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Gross Anatomy of the Spleen

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Overview

• Shape: coffee-bean / kidney-shaped
• Size: 10-13 cm in length, 6-8 cm wide, 3-4 cm thick
• Weight: 150-200 g (range 70-250 g) in a healthy adult; decreases with age
• Colour: soft, bluish-red (fresh state)

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Embryological Development

• Day 12 embryonic: formation of the splanchnic mesodermal plate
• Week 2 of gestation: colonized by erythroid and myeloid progenitor cells
• Up to month 5 of fetal life: major hematopoietic organ (erythropoiesis and myelopoiesis)
• After birth: hematopoietic function ceases (may persist in pathological states like myelofibrosis)
• It migrates to the left upper quadrant with its smooth diaphragmatic surface facing posterosuperiorly

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Position and Relations

• Behind ribs 9-11 in the left lateral chest wall, protected by them
• Its long axis is parallel to the 10th rib
• Its posterior pole is ~2 cm from the body of T10 vertebra
• In healthy adults it is not palpable below the costal margin
• Covered by visceral peritoneum except at the hilum

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Surfaces

Visceral Surface Impressions

1. Gastric impression - largest; against the fundus and body of the stomach (anterosuperior to hilum)
2. Renal impression - posterior to hilum; against the upper pole of the left kidney
3. Colic impression - inferior; against the splenic flexure of the colon
4. Pancreatic impression - against the tail of the pancreas (near the hilum)

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Borders and Poles

Clinical point: The notch on the superior border is palpable in massive splenomegaly and helps distinguish an enlarged spleen from a left kidney (which lacks a notch).

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The Splenic Hilum

• Splenic artery and vein enter/exit
• Lymphatic vessels and nerves pass
• The tail of the pancreas may reach the hilum (present in ~30% of individuals, within 1 cm in ~70%)

• Posterior to hilum - renal impression (left kidney contact)
• Anterior to hilum - gastric impression (stomach and pancreatic tail contact)

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Peritoneal Ligaments

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Vascular Supply

Arterial Supply

• Splenic artery: largest branch of the celiac trunk; highly tortuous; runs along the posterior superior border of the pancreas
• Gives 16-18 pancreatic branches en route
• Two anatomical types at the hilum:
  • Magistral type (30%): single trunk that divides near the hilum
  • Distributed type (70%): arborizes proximally, well before the hilum
• Terminally branches into 4-6 polar arteries (lobar/segmental arteries) and 6 short gastric arteries

Venous Drainage

• Splenic vein: formed by union of several intrasplenic veins + left gastroepiploic vein
• Runs posterior to the pancreas
• Joins the superior mesenteric vein (+ inferior mesenteric vein) to form the portal vein

Nerve Supply

• Sympathetic fibers from the celiac plexus travel along the splenic artery

Lymphatic Drainage

• Lymphatics drain to pancreaticosplenic lymph nodes around the splenic vessels, then to celiac nodes

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Capsule and Internal Architecture (Brief)

• The spleen is encased in a fibroelastic capsule with smooth muscle fibers
• From the capsule, trabeculae extend inward, compartmentalizing the parenchyma
• The parenchyma consists of:
  • White pulp - lymphatic sheaths (PALS) and lymphoid follicles around arterioles; site of immune responses
  • Red pulp - vascular sinuses, venous sinusoids, and splenic cords; site of blood filtration

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Accessory Spleens (Splenunculi)

• Present in up to 20% of the general population; up to 30% in patients with hematologic disease
• Usually pea-sized to egg-sized
• >80% located at the splenic hilum and vascular pedicle
• Other sites (in decreasing frequency): gastrocolic ligament, pancreatic tail, greater omentum, greater curvature of stomach, splenocolic ligament, bowel mesentery, left broad ligament (females), left spermatic cord (males)
• Clinically important: accessory spleens must be removed in splenectomy for hematologic conditions (e.g., ITP) to prevent relapse

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Clinical Correlates

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• Color Atlas of Human Anatomy, Vol. 2 (Internal Organs), Gross Anatomy section
• Gray's Anatomy for Students, Ch. 4 (Abdomen)
• Sabiston Textbook of Surgery, 21e - Splenic Anatomy
• Schwartz's Principles of Surgery, 11e - Embryology and Anatomy of the Spleen

