For education and revision only. Not individual medical advice; check current NICE/BNF and local guidance before clinical use. Clinical safety and terms.
Histology: Muscle, nervous tissue, blood and the lymphoid organs
🔬 Muscle, nervous tissue, blood and the lymphoid organs. The remaining basic tissues - muscle and nervous tissue - and the cells of blood and the immune organs explain conditions as varied as muscular dystrophy, myasthenia gravis, demyelination, peripheral neuropathy, leukaemia, lymphoma and asplenia. Recognising blood cells on a film and understanding the microanatomy of lymph nodes, spleen and thymus are also essential for interpreting haematology and pathology reports. Your four questions: Which muscle type (striated or not, central or peripheral nuclei, branching, intercalated discs)? Which part of the neuron or its support cells is affected? Which blood cell type predominates and is it mature? Which compartment of the lymphoid organ (B-cell follicle, T-cell paracortex, red pulp, white pulp)?
Skeletal Muscle
Long, cylindrical, multinucleated fibres (syncytium formed by fusion of myoblasts) with peripheral nuclei and cross-striations (sarcomeres).
Sarcomere (Z-line to Z-line): A band (myosin thick filaments - dark, stays constant), I band (actin thin filaments only - light; shortens during contraction), H zone (myosin only - shortens), M line. Titin anchors myosin; dystrophin links the cytoskeleton to the sarcolemma and extracellular matrix (dystrophin-glycoprotein complex).
Excitation–contraction coupling: action potential travels down T-tubules → dihydropyridine receptor → ryanodine receptor (RYR1) on the sarcoplasmic reticulum releases Ca²⁺ → Ca²⁺ binds troponin C → tropomyosin moves → myosin binds actin → cross-bridge cycling (ATP needed for detachment - rigor mortis when ATP is depleted). The triad = T-tubule plus two terminal cisternae.
Fibre types:type I (slow-twitch, oxidative, red - myoglobin, many mitochondria - posture, endurance) and type II (fast-twitch, glycolytic, white - sprint, power). Steroid myopathy preferentially atrophies type II fibres.
Striated, branched cells with one or two central nuclei, joined end-to-end by intercalated discs (desmosomes and fascia adherens for mechanical coupling; gap junctions for electrical coupling - functional syncytium).
Abundant mitochondria (about a third of cell volume - aerobic metabolism) and myoglobin; T-tubules at Z-lines (dyads rather than triads); calcium-induced calcium release (RYR2).
Limited regenerative capacity - injury heals by fibrous scar (MI); hypertrophy in response to pressure or volume load.
Specialised conducting tissue - SA node, AV node, bundle of His, Purkinje fibres (large pale cells, few myofibrils, much glycogen - fast conduction).
Atrial myocytes contain granules of atrial natriuretic peptide; ventricular myocytes release BNP when stretched.
Pathology:contraction band necrosis (reperfusion), myocyte disarray (hypertrophic cardiomyopathy - sarcomere protein mutations, e.g. MYH7, MYBPC3), fibrofatty replacement of the right ventricle (arrhythmogenic cardiomyopathy - desmosomal protein mutations), amyloid deposition, lymphocytic myocarditis (viral, checkpoint inhibitors), giant cell myocarditis, Aschoff bodies (rheumatic fever).
Spindle-shaped cells with a single central cigar-shaped nucleus, no striations (actin and myosin not arranged in sarcomeres; attached to dense bodies); gap junctions in visceral (single-unit) smooth muscle.
Locations: walls of hollow organs (gut - inner circular and outer longitudinal layers of the muscularis propria; bladder - detrusor; uterus - myometrium), blood vessels (tunica media), airways, iris, arrector pili.
Contraction - Ca²⁺ binds calmodulin → activates myosin light-chain kinase; slow, sustained, energy-efficient (latch state); regulated by autonomic nerves, hormones (oxytocin), local factors (NO, endothelin) and stretch.
Can divide (hyperplasia - uterus in pregnancy, airway remodelling in asthma, intimal hyperplasia in atheroma and restenosis).
Tumours - leiomyoma (uterine fibroids - commonest tumour in women) and leiomyosarcoma; GIST arises from interstitial cells of Cajal (gut pacemaker cells, KIT/CD117-positive), not smooth muscle.
