Sign in

Blood

Usually weeks 8-9 of a medical physiology course

Blood is the unit where physiology turns into lab values. Every concept here has a number attached — hematocrit, MCV, ferritin, bilirubin, PT, aPTT, D-dimer — and exam questions hand you those numbers and ask which step failed. Organize the unit as three pipelines: making red cells (EPO, iron, B12 and folate), destroying them (macrophages, heme to bilirubin), and stopping bleeding (platelet plug, then the fibrin mesh, then the brakes and the clean-up). Finish with blood groups, because transfusion reactions and hemolytic disease of the newborn are simply antibodies meeting the wrong antigen.

On the PANCE this unit feeds:Hematology · 5%Cardiovascular · 11%

This guide is the frame. The exams are written from your lectures— drop this unit's slides on the dashboard to get flashcards and board-style questions from your own course, and quiz them all semester (a course whose exams re-test earlier units rewards nothing more than early, repeated self-testing). The physiology playbook has the weekly loop.

Drop a lecture

Free30 study kits/mo · 1 diagram deck · 1 board-graded quiz · 2 tutor Qs/wk

Pro $20/mono monthly cap (5 kits/day) · 10 diagram decks · See plans →

Lectures you file for this course live under Physiology → My Lectures in your library — pick it from the Module box as you upload, or from any card's Move menu afterwards.

AI-authored study notes, not faculty-reviewed and not medical advice. Verify every mechanism against your course materials and faculty; programs differ in emphasis.

High-Yield Pearl

Read every blood lab as a pipeline question — is the problem making cells, destroying them, or stopping the bleeding — and the MCV, reticulocyte count, and PT/aPTT pair will tell you which step broke.

