Title: InkBiology / Nutrition, digestion and health evidence
On every note of this deck, unless a note says otherwise:
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Front: DEFINE
Define: Thrombosis.
Back: The formation of a blood clot inside a blood vessel, most often on a ruptured atheroma, which may block the vessel completely.

Front: DEFINE
Define: Indirect active transport.
Back: Transport that is driven by a gradient which was itself established using ATP elsewhere in the cell. Glucose uptake in the ileum is the standard example.

Front: DEFINE
Define: Digestion.
Back: The hydrolysis of large insoluble biological molecules into small soluble molecules that can be absorbed across cell membranes.

Front: CHECK YOURSELF
A case-control study of 600 people with type 2 diabetes and 600 matched controls finds that the cases drank sugar-sweetened drinks more often, with an odds ratio of 1.7. Explain what this study can and cannot establish, and describe the study you would want next.
Back: It establishes an association between recalled consumption of sugar-sweetened drinks and having a diagnosis of type 2 diabetes, measured as an odds ratio of 1.7. Because the investigators chose how many cases and controls to recruit, this is not a risk and should not be reported as a 70% higher risk.
It cannot establish the time order. Both groups were asked after diagnosis, so the drinking may have preceded the disease or followed it, and people who have been told they have diabetes may also recall their past differently from people who have not, and recall bias operates in the direction that inflates the finding.
It cannot rule out confounding. Sugary drink consumption is associated with total energy intake, body mass, income and physical activity, each of which affects diabetes risk independently, and matching controls on age and sex does nothing about any of them.
What comes next is a prospective cohort: recruit people without diabetes, measure consumption at the start and repeatedly afterwards, follow them for a decade or more, and record who is diagnosed. That fixes the time order, gives a genuine relative risk and allows a dose-response to be looked for. A randomised trial of an intermediate outcome, such as insulin sensitivity over a year, would test the mechanism directly even though it could not run long enough to count cases.

Front: DEFINE
Define: Case-control study.
Back: People who already have the disease are compared with matched people who do not, and both groups are asked about past exposure. Fast and efficient for rare diseases; yields an odds ratio, not a risk.

Front: DEFINE
Define: Relative risk.
Back: The risk in the exposed group divided by the risk in the unexposed group; 1 means no association.

Front: DEFINE
Define: Co-transport.
Back: The transport of two substances across a membrane through the same carrier protein at the same time, one moving down its concentration gradient and providing the means for the other to move against its own.

Front: DEFINE
Define: Exopeptidase.
Back: An enzyme that hydrolyses the peptide bond at an end of a chain, removing a single amino acid. Carboxypeptidases work from the end carrying the free carboxyl group, aminopeptidases from the amine end.

Front: DEFINE
Define: Endopeptidase.
Back: An enzyme that hydrolyses peptide bonds within a polypeptide chain, producing shorter chains and so more ends. Pepsin, trypsin and chymotrypsin.

Front: DEFINE
Define: Aneurysm.
Back: A localised bulge in an artery wall that has been weakened, which may rupture and cause severe internal bleeding.

Front: SPOT THE ERROR
Say what is wrong with this claim:
This study followed half a million people, so the result is reliable, because a sample that large settles the question.
Back: A large sample buys precision, not accuracy. It narrows the confidence interval and shrinks random error, and it does nothing at all about confounding: half a million people whose vegetable intake tracks their income measures that bundle very precisely.

Front: SPOT THE ERROR
Say what is wrong with this claim:
HDL and LDL are two kinds of cholesterol, one good and one bad.
Back: There is one cholesterol molecule, and the cholesterol in an HDL particle is chemically identical to the cholesterol in an LDL particle. HDL and LDL are the particles that carry it, differing in density, size, surface proteins and destination.

Front: DEFINE
Define: Physical digestion.
Back: The mechanical breakdown of food into smaller pieces, increasing the surface area available to digestive enzymes without hydrolysing anything.

Front: DEFINE
Define: Randomised controlled trial.
Back: Participants are allocated by chance, so the groups are balanced on every variable, including the ones nobody thought to measure.

Front: DEFINE
Define: Atheroma.
Back: A plaque in the wall of an artery, consisting of lipid, foam cells and cell debris beneath a fibrous cap, which narrows the lumen and stiffens the wall.

Front: DEFINE
Define: Dipeptidase.
Back: An enzyme, bound to the membrane of the ileum epithelium, that hydrolyses a dipeptide into two amino acids.

Front: DEFINE
Define: Absorption.
Back: The movement of the products of digestion from the lumen of the gut, across the epithelium, into the blood or the lymph.

Front: CHECK YOURSELF
A drug under development blocks the sodium-potassium pumps in the epithelial cells of the ileum. Predict and explain its effect on the absorption of glucose, of amino acids and of the products of lipid digestion.
Back: Glucose absorption falls to almost nothing once the existing gradient has run down. The pump is what keeps sodium low inside the cell; without it, sodium no longer moves in down a steep gradient, so the co-transporter has nothing driving it and glucose cannot be taken up against its own gradient.
Amino acid absorption falls by the same mechanism, since amino acids are also carried in on sodium co-transporters.
Absorption of monoglycerides and fatty acids is unaffected. They are non-polar and cross by simple diffusion, using no carrier and no gradient the pump maintains, and the bile salts that deliver them are unaffected too.
The point being tested: a treatment aimed at one transport mechanism affects only the substances that use it, so knowing how each product crosses the membrane is what lets you predict anything.

Front: SPOT THE ERROR
Say what is wrong with this claim:
Bile is the enzyme that digests fat.
Back: Bile contains no enzymes at all. Bile salts emulsify, breaking large lipid droplets into small ones, which changes no chemistry but multiplies the surface available for it. The enzyme is pancreatic lipase.

Front: CHECK YOURSELF
A man of 58 has a total blood cholesterol concentration in the highest fifth for his age. His doctor tells him this is a risk factor for cardiovascular disease, and he replies that his father had the same reading and lived to 92. Explain, in terms of what a risk factor is, why both statements can be true, and what additional information would help.
Back: A risk factor describes a population, not a person. Saying that a high cholesterol concentration is a risk factor means that among many people with that reading, more will have a cardiovascular event over a given period than among people with a lower one. It predicts nothing about any individual.
His father is one observation. A single person with a high reading and a long life is exactly what a probabilistic claim predicts will sometimes happen, so it is not evidence against the association.
Total cholesterol is also the wrong measurement to argue about, because it lumps together cholesterol carried in LDL particles, which is associated with disease, and cholesterol carried in HDL particles, which is not associated with it in the same direction. Two people with identical totals can carry very different LDL concentrations.
What would help is his absolute risk rather than one measurement: LDL specifically, plus blood pressure, smoking status, diabetes, family history and age, combined into an estimated probability of an event over ten years. That turns a risk factor into a number he can weigh against the benefits and drawbacks of treatment.

Front: DEFINE
Define: Cohort study.
Back: A group of people free of the disease is recruited, their exposure is recorded, and they are followed forward in time to see who develops it. Gives incidence and relative risk directly, and gets the time order right by construction.