Week 20 ALL

OMK Week 20 material all

Average blood volume

5 liters of blood; ~7% of body weight

Blood volume men

75 mL/kg

Blood volume women

65 mL/kg

Systemic veins function

main blood reservoir holding 65–70% of blood volume

Systemic arteries function

distribute oxygenated blood under high pressure

Pulmonary circulation volume

10–12% of total blood volume

Heart blood volume

7–8% of total blood volume

Capillary blood volume

~5% of total blood; primary exchange site

Resting CO distribution GI

25% of cardiac output

Resting CO distribution kidneys

20% of cardiac output

Resting CO distribution skeletal muscle

20% of cardiac output

Resting CO distribution brain

13–15% of cardiac output

Resting CO distribution skin

5–10%

Resting CO distribution coronary

4–5%

Artery structure

thick wall, elastic tissue, smooth muscle; low compliance

Arteriole structure

major resistance vessels; regulate TPR and blood flow distribution

Capillary structure

single endothelial layer; site of nutrient and gas exchange

Vein structure

thin walls, large lumen, valves; highly compliant

Pressure definition

force per unit area; measured in mmHg

Pressure gradient

pressure difference that drives blood flow

Transmural pressure

pressure inside vessel minus pressure outside

Hydrostatic pressure

pressure due to gravity; increases with vertical distance

Supine pressure changes

minimal hydrostatic effects; uniform pressures

Standing pressure changes

gravity increases venous pressure in legs and decreases pressure above heart

Flow definition

volume of blood moved per unit time (mL/min)

Resistance definition

opposition to flow determined by radius, viscosity, length

Velocity definition

distance blood travels per time; v = Q/A

Ohm’s law circulation

MAP = CO × TPR; Flow = ΔP / R

Laminar flow

smooth, layered flow with fastest velocity at center

Turbulent flow

disordered flow occurring with high velocity or low viscosity; creates murmurs

Reynolds number

predicts turbulence; Re > 2000 suggests turbulence

Active hyperemia

increased blood flow due to increased metabolism

Reactive hyperemia

increased blood flow following ischemia or occlusion

Local metabolic vasodilation

mediators: decreased O2, increased CO2, H+, K+, adenosine, temperature

Endothelium-derived NO

potent vasodilator that increases cGMP

Endothelin-1

potent vasoconstrictor released by endothelium

Prostacyclin

vasodilator; inhibits platelet aggregation

Autoregulation

local control of blood flow independent of neural input

Law of continuity

Q = velocity × area; small area = higher velocity

Bernoulli principle

increased fluid velocity reduces pressure; relevant in stenosis

Poiseuille’s law

flow proportional to radius^4 and ΔP; inversely to viscosity and length

Windkessel effect

aortic recoil maintains continuous blood flow during diastole

Pulse pressure

systolic minus diastolic pressure; increases with lower arterial compliance

Sympathetic effect vessels

alpha-1 activation causes vasoconstriction

Parasympathetic effect vessels

NO-mediated vasodilation in limited beds

Smooth muscle contraction trigger

increase in intracellular Ca2+

Smooth muscle Ca2+ sources

SR release and extracellular Ca2+ influx

IP3-mediated Ca2+ release

Gq → PLC → IP3 → SR Ca2+ release

Calmodulin role

binds Ca2+ and activates MLCK

MLCK function

phosphorylates myosin light chain to enable cross-bridge cycling

MLCP function

dephosphorylates myosin light chain to relax smooth muscle

Rho kinase role

inhibits MLCP leading to increased contraction

Nitric oxide effect

activates cGMP → activates MLCP → relaxation

Latch state mechanism

maintains force with low ATP consumption

ATP roles in smooth muscle

detaches myosin, re-cocks myosin head, pumps Ca2+ back into SR

MLCK regulation

upregulated by Ca-calmodulin; inhibited by cAMP/PKA

MLCP regulation

inhibited by Rho kinase; activated by NO/cGMP

Genetic variation definition

differences in DNA sequence among individuals

SNV

single nucleotide variant; most common form of variation

Insertion

deletion or addition of one or more nucleotides

Deletion

loss of nucleotides; may cause frameshift

Frameshift mutation

shift in reading frame leading to altered protein

Copy number variation

large-scale duplications or deletions

Microsatellite

repeat of 2–6 bp motifs; highly variable

Structural variant

larger rearrangements such as inversions, deletions, translocations

Epigenetic modification

changes in gene expression without altering DNA sequence

DNA methylation

typically suppresses gene expression

Histone acetylation

increases gene expression by loosening chromatin

Endogenous mutation sources

replication errors, deamination, depurination

Exogenous mutation sources

UV radiation, chemicals, oxidative stress

Hardy-Weinberg equilibrium

state where allele frequencies remain constant in absence of evolutionary forces

Hardy-Weinberg conditions

large population, random mating, no mutation, no migration, no selection

Genome

complete DNA content including coding and non-coding sequences

Exome

all protein-coding exons; rich in disease-causing variants

Whole genome sequencing

sequences entire genome; detects all variant types

Exome sequencing

sequences coding regions only; cost-effective

Point estimate

single statistic describing sample (mean, proportion)

Central tendency

mean, median, mode

Dispersion

variance, standard deviation, range, interquartile range

Standard error of mean

SD divided by sqrt(n); precision of sample mean

Confidence interval

range likely containing population value; narrower = more precise

Hypothesis testing

process determining if observed results differ from expectation

P value

probability results occur by chance under null hypothesis

Type I error

false positive; rejecting true null

Type II error

false negative; failing to reject false null

Clinical significance

practical importance of a finding regardless of p value

Statistical significance

determined by p value; may not reflect clinical importance

Outlier impact

can distort mean, SD, and statistical tests

Normal distribution

symmetric bell curve; mean = median = mode

Positive skew distribution

long tail to right; mean > median > mode

Negative skew distribution

long tail to left; mean < median < mode

Data variable nominal

categories without order (e.g., blood type)

Data variable ordinal

ordered categories (e.g., pain scale)

Data variable discrete

countable values (e.g., number of events)

Data variable continuous

measurements over a range (e.g., weight, height)

Graph misuse

misaligned axes, truncated axes, misleading scales

Cholesterol structure

four fused hydrocarbon rings with hydroxyl group

Cholesterol functions

membrane fluidity; precursor for bile acids, steroid hormones

Saturated fatty acid

all single bonds; straight chains; typically raise LDL

Monounsaturated fatty acid

one double bond; often heart-protective