What the exam asks
Mechanisms, curves, and what happens when each one fails.
  • Plasma, serum, plasma proteins, and hematocrit. Blood is roughly 55% plasma and 45% cells. PLASMA is the fluid of unclotted (anticoagulated) blood and still contains fibrinogen and the clotting factors; SERUM is what remains after blood clots — plasma minus fibrinogen and the factors consumed in clotting. Plasma proteins are made mostly by the liver: ALBUMIN (the most abundant, roughly 55–60% of the total) carries bilirubin, fatty acids, hormones, and drugs, and supplies most of the plasma ONCOTIC pressure (about 25 mmHg) that holds fluid in the capillaries; low albumin (liver failure, nephrotic syndrome, malnutrition) causes edema. Globulins include transport proteins and immunoglobulins; fibrinogen is the clot's substrate. The HEMATOCRIT is the fraction of blood volume occupied by red cells — about 45% in adult men and 40% in women (androgens stimulate erythropoiesis). It falls with anemia or hemodilution and rises with polycythemia or with plasma volume loss (dehydration gives a relative rise with no extra red cells). The mature RBC itself is an anucleate disc without mitochondria that runs on glycolysis alone and relies on the G6PD-driven shunt for antioxidant NADPH.
  • Erythropoiesis and erythropoietin. Red cells arise in the red marrow (in adults, the axial skeleton and proximal long bones) from stem cells through erythroid progenitors, normoblasts that extrude their nucleus, and RETICULOCYTES that still carry ribosomal RNA and circulate about a day before maturing. The driver is ERYTHROPOIETIN, made mainly by peritubular interstitial fibroblasts of the renal cortex. The kidney senses tissue O2 delivery, not PaO2 alone: when O2 falls (anemia, altitude, lung disease, low renal blood flow), the transcription factor HIF escapes its O2-dependent destruction and switches on the EPO gene. EPO prevents apoptosis of erythroid progenitors, so output rises over days and the reticulocyte count climbs. Chronic kidney disease removes the source — a normocytic anemia with an inappropriately low EPO — while a hypoxic stimulus or an EPO-secreting tumor causes secondary polycythemia.
  • Hemoglobin structure and oxygen content. Adult hemoglobin (HbA) is a tetramer of two alpha and two beta globins, each carrying one heme whose ferrous (Fe2+) iron binds one O2 — four O2 per molecule, with cooperative binding that makes the dissociation curve sigmoid. Fetal hemoglobin (alpha2-gamma2) binds 2,3-BPG poorly and so holds O2 more tightly, pulling it across the placenta. Arterial O2 CONTENT ≈ 1.34 × Hb (g/dL) × SaO2 + 0.003 × PaO2 — about 20 mL O2/dL normally, almost all of it bound to hemoglobin. Anemia lowers content with a normal PaO2 and saturation. Carbon monoxide binds heme with roughly 200 times the affinity of O2, taking sites out of service AND shifting the curve left so the remaining O2 is released poorly. Oxidized (Fe3+) methemoglobin cannot carry O2 at all.
  • Iron — absorption, transport, storage, and hepcidin. Dietary iron is absorbed in the DUODENUM: nonheme iron is reduced to Fe2+ and taken up by DMT1, and heme iron is absorbed separately. The enterocyte either keeps iron as FERRITIN (lost when the cell sheds) or exports it through FERROPORTIN, the only cellular iron exporter, after which it is oxidized and loaded onto TRANSFERRIN for plasma transport to the marrow, which takes it up by transferrin-receptor endocytosis. Stores sit as ferritin (and hemosiderin) in macrophages and hepatocytes; serum ferritin tracks those stores but also rises as an acute-phase reactant. There is no regulated excretion route, so the body controls iron at the entry: the liver hormone HEPCIDIN binds ferroportin and causes its degradation, trapping iron in enterocytes and macrophages. Hepcidin rises with iron overload and inflammation (IL-6) and falls with iron deficiency, hypoxia, and increased erythropoiesis.
  • Red cell lifespan and heme breakdown. An RBC lives about 120 days. Aged cells are removed mainly by splenic macrophages (extravascular hemolysis). Globin is recycled as amino acids and iron returns to transferrin; heme is opened by HEME OXYGENASE to biliverdin (releasing CO) and reduced to UNCONJUGATED bilirubin, which is lipid-soluble, travels bound to albumin, and cannot enter urine. The liver takes it up and conjugates it with glucuronic acid (UDP-glucuronosyltransferase), making water-soluble CONJUGATED bilirubin that is secreted into bile. Gut bacteria convert it to urobilinogen, most of which becomes stercobilin (brown stool); a fraction is reabsorbed and some is excreted in urine as urobilin. Hemolysis raises unconjugated bilirubin, LDH, and the reticulocyte count and lowers haptoglobin; INTRAVASCULAR hemolysis also releases free hemoglobin into plasma and urine.
