Mitochondria produce ATP through oxidative phosphorylation, providing energy for cellular functions.

Lysosomes contain acid hydrolases that digest cellular debris and foreign material.

Ribosomes attached to RER give it a “rough” appearance and synthesize proteins for secretion.

Golgi apparatus modifies, sorts, and packages proteins into vesicles for secretion or intracellular use.

Mitochondria have their own circular DNA and double membrane (outer and inner with cristae).

S (Synthesis) phase is when DNA replicates to double the genetic material.

G1 phase is typically the longest, involving cell growth and preparation for DNA synthesis.

In metaphase, chromosomes align at the metaphase plate (cell equator).

Anaphase involves separation of sister chromatids toward opposite poles by spindle fibers.

Telophase involves nuclear envelope reformation around separated chromosomes and chromatin decondensation.

Mitosis produces two genetically identical diploid daughter cells from one parent cell.

Crossing over (genetic recombination) occurs during prophase I when homologous chromosomes pair and exchange segments.

Meiosis produces four genetically distinct haploid gametes from one diploid parent cell.

Meiosis I is the reductional division where homologous chromosomes separate, halving the chromosome number.

During prophase I, homologous chromosomes pair to form bivalents (synapsis).

Seminiferous tubules in the testes are the site of sperm production.

Sertoli cells (nurse cells) nourish and support developing spermatocytes.

One primary spermatocyte undergoes meiosis I to form two secondary spermatocytes, then meiosis II to form four spermatids (which mature into spermatozoa).

Leydig cells (interstitial cells) in the testes produce testosterone under LH stimulation.

Primary oocytes are arrested in prophase I (diplotene stage) from fetal life until ovulation.

The secondary oocyte remains arrested at metaphase II until sperm penetration triggers completion of meiosis II.

One primary oocyte produces one functional ovum and three polar bodies (which degenerate).

First polar body is released after meiosis I, containing minimal cytoplasm and one set of chromosomes.

Estrogen from developing follicles stimulates endometrial proliferation and thickening.

LH surge triggers ovulation approximately 36 hours after its peak.

Corpus luteum secretes both progesterone (primarily) and estrogen to maintain the endometrium.

The secretory (uterine) phase corresponds to the luteal (ovarian) phase, both dominated by progesterone from corpus luteum.

The ampulla (widest part) is the typical site of fertilization, where sperm meets the ovum.

The acrosome (cap over sperm head) releases hyaluronidase and acrosin enzymes to penetrate the corona radiata and zona pellucida.

The cortical reaction hardens the zona pellucida after first sperm entry, preventing additional sperm from entering (blocking polyspermy).

The zona pellucida is an acellular glycoprotein layer surrounding the oocyte, crucial for species-specific sperm binding and preventing polyspermy.

Normal implantation occurs in the upper posterior wall of the uterine body, which has optimal blood supply.

Implantation begins around day 6-7 post-fertilization when the blastocyst hatches from zona pellucida and attaches to endometrium.

95% of ectopic pregnancies occur in the fallopian tube, most commonly the ampulla.

Trophoblast differentiates into outer syncytiotrophoblast (invasive, multinucleated) and inner cytotrophoblast.

Ectoderm forms the nervous system (neural tube), epidermis, and sensory organs.

Endoderm forms the epithelial lining of the GI tract, respiratory tract, and associated glands (liver, pancreas).

Mesoderm (specifically somites) forms skeletal muscle, bone, cartilage, and cardiovascular structures.

Ectoderm forms the epidermis (surface ectoderm) while mesoderm forms the dermis.

Thyroid epithelium develops from endodermal outgrowth at foramen cecum of tongue.

Week 3 features gastrulation (formation of ectoderm, mesoderm, endoderm) and primitive streak formation.

Week 2 forms the bilaminar disc (epiblast and hypoblast) plus amniotic cavity and yolk sac.

Neurulation (neural plate folding into neural tube) begins late week 3 and continues into week 4.

The primitive heart tube begins beating around day 22-23 (late week 3/early week 4), making it the first functional organ.

Proximal means closer to the point of attachment or origin (e.g., shoulder is proximal to elbow).

In anatomical position, the body stands erect, arms at sides, palms facing forward (anterior/supinated).

The sagittal plane divides the body into right and left portions.

The coronal (frontal) plane divides the body into anterior (front) and posterior (back) portions.

Femur is a long bone with a shaft (diaphysis) and two ends (epiphyses), found in limbs for leverage and movement.

Carpals are short bones (cube-shaped) that provide stability with limited movement in the wrist.

The patella is a sesamoid bone embedded within the quadriceps tendon, protecting the knee and increasing mechanical advantage.

Scapula is a flat bone providing muscle attachment and protection.

The knee is a hinge joint (modified) allowing primarily flexion and extension.

The hip is a ball-and-socket joint with the femoral head articulating with the acetabulum, allowing multiaxial movement (flexion, extension, abduction, adduction, rotation).

Pivot joints (atlantoaxial, proximal radioulnar) allow rotation around a longitudinal axis.

Syndesmoses are fibrous joints connected by interosseous ligaments (tibiofibular, radioulnar) allowing limited movement.

Skeletal muscle is voluntarily controlled, striated (banded), and multinucleated.

Cardiac muscle (myocardium) is found only in the heart, featuring branched striated fibers with intercalated discs.

Smooth muscle lines hollow organs including intestines, blood vessels, and bladder.

The thoracic duct drains into the venous system at the junction of left subclavian and left internal jugular veins.

The thymus is the site of T-lymphocyte maturation and selection.

The spleen is the largest lymphoid organ, filtering blood and storing platelets and red blood cells.

Peyer’s patches are aggregated lymphoid follicles in the ileum (terminal small intestine) on the antimesenteric border.

The CNS comprises the brain and spinal cord, protected by meninges and bone.

Sympathetic outflow arises from T1-L2 (thoracolumbar) spinal segments.