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Classification and Clinical Significance of Plasma Proteins

1. Introduction

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2. Classification of Plasma Proteins

A. By Electrophoretic Mobility (Clinical Standard)

B. By Function

C. By Site of Synthesis

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3. Individual Proteins and Their Clinical Significance

ALBUMIN

• MW: 69,000 Da | Half-life: ~20 days | Normal: 3.5-5.0 g/dL
• Functions:
  • Maintains plasma oncotic pressure (responsible for ~80% of total oncotic pressure)
  • Major transport protein: carries bilirubin, fatty acids, drugs (warfarin, aspirin), hormones, Ca²+, Mg²+, bilirubin
  • Acts as a labile protein reserve (amino acid reservoir)
  • Negative acute phase reactant - synthesis falls during inflammation (IL-6 suppresses it)
• Clinical significance:
  • Hypoalbuminemia → edema, ascites (Starling forces shift fluid to extravascular compartment)
  • Seen in: liver cirrhosis, nephrotic syndrome (urinary loss up to 20 g/day), malnutrition, protein-losing enteropathy, burns (liters of protein-rich fluid can be lost daily), chronic infection/inflammation
  • Serum albumin is a strong predictor of mortality across many diseases
  • Drug binding affected: low albumin → higher free (active) drug levels → toxicity risk
  • Albumin-to-globulin (A:G) ratio: normally >1; reversal in liver disease and multiple myeloma

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FIBRINOGEN (β-globulin)

• MW: 340,000 Da | Half-life: ~4-6 days | Normal: 200-400 mg/dL
• Functions: Precursor of fibrin; polymerizes into long fibrin threads during coagulation (thrombin cleaves fibrinopeptides A and B to form fibrin monomer)
• Clinical significance:
  • Elevated: Acute phase reactant - rises in infection, inflammation, pregnancy, myocardial infarction; independent cardiovascular risk factor
  • Decreased/absent: Disseminated intravascular coagulation (DIC), liver failure, afibrinogenemia
  • Prothrombin time (PT) / INR measures fibrinogen-dependent coagulation; worsening PT in acute hepatitis = poor prognosis

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IMMUNOGLOBULINS (γ-globulins)

• Synthesized exclusively by plasma cells (B lymphocytes)
• IgG: Most abundant; secondary immune response; only Ig that crosses placenta
• IgA: Predominant in secretions (saliva, colostrum, tears)
• IgM: First antibody in primary immune response; pentameric; activates complement most effectively
• IgD: B-cell surface receptor
• IgE: Mediates Type I hypersensitivity; elevated in parasitic infections and allergies
• Clinical significance:
  • Polyclonal hypergammaglobulinemia: broad γ-peak; seen in chronic infection, liver cirrhosis, autoimmune disease
  • Monoclonal gammopathy (M-spike): narrow sharp peak; seen in multiple myeloma, Waldenström macroglobulinemia, MGUS
  • Hypogammaglobulinemia: increased susceptibility to bacterial infections; seen in agammaglobulinemia, common variable immunodeficiency (CVID)

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α1-ANTITRYPSIN (α1-globulin)

• MW: ~55 kDa | Major serine protease inhibitor (serpin) in plasma
• Inhibits trypsin, elastase, collagenase, chymotrypsin; protects lung tissue from neutrophil elastase
• Clinical significance:
  • Deficiency (homozygous PiZZ genotype): emphysema (unopposed elastase destroys alveoli), liver cirrhosis (abnormal protein accumulates in hepatocytes)
  • Elevated as positive acute phase reactant in infection, inflammation

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HAPTOGLOBIN (α2-globulin)

• MW: ~100 kDa | Synthesized in liver
• Binds free hemoglobin (from hemolyzed RBCs) → Hb-Hp complex taken up by macrophages → prevents iron and Hb loss in urine
• Half-life of free haptoglobin: ~5 days; Hb-Hp complex: ~90 min (rapidly cleared)
• Clinical significance:
  • Decreased or absent: Marker of intravascular hemolysis (haptoglobin consumed faster than it is synthesized) - seen in hemolytic anemia, transfusion reactions, malaria
  • Elevated: Positive acute phase reactant; elevated in infections, inflammation
  • Elevated in some cancers (haptoglobin-related protein)