  • Vitamin B12 and folate. Both are needed for DNA synthesis (thymidine), so deficiency of either produces MEGALOBLASTIC anemia — large red cells (high MCV), hypersegmented neutrophils, and ineffective erythropoiesis. B12 is freed from food by acid and pepsin, carried by haptocorrin, released in the duodenum by pancreatic proteases, bound to INTRINSIC FACTOR from gastric parietal cells, and absorbed in the TERMINAL ILEUM; liver stores last years. Folate is absorbed in the jejunum and stores last only months, so dietary deficiency appears quickly (alcohol use, pregnancy). Both deficiencies raise homocysteine; only B12 deficiency raises METHYLMALONIC ACID, because B12 is also a cofactor for methylmalonyl-CoA mutase. B12 deficiency can damage the dorsal columns and corticospinal tracts; giving folate alone can correct the anemia while the neurologic injury progresses.
  • Red cell indices and anemia classification. Anemia is a low hemoglobin or hematocrit; the first sorting step is the MEAN CORPUSCULAR VOLUME. MICROCYTIC (MCV below about 80 fL) means a hemoglobin-synthesis problem: iron deficiency, thalassemia, anemia of chronic disease (sometimes), sideroblastic anemia, or lead. MACROCYTIC (above about 100 fL): megaloblastic from B12 or folate deficiency, or non-megaloblastic from alcohol, liver disease, or hypothyroidism. NORMOCYTIC: sort by the RETICULOCYTE count — high means the marrow is responding to loss or hemolysis; low means underproduction (chronic kidney disease, early iron deficiency, anemia of chronic disease, marrow failure). The iron panel then separates iron deficiency (low ferritin, high TIBC/transferrin, low saturation) from anemia of chronic disease (low serum iron, low or normal TIBC, normal or high ferritin — hepcidin is hiding the iron). MCH and MCHC report hemoglobin per cell; RDW rises when cell sizes vary.
  • Leukocytes in brief. Granulocytes: NEUTROPHILS (the most abundant white cells, roughly half to two-thirds, first to arrive in acute bacterial inflammation, circulating only hours), EOSINOPHILS (parasites and allergy), and BASOPHILS (histamine, least common). Agranulocytes: LYMPHOCYTES (B, T, and NK cells of adaptive and innate immunity) and MONOCYTES, which leave the blood to become tissue macrophages. A 'left shift' is an increase in immature band neutrophils during acute infection. Colony-stimulating factors (G-CSF, GM-CSF) drive myeloid production, and a leukocyte count must be read with its differential.
  • Platelets and primary hemostasis. Platelets are anucleate fragments of marrow MEGAKARYOCYTES, produced under THROMBOPOIETIN (made mainly by the liver), living about 7–10 days, with about a third pooled in the spleen. Injury triggers vasoconstriction, then the platelet plug. ADHESION: von Willebrand factor (from endothelial Weibel-Palade bodies and platelet alpha granules) binds exposed subendothelial COLLAGEN and grabs platelet GPIb. ACTIVATION: platelets change shape and release dense-granule ADP (acting on P2Y12) and Ca2+ and make THROMBOXANE A2 through COX-1; both recruit more platelets, and TXA2 also constricts. AGGREGATION: activated GPIIb/IIIa binds FIBRINOGEN, which bridges platelet to platelet. Intact endothelium keeps the plug local by releasing prostacyclin (PGI2) and nitric oxide. Aspirin irreversibly blocks COX-1, clopidogrel blocks P2Y12, and GPIIb/IIIa inhibitors block the final common step.
  • Coagulation, its brakes, and fibrinolysis. The cascade builds a fibrin mesh on the platelet plug. EXTRINSIC: tissue factor on subendothelial cells binds factor VIIa and activates X (and IX) — the physiologic trigger. INTRINSIC: XII → XI → IX, and IXa with its cofactor VIIIa activates X. COMMON: Xa with cofactor Va (prothrombinase) converts prothrombin (II) to THROMBIN, which cleaves fibrinogen to fibrin, activates XIII to crosslink it, and feeds back to activate V, VIII, XI, and platelets. The reactions need Ca2+ and phospholipid surfaces. Factors II, VII, IX, X and proteins C and S require vitamin K–dependent gamma-carboxylation. BRAKES: antithrombin inactivates thrombin and Xa (heparin accelerates it); thrombin bound to endothelial thrombomodulin activates PROTEIN C, which with PROTEIN S cleaves Va and VIIIa; TFPI shuts off the TF–VIIa start. CLEAN-UP: tissue plasminogen activator converts plasminogen to PLASMIN on fibrin, releasing fibrin degradation products, including D-DIMER from crosslinked fibrin.
