HSCI 333 final

Homeostasis

Maintenance of stable internal conditions despite external changes.

- depend on constant energy input from external environment to reduce entropy and maintain order of internal environment

regulation of Arterial Blood Pressure (ABP)

baroreceptor system: baroreceptor cells sense pressure found in aortic arch and carotid arteries → stimulated by stretch of arterial wall when ABP is high → impulses inhibit vasomotor center in CNS → diminishes heart activity & drives dilation of peripheral blood vessels → reduce ABP

Negative Feedback for blood glucose

High blood glucose → pancreas secretes insulin into blood → insulin helps liver stores glycogen, muscle cells store glycogen & build proteins, adipose tissue uses glucose from blood for fat → lower glucose level

negative feed back for blood calcium

Blood calcium level high → thyroid gland releases calcitonin → stimulates CA2+ deposition in bones, reduce CA2+ uptake in kidneys → lower blood CA2+ level

Parturition

Process of childbirth involving positive feedback.

positive feedback for blood calcium

Blood calcium level low - parathyroid glands release PTH → inc Ca2+ uptake in intestines & kidneys, stimulates Ca2+ release from bones → inc blood Ca2+ level

Core Body Temperature Regulation

lower/ higher than set point → sensor → hypothalamus → (lower) shivering to generate heat, (higher) constriction of blood vessels in skin

Explain the 60-40-20 rule

- total body water: 60% of adult weight is fluid (42L)

- intracellular fluid (ICF): 40% of body weight; 28L within cells.

- extracellular fluid (ECF): 20% of body weight (plasma 20%, interstitial fluid 80%), 14L outside cells

how are materials exchange (CO2, O2)

waste:: cell produce CO2 --> diffuse to ECF --> plasma --> exit from lungs

nutrients: blood pick up O2 from alveoli by diffusion, cardiovascular system delivers oxygenated blood to cells

blood composition

formed elements 45%: RBC, WBC, platelets

plasma 55%: water (95%), electrolytes, proteins, hormones, gases, nutrients, wastes

leukocytes

WBC, Defend against infections and foreign invaders/ abnormal cells

enthrocytes

RBC, transport O2 to cells, CO2 away from tissues (99% of formed element)

electrolytes

ions that control cell function and volume and electrical charge across cells, maintain homeostasis

proteins in plasma

albumins maintain blood volume, transport electrolyes, hormones, wastes & globolins as antibodies, transport substance

arteries, capillaries, venules structure

Arteries (withstand high pressure), 3 layer wall (thin inner epithelium/ intima, thick smooth muscle/ media, outer connective tissues/ adventitia)

Capillaries: made of one cell layer of endothelial tissue, large SA

veins: 3 layer wall (thin inner epithelium, thin smooth muscle layer, thinner outer connective tissues), valves, lower pressure, larger volume than artery

Cardiac Cycle

systole (atria → ventricle contraction), diastole (chambers relax, atria fill with blood)

Phlebotomy

Practice of drawing blood for clinical purposes, found in Egyptian history

idea of the four humors (blood element)

1. blood (RED, hot, wet, air)

2. yellow bile (YELLOW, fire, hot, dry)

3. black bile (black, earth, dry, cold)

4. phlegm (blue, water, cold, wet)

- found in greek history, introduced by hippocrates

role of spleen in blood production

Filters and recycles blood cells

transubstatiation

blood to wine/ wine to blood

what blood is bright red

oxygenated blood

transmutation

lead to gold

congealing process

factors promote and inhibit coagulable lymph (not just cold temp)

hirudin

anticoagulant secreted to prevent blood clotting

what is the first ever blood transfusion experiment

dog to dog by richard lower

Parabiosis

experimental technique where model organisms have shared blood supplies by connecting their circulatory system

Plasma-rich treatment

Accelerates injury repair in sports.

- found to improves people's appearance memory, strength

- suggest that factors in plasma can help restore brain function (can be used to treat neurodegenerative disease)

3 main problems on blood transfusion historically

clotting, infection, immune reaction

why is it called Rh

antisera produced in rabbits/ guinea pigs reacted to rhesus monkey blood and caucasian popn

how was clotting problem solved

- sodium citrate showed to prevent blood clotting (also used oxalate, sulfate)

- Glucose-citrate combination extend storage for weeks

optimum citrate conc

0.2%

functions of plasma fraction

helpful for victims of blood loss

Glycerol addition

Enables long-term storage of blood products.