The vagus nerve (CN X) carries parasympathetic fibers to thoracic and abdominal viscera (heart, lungs, GI tract to splenic flexure).

Pelvic splanchnic nerves (S2-S4) provide parasympathetic supply to the bladder (detrusor contraction).

Mucous membranes line cavities that open to the exterior (respiratory, GI, urogenital tracts).

Pleura is the serous membrane surrounding the lungs (visceral) and lining the thoracic wall (parietal).

Visceral serous membrane directly covers the organ surface (e.g., visceral pleura on lungs).

Connective tissue features scattered cells within abundant extracellular matrix (fibers and ground substance).

Nervous tissue comprises neurons (signal transmission) and neuroglia (support cells including astrocytes, oligodendrocytes, microglia).

Stratified squamous epithelium (keratinized in skin, non-keratinized in oral cavity/esophagus) protects against abrasion.

The small intestine has simple columnar epithelium with goblet cells (mucus-secreting) for absorption and protection.

Transitional epithelium (urothelium) lines the urinary tract (bladder, ureters, renal pelvis), allowing stretching.

The trachea and upper respiratory tract have pseudostratified ciliated columnar epithelium with goblet cells (respiratory epithelium) for mucociliary clearance.

The basement membrane has two components: basal lamina (produced by epithelial cells, contains laminin/collagen IV) and reticular lamina (produced by connective tissue, contains collagen III).

Laminin is a glycoprotein in the basal lamina that helps anchor epithelial cells via integrins.

Fibroblasts are the primary cells producing collagen, elastin, and ground substance in connective tissue.

In adults, red bone marrow (in flat bones, vertebrae, proximal long bones) is the primary hematopoietic site.

Cholesterol acts as a bidirectional buffer for membrane fluidity, increasing it at low temperatures and decreasing it at high temperatures.

Band 3 is a vital integral membrane protein that functions as a chloride-bicarbonate exchanger, crucial for CO2 transport in red blood cells.

Fick’s law dictates that the diffusion rate is directly proportional to surface area and concentration gradient, and inversely proportional to thickness.

Oxytocin release during labor causes uterine contractions, which further stretch the cervix, stimulating even more oxytocin release until delivery occurs.

The resting membrane is highly permeable to potassium via leak channels, bringing the RMP close to the potassium equilibrium potential.

The Nernst equation calculates the electrical potential that exactly opposes the concentration gradient of a single specific permeant ion.

Depolarization is caused by a massive, rapid increase in sodium conductance as voltage-gated sodium channels open, driving the potential toward +65 mV.

As sodium channels inactivate, delayed voltage-gated potassium channels open, allowing potassium to rapidly exit the cell and restore the negative membrane potential.

The electrogenic pump utilizes ATP to actively extrude 3 sodium ions while bringing 2 potassium ions into the cell, restoring resting gradients.

Kinesin is a molecular motor protein that mediates fast anterograde transport along microtubules toward the plus end at the nerve terminal.

Phagocytosis (“cell eating”) is a form of endocytosis where the cell membrane invaginates to engulf large particles like bacteria or dead tissue.

Mature erythrocytes lack a nucleus and organelles, limiting their lifespan to approximately 120 days before they are destroyed by the reticuloendothelial system.

After birth, red bone marrow becomes the exclusive site of red blood cell production, notably in the membranous bones like the sternum and ilium.

Erythropoietin (EPO) stimulates the bone marrow to produce RBCs in response to tissue hypoxia, preventing anemia.

Vitamin B12 (cobalamin) and folic acid are essential for DNA synthesis; deficiency leads to maturation failure and macrocytic (megaloblastic) anemia.

Iron is essential for hemoglobin synthesis; lack of iron leads to small (microcytic) and pale (hypochromic) red blood cells.

Autoantibodies destroy gastric parietal cells, causing a lack of intrinsic factor, which is necessary for Vitamin B12 absorption in the terminal ileum.

Polycythemia vera involves a genetic mutation (often JAK2) causing unregulated, excessive production of red blood cells, drastically increasing blood viscosity.

Chronic hypoxia (from high altitude or chronic lung disease) triggers the kidneys to continuously secrete erythropoietin, increasing RBC production.

Neutrophils are highly motile phagocytes that rapidly migrate to sites of inflammation to engulf and destroy invading bacteria via respiratory burst.

Eosinophils release highly toxic proteins, such as major basic protein, which physically destroy large parasitic helminths that cannot be phagocytosed.

Both basophils and mast cells contain prominent cytoplasmic granules loaded with histamine and heparin, playing key roles in Type I hypersensitivity reactions.

Monocytes circulate in the blood for a short time before migrating into tissues, where they dramatically enlarge and differentiate into powerful tissue macrophages.

This widespread network of tissue macrophages filters and destroys microbes, old red blood cells, and cellular debris from blood and lymph.

Inflammatory mediators like histamine cause endothelial cells to contract, increasing permeability and allowing protein-rich fluid to leak, causing tissue edema (swelling).

Chemotaxis is the unidirectional migration of immune cells directed by chemical attractants, such as bacterial toxins, complement proteins (C5a), and chemokines.

Opsonins, primarily IgG antibodies and the complement protein C3b, coat pathogens, allowing phagocytes with corresponding receptors to easily bind and ingest them.

Upon activation, B lymphocytes differentiate into plasma cells, which are specialized “factories” that secrete massive quantities of antigen-specific antibodies into circulation.

IgG is the dominant antibody in the secondary immune response, providing long-term systemic immunity and protecting the fetus via placental transfer.

Secretory IgA acts as a vital first line of defense on mucosal surfaces by neutralizing pathogens before they can invade the epithelium.

IgM is the first antibody isotype secreted by B cells during a primary infection, forming a large pentamer highly effective at complement activation.

Cytotoxic T lymphocytes (CD8+) directly recognize and induce apoptosis in host cells presenting endogenous viral or tumor antigens via MHC Class I.