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TRANSFERRIN (β-globulin)

• MW: ~76 kDa (glycoprotein) | Synthesized in liver
• Transports Fe3+ in the plasma; contains 2 high-affinity binding sites for Fe3+
• Normal plasma [Tf]: ~300 mg/dL → total iron-binding capacity (TIBC) ~300 μg/dL
• Normally ~30% saturated with iron
• Clinical significance:
  • Elevated (low % saturation): Iron deficiency anemia (liver makes more transferrin to compensate; TIBC ↑, saturation ↓ <16%)
  • Decreased (high % saturation): Iron overload (hemochromatosis; TIBC ↓, saturation >45%)
  • Carbohydrate-deficient transferrin (CDT): biomarker of chronic alcoholism

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CERULOPLASMIN (α2-globulin)

• MW: ~132 kDa | Copper-containing glycoprotein (ferroxidase activity)
• Carries >90% of plasma copper; also functions as ferroxidase (oxidizes Fe2+ to Fe3+)
• Clinical significance:
  • Decreased: Wilson disease (autosomal recessive copper accumulation), Menkes disease, chronic hepatitis, nephrotic syndrome
  • Elevated: Pregnancy, estrogen therapy, cholestasis, hemochromatosis, and as a positive acute phase reactant
  • Low ceruloplasmin + Kayser-Fleischer rings + neuropsychiatric symptoms = Wilson disease

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C-REACTIVE PROTEIN (CRP) (β/γ region)

• MW: ~115 kDa; pentameric protein
• Named because it reacts with the C-polysaccharide of Streptococcus pneumoniae
• Synthesized in liver; one of the most sensitive acute phase reactants
• Activates the classical complement pathway
• Normal: <10 mg/L; rises 100-1000-fold within hours of infection/tissue injury
• Clinical significance:
  • Elevated: Bacterial infection, MI, autoimmune disease, malignancy, post-surgery
  • Useful in: monitoring antibiotic response, distinguishing bacterial vs. viral infection (CRP much higher in bacterial)
  • High-sensitivity CRP (hsCRP): cardiovascular risk stratification
  • Notable: CRP stays normal/low in systemic lupus erythematosus (SLE) unless infection is present

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α-FETOPROTEIN (AFP)

• Normal fetal plasma protein; falls to adult levels by 1 year of age
• Clinical significance:
  • Mild increase → hepatocellular regeneration in acute/chronic hepatitis
  • Markedly elevated → Hepatocellular carcinoma (HCC) (tumor marker)
  • Also elevated in: yolk sac tumors (germ cell), neural tube defects (in maternal serum), Down syndrome (low AFP)

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TRANSTHYRETIN (Prealbumin)

• MW: ~55 kDa | Half-life: 24-48 hours (shortest of all liver-made proteins)
• Transports thyroxine (T4) and retinol (via retinol-binding protein complex)
• Clinical significance:
  • Short half-life makes it the most sensitive indicator of current hepatic synthetic function and nutritional status
  • Decreased: malnutrition, liver disease (cirrhosis), acute inflammation
  • Serial monitoring used in nutritional assessment (better than albumin due to short half-life)

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α2-MACROGLOBULIN

• MW: ~720 kDa (largest plasma protein)
• Broad-spectrum protease inhibitor; "traps" proteases (trypsin, chymotrypsin, plasmin, thrombin)
• Clinical significance:
  • Elevated in nephrotic syndrome (too large to be lost in urine, so relative increase while smaller proteins are lost)
  • Elevated in liver disease and diabetes

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4. Acute Phase Response

Clinical pearl: Albumin and transthyretin fall in acute phase states, which is why a low albumin may reflect acute inflammation rather than malnutrition alone.

