels in the body, acting as a key player in iron homeostasis.

Signup and view all the flashcards

What is Ferroportin?

Ferroportin is a protein found on the surface of cells that allows iron to be transported out of the cell into the bloodstream. Hepcidin binds to ferroportin and causes its degradation, effectively trapping iron inside cells.

Signup and view all the flashcards

How does Hepcidin regulate iron levels when they are high?

When iron levels are high, the liver releases more hepcidin, which then binds to ferroportin on the surface of cells, leading to its degradation. This keeps iron trapped within cells, preventing excess iron from entering the bloodstream.

Signup and view all the flashcards

How does Hepcidin regulate iron levels when they are low?

When iron levels are low, the liver releases less hepcidin. This allows ferroportin to function properly, leading to increased iron absorption from the gut and release from storage sites.

Signup and view all the flashcards

What is Hereditary Hemochromatosis (HH)?

Hereditary hemochromatosis (HH) is a genetic disorder caused by mutations in the HFE gene. These mutations lead to a loss of function of the HFE protein, which normally helps regulate hepcidin production.

Signup and view all the flashcards

How does the HFE protein affect iron absorption?

The HFE protein normally interacts with the transferrin receptor, reducing its affinity for transferrin. However, in HH, mutated HFE protein cannot bind to the transferrin receptor, resulting in excessive iron absorption.

Signup and view all the flashcards

What is Hemosiderosis?

Iron overload, also known as hemosiderosis, is a condition where excessive iron accumulates in the body. It can result from various causes, such as accidental poisoning, frequent blood transfusions, or genetic disorders like hereditary hemochromatosis.

Signup and view all the flashcards

What are the consequences of Chronic hemochromatosis?

Chronic hemochromatosis can lead to a variety of complications, including bronzed pigmentation of the skin, and damage to vital organs like the liver and pancreas. This can ultimately result in diabetes mellitus, a condition known as “bronze diabetes”.

Signup and view all the flashcards

What is porphyria?

A porphyria affects heme synthesis, leading to the accumulation of porphyrin precursors. The accumulation of these substances in the body can lead to a variety of symptoms, including photosensitivity, neurological problems, and abdominal pain.

Signup and view all the flashcards

What role does vitaimn B6 play in heme biosynthesis?

d-Aminolevulinic acid synthase (ALAS) is the rate-limiting enzyme in heme synthesis. It requires vitamin B6 (pyridoxine) to function. This means that any deficiency in vitamin B6 can impact the overall rate of heme synthesis.

Signup and view all the flashcards

How is Iron incorporated into Heme?

Iron, in its Ferrous (Fe2+) form, is directly incorporated into protoporphyrin IX by the enzyme ferrochelatase, forming heme.

Signup and view all the flashcards

Where does most heme synthesis take place?

The liver and erythroid progenitor cells within the bone marrow are the two main sites of heme synthesis in the body.

Signup and view all the flashcards

How is heme synthesis regulated?

Heme feedback inhibits ALA synthase (ALAS), the rate-limiting enzyme in heme synthesis. This is a negative feedback loop that helps maintain heme levels within a healthy range.

Signup and view all the flashcards

What are the different isoforms of ALAS?

There are two isoforms of ALAS; ALAS1 found in non-erythroid cells and ALAS2 found in erythroid cells. Both are involved in heme synthesis, but ALAS2 is particularly critical for hemoglobin production in red blood cells.

Signup and view all the flashcards

What is X-linked sideroblastic anemia?

Genetic deficiencies of ALAS2 can lead to X-linked sideroblastic anemia, a condition characterized by the inability to produce enough heme for red blood cells.

Signup and view all the flashcards

Acute Intermittent Porphyria (AIP)

An inherited metabolic disorder caused by deficiency in the enzyme uroporphyrinogen I synthase (hydroxymethylbilane synthase), leading to accumulation of porphyrin precursors in the body.

Signup and view all the flashcards

Uroporphyrinogen I Synthase (Hydroxymethylbilane Synthase)

The enzyme involved in the biosynthesis of heme that is deficient in Acute Intermittent Porphyria (AIP).

Signup and view all the flashcards

Aminolevulinic Acid (ALA) and Porphobilinogen

Accumulation of these molecules in the blood and cerebrospinal fluid can lead to neurological symptoms and metabolic abnormalities.