Helper T cells release specific cytokines (like Interleukin-2 and Interferon-gamma) that activate and recruit B cells, cytotoxic T cells, and macrophages.

The classical pathway triggers when the C1 complex binds to the Fc portion of IgM or IgG antibodies that are already attached to an antigen.

C3b covalently attaches to the surface of pathogens, allowing macrophages and neutrophils expressing C3b receptors to easily grip and engulf the microbe.

The terminal complement proteins assemble to form a transmembrane pore (MAC) that disrupts osmotic balance, causing rapid lysis of the pathogen.

Allergen cross-linking of IgE antibodies bound to the surface of mast cells and basophils triggers immediate massive degranulation of histamine.

Type II hypersensitivity involves cytotoxic IgG or IgM antibodies directed against fixed cellular antigens, such as maternal anti-Rh antibodies attacking fetal RBCs.

Type III hypersensitivity is driven by the deposition of circulating soluble antigen-antibody immune complexes in tissues, inciting severe complement-mediated inflammation.

Type IV hypersensitivity is entirely cell-mediated (T cells and macrophages), independent of antibodies, taking 48-72 hours to reach a peak clinical response.

Vascular spasm (constriction) occurs instantly via local myogenic reflexes and potent vasoconstrictors like endothelin and thromboxane A2 to massively reduce blood loss.

Platelets adhere to exposed subendothelial collagen, become activated, and aggregate to rapidly form a soft, temporary plug at the injury site.

Von Willebrand factor (vWF) acts as a crucial molecular bridge connecting platelet surface receptors (Glycoprotein Ib) directly to the damaged vascular collagen.

Thromboxane A2 (TXA2) is produced by platelet COX-1 and strongly promotes further platelet aggregation and intense vascular constriction.

Healthy endothelium secretes Prostacyclin (PGI2) and Nitric Oxide (NO), which potently inhibit platelet activation and promote local vasodilation to ensure continuous blood flow.

The coagulation cascade culminates in the enzymatic conversion of soluble fibrinogen into insoluble fibrin polymer threads, creating a definitive, stable blood clot.

Tissue Factor is released by severely traumatized extravascular tissues and binds with Factor VII to rapidly trigger the explosive extrinsic coagulation cascade.

Factor XII (Hageman factor) autoactivates upon exposure to negatively charged subendothelial collagen or glass, starting the longer intrinsic cascade.

Factor Xa, combining with Factor Va, calcium, and platelet phospholipids, forms the prothrombinase complex, marking the start of the common pathway.

The prothrombinase complex (Xa, Va, Ca++, phospholipids) powerfully cleaves prothrombin (Factor II) into thrombin (Factor IIa), the most critical enzyme in coagulation.

Thrombin cleaves small peptides from soluble fibrinogen, creating fibrin monomers that rapidly polymerize to form the structural basis of the clot.

Thrombin activates Factor XIII, which forms strong covalent bonds between adjacent fibrin molecules, transforming a soft clot into a tough, retracting clot.

Calcium (Factor IV) binds to the gamma-carboxyglutamate residues of Vitamin K-dependent factors, physically anchoring them to negative platelet phospholipid surfaces.

Vitamin K acts as an essential cofactor for the gamma-carboxylation of glutamic acid residues on these factors, allowing them to effectively bind calcium.

Plasminogen is converted to active plasmin by tissue plasminogen activator (tPA); plasmin forcefully digests fibrin threads, dissolving the established thrombus.

A genetic lack of Factor VIII severely disrupts the intrinsic coagulation pathway, leading to massive, life-threatening joint and deep muscle hemorrhages.

Factor IX deficiency also blocks the intrinsic pathway, producing severe bleeding identical to Hemophilia A, requiring specific Factor IX replacement therapy.

A deficiency or defect in vWF profoundly impairs primary hemostasis (platelet plug formation) and causes a secondary decrease in Factor VIII stability.

Since Vitamin K is essential for factors in both the extrinsic (VII) and intrinsic/common (II, IX, X) pathways, both PT and aPTT are elevated.

Antithrombin III binds and permanently inactivates thrombin and other active serine proteases, preventing runaway, massive systemic blood coagulation.

Active Protein C, utilizing Protein S as a cofactor, specifically cleaves and disables the massive accelerator cofactors Va and VIIIa, halting the cascade.

Thrombocytopenia (low platelet count) prevents adequate primary hemostasis, leading to spontaneous micro-hemorrhages in the skin and mucous membranes.

ABO blood typing is determined by complex inherited carbohydrate antigens (agglutinogens) permanently expressed on the surface of the erythrocyte membrane.

Individuals develop plasma antibodies against the ABO antigens they *lack*; since type AB individuals possess both A and B antigens, they produce no ABO antibodies.

Type O negative red blood cells lack A, B, and Rh(D) antigens, so they will not violently trigger an immune response when given to any recipient.

ABO antibodies are large, naturally occurring IgM pentamers that avidly fix complement, causing rapid, fatal intravascular hemolysis if mismatched blood is transfused.

Anti-Rh antibodies are acquired IgG molecules that easily cross the placental barrier, posing a severe risk to an Rh-positive fetus during pregnancy.

If an Rh-negative mother is sensitized to Rh-positive fetal blood, she produces IgG anti-D antibodies that aggressively attack subsequent Rh-positive fetuses.

RhoGAM contains synthetic anti-D IgG that rapidly masks and clears any stray fetal Rh-positive cells before the mother’s immune system can recognize them.

This is a Type II cytotoxic reaction where preformed maternal/recipient IgM antibodies directly attack the donor’s RBC antigens, inducing rapid complement-mediated lysis.

MHC Class I presents endogenous (intracellular) antigens to CD8+ cytotoxic T cells, enabling the immune system to constantly monitor all nucleated host cells for viral infection.

Professional APCs (macrophages, dendritic cells, B cells) utilize MHC Class II to present exogenous antigens to CD4+ helper T cells to initiate targeted immune responses.

