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The method Topics Home Free lesson
Topics

Basic science, read two ways.

Molecular depth
Go down to the molecule. The enzyme, the channel, the receptor, the toxin, the membrane lipid. Every disease has a part you can name.
The deep why
Go down the chain of reasons. Why does the structure suit the job, why does this break give this sign, and why does this drug fix it?
Molecular core Microbiology Anatomy, histology, physiology
FEATURED LESSON · OPEN NOW
Megaloblastic anemia: four doors, one stalled nucleotide
B12 and the methyl-folate trap, folate deficiency, vitamin metabolism defects, and orotic aciduria. The lab fingerprints that tell them apart, and why folic acid alone is a trap.
Molecular core

Biochemistry, genetics, cell biology.

The machinery that every other subject depends on.

BIOCHEMISTRY · OPEN
Pyrimidine synthesis and orotic aciduria
UMP synthase fails, so there is no dTMP and B12 and folate do nothing. High orotic acid with high ammonia means OTC deficiency instead.
BIOCHEMISTRY · OPEN
One-carbon metabolism
Folate, B12, homocysteine and methionine in one loop. The methyl-folate trap, and the cblC, cblE and cblG defects.
GENETICS
DNA repair syndromes
Nucleotide excision repair fails in xeroderma pigmentosum. Mismatch repair fails in Lynch syndrome. Ataxia telangiectasia is a double-strand break defect.
CELL BIOLOGY
Protein trafficking
I-cell disease loses the mannose-6-phosphate tag, so lysosomal enzymes leave the cell instead of reaching the lysosome.
PHARMACOLOGY
Antimetabolites
Methotrexate blocks DHFR, 5-FU blocks thymidylate synthase, hydroxyurea blocks ribonucleotide reductase. Three drugs, three steps.
Microbiology

Cell and molecular biology of bacteria, fungi and parasites, and how they meet the human host.

Bacteria
THEIR CELL
Peptidoglycan is built by penicillin-binding proteins, which is where beta-lactams act. Gram-negative outer membranes carry LPS, and its lipid A is the toxic part.
THE MEETING POINT
Lipid A binds TLR4 and drives septic shock. Toxins are enzymes: diphtheria toxin ADP-ribosylates EF-2, cholera toxin locks Gs on, pertussis toxin locks Gi off, and Shiga toxin cuts 28S rRNA.
EVASION
Protein A grabs the Fc end of IgG, M protein blocks phagocytosis, and IgA protease cleaves mucosal antibody.
Fungi
THEIR CELL
Fungi are eukaryotes, so their membrane uses ergosterol where ours uses cholesterol. The wall is chitin and beta-glucan, which humans do not make.
WHY THE DRUGS WORK
Azoles inhibit 14-alpha-demethylase and terbinafine inhibits squalene epoxidase, both in ergosterol synthesis. Amphotericin B binds ergosterol and makes pores. Echinocandins block beta-glucan synthase.
THE MEETING POINT
Thermal dimorphs grow as mold in the soil and as yeast at 37°C. Control depends on T-cell immunity, so defects there open the door to Candida and Pneumocystis.
Parasites
THEIR CELL
Plasmodium digests hemoglobin in its food vacuole and detoxifies the heme into hemozoin. Chloroquine blocks that step, so toxic heme builds up inside the parasite.
THE MEETING POINT
P. vivax enters red cells through the Duffy antigen. P. falciparum displays PfEMP1, which sticks infected cells to vessel walls. Sickle trait protects against it.
EVASION
Trypanosomes swap their surface coat (VSG), so each antibody wave arrives late. Vivax and ovale leave dormant hypnozoites in the liver, which is why primaquine is needed.
Structure and function

Anatomy, histology and physiology. The shape explains the job.

Anatomy
Fracture level predicts the nerve. A surgical neck fracture of the humerus threatens the axillary nerve. A midshaft fracture threatens the radial nerve in its spiral groove.
Embryology explains the odd route. The left recurrent laryngeal nerve hooks under the ligamentum arteriosum, so a thoracic aneurysm can cause hoarseness.
Histology
Epithelium follows stress. Barrett esophagus replaces stratified squamous cells with columnar cells and goblet cells, which is intestinal metaplasia from chronic acid exposure.
Type II pneumocytes do two jobs. They make surfactant and they regenerate type I cells after injury.
Physiology
A transporter explains the electrolyte. Loop diuretics block NKCC2 in the thick ascending limb. The lumen-positive voltage that pulls Ca²⁺ and Mg²⁺ through the paracellular path disappears, so both are lost.
Curves are mechanisms. Frank-Starling follows from sarcomere length and calcium sensitivity, and a failing ventricle sits on a flatter curve.
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