Signup and view all the flashcards

Drugs that Induce Cytochrome P-450 Synthesis

Drugs that induce the synthesis of cytochrome P-450 in the liver can worsen AIP by depleting the pool of free heme, leading to increased ALA synthase activity and the accumulation of porphyrin precursors.

Signup and view all the flashcards

Carbohydrate-rich Diet

A carbohydrate-rich diet helps manage AIP by repressing the synthesis of ALA synthase, reducing the formation of porphyrin precursors.

Signup and view all the flashcards

Treatment of AIP Acute Attacks

Withdrawal of offending drugs (e.g., barbiturates) and administration of hematin are crucial for treating an acute attack.

Signup and view all the flashcards

Long-Term Management of AIP

Long-term management of AIP includes avoiding precipitating factors, maintaining a carbohydrate-rich diet, and promptly addressing any acute attacks.

Signup and view all the flashcards

Study Notes

Porphyrin/Heme Metabolism and Iron Homeostasis

  • Marks' Basic Medical Biochemistry, 6th edition, chapter 42 (pages 939–944)
  • Biochemistry, Cell and Molecular Biology, and Genetics, Part V, chapter 36 (pages 301-312)
  • Pathologic Basis of Disease 10th Edition, chapter 14 (pages 655-658) and chapter 18 (pages 848-850)

Learning Objectives

  • Outline the biochemical pathway and regulatory steps of heme biosynthesis
  • Describe the signs and symptoms of vitamin B6 deficiency anemia
  • Describe the signs and symptoms of lead poisoning
  • Describe the signs and symptoms of iron deficiency anemia
  • Distinguish differences in diagnosis between vitamin B6 deficiency anemia, lead poisoning, and iron deficiency anemia.
  • Describe the metabolism of bilirubin and the types of jaundice
  • Outline the types of porphyrias
  • Explain iron absorption, transport, and storage in the body
  • Explain how iron levels are regulated in the body
  • Explain diagnostic tests for iron deficiency
  • Describe the molecular and clinical findings of hemochromatosis
  • Describe the process of heme degradation and bilirubin excretion

Hemoglobin Biosynthesis

  • Heme synthesis is coordinated with globin chain synthesis
  • Involves the coordinated use of amino acids
  • Takes place in the mitochondria

Structure of Heme (iron protoporphyrin IX)

  • Heme is a prosthetic group for hemoglobin, myoglobin, cytochromes, cyclooxygenase, catalase, and cytochrome P-450 enzymes.
  • Protoporphyrin IX binds various metals (e.g., iron)

Heme Biosynthesis Pathway (Detailed)

  • Succinyl CoA and glycine combine to form 8-aminolevulinate acid (ALA)
  • Two molecules of ALA condense to form porphobilinogen
  • Series of enzymatic reactions convert porphobilinogen to protoporphyrin IX
  • Iron is incorporated into protoporphyrin IX to form heme

Heme Biosynthesis - Location and Rate-Limiting Step

  • Primarily occurs in the liver and bone marrow erythroid progenitor cells
  • ALA synthase (ALAS) is the rate-limiting enzyme and requires pyridoxine (vitamin B6)
  • Heme inhibits ALA synthase via negative feedback

Disorders of Heme Synthesis

  • Acquired: Vitamin B6 deficiency, iron deficiency, lead poisoning
  • Congenital: Porphyrias

8-Aminolevulinate Synthase (ALAS)

  • Two isoforms exist: ALAS1 (non-erythroid) and ALAS2 (erythroid)
  • ALAS1 expression increases in response to toxins and drugs
  • ALAS2 expression is increased by hypoxia and erythropoietin

Effects of Lead Poisoning in Heme Biosynthesis

  • Lead inactivates ALA dehydratase and ferrochelatase enzymes
  • Acts as a competitive inhibitor of iron, preventing insertion into protoporphyrin IX
  • Increased 8-ALA and PPIX in urine indicate lead poisoning
  • Anemia, microcytic, hypochromic, and sideroblastic, due to lack of hemoglobin