The CD8 co-receptor specifically physically binds to the non-polymorphic region of the MHC Class I molecule, ensuring cytotoxic T cells only attack virally infected or tumor cells.

The CD4 co-receptor rigidly restricts Helper T cells to interacting solely with MHC Class II molecules on professional antigen-presenting cells.

Highly polymorphic HLA (MHC) molecules strongly differ between individuals; foreign MHC molecules are fiercely targeted by host T cells, causing rapid cellular rejection.

Factor XII undergoes a potent conformational change upon encountering collagen, activating the intrinsic pathway which is evaluated by the aPTT test.

Total O2 content overwhelmingly depends on O2 physically bound to Hb (determined by Hb mass and saturation), while dissolved O2 (PaO2) contributes only a tiny fraction.

In states of cellular hypoxia, HIF-1 powerfully stimulates the renal synthesis of EPO to drastically increase erythrocyte production and restore vital oxygen delivery.

A rightward shift violently decreases Hb’s affinity for O2, allowing the massive unloading of required oxygen directly to the acidic, hypercapnic, hot exercising muscle tissues.

Peripheral chemoreceptors are exquisitely sensitive to dissolved O2 (PaO2), not Hb saturation; since CO does not affect dissolved O2, the classic hypoxic ventilatory drive is absent.

NK cells are innate lymphocytes that rapidly recognize cells lacking normal MHC Class I expression and kill them instantly via perforin and granzymes.

The alternative pathway bypasses antibodies entirely and is triggered instantly by spontaneous C3b binding directly to foreign pathogen surfaces, crucial for innate defense.

Immature T cells migrate from the bone marrow to the thymus, where they undergo rigorous positive and negative selection to prevent deadly autoimmune reactions.

Langerhans cells are potent resident dendritic cells in the skin that avidly capture trespassing antigens and migrate to lymph nodes to rapidly activate T cells.

Administering exogenous immunoglobulins provides instant defense without activating the host’s own immune system, meaning no long-term memory cells are generated.

RDW quantitatively measures anisocytosis (variation in RBC size), which is characteristically highly elevated in severe iron deficiency anemia but normal in thalassemia trait.

Mutations in spectrin or ankyrin completely disrupt the RBC’s flexible biconcave shape, creating rigid spheres that become trapped and prematurely destroyed in the spleen.

Hepcidin binds and utterly destroys ferroportin on enterocytes, fiercely preventing iron absorption into the blood when systemic iron stores are excessively high.

Folate or Vitamin B12 deficiency halts crucial DNA replication, drastically preventing nuclear maturation and division, while the cytoplasm continues to rapidly expand.

Thalassemia involves a severe genetic defect in globin chain synthesis, producing tiny, pale cells (microcytosis) but maintaining entirely normal or elevated body iron stores.

Basophils are the rarest circulating leukocytes, massively packed with histamine granules and heavily involved in mediating severe systemic allergic reactions.

Neutrophils (~60%) dominate, followed sequentially by Lymphocytes (~30%), Monocytes (~6%), Eosinophils (~3%), and Basophils (~1%).

Massive cross-linking of IgE triggers explosive mast cell degranulation of histamine, which violently dilates arterioles and induces massive fluid extravasation, dropping blood pressure.

Aspirin permanently acetylates and destroys COX-1, completely preventing the synthesis of thromboxane A2 for the entire 7-10 day lifespan of the platelet.

Glanzmann thrombasthenia completely prevents platelets from binding to fibrinogen, effectively abolishing platelet aggregation despite perfectly normal platelet counts and vWF levels.

Warfarin destroys Vitamin K-dependent factor synthesis; since Factor VII (extrinsic pathway) has the absolute shortest half-life, the PT wildly elongates first.

Runaway systemic activation of coagulation consumes all available platelets and clotting factors (causing bleeding), while simultaneously depositing massive fibrin clots in microvessels (causing ischemia).

Heparin binds to Antithrombin III, accelerating its inactivation of Thrombin (Factor IIa) and Factor Xa by over 1000-fold, rapidly arresting the coagulation cascade.

The liver is the exclusive factory for nearly all plasma coagulation factors (except Factor VIII and vWF); its destruction rapidly collapses secondary hemostasis.

A perfectly intact, smooth glycocalyx repels platelets and prevents the disastrous exposure of subendothelial collagen, halting intrinsic activation, while simultaneously secreting protective PGI2 and NO.

Mitochondria generate ATP through oxidative phosphorylation, providing energy for cellular functions–hence “powerhouse.” Ribosomes synthesize proteins.

Ribosomes attached to the ER surface give it a rough appearance and are responsible for protein synthesis.

Smooth ER lacks ribosomes and is involved in lipid synthesis, steroid hormone production, and drug detoxification.

Golgi apparatus modifies proteins (glycosylation, sulfation), sorts, and packages them into vesicles for secretion or delivery.

Lysosomes contain acid hydrolases that break down macromolecules, damaged organelles, and pathogens.

Passive transport moves substances down their concentration gradient without ATP.

Na⁺/K⁺-ATPase pumps 3 Na⁺ out and 2 K⁺ into the cell per ATP hydrolyzed, maintaining electrochemical gradient.

Osmosis is the passive movement of water toward higher solute concentration to equalize osmotic pressure.

Facilitated diffusion uses carrier or channel proteins to transport molecules down their gradient without ATP.

SGLT1 (sodium-glucose cotransporter) uses the sodium gradient established by Na⁺/K⁺-ATPase to drive glucose uptake–secondary active transport.

RNA contains uracil instead of thymine found in DNA.

DNA contains deoxyribose (lacks 2′-OH group), while RNA contains ribose.

Watson and Crick proposed the double helix model in 1953.

Adenine-thymine base pairs have 2 hydrogen bonds, while guanine-cytosine pairs have 3.

Transfer RNA (tRNA) carries specific amino acids to ribosomes, recognizing mRNA codons via anticodons. mRNA carries genetic code. rRNA forms ribosome structure. snRNA is involved in splicing.

