Red blood cells and hemoglobin

In negative feedback, the response pushes the variable back toward its set point, so it opposes, or removes, the stimulus that started the loop.

• It amplifies the stimulus:
• Correct: It opposes the stimulus:
• It has no effect on the stimulus:

Most erythropoietin comes from cells in the kidneys that sense low oxygen. The marrow is its target, not its source.

• The liver:
• Correct: The kidneys:
• The red bone marrow:

The hematocrit is the percentage of a blood sample's volume made up of red blood cells.

• Correct: 45% of the blood volume is red blood cells:
• 45% of the blood's cells are red blood cells:
• The blood holds 45 g of red cells per liter:

Thin air lowers the oxygen reaching the kidneys. Through the erythropoiesis feedback loop, EPO rises within hours and the marrow speeds up. EPO eases back from its early peak over the following days, but the extra red cells keep coming for weeks. Her red cell count, hematocrit and hemoglobin climb, and the cost is thicker blood.

• Reticulocyte count: up. EPO makes more erythroid precursors survive and mature, so more young red cells enter the blood each day.
• Red blood cell count: up. Weeks of faster production add more red cells than are destroyed.
• Hematocrit: up. The red cell volume has grown, so red cells are a larger share of the blood's volume.
• Hemoglobin per liter of blood: up. More red cells in each liter means more hemoglobin in each liter.
• Blood viscosity: up. Viscosity depends mostly on the hematocrit, which has risen.

Macrophages break down old red cells, split off the iron and open the heme ring into biliverdin, then bilirubin. Poorly soluble bilirubin rides on albumin to the liver, which conjugates it and secretes it in bile. In the intestine, bacteria later turn it into urobilinogen and then brown stercobilin.

• Correct order: 1. A macrophage in the spleen engulfs an old red cell 2. Heme is split from globin, and its iron is removed 3. The ring is opened to form green biliverdin 4. Biliverdin is converted to yellow bilirubin 5. Bilirubin travels in the plasma bound to albumin 6. Liver cells conjugate bilirubin and secrete it in bile

Each heavy period removes iron in the lost red cells. Over months her stores run out, which a low plasma ferritin shows. Without iron, erythroblasts cannot fill with hemoglobin, so the cells come out small and pale.

• Too little vitamin B12 in the diet: A lack of B12 stalls DNA synthesis, so red cells come out large, not small, and ferritin is normal.
• Failing kidneys: Kidney failure lowers EPO, but the cells it produces are normal in size and iron stores are normal.
• Correct: Iron deficiency from blood loss: Correct. Small, pale cells with empty iron stores point to iron deficiency.
• Early destruction of red cells: Early destruction raises the reticulocyte count and the bilirubin, and the body keeps the recovered iron, so ferritin would not be low.

A high reticulocyte count shows a healthy marrow working hard, so the red cells are being lost, not underproduced. Jaundice shows that heme is being broken down faster than the liver can clear bilirubin. Together they point to hemolysis, early destruction of red cells.

• Aplastic anemia: In aplastic anemia the marrow has failed, so the reticulocyte count is very low.
• Correct: Early destruction of red cells: Correct. Fast destruction explains both the jaundice and the busy marrow.
• Iron-deficiency anemia: Without iron, the marrow cannot respond, so reticulocytes stay low and ferritin is low.
• Anemia of long-standing kidney failure: With too little EPO, the marrow is not driven to respond, so reticulocytes stay low, and there is no extra bilirubin.

Pale feces mean no bilirubin is reaching the intestine to become brown stercobilin. Dark urine means conjugated bilirubin, the water-soluble kind, is backing up into the blood and spilling into the urine. Both fit a blockage after the liver, such as a gallstone.

• Red cells are breaking down too fast: Fast breakdown raises mostly unconjugated bilirubin, which cannot enter urine, and more pigment reaches the gut, not less. Feces would not be pale.
• Her liver cells cannot take up bilirubin: If the liver could not take up bilirubin, the excess would be unconjugated, which does not darken urine.
• Correct: Bile cannot drain from the liver into the intestine: Correct. A blocked outflow sends conjugated bilirubin back into the blood.
• Her kidneys are excreting too little urobilin: Urobilin is a small share of pigment and does not cause jaundice. Less of it would make urine paler, not darker.

HbS forms fibers when it has given up its oxygen, and it does so faster the more concentrated it is. Low oxygen makes more HbS unload; dehydration shrinks the cell and concentrates the HbS. Stiff sickled cells then jam small vessels.

• Both raise erythropoietin and so the number of new sickle cells: New red cells take days to make, and a crisis starts within hours. Fiber formation, not new cells, is the trigger.
• Both make the spleen release stored sickle cells: The spleen does not store and release sickle cells. It is damaged by them.
• Both make hemoglobin S bind oxygen too tightly: The problem is the opposite: sickling happens after HbS has let go of its oxygen.
• Correct: Both favor HbS fibers: less oxygen bound, or HbS packed tighter: Correct. Less oxygen bound and a more crowded cell both speed fiber formation.

A wound loses whole blood, cells and plasma in the same proportion, so the hematocrit is unchanged at first. Over the next hours, fluid moves into the blood from the tissues and dilutes the remaining cells, and the hematocrit falls. A normal early hematocrit does not rule out a large bleed.

• He cannot have lost much blood, or his hematocrit would be low: The hematocrit is a ratio; it cannot show a loss of volume in the first minutes.
• His marrow has already replaced the lost red cells: Making red cells takes days, and reticulocytes rise only after 3–5 days.
• The test is wrong: bleeding lowers the hematocrit at once: The value is expected. The fall comes later, as plasma is refilled.
• Correct: He lost cells and plasma together, so the ratio has not changed yet: Correct. The ratio falls only once fluid moves in to refill the plasma.