Week 20 RAT

OMK Block 3 Week 20 PLOs

Average total blood volume

5L (7% of body weight); men 75 mL/kg, women 65 mL/kg

Systemic veins & venules

Contain 65–70% of blood volume; major reservoir

Systemic arteries

Contain 10–15% of blood; pressure reservoir

Pulmonary circulation

Contains 10–12% of blood; low-pressure system

Heart chambers

Contain 7–8% of blood volume

Capillaries

Contain 5% of blood; site of exchange

Cardiac output distribution at rest

GI tract/liver 25%, kidneys 20%, skeletal muscle 20%, brain 13–15%, skin 5–10%, coronary 4–5%, other <5%

Arteries structure

Thick walls, smooth muscle, elastic tissue; low compliance

Arteries function

Carry blood under high pressure; maintain flow via elastic recoil

Arterioles structure

Small diameter, thick smooth muscle layer

Arterioles function

Major resistance vessels; regulate flow and TPR

Capillaries structure

Single endothelial layer; no muscle

Capillaries function

Site of gas, nutrient, and waste exchange

Venules & veins structure

Thin walls, large lumens, valves; less smooth muscle

Venules & veins function

Return blood to heart; volume reservoir; high compliance

Pressure

Force per unit area (mmHg)

Pressure gradient

Difference between two points driving flow

Transmural pressure

P(inside) – P(outside); determines vessel diameter and wall tension

Hydrostatic pressure

Pressure from gravity in a fluid column; increases with depth

Mean arterial pressure (MAP)

≈93 mmHg

Aortic pressure

120/80 mmHg

Arteriolar pressure

80→35 mmHg; greatest pressure drop

Capillary pressure

35→15 mmHg

Venous pressure

15→5 mmHg; right atrium 2–5 mmHg

Supine pressure

Hydrostatic effects minimal

Upright pressure

Gravity ↑ venous pressure in legs; ↓ pressure in upper body; valves prevent pooling

Flow (Q)

Volume per unit time (mL/min)

Resistance (R)

Opposition to flow; depends on radius, viscosity, and length

Velocity (v)

Distance per time (cm/s); v = Q/A

Flow equation

MAP = CO × TPR

Laminar flow

Smooth, layered flow; highest velocity at center; Re < 2000

Turbulent flow

Chaotic, mixing flow; Re > 2000; caused by ↑ velocity, ↑ diameter, ↓ viscosity

Active hyperemia

Increased blood flow with ↑ metabolism

Local vasodilators

↓O₂, ↑CO₂, ↑H⁺, ↑K⁺, ↑adenosine, ↑temperature

Reactive hyperemia

Transient ↑ flow after occlusion removal

Endothelium-derived factors

Nitric oxide (dilator), endothelin-1 (constrictor), prostacyclin (dilator)

Cholesterol structure

Steroid nucleus, OH at C3, hydrocarbon tail at C17, double bond in ring B

Cholesterol functions

Membrane fluidity; precursor for bile acids, steroid hormones, vitamin D3

Chylomicrons

High TG, low protein; transport dietary TGs to tissues

Chylomicron remnants

Cholesterol-rich; deliver dietary cholesterol to liver via ApoE

VLDL

High TG, some cholesterol; transport hepatic TGs to tissues

LDL

Cholesterol-rich; deliver cholesterol to tissues (“bad”)

HDL

High protein; reverse cholesterol transport (“good”)

Exogenous lipid pathway

Dietary lipids → chylomicrons (ApoB-48) → LPL hydrolyzes TGs → remnants to liver via ApoE

Endogenous lipid pathway

Liver lipids → VLDL (ApoB-100) → LPL forms IDL → LDL → tissues via LDL receptors; HDL returns cholesterol to liver

Single-nucleotide variants (SNVs)

Single base substitution (e.g. sickle cell)

Insertions/deletions (indels)

Addition or loss of nucleotides (e.g. frameshift)

Copy number variations (CNVs)

Gain or loss of large DNA segments (e.g. DiGeorge)

Microsatellites (STRs)

Short repeating DNA units (e.g. Huntington’s)

Chromosomal rearrangements

Translocations, inversions, duplications, deletions (e.g. Philadelphia chromosome)

Epigenetic modifications

DNA methylation, histone acetylation; alter expression without sequence change

Endogenous mutation sources

DNA replication errors, deamination (C→U), depurination, repair/recombination errors

Exogenous mutation sources

Radiation, chemical mutagens, viruses, oxidative stress

Hardy-Weinberg equilibrium

Frequencies constant if no drift, mutation, migration, selection, or nonrandom mating

Hardy-Weinberg uses

Estimate carrier frequency; predict risk; check genotyping accuracy

Hardy-Weinberg limitations

Assumptions rarely met; real populations deviate

Genome

All DNA (coding + noncoding) in nucleus and mitochondria

Exome

All protein-coding regions (exons); ~85% of disease mutations

Mean

Arithmetic average; affected by outliers

Median

Middle value; resistant to outliers

Mode

Most frequent value; used for categorical data

Variance

Average of squared deviations from mean

Standard deviation (SD)

Square root of variance; spread of data

Standard error (SE)

SD/√n; variability of sample means around population mean

P value

Probability results occurred by chance under null hypothesis

Alpha (α)

Significance threshold, often 0.05

Interpretation of P value

P < α → reject null; P ≥ α → fail to reject null

Type I error

False positive; reject true null; false claim of difference

Type II error

False negative; fail to reject false null; miss real effect

Power

1 – β; low power ↑ Type II error risk

Cholesterol structural feature

Four fused hydrocarbon rings with –OH at C3, hydrocarbon tail at C17

Saturated fatty acid

All single bonds; straight chain; solid at room temp

Monounsaturated fatty acid

One cis double bond; one kink

Polyunsaturated fatty acid

≥2 cis double bonds; flexible; oxidized easily

Omega-6 fatty acid

First double bond at C6 from ω-end; linoleic family

Omega-3 fatty acid

First double bond at C3 from ω-end; α-linolenic, EPA, DHA

Short-chain fatty acid

≤6 carbons; soluble; gut-derived

Medium-chain fatty acid

6–12 carbons; rapidly metabolized

Long-chain fatty acid

≥14 carbons; need carnitine transport

Even-chain fatty acid

2-carbon units from acetyl-CoA; normal human synthesis

Odd-chain fatty acid

Ends in propionyl-CoA; from dairy/bacteria

Essential fatty acids

Linoleic and α-linolenic acids; cannot be synthesized