  • Blood groups, transfusion reactions, and hemolytic disease of the newborn. ABO antigens are carbohydrates on red cells; people form naturally occurring IgM antibodies against the antigens they lack (group A has anti-B; group O has both anti-A and anti-B). Group O red cells can go to anyone; group AB patients can receive any ABO type of red cells, and AB plasma can go to anyone. The Rh(D) antigen is a protein, and anti-D appears only after exposure (transfusion or pregnancy) and is IgG. An ABO-incompatible transfusion causes an ACUTE hemolytic reaction within minutes: complement-mediated intravascular hemolysis, fever, flank pain, hypotension, hemoglobinuria, and possibly DIC. HEMOLYTIC DISEASE OF THE NEWBORN occurs when maternal IgG crosses the placenta: an Rh-negative mother sensitized by a first Rh-positive fetus makes anti-D that attacks the next Rh-positive fetus (anemia, hyperbilirubinemia, hydrops). Anti-D immune globulin given during pregnancy and after delivery prevents sensitization. ABO disease (usually a group O mother) can occur in a first pregnancy and is usually mild.
Worth drilling · 40 concepts
Each with the one fact that identifies it. Your course's slides are the authority; use this to check your list against.
  1. 1Plasma — the fluid of unclotted blood, fibrinogen and clotting factors included
  2. 2Serum — plasma minus fibrinogen and the clotting factors consumed by clotting
  3. 3Albumin — most abundant plasma protein; main source of plasma oncotic pressure
  4. 4Hematocrit — percentage of blood volume occupied by red cells
  5. 5Erythropoietin — renal peritubular fibroblast hormone released when kidney O2 delivery falls
  6. 6Reticulocyte — young RBC with residual RNA; its count measures marrow response
  7. 7Fetal hemoglobin — alpha2-gamma2; binds 2,3-BPG poorly, so higher O2 affinity
  8. 8Ferritin — intracellular iron store; serum level tracks body iron and rises with inflammation
  9. 9Transferrin — plasma iron carrier; TIBC rises when iron is scarce
  10. 10Ferroportin — the only cellular iron exporter, on enterocytes and macrophages
  11. 11Hepcidin — liver hormone that degrades ferroportin; raised by inflammation
  12. 12Unconjugated bilirubin — albumin-bound, lipid-soluble heme product that never enters urine
  13. 13Bilirubin glucuronide — conjugated, water-soluble form the liver secretes into bile
  14. 14Haptoglobin — plasma protein that binds free hemoglobin; falls in hemolysis
  15. 15Intrinsic factor — parietal-cell protein required for B12 absorption in the terminal ileum
  16. 16Methylmalonic acid — rises in B12 deficiency but not in folate deficiency
  17. 17Folate — jejunal absorption, stores last only months; deficiency is megaloblastic
  18. 18Megaloblastic anemia — macrocytosis with hypersegmented neutrophils from impaired DNA synthesis
  19. 19Microcytosis — MCV below about 80 fL; a hemoglobin-synthesis defect such as iron deficiency
  20. 20Anemia of chronic disease — hepcidin traps iron: low serum iron, low TIBC, normal or high ferritin
  21. 21Neutrophil — most abundant leukocyte; first phagocyte in acute bacterial inflammation
  22. 22von Willebrand factor — bridges exposed collagen to platelet GPIb and carries factor VIII
  23. 23Glycoprotein Ib — platelet adhesion receptor for vWF; absent in Bernard-Soulier syndrome
  24. 24Fibrinogen receptor (GPIIb/IIIa) — activated integrin that aggregates platelets; absent in Glanzmann
  25. 25Thromboxane A2 — COX-1 platelet product that aggregates and constricts; aspirin blocks it
  26. 26P2Y12 receptor — platelet ADP receptor blocked by clopidogrel
  27. 27Tissue factor — subendothelial protein that binds factor VIIa to start clotting
  28. 28Prothrombin time — tests extrinsic and common factors (VII, X, V, II, fibrinogen); tracks warfarin
  29. 29Activated partial thromboplastin time — tests intrinsic and common factors; monitors unfractionated heparin
  30. 30Vitamin K–dependent factors — II, VII, IX, X plus proteins C and S; need gamma-carboxylation
  31. 31Factor XIII — thrombin-activated transglutaminase that crosslinks fibrin
  32. 32Antithrombin — inactivates thrombin and factor Xa; heparin accelerates it
  33. 33Activated protein C — made by thrombin-thrombomodulin; with protein S cleaves Va and VIIIa
  34. 34Tissue factor pathway inhibitor — shuts down the TF–VIIa–Xa starting complex
  35. 35Tissue plasminogen activator — endothelial enzyme converting plasminogen to plasmin on fibrin
  36. 36D-dimer — breakdown product of crosslinked fibrin; a sensitive rule-out for thrombosis
  37. 37Universal red cell donor — group O: no A or B antigen on the cells
  38. 38Rh D antigen — protein antigen; anti-D is IgG and forms only after exposure
  39. 39Acute hemolytic transfusion reaction — ABO mismatch: preformed IgM, complement, intravascular hemolysis
  40. 40Hemolytic disease of the newborn — maternal IgG crosses the placenta against fetal red cells
Practice it
Active recall over the drill list — flip and claim, match the pairs, produce the answers cold, fill in the diagram, or read the curves like the exam does.