Semiconservative replication means each daughter molecule contains one parental (conserved) strand and one newly synthesized strand, as proven by Meselson-Stahl experiment.

Helicase breaks hydrogen bonds between base pairs, unwinding DNA at the replication fork.

DNA polymerase adds nucleotides only to the 3′-OH end, synthesizing in 5′ to 3′ direction.

The lagging strand is synthesized discontinuously as short Okazaki fragments (100-200 nucleotides in eukaryotes) because DNA polymerase can only work 5′ to 3′.

Primase synthesizes short RNA primers (8-12 nucleotides) that provide the 3′-OH group needed for DNA polymerase to begin synthesis.

Blood pH is tightly regulated between 7.35–7.45.

Bicarbonate buffer (H₂CO₃/HCO₃⁻) is the main extracellular buffer, regulated by lungs (CO₂) and kidneys (HCO₃⁻).

Buffers contain weak acid and its conjugate base, neutralizing both added acids (by conjugate base) and added bases (by weak acid), maintaining stable pH within buffering capacity.

Henderson-Hasselbalch equation: pH = pKa + log([conjugate base]/[acid]).

Brønsted-Lowry defines acids as proton (H⁺) donors and bases as proton acceptors.

PH is a logarithmic scale; each unit represents 10-fold change in H⁺ concentration. pH 3 to pH 5 = 2 units = 10² = 100 times more acidic.

At pH = pKa, the Henderson-Hasselbalch equation shows log(1) = 0, meaning [acid] = [conjugate base].

Carbonic acid is a weak acid that partially dissociates (H₂CO₃ ⇌ H⁺ + HCO₃⁻).

Glucose is a monosaccharide (single sugar unit) with 6 carbons (hexose).

Sucrose (glucose + fructose) is table sugar from sugarcane/beets.

Glycogen is the animal storage polysaccharide found in liver (maintains blood glucose) and muscle (provides energy for contraction).

Lactose (milk sugar) = glucose + galactose linked by β-1,4-glycosidic bond.

Cellulose has β-1,4-glycosidic bonds that human enzymes cannot hydrolyze (we lack cellulase).

The anomeric carbon is the carbonyl carbon (C1 in aldoses like glucose) that becomes a chiral center upon ring formation, creating α and β anomers.

Glycogen is highly branched with α-1,4 linear bonds and α-1,6 branch points (every 8-12 residues).

Most enzymes are proteins (some are RNA = ribozymes).

The active site is a 3D pocket where substrate binds and catalysis occurs.

Lock and key model (Fischer) proposes rigid complementary shapes between enzyme (lock) and substrate (key).

Oxidoreductases catalyze electron transfer (oxidation-reduction).

Competitive inhibitors structurally resemble substrate and compete for active site binding.

NAD⁺ (nicotinamide adenine dinucleotide) is derived from niacin (vitamin B3).

Km equals substrate concentration when reaction velocity is half of Vmax (V = Vmax/2).

Heme contains iron (Fe²⁺) at the center of protoporphyrin IX ring, enabling oxygen binding.

Liver stores most body iron as ferritin and hemosiderin.

Transferrin is the plasma protein that transports iron (2 Fe³⁺ ions per molecule) to tissues.

Ferritin is the major intracellular iron storage protein, found mainly in liver, spleen, and bone marrow.

Ferrous iron (Fe²⁺) is absorbed better than ferric (Fe³⁺).

ALA synthase (δ-aminolevulinic acid synthase) is the rate-limiting enzyme, catalyzing glycine + succinyl-CoA → ALA.

Heme synthesis begins and ends in mitochondria (ALA synthase, ferrochelatase), with intermediate steps in cytoplasm.

Heme → biliverdin (green) → bilirubin (yellow).

Unconjugated (indirect) bilirubin is lipid-soluble and toxic, so it binds albumin for safe transport to liver.

Hepatocytes conjugate bilirubin with glucuronic acid (via UDP-glucuronosyltransferase), making it water-soluble for biliary excretion.

In sickle cell disease, glutamic acid at position 6 of β-chain is replaced by valine (GAG→GTG mutation).

Thalassemias result from decreased or absent synthesis of α or β globin chains (quantitative defect), causing imbalanced chain production.

HbA (97% of adult hemoglobin) = α₂β₂.

HbF (α₂γ₂) binds 2,3-BPG less effectively than HbA because γ chains have reduced BPG binding.

Peptide bonds form between carboxyl group of one amino acid and amino group of another (condensation reaction).

Primary structure = amino acid sequence.

Secondary structure involves local folding patterns stabilized by hydrogen bonds between backbone atoms. α-helix is coiled; β-sheet is pleated.

Cysteine has a thiol (-SH) group that forms disulfide bonds (Cys-S-S-Cys), stabilizing protein structure.

Essential amino acids cannot be synthesized by humans and must come from diet (9 essential: His, Ile, Leu, Lys, Met, Phe, Thr, Trp, Val).

Denaturation disrupts secondary, tertiary, and quaternary structures while preserving primary sequence, leading to loss of function.

At pI, the amino acid exists as a zwitterion with equal positive and negative charges (net charge = 0).

Albumin comprises 55-60% of plasma proteins (~3.5-5 g/dL).

Albumin’s high concentration and inability to cross capillary walls creates oncotic (colloid osmotic) pressure, retaining fluid in vessels.

Albumin is a negative acute phase reactant–it decreases during inflammation.

Ceruloplasmin carries ~95% of plasma copper and has ferroxidase activity.

IgG is most abundant (~75-80% of serum immunoglobulins), crosses placenta, and provides long-term immunity.

IgM is produced first during primary immune response (pentameric, highly efficient at agglutination and complement activation).

Each antibody has 2 identical heavy chains and 2 identical light chains linked by disulfide bonds, forming a Y-shaped structure.

Cholesterol acts as a fluidity buffer in cell membranes–it prevents excessive fluidity at high temperatures and prevents rigidity at low temperatures.