Blood substitutes

- manufacturing blood

- saline/ other balanced salt solution

- albumin

- coconut milk

- synthetic forms

splenic anemia

- spleen dysfunction, produce "black bile", swell up in many situation

splenectomy

cutting the spleen to cure splenic anemia

Perfluorochemicals

Synthetic hemoglobin substitutes for oxygen transport.

Hematocrit

Tool measuring blood cell levels, stain cells to judge quality

Aplastic anemia

Condition with insufficient red blood cell production, fatty appearance of the bone marrow

Pernicious anemia

Low RBC counts, megaloblastic appearance (large RBC)

Erythropoiesis

Production of red blood cells.

what are the extrinsic and intrinsic factor to prevent pernicious anemia

extrinsic: meat consumption

intrinsic: body/ stomach component

Vitamin B12

- extrinsic factor that we absorb from intestine (made by bacteria in GI tract)

- Essential for generating folic acid --> Vitamin B12 and folic acid is crucial for thymine synthesis, DNA replication, cell replication, hemoglobin synthesis

glycoprotein

intrinsic factor, made by gastric parietal cells to aid VB12 absorption

Emergent properties

When simple parts come together, they create something more complex and unique that you cannot see in the parts alone.

- ex: water shows unique traits such as universal solvent, but H and O itself does not show this property

Diffusion

Passive movement from high to low concentration that follow the 2nd law of thermodynamics

Osmosis

Water movement across semi-permeable membranes from high to low water potential

Oncotic Pressure

Osmotic pressure due to proteins in blood.

fluid exchange at capillary beds due to osmotic & blood (hydrostatic) pressure forces

- high conc of proteins (albumin) in blood create high osmotic forces

At arteriole: blood pressure (32 mmHg), osmotic pressure (25 mmHg) → net pressure out (water, O2, amino acid)

At venule: blood pressure (15mmHg), osmotic pressure (25 mmHg), net pressure in (water, wastes, CO2)

lymph fluid collection (2 phases)

lymph retrieves ECF and bring it back to blood (one way) at subclavian veins

- expansion phase: hydrostatic pressure in intersititium Pif > initial lymphatic pressure Pl --> open microvalves --> fluid enter vessels outside

- compression phase: Pl inc --> closing microvalves --> open secondary lymph valves --> fluid flow downstream

Continuous Capillary

- most common, allows selective diffusion of small molecules with small vesicles assist in transport across capillary wall (outermost basement membrane)

Fenestrated Capillary

- found in kidney, small intestine

- Contains small fenestration (pores) for faster exchange of larger molecules. (nutrients, wastes, hormones)

Sinusoidal Capillary

Large fenestration between endothelial and basement membrane for passage of proteins and cells.

- found in liver

blood pH buffer

- bicarbonate (HCO3-)

- HCO3- + H+ <--> H2CO3 <--> CO2 + H2O

what will happen if blood pH is too low/ high

low: acidemia/ acidosis

high: alkalemia/ alkalosis

what do we need O2 as e-aste acceptor

Essential for accept electrons stripped away during aerobic respiration and oxidation

Hemoglobin structure

Protein + prosthetic group --> heme group (contains iron that bind single O2)

- 4 protein subunits: 2 alpha (α)-globin proteins, 2 beta (β)-globin proteins --> assemble to a tetramer

origin of hemoglobin

evolved from ancestral protein similar to myoglobin (an oxygen-binding protein found in muscle tissue)

what is heme

a type of porphyrin

- excellent shape for coordinating metals and absorbing e- and energy

2 redox state of iron atom in heme group

LEO: losing electrons in oxidation, GER: gaining electrons is reduction

- Fe3+/ ferric form is oxidised (methemoglobin form), Fe2+/ ferrous form is reduced

- The reduced form (Fe2+) binds O2 and oxidizes Hb → release of O2 reverses this and go back to reduced state

coorperativity of O2 binding

- it is an emergent property of hemoglobin, binding O2 increase affinity for additional binding

