Blood

Values

Haematocrit (Hct) is the percentage of blood volume occupied by RBCs.

When blood is centrifuged, it separates into three layers:

• Top: plasma.
• Middle: buffy coat containing leukocytes and platelets.
• Bottom: erythrocytes.

Clinical correlations

• Dehydration → plasma volume decreases → apparent haematocrit rises (haemoconcentration).
• Acute haemorrhage → both RBCs and plasma are initially lost proportionally, so haematocrit may initially remain normal.
• Chronic inflammation → fibrinogen may increase → erythrocyte sedimentation rate (ESR) rises.

Plasma, serum and plasma proteins

Plasma is approximately 92% water. Although proteins form only a small proportion, they have major effects on oncotic pressure, immunity, transport and coagulation.

Plasma versus serum

Major plasma proteins

High-yield pearl: Albumin is the major contributor to plasma colloid oncotic pressure. A reduction in plasma albumin favours movement of fluid into the interstitial space, promoting oedema.

Haematopoiesis — production of blood cells

Haematopoiesis is the continuous production of RBCs, WBCs and platelets from haematopoietic stem cells (HSCs). Because mature blood cells have limited lifespans, bone marrow must continuously replace them.

Haematopoietic stem-cell lineages

Sites of haematopoiesis by age

In adults, active red marrow is concentrated in the vertebrae, ribs, sternum, pelvis, skull and proximal long bones.

Extramedullary haematopoiesis means blood-cell production outside bone marrow. In adults, it suggests an underlying problem such as myelofibrosis or severe chronic anaemia.

Regulators of haematopoiesis

Clinical correlation: chronic kidney disease (CKD)

Renal hypoxia normally increases EPO production. In CKD, inadequate EPO production can cause a normocytic, normochromic anaemia despite otherwise functional bone marrow.

Erythropoiesis — RBC development

The main sequence is:

HSC → myeloid progenitor → erythroid progenitor → proerythroblast → erythroblasts → reticulocyte → mature erythrocyte

During maturation:

1. Haemoglobin synthesis increases.
2. The nucleus condenses and is expelled.
3. The reticulocyte enters the circulation.
4. Residual RNA disappears over approximately 1–2 days.

Reticulocyte count: the key to evaluating anaemia

Exam strategy: When assessing anaemia, first ask whether the marrow is underproducing RBCs or compensating for blood loss/haemolysis.

Bone marrow disorders

Erythrocytes (RBCs)

RBCs are specialised for oxygen and carbon dioxide transport. Their biconcave shape increases surface area, reduces diffusion distance and provides flexibility for passage through narrow capillaries and splenic sinusoids.

Structure and function

Because mature RBCs lack mitochondria, they do not consume the oxygen they transport.

Haemoglobin and myoglobin

Each heme contains ferrous iron (Fe²⁺), which binds oxygen reversibly.

Bohr effect versus Haldane effect

These are commonly confused in physiology questions.

Oxygen–haemoglobin dissociation curve

A right shift means haemoglobin has lower O₂ affinity and releases more oxygen to tissues at a given P_O2. A left shift means higher O₂ affinity and less unloading.

Carbon dioxide transport and the chloride shift

CO₂ is transported in three main forms:

• In tissues: bicarbonate leaves the RBC and chloride enters to maintain electrical neutrality — the chloride shift.
• In lungs: the process reverses; bicarbonate enters the RBC, CO₂ is regenerated and exhaled.
• Deoxygenated haemoglobin buffers H⁺, facilitating CO₂ carriage in tissues.

Special forms of haemoglobin

RBC lifecycle, bilirubin and iron metabolism

RBC lifecycle

• Average lifespan: 120 days.
• Senescent RBCs are removed mainly by macrophages in the spleen.
• Iron is recycled and returned to transferrin.
• The porphyrin ring is degraded to bilirubin.
• The liver conjugates bilirubin and excretes it into bile.

Haemolysis → increased unconjugated (indirect) bilirubin, potentially causing jaundice and pigment gallstones.

Iron transport and storage

Hepcidin is the central regulator of iron availability. Increased hepcidin reduces intestinal iron absorption and traps iron within macrophages and storage sites. This contributes to anaemia of chronic disease.

Iron absorption

• Main site: duodenum and proximal jejunum.
• Vitamin C enhances absorption.
• Tannins, phytates and calcium can reduce absorption.

Leukocytes (WBCs)

Leukocytes protect against pathogens and coordinate inflammation. Unlike RBCs, they can leave blood vessels and enter tissues.

Normal differential count

Clinical patterns in WBC counts

Leukocyte migration into tissues

The sequence is:

Rolling → firm adhesion → diapedesis → chemotaxis

Lymphocyte subtypes

High-yield HIV pearl: HIV targets CD4⁺ helper T cells. The CD4:CD8 ratio is normally around 2:1 and can fall below 1 in advanced HIV/AIDS.

• B cells differentiate into antibody-secreting plasma cells and memory B cells.
• NK cells can kill infected or malignant cells without the antigen-specific recognition required by conventional cytotoxic T cells.

Platelets

Platelets are cytoplasmic fragments of megakaryocytes, produced under the influence of thrombopoietin.

Platelet granules

Platelet receptors and drugs

Dental clinical correlations

• Ask about prolonged bleeding, easy bruising, epistaxis, menorrhagia and family history before invasive dental procedures.
• Aspirin and clopidogrel can increase post-extraction bleeding because platelet function is impaired.
• Patients with haemophilia may require factor replacement and specialist planning before invasive treatment.
• Significant thrombocytopenia may require modification of treatment and specialist advice; the appropriate platelet threshold depends on the procedure and clinical circumstances.