Crenation (shrinkage with spiky projections) occurs when cells are placed in hypertonic solutions–water moves out by osmosis.

Facilitated diffusion uses carrier proteins (GLUT transporters) to move glucose down its concentration gradient without ATP.

The Na⁺/K⁺-ATPase normally pumps 3 Na⁺ out and 2 K⁺ in.

Simple diffusion through the lipid bilayer depends on lipid solubility (higher = faster) and molecular size (smaller = faster).

Potassium leak channels allow K⁺ efflux, maintaining the negative resting potential (around -70mV).

During the absolute refractory period, voltage-gated Na⁺ channels are inactivated (h-gate closed) and cannot respond to any stimulus until they reset.

The Nernst equation shows that equilibrium potential depends on the ion concentration gradient.

Cardiac phase 0 involves fast Na⁺ channels (like neurons) but also has L-type Ca²⁺ channels that contribute to the plateau.

If inactivation gates cannot close, Na⁺ channels remain open, causing prolonged Na⁺ influx and sustained depolarization.

Chemotaxis is directed cell movement along a chemical concentration gradient, used by leukocytes to reach infection sites.

Immotile cilia (Primary Ciliary Dyskinesia/Kartagener syndrome) causes impaired mucociliary clearance, leading to chronic respiratory infections, sinusitis, and bronchiectasis.

Amoeboid movement relies on actin polymerization (assembly) at the leading edge, pushing the membrane forward as pseudopodia.

Peritubular interstitial cells of the kidney sense hypoxia through HIF (Hypoxia-Inducible Factor) and produce 90% of erythropoietin.

EPO primarily acts on CFU-E (Colony Forming Unit-Erythroid) and proerythroblasts, promoting their survival and proliferation.

Old RBCs are removed by macrophages of the reticuloendothelial system primarily in the spleen (major) and liver.

Osmotic fragility tests RBC resistance to hypotonic solutions.

High reticulocyte count indicates active bone marrow response to RBC loss (hemolysis or hemorrhage).

Low MCV (70 fL, normal 80-100) indicates microcytic anemia.

Parietal cells produce intrinsic factor (IF), essential for B12 absorption in the terminal ileum.

Damaged kidneys produce insufficient erythropoietin (EPO), reducing bone marrow stimulation.

Sickle cell disease results from glutamic acid → valine substitution at position 6 of beta-globin (HbS).

High altitude causes chronic hypoxia, stimulating appropriate EPO increase from kidneys–this is physiological secondary polycythemia.

Polycythemia vera shows elevated all three cell lines, low EPO (marrow is autonomous), and aquagenic pruritus.

Left shift (immature neutrophils in blood) indicates acute demand exceeding mature neutrophil reserves–typically acute bacterial infection.

Eosinophils are primary defense against parasites (helminths) and are elevated in allergies.

Histamine is the primary preformed mediator causing immediate allergic symptoms–vasodilation, increased permeability, bronchoconstriction.

Monocytes differentiate into tissue macrophages (Kupffer cells, alveolar macrophages, microglia) and dendritic cells.

Kupffer cells are liver macrophages that filter portal blood, removing bacteria and debris.

Howell-Jolly bodies (nuclear remnants) are normally removed by splenic macrophages through pitting.

Selectins (E-selectin, P-selectin on endothelium) bind to carbohydrate ligands on neutrophils, causing rolling.

Vasodilation increases blood flow to the area, causing redness (rubor) and warmth (calor).

Pus consists mainly of dead/dying neutrophils, destroyed bacteria, and liquefied tissue debris (pyogenic inflammation).

Chronic inflammation features macrophages, lymphocytes, and plasma cells (mononuclear cells).

DiGeorge syndrome causes thymic aplasia, resulting in T-cell deficiency and impaired cell-mediated immunity.

Dendritic cells are the most potent APCs, essential for activating naïve T cells and initiating adaptive immunity.

MHC Class I presents endogenous (intracellular) antigens to CD8+ cytotoxic T cells.

NK cells have inhibitory receptors for MHC Class I.

CD4+ helper T cells (especially Th2) provide cytokines (IL-4, IL-21) that stimulate B-cell class switching.

Secondary/anamnestic response is faster (memory cells activated), produces higher titers of high-affinity IgG (affinity maturation).

IL-2 is the major T-cell growth factor, acting in autocrine and paracrine fashion to stimulate T-cell proliferation.

Humoral immunity (antibodies) is critical for extracellular encapsulated bacteria (opsonization needed for phagocytosis).

IFN-γ is the key macrophage-activating cytokine from Th1 cells, enhancing intracellular killing (increased ROS, NO).

Memory cells activate faster with lower antigen threshold and mount stronger responses (immunological memory).

MAC (C5b-C9) forms a transmembrane pore causing osmotic lysis–C9 polymerizes to form the actual pore.

Neisseria species are uniquely susceptible to MAC-mediated lysis because their thin cell wall lacks protection.

All three pathways generate C3 convertase, which cleaves C3 into C3a and C3b–the central amplification step.

Anaphylatoxins (C3a, C5a) trigger mast cell/basophil degranulation, increasing vascular permeability and inflammation.

Type I (immediate/anaphylactic) hypersensitivity involves IgE bound to mast cells, which degranulate upon allergen cross-linking.

Histamine is the main pre-formed (stored) mediator in mast cell granules, causing immediate symptoms.

Type II (cytotoxic) hypersensitivity involves antibodies (IgG/IgM) against cell surface antigens (ABO incompatibility), causing complement-mediated lysis or ADCC.

Type III hypersensitivity involves antigen-antibody (immune) complex deposition in tissues, activating complement and causing inflammation (SLE nephritis).

Type IV (delayed-type) hypersensitivity involves sensitized T cells (Th1) releasing cytokines (IFN-γ), recruiting macrophages causing induration.

Vasodilation and increased permeability cause plasma leak, decreased venous return, and distributive shock.