Enteric neurons, not smooth muscle, coordinate gut motility - Hirschsprung disease is absence of ganglion cells (myenteric and submucosal plexuses) in the distal bowel, diagnosed by rectal suction biopsy (acetylcholinesterase staining, calretinin loss); achalasia is loss of myenteric ganglion cells in the oesophagus.
Neuron structure: cell body (soma - large nucleus with prominent nucleolus; Nissl substance = rough ER, basophilic), dendrites (receive input), axon (arises from the axon hillock - initial segment where action potentials begin), axon terminals.
Axonal transport - anterograde (kinesin) and retrograde (dynein); retrograde transport carries tetanus toxin, rabies, herpes viruses and polio to the CNS.
Synapses - chemical (neurotransmitter vesicles, synaptic cleft about 20 nm, postsynaptic receptors) and electrical (gap junctions).
Responses to injury:red neurons (acute ischaemic injury - shrunken, eosinophilic cytoplasm, pyknotic nucleus - 12–24 hours after hypoxia), chromatolysis (cell body swelling and dispersal of Nissl substance after axonal injury), Wallerian degeneration (degeneration of the axon distal to a cut).
Inclusions in neurodegenerative disease:neurofibrillary tangles (hyperphosphorylated tau) and amyloid plaques (Aβ) in Alzheimer's disease; Lewy bodies (α-synuclein) in Parkinson's disease and dementia with Lewy bodies; Pick bodies (tau) in frontotemporal dementia; TDP-43 inclusions in motor neuron disease and FTD; Negri bodies in rabies; spongiform change in prion disease.
Selective vulnerability to hypoxia - hippocampal CA1 pyramidal cells, cerebellar Purkinje cells, neocortical layers 3, 5 and 6 (laminar necrosis).
Reactive (infection, iron deficiency, bleeding, post-splenectomy), essential thrombocythaemia
Red cell lifespan about 120 days (removed by splenic macrophages); reticulocytes (polychromatic cells) indicate marrow response - raised in haemolysis and bleeding.
Blood film abnormalities:
Finding
Cause
Target cells
Liver disease, haemoglobinopathies (thalassaemia, HbC), hyposplenism, iron deficiency
Sites of haematopoiesis: yolk sac (weeks 3–8) → liver and spleen (fetal months 2–7) → bone marrow (from month 5 onwards; the only site after birth). In adults red marrow is limited to the axial skeleton (vertebrae, pelvis, sternum, ribs, skull) and proximal femur and humerus. Extramedullary haematopoiesis returns in myelofibrosis and severe haemolysis (thalassaemia - hepatosplenomegaly, bone expansion).
Haematopoietic stem cells (CD34+) → common myeloid progenitor (red cells, platelets via megakaryocytes, granulocytes, monocytes) and common lymphoid progenitor (B, T, NK cells).
Growth factors:erythropoietin (kidney - anaemia of CKD), G-CSF (neutrophils - used after chemotherapy and for stem cell mobilisation), thrombopoietin (liver - TPO receptor agonists romiplostim and eltrombopag in ITP), IL-3, GM-CSF.
Marrow cellularity about 100 − age (%) (fat replaces haematopoietic tissue with age); myeloid:erythroid ratio about 3:1.
Bone marrow examination - aspirate (cell morphology, iron stores - Perls', flow cytometry, cytogenetics) and trephine (cellularity, architecture, fibrosis, infiltration - "dry tap" in myelofibrosis and some leukaemias); usually from the posterior iliac crest.
Megakaryocytes - very large multilobed cells producing platelets; increased in ITP (peripheral destruction) and ET; abnormal in myelodysplasia.
Structure: capsule → subcapsular sinus → cortex (B-cell follicles - primary follicles; secondary follicles with germinal centres after antigen exposure - centroblasts and centrocytes, tingible body macrophages, follicular dendritic cells; mantle zone) → paracortex (T cells, high endothelial venules where lymphocytes enter from blood) → medulla (medullary cords with plasma cells and macrophages; medullary sinuses) → efferent lymphatic at the hilum.
Lymph flow - afferent lymphatics → sinuses (antigen sampling by macrophages and dendritic cells) → efferent.