Haemostasis: primary and secondary

Haemostasis prevents blood loss after vessel injury while limiting clot formation to the appropriate site.

Three stages

1. Vascular spasm: vasoconstriction reduces blood loss.
2. Primary haemostasis: platelets adhere, activate and aggregate to form a temporary platelet plug.
3. Secondary haemostasis: thrombin generates fibrin, stabilising the platelet plug.

Fibrinolysis subsequently breaks down the fibrin clot as healing progresses.

Primary haemostasis — platelet plug formation

Defects in primary haemostasis typically cause immediate mucocutaneous bleeding.

Secondary haemostasis — coagulation cascade

The coagulation cascade generates thrombin (factor IIa), which converts fibrinogen into fibrin.

Simplified sequence:

• Tissue factor activates factor VII.
• Intrinsic pathway involves XII → XI → IX, with VIII as a cofactor.
• Both pathways converge at factor X.
• Xa with Va converts prothrombin (II) into thrombin (IIa).
• Thrombin converts fibrinogen (I) into fibrin.
• Factor XIII cross-links fibrin to stabilise the clot.

Thrombin is the central amplifier: it forms fibrin, activates platelets and activates factors V, VIII, XI and XIII.

Important coagulation factors

Vitamin K-dependent proteins

Vitamin K is needed for hepatic gamma-carboxylation, allowing certain clotting proteins to bind calcium and function at phospholipid surfaces.

Vitamin K-dependent factors: II, VII, IX, X, proteins C and S.

• Warfarin inhibits vitamin K epoxide reductase, reducing active vitamin K recycling.
• The liver may still produce the proteins, but under-carboxylated forms are functionally defective.
• Factor VII has a short half-life, so PT/INR usually rises first in vitamin K deficiency or during warfarin therapy.

Causes of vitamin K deficiency include fat malabsorption, biliary obstruction, prolonged antibiotic use and inadequate neonatal stores. Neonates receive vitamin K prophylaxis because their stores are low and gut flora are immature.

Coagulation tests and their interpretation

Rapid interpretation

Mixing study

• Prolonged test corrects after mixing with normal plasma → suggests a factor deficiency.
• Fails to correct → suggests an inhibitor, such as lupus anticoagulant or a specific factor inhibitor.

Natural anticoagulants

Fibrinolysis

Fibrinolysis

The fibrinolytic system removes fibrin as the clot is no longer required.

tPA → converts plasminogen to plasmin → plasmin degrades fibrin → fibrin degradation products, including D-dimer.

• Thrombolytics such as alteplase promote clot dissolution.
• Tranexamic acid inhibits fibrinolysis and can help control oral bleeding.

Dry socket (alveolar osteitis)

Dry socket typically presents with increasing pain 2–4 days after extraction, associated with partial or complete loss of the socket clot.

Mechanism

1. A fibrin clot normally protects the socket and provides a scaffold for healing.
2. Increased local fibrinolysis activates plasminogen.
3. Plasmin breaks down the fibrin clot.
4. Exposed bone and nerve endings produce severe pain.

Risk factors: smoking, oral contraceptive use, difficult extraction, mandibular molars, local inflammation and previous dry socket.

Prevention and management

• Use careful extraction technique.
• Avoid smoking and activities that dislodge the clot during early healing.
• Management commonly includes gentle irrigation and a suitable medicated dressing for symptom relief.
• Tranexamic acid is an antifibrinolytic, but it is not a universal preventive treatment for dry socket.

Blood groups — ABO system

ABO blood groups are determined by carbohydrate antigens on RBC membranes. Plasma contains antibodies against the ABO antigens that the individual lacks.

Universal donor and recipient

• O negative: universal donor for packed RBCs in emergency teaching.
• AB positive: universal recipient for packed RBCs.
• AB plasma: universal plasma donor with respect to ABO antibodies.
• Group O: universal plasma recipient with respect to ABO compatibility.

These are simplified compatibility rules; actual transfusion still requires appropriate testing and consideration of other blood-group antigens.

Blood typing and crossmatching

Agglutination during testing indicates an antigen–antibody reaction.

Rh system and haemolytic disease of the newborn

The most clinically important Rh antigen is D.

• Rh-positive individuals express the D antigen.
• Rh-negative individuals do not express D.
• Anti-D antibodies are generally formed after sensitisation rather than being naturally present.

Rh incompatibility sequence

1. An Rh-negative mother is exposed to Rh-positive fetal RBCs.
2. Maternal sensitisation leads to production of anti-D IgG.
3. In a subsequent Rh-positive pregnancy, maternal IgG crosses the placenta.
4. Fetal RBC destruction can cause haemolytic disease of the fetus and newborn, severe anaemia, hydrops fetalis or neonatal jaundice.

Prevention: Rho(D) immune globulin (RhoGAM) prevents maternal sensitisation when given at recommended times and after relevant sensitising events.

Direct versus indirect Coombs test

ABO haemolytic disease of the newborn can occur in a first pregnancy, particularly when a group O mother has relevant IgG anti-A or anti-B antibodies.

Transfusion reactions

Key distinction:

• TRALI: transfusion-related acute lung injury; pulmonary oedema is not primarily due to fluid overload.
• TACO: transfusion-associated circulatory overload; excess volume causes pulmonary congestion.

An acute haemolytic transfusion reaction is a medical emergency because it can cause shock, renal injury and DIC.