Allostery

- drive binding of O2

- Shape change in proteins enhancing ability for O2--Fe2+ interaction

does Hb still bind with O2 even when O2 pressure is low

yes, Hb is good at binding O2, is saturated even at low pressure

function of hemoglobin polypeptides

to ensure heme/ Fe binding to O2 is not too tight and is reversible

why is CO bad for us

CO irreversibly binds heme, makes blood bright

Bohr Effect

O2 release due to increased CO2 and temp and decreased pH. (reduce affinity)

Hemostasis

Process to prevent blood loss through clotting. (aka thrombosis, coagulation)

- thrombus = clot

key clot formers

platelets, fibrinogen, thrombin, coagulation factors (vitamin K produce thrombin), Ca2+ (binds with citrate)

thrombocytopenia

lack of platelets

Clotting Factors

Proteins necessary for blood coagulation.

- Lack of these can produce deficiencies in blood clotting (hemophilia)

key clot inhibitors

antithrombin, heparin

Key clot dissolvers

fibrinolysis (tPA, plasminogen)

factors of evolution

recombination, mutation, environment, mating

Mutation

Source of genetic variation in organisms.

- include insertion, deletion, substitution, duplication, rearrangement

3 types of hemoglobin mutation

- at protein coding region, altering protein sequence (HbS, HbC, HbE)

- at mRNA splicing region (affect mRNA maturation and stability)

- at gene regulatory region (affect mRNA production)

- can occur tgt

Recombination

Process of genetic material exchange during meiosis. (independent assortment)

HbS Variant

HbS variant caused by a single nucleotide mutation (GAG → GTG), leading to difference in protein sequence

relative fitness of genotypes of Hb allele

1. HbA/HbA: reduced fitness due to malaria susceptibility

- Fitness coefficient (Waa)=0.9

2. HbS/HbS: reduced fitness due to RBC sickle cell anemia

- Wss=0.2

3. HbA/HbS: increased fitness due to protection against malaria and no anemia

- Wss=1.0

Sickle Cell Anemia

- Molecular disease affecting red blood cell shape

- causing capillary blockade --> higher risk for ishchemia/ infraction/ hemorrhage

- causing overgrowth of bones (naturopathy) to support erythropoiesis

first test for sickle cell anemia

emmel's test: show sickling under reduced oxygen conditions

electrophoresis

find that there are 2 forms and designate the sickling associated allele (HbS)

X-ray Crystallography

Technique revealing 3D structure of hemoglobin.

what happen to HbS in deoxygenated state

HbS stick to each other and form tactoids that deform RBC

Thalassemia

Anemic condition linked to decreased expression level and amount of beta-globin gene variants.

both sickle cell anemia and thalassemias were categorized under...

hemoglobinopathies

- variation in sequence, structure, stability, expression of Hb

Codominance

Both alleles expressed equally in phenotype.

ABO gene encodes...

glycosylation enzyme and ceates glycoproteins and glycolipids on the surface of RBC (antigen)

benefit of sickle cell anemia and thalassemia

- RBC are host cells for part of malaria parasitic life cycle --> but with HbS they are poor host (alter cytoskeleton) --> prevent parasitic proteins from working properly and completing their life cycle

- thalassemia reduce infectivity of RBC and inc clearance of infected cells

Blood quantum

Measure of heritage/ ancestry is counted

Hypodescent

Classification of mixed heritage as inferior (lower status)

One drop rule

1/32 black legally defines black identity.

Second-generation cut-off rule

Non-identity with only ¼ Indian blood.

Blood purity

Concept of inherent superiority of bloodlines.

Eugenics movement

Defined racial purity to justify oppression, reinforce existing hierarchy, promote superior races

Genotype

Specific DNA sequence for a trait.

Phenotype

Physical expression of genotype influenced by environment.

Gene

DNA sequence that codes for proteins.

Allele

Specific version of a gene.

Ploidy

Number of chromosome sets in a cell.

- Haploid: one copy (1n), Diploid (2n), aneuploid: uneven copy sets

Homozygous vs heterozygous

homozygous: Two identical alleles at a gene locus.

heterozygous: 2 diff allele at a gene