Every concept on the drill list, one card at a time — the name up front, the fact that identifies it on the flip. Claim each card honestly and the deck learns what to lead with next time. Progress lives in this browser only.

What everyone misses
The distinctions that lose points on this material, year after year.
  • Plasma is not serum. Serum has no fibrinogen and lacks the factors consumed in clotting; plasma keeps them because an anticoagulant (citrate, EDTA, heparin) stopped the clot. A question asking which fluid you would use to measure clotting factors or fibrinogen wants plasma — citrated plasma for the PT and aPTT, since citrate binds the Ca2+ the cascade needs and the lab adds it back.
  • Anemia leaves PaO2 and saturation normal. Hemoglobin concentration does not appear in PaO2 or SaO2. A patient with a hemoglobin of 7 g/dL has a normal PaO2, a normal pulse oximetry reading, and about half the normal O2 content. Carbon monoxide is the trap twist: PaO2 is normal and a standard pulse oximeter reads falsely high, because it cannot tell carboxyhemoglobin from oxyhemoglobin.
  • Ferritin is an acute-phase reactant. A low ferritin essentially proves iron deficiency, but a normal or high ferritin does not exclude it in an inflamed patient. That is why anemia of chronic disease and iron deficiency are separated with the whole panel — TIBC is high in iron deficiency and low or normal in chronic disease — and why the two can coexist.
  • Folate fixes the blood, not the nerves. Giving folate to a B12-deficient patient can correct the megaloblastic anemia while the demyelination progresses. Check B12 (and methylmalonic acid, which rises only with B12 deficiency) before treating a macrocytic anemia with folate alone.
  • PT and aPTT test different arms. PT = extrinsic plus common (VII is the unique factor); aPTT = intrinsic plus common (XII, XI, IX, VIII). Hemophilia A and B prolong the aPTT only. Warfarin prolongs the PT first because factor VII has the shortest half-life. Neither test measures platelets — a platelet disorder or von Willebrand disease shows mucocutaneous bleeding with a normal PT.
  • Rh disease needs a prior exposure; ABO disease does not. Anti-D is not naturally occurring, so Rh hemolytic disease usually spares the first pregnancy and strikes the next Rh-positive fetus after sensitization. Anti-A and anti-B are mostly IgM and cannot cross the placenta, but group O mothers make some IgG anti-A/anti-B, so ABO disease can affect a first baby — usually mildly.
Clinical correlations
Where this unit shows up again — in clinic, on rotations, and on the boards.
  • Iron deficiency anemia. The most common anemia worldwide: fatigue, pica, spoon nails, and a microcytic, hypochromic smear with a high RDW. Labs: low ferritin, low serum iron, high TIBC, low transferrin saturation. In an adult man or a postmenopausal woman, iron deficiency means blood loss until proven otherwise — usually the GI tract — so the workup looks for the source, not just the deficit.
  • Pernicious anemia. Autoimmune destruction of parietal cells (with antibodies to intrinsic factor) stops B12 absorption. Macrocytic anemia, hypersegmented neutrophils, glossitis, and possibly subacute combined degeneration — loss of vibration and position sense with spasticity. Methylmalonic acid and homocysteine are both high. Because oral absorption depends on intrinsic factor, replacement is traditionally parenteral (high-dose oral B12 also works through passive absorption).
  • Anemia of chronic kidney disease. Failing kidneys make too little erythropoietin, producing a normocytic, hypoproliferative anemia with a low reticulocyte count. Treatment is an erythropoiesis-stimulating agent plus enough iron to use it. The same physiology explains EPO misuse in endurance sport: a higher hematocrit raises O2 content, and raises viscosity and thrombosis risk with it.
  • Hemolytic anemia and jaundice. Rapid red cell destruction produces anemia with reticulocytosis, high LDH, low haptoglobin, and unconjugated hyperbilirubinemia; pigment gallstones follow chronic hemolysis. Hereditary spherocytosis and warm autoimmune hemolytic anemia (positive direct Coombs test) destroy cells in the spleen; G6PD deficiency (Heinz bodies, bite cells after an oxidant drug or fava beans) and mismatched transfusion are the classic intravascular settings.
  • Hemophilia vs von Willebrand disease. Hemophilia A (factor VIII) and B (factor IX) are X-linked: deep bleeding into joints and muscles, prolonged aPTT, normal PT and platelet count. Von Willebrand disease, the most common inherited bleeding disorder, is usually autosomal dominant: mucosal bleeding (nosebleeds, heavy menses), abnormal platelet function testing, and sometimes a prolonged aPTT because vWF protects factor VIII. Desmopressin releases stored vWF and helps mild forms of both vWD and hemophilia A.
  • Disseminated intravascular coagulation. Sepsis, trauma, obstetric catastrophe, or malignancy floods the circulation with tissue factor; clotting runs everywhere, consuming platelets and factors, while fibrinolysis runs behind it. The result is thrombosis and bleeding together: low platelets, prolonged PT and aPTT, low fibrinogen, high D-dimer, and schistocytes on the smear. Treat the cause and replace what is consumed.
  • Warfarin, heparin, and their reversal. Warfarin blocks vitamin K epoxide reductase, so newly made II, VII, IX, and X lack gamma-carboxylation; it is monitored with the PT/INR and reversed with vitamin K plus prothrombin complex concentrate. Because protein C also falls fast, early warfarin can be briefly procoagulant — the basis of warfarin skin necrosis and of bridging with heparin. Unfractionated heparin boosts antithrombin, is monitored with the aPTT (or anti-Xa level), and is reversed with protamine; heparin can also trigger immune thrombocytopenia with paradoxical thrombosis.

Frequently asked

← Endocrine PhysiologyCardiovascular Physiology →