Cell Biology · Human Genetics · Pharmacology Principles

General Principles · 3 min read

Cell Biology · Human Genetics · Pharmacology Principles

Cell Structure

Plasma membrane: phospholipid bilayer with embedded proteins. Fluid mosaic model. Functions include selective permeability, signal transduction, cell recognition.

Nucleus contains genetic material, nucleolus (ribosome synthesis). Nuclear envelope has double membrane with nuclear pores.

Endoplasmic reticulum

rough ER (ribosomes, protein synthesis), smooth ER (lipid synthesis, detoxification, calcium storage).

Golgi apparatus

protein modification, sorting, packaging.

Mitochondria

ATP production, apoptosis regulation. Maternal inheritance of mitochondrial DNA.

Lysosomes

contain hydrolytic enzymes for intracellular digestion. Lysosomal storage diseases result from enzyme deficiencies (Tay-Sachs, Gaucher, Niemann-Pick).

Peroxisomes

beta-oxidation of very-long-chain fatty acids, detoxification.

Cell Cycle

Phases: G1 (growth), S (DNA synthesis), G2 (preparation for mitosis), M (mitosis). G0 is quiescent state.

Cyclins and cyclin-dependent kinases (CDKs) regulate progression. Checkpoints: G1/S (DNA damage check), G2/M (replication completion check), spindle checkpoint (chromosome attachment).

Tumor suppressors (p53, Rb) inhibit cell cycle. Oncogenes promote cell proliferation.

Cell Death

Apoptosis: programmed cell death, characterized by cell shrinkage, chromatin condensation, apoptotic bodies, no inflammation. Caspases are key executioners.

Necrosis: pathologic cell death from injury, characterized by cell swelling, membrane rupture, inflammation.

Inheritance Patterns

Autosomal dominant

affected individuals in every generation, 50% offspring risk, males and females equally affected. Examples: Huntington disease, Marfan syndrome, neurofibromatosis type 1, familial hypercholesterolemia.

Autosomal recessive

often skips generations, 25% offspring risk when both parents are carriers, consanguinity increases risk. Examples: cystic fibrosis, sickle cell disease, phenylketonuria, Tay-Sachs disease.

X-linked recessive

primarily affects males, transmitted by carrier females, no male-to-male transmission. Examples: hemophilia A and B, Duchenne muscular dystrophy, G6PD deficiency.

X-linked dominant

affects males and females, may be lethal in males. Example: Rett syndrome.

Mitochondrial inheritance

maternal transmission, variable expression. Examples: Leber hereditary optic neuropathy, MELAS.

Chromosomal Abnormalities

Aneuploidy: abnormal chromosome number. Trisomy 21 (Down syndrome): intellectual disability, characteristic facies, congenital heart defects, increased Alzheimer risk. Trisomy 18 (Edwards syndrome): severe intellectual disability, rocker-bottom feet, clenched fists, early death. Trisomy 13 (Patau syndrome): holoprosencephaly, cleft lip/palate, polydactyly.

Sex chromosome abnormalities: Turner syndrome (45,X) — short stature, webbed neck, streak gonads, coarctation of aorta. Klinefelter syndrome (47,XXY) — tall stature, gynecomastia, small testes, infertility.

Genetic Testing Concepts

Sensitivity: ability to detect disease when present (true positive rate). Specificity: ability to rule out disease when absent (true negative rate). Positive predictive value: probability of disease given positive test. Negative predictive value: probability of no disease given negative test.

Pharmacokinetics

Absorption

bioavailability is fraction of drug reaching systemic circulation. IV administration has 100% bioavailability. First-pass metabolism reduces oral bioavailability.

Distribution

volume of distribution (Vd) reflects drug distribution in body compartments. High Vd indicates extensive tissue binding. Protein binding affects free drug concentration.

Metabolism

primarily hepatic. Phase I reactions (oxidation, reduction, hydrolysis) via cytochrome P450 enzymes. Phase II reactions (conjugation) increase water solubility. CYP450 inducers (rifampin, phenytoin, carbamazepine) increase metabolism. CYP450 inhibitors (ketoconazole, erythromycin, grapefruit juice) decrease metabolism.

Elimination

renal excretion is primary route for many drugs. Half-life is time for plasma concentration to decrease by 50%. Steady state reached after approximately 4-5 half-lives.