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5. Serum Protein Electrophoresis (SPEP) Patterns - Clinical Correlates

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6. Half-Lives of Key Plasma Proteins

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• Harper's Illustrated Biochemistry, 32e, Chapter 52 (Plasma Proteins)
• Tietz Textbook of Laboratory Medicine, 7e, Chapters 22 & 51
• Guyton & Hall Textbook of Medical Physiology, Functional Roles of Plasma Proteins
• Medical Physiology (Boron & Boulpaep), Plasma Proteins section

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Differential Leukocyte Count (DLC) - Physiology

Overview

1. Granulocytes (polymorphonuclear cells) - have abundant specific granules and a polymorphic/multilobed nucleus
2. Agranulocytes - lack specific granules; have a spherical or indented (not lobed) nucleus

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Classification of WBCs

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Normal DLC Values

Memory mnemonic: "Never Let Monkeys Eat Bananas" - Neutrophils (60%), Lymphocytes (30%), Monocytes (6%), Eosinophils (3%), Basophils (1%)

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Genesis of WBCs

• Myelocytic lineage (bone marrow): Myeloblast → Promyelocyte → Myelocyte → Metamyelocyte → Band cell → Mature granulocyte/Monocyte
• Lymphocytic lineage (bone marrow + lymphoid tissues): Lymphoblast → T and B lymphocytes, plasma cells

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Individual WBCs - Morphology, Function, and Clinical Significance

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1. NEUTROPHILS (Polymorphonuclear Neutrophils / PMNs)

• Primary (azurophilic) granules - lysosomes containing myeloperoxidase, defensins, lysozyme, elastase
• Secondary (specific) granules - lactoferrin, collagenase, B12-binding proteins, alkaline phosphatase

• First responders in acute bacterial infection (arrive within minutes to hours)
• Phagocytosis of bacteria, fungi, cellular debris
• Chemotaxis - migrate toward sites of infection following chemotactic signals (C5a, IL-8/CXCL8, LTB4, fMLP)
• Diapedesis - squeeze through endothelial gaps via P-selectin/integrin interactions
• Oxidative burst (respiratory burst): NADPH oxidase generates superoxide → H2O2 → hypochlorous acid (HOCl) via myeloperoxidase

"Left shift": Appearance of band (stab) neutrophils and immature forms in the blood, indicating accelerated marrow release. Normal band neutrophils = 3-5%.

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2. EOSINOPHILS

• Kill helminthic parasites (worms too large to phagocytose): degranulate and release MBP directly onto parasite surface
• Modulate inflammation in allergic reactions: produce prostaglandins, leukotrienes; take up antigen-antibody complexes
• Phagocytose antigen-antibody complexes
• Respond to IL-5 (from Th2 cells) for proliferation and differentiation

"NAACP" mnemonic for eosinophilia: Neoplasm, Asthma/Allergy, Addison's disease, Collagen vascular disease, Parasites

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3. BASOPHILS

• Carry IgE receptors (FcεRI) on their surface - central to Type I hypersensitivity (anaphylaxis, atopy)
• On cross-linking of IgE by antigen → degranulation → histamine release (vasodilation, bronchoconstriction, itching)
• Release heparin (local anticoagulant), serotonin, SRS-A (slow reacting substance of anaphylaxis = LTC4, LTD4, LTE4)
• Functionally related to mast cells in tissues (mast cells are tissue-resident counterparts)

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4. MONOCYTES

• Immature phagocytes in blood - limited phagocytic ability while in circulation
• Exit blood → enter tissues → differentiate into tissue macrophages (swell up to 60-80 µm)
• Macrophages perform: phagocytosis of bacteria/dead cells/debris, antigen presentation (MHC II), cytokine secretion, activation of adaptive immunity

All macrophages together with monocytes form the Reticuloendothelial System (RES) - also called the Monocyte-Macrophage System

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5. LYMPHOCYTES

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Summary Table

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Life Spans

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Diapedesis and Chemotaxis (How WBCs Reach Infection Sites)

1. Margination - WBCs move to periphery of vessel (slow rolling)
2. Pavementing - WBCs stick to endothelium via P-selectin (expressed on endothelium) binding glycosylated ligands on WBCs
3. Adhesion - Firm attachment via integrins (ICAM-1/LFA-1 interaction)
4. Diapedesis - WBCs squeeze through gaps between endothelial cells (postcapillary venules)
5. Chemotaxis - Migration toward chemoattractants: C5a, IL-8 (CXCL8), LTB4, fMLP (bacterial peptides)

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• Guyton & Hall Textbook of Medical Physiology, 14e, Chapter 34 - General Characteristics of Leukocytes
• Junqueira's Basic Histology, 17e, Chapter 12 - Leukocytes
• Henry's Clinical Diagnosis and Management by Laboratory Methods - Differential Leukocyte Count