Reactive patterns:follicular hyperplasia (B-cell response - rheumatoid arthritis, early HIV, toxoplasmosis, syphilis), paracortical hyperplasia (T-cell response - viral infections such as EBV, drug reactions, dermatopathic lymphadenopathy), sinus histiocytosis (draining a tumour or inflammation), granulomas (TB, sarcoid, cat scratch disease - stellate microabscesses), necrotising (Kikuchi disease).
Neoplasia:Hodgkin lymphoma (Reed–Sternberg cells - "owl-eye" binucleate, CD15+ CD30+, in a background of reactive cells), non-Hodgkin lymphomas (follicular - neoplastic follicles, BCL-2+; diffuse large B-cell - sheets of large cells; Burkitt - starry sky, Ki-67 ~100%; mantle cell - cyclin D1+), metastatic carcinoma (in sinuses first; sentinel node).
Who needs a node biopsy? - persistent (>6 weeks) unexplained lymphadenopathy, nodes >2 cm, hard, fixed or supraclavicular, with B symptoms or splenomegaly (NICE NG12 - urgent referral criteria). Excision biopsy (whole node, fresh) is preferred for suspected lymphoma; FNA is inadequate.
White pulp - lymphoid tissue: periarteriolar lymphoid sheaths (PALS - T cells) around central arterioles, and B-cell follicles with a marginal zone (B cells responding to polysaccharide antigens - the reason asplenic patients are vulnerable to encapsulated bacteria).
Red pulp - splenic cords (of Billroth) and venous sinusoids; filters blood, removing old, damaged or antibody-coated red cells (spherocytes, sickle cells, autoimmune haemolysis, ITP platelets) and inclusions ("pitting" of Howell–Jolly bodies, Heinz bodies, malaria parasites); stores platelets (about a third) and monocytes.
Thymus - in the anterior superior mediastinum; large in childhood, involutes after puberty (replaced by fat). Cortex (dense immature thymocytes - positive selection for MHC recognition) and medulla (paler - negative selection of self-reactive T cells by AIRE-expressing epithelial cells; Hassall's corpuscles). AIRE mutation → autoimmune polyendocrine syndrome type 1 (hypoparathyroidism, Addison's, mucocutaneous candidiasis). DiGeorge syndrome - thymic aplasia. Thymoma - associated with myasthenia gravis, red cell aplasia and hypogammaglobulinaemia (Good's syndrome); thymic hyperplasia in myasthenia (thymectomy helps).
MALT (mucosa-associated lymphoid tissue) - Peyer's patches (terminal ileum - M cells sample antigens; lead point for intussusception in children), tonsils and adenoids (Waldeyer's ring), appendix, bronchus-associated lymphoid tissue; IgA production. MALT lymphoma (marginal zone lymphoma) of the stomach is driven by H. pylori and may regress after eradication.
Scenario. A man cannot extend his wrist after falling asleep with his arm over a chair. Nerve conduction studies at 3 weeks show conduction block at the spiral groove with preserved distal amplitudes. What is the prognosis?
Answer: Radial nerve neurapraxia (focal demyelination without axonal loss) - full recovery is expected over weeks to a few months. A wrist splint maintains function meanwhile. Reduced distal amplitudes would indicate axonal loss (axonotmesis) with slower recovery.
Scenario. Why does a patient after splenectomy need vaccines and antibiotic prophylaxis, and what is seen on the blood film?
Answer: Loss of splenic marginal zone B cells (IgM responses to polysaccharide capsules) and filtering function → risk of overwhelming infection with pneumococcus, Hib and meningococcus. Vaccinate (pneumococcal, Hib/MenC, MenACWY, MenB, annual influenza), give prophylactic antibiotics, and a standby course and alert card. Film shows Howell–Jolly bodies, target cells and raised platelets.
Scenario. A patient with multiple sclerosis asks why the brain cannot repair itself like a cut nerve in the arm.
Answer: CNS myelin is made by oligodendrocytes, each myelinating many axons; after injury, astrocytic scar and inhibitory myelin proteins prevent axon regrowth and remyelination is limited. In the PNS, Schwann cells and the endoneurial tube guide regenerating axons and remyelinate them.