Pharmacodynamics

Drug-receptor interactions: agonists activate receptors; antagonists block receptors. Potency reflects drug concentration needed for effect (related to affinity). Efficacy reflects maximum response achievable.

Dose-response relationships: therapeutic index = LD50/ED50 (higher is safer). Narrow therapeutic index drugs require monitoring (warfarin, lithium, digoxin, phenytoin, theophylline).

Adverse Drug Reactions

Type A (augmented)

predictable, dose-dependent, related to pharmacologic action.

Type B (bizarre)

unpredictable, not dose-dependent, includes allergic reactions and idiosyncratic reactions.

Drug-drug interactions

pharmacokinetic (affecting absorption, distribution, metabolism, excretion) or pharmacodynamic (additive, synergistic, antagonistic effects).

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Cell Biology · Human Genetics · Pharmacology Principles

Cell Structure

Plasma membrane: phospholipid bilayer with embedded proteins. Fluid mosaic model. Functions include selective permeability, signal transduction, cell recognition.

Nucleus contains genetic material, nucleolus (ribosome synthesis). Nuclear envelope has double membrane with nuclear pores.

Endoplasmic reticulum

rough ER (ribosomes, protein synthesis), smooth ER (lipid synthesis, detoxification, calcium storage).

Golgi apparatus

protein modification, sorting, packaging.

Mitochondria

ATP production, apoptosis regulation. Maternal inheritance of mitochondrial DNA.

Lysosomes

contain hydrolytic enzymes for intracellular digestion. Lysosomal storage diseases result from enzyme deficiencies (Tay-Sachs, Gaucher, Niemann-Pick).

Peroxisomes

beta-oxidation of very-long-chain fatty acids, detoxification.

Cell Cycle

Phases: G1 (growth), S (DNA synthesis), G2 (preparation for mitosis), M (mitosis). G0 is quiescent state.

Cyclins and cyclin-dependent kinases (CDKs) regulate progression. Checkpoints: G1/S (DNA damage check), G2/M (replication completion check), spindle checkpoint (chromosome attachment).

Tumor suppressors (p53, Rb) inhibit cell cycle. Oncogenes promote cell proliferation.

Cell Death

Apoptosis: programmed cell death, characterized by cell shrinkage, chromatin condensation, apoptotic bodies, no inflammation. Caspases are key executioners.

Necrosis: pathologic cell death from injury, characterized by cell swelling, membrane rupture, inflammation.

Inheritance Patterns

Autosomal dominant

Autosomal recessive

often skips generations, 25% offspring risk when both parents are carriers, consanguinity increases risk. Examples: cystic fibrosis, sickle cell disease, phenylketonuria, Tay-Sachs disease.

X-linked recessive

primarily affects males, transmitted by carrier females, no male-to-male transmission. Examples: hemophilia A and B, Duchenne muscular dystrophy, G6PD deficiency.

X-linked dominant

affects males and females, may be lethal in males. Example: Rett syndrome.

Mitochondrial inheritance

maternal transmission, variable expression. Examples: Leber hereditary optic neuropathy, MELAS.

Chromosomal Abnormalities

Genetic Testing Concepts

Pharmacokinetics

Absorption

bioavailability is fraction of drug reaching systemic circulation. IV administration has 100% bioavailability. First-pass metabolism reduces oral bioavailability.

Distribution

volume of distribution (Vd) reflects drug distribution in body compartments. High Vd indicates extensive tissue binding. Protein binding affects free drug concentration.

Metabolism

Elimination

renal excretion is primary route for many drugs. Half-life is time for plasma concentration to decrease by 50%. Steady state reached after approximately 4-5 half-lives.

Pharmacodynamics

Dose-response relationships: therapeutic index = LD50/ED50 (higher is safer). Narrow therapeutic index drugs require monitoring (warfarin, lithium, digoxin, phenytoin, theophylline).

Adverse Drug Reactions

Type A (augmented)

predictable, dose-dependent, related to pharmacologic action.

Type B (bizarre)

unpredictable, not dose-dependent, includes allergic reactions and idiosyncratic reactions.

Drug-drug interactions

pharmacokinetic (affecting absorption, distribution, metabolism, excretion) or pharmacodynamic (additive, synergistic, antagonistic effects).

Finished reading?

Lock it in with a quick General Principles quiz.

Quiz me Next chapter →

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