Lead Poisoning Symptoms

  • Symptoms range from mild to severe, depending on exposure levels
  • Mild: lethargy, anorexia, abdominal discomfort, arthralgia
  • Moderate: anemia, headache, abdominal cramps, peripheral neuropathy, gingival and long bone lead lines
  • Severe: convulsions, coma, encephalopathy, and renal failure

Porphyrias

  • Caused by deficiencies in heme-synthesizing enzymes
  • Lead to accumulation of porphyrin precursors
  • Neurological symptoms (e.g., seizures, mental disturbance) and photosensitivity. Can also include skin photosensitivity

Dietary Iron Absorption

  • Heme iron (animal products) is more readily absorbed than non-heme iron (plant products)
  • Vitamin C increases non-heme iron absorption
  • Other compounds inhibit iron absorption (e.g., antacids, polyphenols)

Iron Homeostasis

  • Tightly regulated at cellular and systemic levels
  • Iron is shielded from oxygen by binding to proteins (e.g., ferritin, transferrin)
  • Iron regulatory proteins (IRPs) control gene expression of iron-related proteins.
  • Hepcidin regulates iron absorption and storage (particularly in macrophages)
  • Body iron stores are responsible for the level of hepcidin

Iron Deficiency

  • Causes microcytic, hypochromic anemia
  • Symptoms: fatigue, feelings of faintness, abnormal sensations (cold or extremities), shortness of breath, immunosuppression, intellectual/behavioral problems
  • Causes: dietary lack, impaired absorption, acute blood loss, increased requirements

Iron Deficiency Diagnosis

  • Blood tests measure hemoglobin, hematocrit, total iron-binding capacity (TIBC), ferritin, and transferrin saturation
  • Low hemoglobin, low ferritin, and high TIBC are suggestive of iron deficiency

Tests to measure Iron Levels

  • Serum Iron: measures the amount of iron in the blood
  • Serum Ferritin: measures stored iron
  • Transferrin level (TIBC): measures the amount of transferrin in the blood
  • Transferrin saturation: calculated to evaluate the amount of iron bound to transferrin
  • Used to diagnose and monitor iron deficiency and overload

Iron Overload (Hemosiderosis/Hemochromatosis)

  • Abnormal iron accumulation
  • Causes: genetic mutations, frequent blood transfusions, or accidental poisoning
  • Systemic damage

Bilirubin Metabolism and Excretion

  • Breakdown of heme from red blood cells yields bilirubin
  • Bilirubin is transported to the liver, conjugated, and excreted into bile.
  • This pathway leads to the production of urobilinogen that is mostly processed into stercobilin and excreted in feces. A smaller portion is excreted in urine.

Jaundice (Hyperbilirubinemia)

  • Increased plasma bilirubin levels
  • Caused by an imbalance between bilirubin production and excretion
  • Various causes (prehepatic, hepatocellular, and posthepatic)

Types of Jaundice (Clinical Correlations)

  • Prehepatic: hemolytic conditions (increased RBC breakdown)
  • Hepatocellular: liver damage (impaired bilirubin processing/conjugation)
  • Posthepatic: blockage in bile ducts (impaired bilirubin excretion)

Additional Specific Conditions

  • Neonatal Jaundice: Late onset of bilirubin conjugation, breakdown of fetal hemoglobin, or prematurity.
  • Gilbert's Syndrome: Benign, inherited liver disorder; reduced UDP-glucuronyl transferase activity

Studying That Suits You

Use AI to generate personalized quizzes and flashcards to suit your learning preferences.

Quiz Team

Related Documents

Description

Test your knowledge on various types of anemia, their causes, and the effects of lead poisoning. This quiz covers key symptoms, laboratory tests, and treatment options related to impaired heme biosynthesis and iron deficiencies. Understand the critical roles of vitamin B6 and other factors in blood health.

More Like This

Anemia Types and Causes
24 questions

Anemia Types and Causes

ComprehensiveNebula avatar
ComprehensiveNebula
Anemia Types and Treatments
24 questions

Anemia Types and Treatments

StimulativeTrigonometry1693 avatar
StimulativeTrigonometry1693
Understanding Anemia and Its Types
40 questions

Understanding Anemia and Its Types

Darling talent avatar
Darling talent
Use Quizgecko on...
Browser
Open
Browser
Browser