Blood And Body Defences Flashcards
(202 cards)
Which statement best describes the RBC membrane’s key function?
Maintaining RBC shape and deformability. RBC membrane skeletal proteins (e.g., spectrin) and lipid bilayer organization allow red cells to squeeze through narrow capillaries without hemolysis.
A deficiency of glucose-6-phosphate dehydrogenase (G6PD) primarily leads to:
Decreased protection against oxidative stress. Without adequate G6PD, RBCs cannot generate sufficient NADPH, which is needed to keep glutathione reduced and prevent oxidative damage.
In the pentose phosphate shunt, the formation of NADPH is essential because NADPH:
Keeps glutathione in its reduced form. Reduced glutathione neutralizes harmful reactive oxygen species, safeguarding RBCs from oxidative damage.
A drop in 2,3-DPG concentration in RBCs is most likely to:
Increase hemoglobin’s affinity for oxygen. Lower 2,3-DPG means hemoglobin remains in a higher-affinity state, reducing oxygen release to tissues.
The conversion of methemoglobin (MetHb) to functional hemoglobin requires RBCs to have adequate:
NADH generated from glycolysis. Methemoglobin reductase uses NADH to reduce Fe3+ back to Fe2+, restoring hemoglobin’s oxygen-carrying capacity.
Definition of Haematocrit (Hct)
Haematocrit is the percentage of whole blood volume occupied by RBCs. It is typically measured by centrifuging blood and calculating packed cell volume relative to total volume.
Composition of RBC Membrane
The RBC membrane is ~50% protein, 40% lipid, and 10% carbohydrate by weight. This balanced structure helps maintain flexibility, shape, and surface markers.
Role of Ankyrin in RBCs
Ankyrin is a peripheral membrane protein that anchors spectrin (cytoskeleton) to the integral membrane protein Band 3. This linkage preserves RBC membrane stability and biconcave shape.
Function of GLUT1 in RBCs
GLUT1 is a passive glucose transporter on RBC membranes. It facilitates glucose entry down its concentration gradient, providing the primary fuel for RBC glycolysis.
What is Hereditary Spherocytosis?
A membrane-cytoskeleton defect (often in spectrin or ankyrin) causing spherical RBCs with decreased deformability. These RBCs are prone to hemolysis, often destroyed in the spleen.
Importance of Flippase and Floppase
Flippase and floppase are ATP-dependent transporters that move phospholipids (e.g., PS, PE, PC, SM) between leaflets of the RBC membrane. They maintain phospholipid asymmetry and membrane integrity.
2,3-DPG’s Effect on Oxygen Affinity
2,3-DPG binds deoxyhemoglobin, stabilizing the low-affinity T (tense) state. This right-shifts the oxygen dissociation curve, promoting oxygen release to tissues under physiological conditions.
Pentose Phosphate Shunt Key Function
Generates NADPH, vital for keeping glutathione in the reduced form (GSH). RBCs rely on this to neutralize reactive oxygen species, preventing hemolysis from oxidative stress.
Why RBCs Lack Mitochondria
RBCs expel their organelles (including mitochondria) during maturation. This maximizes space for hemoglobin but restricts them to anaerobic glycolysis for ATP production.
Role of Spectrin in RBCs
Spectrin is a cytoskeletal protein forming a lattice beneath the membrane, maintaining biconcavity and elasticity. Defects lead to abnormal shapes (e.g., spherocytes) and increased fragility.
Which hormone is the central regulator of systemic iron homeostasis by binding to ferroportin and inducing its internalization?
Hepcidin
In the duodenum, dietary non‐heme iron is primarily absorbed in which oxidation state?
Ferrous (Fe²⁺)
Non‐heme iron is reduced from its ferric (Fe³⁺) form to the ferrous (Fe²⁺) form before absorption via DMT1 in the duodenum.
Which transporter is responsible for importing ferrous iron (Fe²⁺) into enterocytes?
DMT1 (divalent metal transporter 1)
DMT1 facilitates the uptake of ferrous iron from the intestinal lumen into the enterocytes, which is a key step in dietary iron absorption.
Under conditions of low intracellular iron, what effect does the IRP/IRE system have on ferritin translation and transferrin receptor expression?
It decreases ferritin translation and increases transferrin receptor expression
When iron is scarce, iron regulatory proteins (IRPs) bind to iron response elements (IREs) on mRNAs, thereby inhibiting ferritin synthesis (reducing storage) while stabilizing transferrin receptor mRNA to promote iron uptake.
Which condition upregulates hepcidin production, thereby reducing iron export from cells?
Inflammation
Inflammatory cytokines, especially IL-6, stimulate hepcidin production, which then binds to ferroportin to limit iron export, contributing to iron sequestration during inflammation.
Which protein is the sole known iron exporter in cells such as enterocytes and macrophages?
Ferroportin
Ferroportin is responsible for exporting iron from cells into the bloodstream; its activity is tightly regulated by hepcidin to maintain iron balance.
A mutation that renders ferroportin resistant to hepcidin binding would most likely lead to what condition?
Systemic iron overload
If ferroportin is resistant to hepcidin, it remains active regardless of regulatory signals, causing excessive iron export and subsequent accumulation in the body.
Which mechanism best explains the pathophysiology of anemia of chronic disease in terms of iron homeostasis?
Elevated hepcidin levels causing impaired iron release from storage
In chronic inflammatory states, high hepcidin levels trap iron in storage sites (such as macrophages), reducing its availability for red blood cell production and leading to anemia.
What is the critical mechanism for preventing free iron–induced oxidative damage within cells?
Binding of iron to ferritin for safe storage
Ferritin sequesters free iron, preventing it from participating in redox reactions that generate harmful free radicals, thereby protecting cells from oxidative damage.