Von Willebrand Factor (vWF) bridges subendothelial collagen to platelet GPIb receptor, enabling initial adhesion.

Alpha granules contain adhesive proteins (fibrinogen, vWF, thrombospondin), growth factors (PDGF), and PF4.

Aspirin inhibits COX-1 in platelets, blocking TXA2 synthesis (promotes aggregation and vasoconstriction).

Factor Va is the essential cofactor in the prothrombinase complex (Xa + Va + Ca²⁺ + phospholipid) that converts prothrombin to thrombin.

Tissue factor (TF) binds Factor VII/VIIa, forming the TF-VIIa complex that initiates the extrinsic pathway.

Vitamin K-dependent factors are II, VII, IX, X (plus protein C and S).

Factor VII is exclusively in the extrinsic pathway.

Tissue plasminogen activator (tPA) from endothelium is the primary physiological activator of plasminogen.

Normal platelet count but prolonged bleeding time with normal PT/aPTT indicates qualitative platelet defect (e.g., Glanzmann’s, Bernard-Soulier).

Hemophilia A (Factor VIII deficiency) causes deep tissue/joint bleeding (hemarthroses) with prolonged aPTT (intrinsic pathway).

VWF both mediates platelet adhesion (primary hemostasis) AND stabilizes Factor VIII (prolongs its half-life). vWD affects both functions.

Factor VIII is synthesized primarily by liver sinusoidal endothelial cells and extrahepatic endothelium, not hepatocytes.

Factor V Leiden has a point mutation making it resistant to cleavage by activated Protein C (APC)–normally APC inactivates Va.

Heparin binds antithrombin, causing conformational change that enhances its activity 1000-fold against thrombin and Factor Xa.

Activated Protein C (APC) with Protein S as cofactor cleaves and inactivates Factor Va and VIIIa (cofactors that amplify coagulation).

Homocysteine causes endothelial injury, oxidative stress, increased smooth muscle proliferation, and prothrombotic state.

Type AB has both A and B antigens on RBCs and no anti-A or anti-B antibodies (universal recipient for ABO).

ABO isohemagglutinins are primarily IgM (naturally occurring, likely from gut bacteria cross-reactive antigens).

Reverse typing tests patient serum against known A and B reagent RBCs to detect isohemagglutinins, confirming forward typing results.

Rh D antigen is the most immunogenic and clinically significant. “Rh-positive” = D antigen present; “Rh-negative” = D absent.

Acute hemolytic transfusion reaction (ABO mismatch) causes intravascular hemolysis within minutes–fever, hypotension, flank pain, hemoglobinuria, DIC.

Febrile non-hemolytic reactions result from cytokines (IL-1, IL-6, TNF) accumulated during storage or recipient antibodies against donor WBC antigens.

TRALI is caused by donor anti-HLA or anti-neutrophil antibodies that activate recipient neutrophils in pulmonary vasculature, causing capillary leak.

Transfusional iron overload (hemosiderosis) deposits iron in heart (cardiomyopathy), liver (cirrhosis), and endocrine glands (diabetes, hypogonadism).

First pregnancy sensitizes the mother (IgM initially, then IgG).

Severe anemia triggers extramedullary hematopoiesis in fetal liver and spleen, releasing immature nucleated RBCs (erythroblasts) into circulation.

Anti-D immunoglobulin (RhoGAM) binds and destroys fetal Rh+ RBCs that enter maternal circulation, preventing maternal B-cell sensitization.

Unconjugated bilirubin crosses blood-brain barrier and deposits in basal ganglia, hippocampus, and brainstem nuclei (especially subthalamic nucleus, globus pallidus), causing kernicterus.

HLA genes are clustered on the short arm of chromosome 6 (6p21.3).

Beta-2 microglobulin (β2M) is the non-polymorphic light chain that associates with all HLA Class I heavy chains (HLA-A, B, C).

HLA Class II is constitutively expressed on professional APCs (dendritic cells, macrophages, B cells) and thymic epithelium.

HLA-A, B (Class I) and HLA-DR (Class II) are most important for transplant matching–they are highly polymorphic and immunogenic.

Acute GVHD classically affects skin (rash), liver (elevated bilirubin), and GI tract (diarrhea)–epithelia-rich organs.

HLA-B27 is strongly associated with seronegative spondyloarthropathies, especially ankylosing spondylitis (>90% association).

Antiporters move two different substances in opposite directions (e.g., Na+/Ca2+ exchanger).

Na+/K+-ATPase is a primary active transporter using energy directly from ATP hydrolysis (3 Na+ out, 2 K+ in per ATP).

Transferrin is the plasma protein that transports iron to tissues, especially bone marrow.

Haptoglobin binds free hemoglobin, forming a complex removed by hepatic macrophages, preventing renal damage.

HbF’s higher O2 affinity allows it to grab oxygen from maternal HbA at the placenta (HbA has lower affinity).

Rightward shift = decreased affinity = hemoglobin releases O2 more readily (increased delivery).

Methemoglobin has iron oxidized to Fe3+ (ferric), which cannot bind O2 (normal deoxy/oxy Hb has Fe2+).

Somatic hypermutation (SHM) introduces point mutations in Ig variable regions during germinal center reaction, enabling affinity maturation.

Maternal antibodies (IgG via placenta, IgA via breast milk) provide passive immunity–preformed antibodies without active immune response.

Maternal IgG (half-life ~21 days) declines while infant immune system is still developing–nadir around 3-6 months (transient hypogammaglobulinemia).

D-dimer is produced when plasmin cleaves cross-linked fibrin.

DIC causes consumption of factors (prolonged PT/aPTT), platelets (thrombocytopenia), and fibrinogen, with reactive fibrinolysis (elevated D-dimer).

Dynein arms are associated with microtubules in cilia and flagella (Kartagener syndrome).

Lysosomes maintain acidic pH (~5.0) through V-type (vacuolar) H⁺-ATPase, which pumps protons into the lysosomal lumen.

