Related Subjects:
|Iron deficiency Anaemia
|Haemolytic anaemia
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|Myelodysplasia
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๐ฉธ Haemoglobin is a vital protein in red blood cells that transports oxygen from the lungs to tissues and returns carbon dioxide for exhalation. It is essential for maintaining tissue oxygenation and overall metabolic function.
๐ฌ Structure of Haemoglobin
- Haemoglobin is a tetrameric protein with four subunits:
- Each subunit contains a heme group and a globin chain.
- Heme = porphyrin ring + iron (Feยฒโบ) ion, binding one Oโ molecule.
- Globin = polypeptide chains supporting structure & regulating oxygen binding/release.
- Most common in adults = HbA (ฮฑโฮฒโ).
โ๏ธ Formation of Haem
๐ก Key Point: Haem is essential not only for haemoglobin but also for myoglobin and cytochromes. Synthesis occurs in the bone marrow & liver.
๐งช Steps in Haem Synthesis
- ฮด-Aminolevulinic Acid (ALA) Formation: Glycine + Succinyl-CoA โ ALA via ALA synthase (rate-limiting, requires Vit B6).
- ALA โ Porphobilinogen (PBG): Catalysed by ALA dehydratase (inhibited by lead).
- Uroporphyrinogen III Formation: Hydroxymethylbilane โ uroporphyrinogen III.
- Coproporphyrinogen III Formation: Decarboxylation step.
- Protoporphyrinogen IX: Conversion inside mitochondria.
- Protoporphyrin IX: Formed by oxidation.
- Final Step: Ferrochelatase inserts Feยฒโบ into protoporphyrin IX โ Haem.
โ๏ธ Regulation
- Controlled at ALA synthase step.
- โฌ๏ธ Anaemia โ โ ALA synthase activity.
- โฌ๏ธ Haem โ negative feedback on ALA synthase.
๐ Clinical Relevance of Haem Synthesis
- Porphyrias = enzyme deficiencies โ neuro/skin symptoms.
- Lead poisoning = inhibits ALA dehydratase + ferrochelatase โ anaemia, neurological features.
๐งฌ Types of Haemoglobin
| Type | Composition | Normal Proportion | Key Features |
|---|
| HbA | ฮฑโฮฒโ | ~97% | Normal adult haemoglobin |
| HbAโ | ฮฑโฮดโ | ~2-3% | Slightly higher in ฮฒ-thalassemia trait |
| HbF | ฮฑโฮณโ | <1% adults
Predominant in fetus | Higher Oโ affinity โ helps placental transfer |
| HbS | Mutated ฮฒ chain | Pathological | Sickle cell disease |
| HbC | Mutated ฮฒ chain | Pathological | HbC disease with haemolysis |
๐งญ Function of Haemoglobin
- Oโ Transport: Lungs โ tissues (oxyhaemoglobin).
- COโ Transport: Tissues โ lungs (carbaminohaemoglobin).
- Buffering: Binds Hโบ to maintain pH stability.
๐ OxygenโHaemoglobin Dissociation Curve
- S-shaped (sigmoidal) curve showing % saturation vs pOโ.
- Right Shift = โฌ๏ธ Oโ affinity โ easier release to tissues (โ COโ, โ Hโบ, โ temp, โ 2,3-BPG).
- Left Shift = โฌ๏ธ Oโ affinity โ easier loading in lungs (โ COโ, โ Hโบ, โ temp, โ 2,3-BPG, HbF).
๐ก Exam Tip: โRight shift = Releaseโ (easy way to remember).
๐ฉธ Clinical Relevance
- Anaemias: Nutritional (iron, B12, folate), genetic (thalassemia, sickle cell), chronic disease.
- Haemoglobinopathies: HbS, HbC, thalassemias โ haemolysis, anaemia, organ damage.
- CO Poisoning: CO binds Hb with 200x affinity vs Oโ โ tissue hypoxia.
- Methaemoglobinemia: Feยณโบ form cannot bind Oโ โ hypoxia despite normal Oโ levels.
๐ Summary
Haemoglobin = ๐ฉธ oxygen transporter, COโ remover, and pH buffer.
Its complex structure allows precise regulation. Disorders of synthesis (porphyrias, lead poisoning) or structure (sickle cell, thalassemias) underline its clinical importance.
Understanding shifts in the Oโ curve and genetic variants is high-yield for exams and practice.