Misfolded proteins from the rough endoplasmic reticulum (RER) undergo ER-associated degradation (ERAD) via the ubiquitin-proteasome system.

Smooth endoplasmic reticulum (SER) contains cytochrome P450 enzymes, which metabolize drugs, toxins, and alcohol.

I-cell disease results from deficient N-acetylglucosamine-1-phosphotransferase, which fails to add mannose-6-phosphate (M6P) tags to lysosomal enzymes in the cis-Golgi.

Cohesin holds sister chromatids together until anaphase.

The spindle assembly checkpoint inhibits the anaphase-promoting complex/cyclosome (APC/C) until all kinetochores are properly attached.

Centrosomes (containing centrioles) organize mitotic spindle poles and normally duplicate once per S-phase.

The cleavage furrow contains a contractile ring of actin filaments and myosin II motor proteins that constrict to divide the cytoplasm during cytokinesis.

Taxol stabilizes microtubules, preventing the dynamic instability required for proper kinetochore-microtubule attachment and chromosome alignment.

The synaptonemal complex is fully formed during pachytene, when homologous chromosomes are completely synapsed, and crossing over (recombination) occurs.

Nondisjunction in anaphase I involves failure of homologous chromosomes to separate, with both homologs going to one daughter cell.

Primary oocytes arrest at diplotene stage (also called dictyate) of prophase I from fetal life until ovulation, potentially for decades.

Independent assortment occurs at metaphase I when bivalents (homologous pairs) align randomly at the metaphase plate.

Before anaphase II, each chromosome consists of 2 sister chromatids joined at the centromere (haploid but replicated: n, 2c).

FSH receptors on Sertoli cells activate intracellular signaling that supports spermatocyte meiosis and early spermiogenesis.

The Golgi apparatus packages hydrolytic enzymes (hyaluronidase, acrosin) into vesicles that coalesce to form the acrosomal cap covering the sperm nucleus.

Tight junctions between Sertoli cells form the blood-testis barrier, creating an immunologically privileged adluminal compartment for meiotic and post-meiotic germ cells.

The sperm flagellum contains a 9+2 axoneme: nine peripheral microtubule doublets surrounding two central singlet microtubules, identical to motile cilia.

Mature spermatozoa are released from Sertoli cell cytoplasm into the tubular lumen at the adluminal compartment during spermiation.

Primordial follicles contain a primary oocyte surrounded by a single layer of flattened (squamous) granulosa cells.

Granulosa cells secrete follicular fluid (liquor folliculi) rich in hyaluronic acid, hormones, and proteins, creating the antrum in secondary follicles.

The dominant follicle acquires LH receptors on granulosa cells, allowing response to the LH surge that triggers ovulation and luteinization.

The ovulated secondary oocyte arrests at metaphase II until sperm penetration triggers calcium waves that inactivate cytostatic factor (CSF), allowing completion of meiosis II.

The corpus luteum begins regressing (luteolysis) around days 10-12 post-ovulation if no pregnancy occurs, though it remains functional until approximately day 14.

The stratum basalis (basal layer) contains stem cells and is supplied by straight arteries, surviving menstruation.

Spiral arteries supply the functionalis layer and undergo characteristic coiling during the secretory phase.

Granulosa lutein cells (large luteal cells) produce the majority (~80%) of progesterone in the corpus luteum.

HCG binds to LH receptors on corpus luteum cells because hCG and LH share similar β-subunits.

The fertile window spans approximately days 10-17, considering sperm survival (3-5 days before ovulation) and oocyte viability (~24 hours after).

Capacitation occurs in the uterus and fallopian tubes over several hours, involving removal of cholesterol, increased membrane fluidity, and tyrosine phosphorylation preparing sperm for acrosome reaction.

Calcium influx triggered by ZP3 binding activates the acrosome reaction.

Cortical granule enzymes cleave and modify ZP3, preventing additional sperm from binding and initiating acrosome reaction.

Implantation begins around day 6-7 post-fertilization when the hatched blastocyst attaches to endometrium (usually posterior superior uterine wall).

Syncytiotrophoblast secretes multiple enzymes including collagenases, plasminogen activators, and matrix metalloproteinases (MMPs) that degrade extracellular matrix for invasion.

Approximately 70-80% of tubal ectopic pregnancies occur in the ampulla, the widest portion where fertilization normally occurs.

Neural crest cells originate from neuroectoderm (ectoderm) at the lateral borders of the neural plate.

Endoderm forms liver parenchyma (hepatocytes, biliary epithelium) from the hepatic diverticulum of foregut.

Neurulation is the process where the neural plate folds to form the neural tube, beginning around week 3.

Sclerotome cells migrate medially to surround the neural tube and notochord, forming vertebrae, ribs, and part of skull base (occipital bone).

The epiblast gives rise to all three germ layers (ectoderm, mesoderm, endoderm) and therefore the entire embryo proper.

The primitive streak appears at day 15 on the epiblast surface, establishing craniocaudal axis.

Weeks 3-8 (embryonic period) involve organogenesis when major organ systems are forming, making this the most sensitive period for teratogenic effects.

Embryonic folding incorporates the dorsal part of yolk sac into the embryo as the primitive gut (foregut, midgut, hindgut), which develops into the GI tract lining.

External genitalia become distinguishable between males and females around week 12, though complete development continues.

The right iliac (inguinal) region lies medial to the ASIS and inferior to the umbilicus on the right side, containing the cecum and appendix.

A transverse (horizontal/axial) plane divides the body into superior and inferior portions, showing anterior-posterior relationships between structures at the same level.

Abduction (and adduction) of limbs occurs in the coronal (frontal) plane, moving limbs away from (abduction) or toward (adduction) the body’s midline.

Superficial fascia (subcutaneous tissue/hypodermis) lies between skin and deep fascia, containing fat, cutaneous nerves, and superficial vessels.

Proximal means closer to the trunk or point of attachment (origin) of a limb.