Cardiovascular System

• System has 4 chambered heart, blood vessels, and blood

Heart

• 2 pumps, different circulations in series
  • Right = pulmonary
  • Left = systemic
• Venae cavae/pulmonary veins supply blood to atria
• Atria push blood into ventricles

Valves

• AV valves separate atria and ventricles
  • Right = tricuspid valve
  • Left = bicuspid (mitral) valve
• Semilunar valves separate ventricles and aorta
  • Right = pulmonary valve
  • Left = aortic valve
  • 3 leaflets

Electrical conduction

• Order of excitation:
  • SA node → AV node → bundle of His → Purkinje fibers
• Starts at SA node → atria contract → ↑ atrial pressure (atrial kick)
• AV nodal delay allows ventricles to fill
• Bundle of His in interventricular septum → Purkinje fibers
• Cells connected by intercalated discs with gap junctions
• SA node intrinsic rate: 60–100 bpm
  • Athletes: 40–50 bpm
• Autonomic control:
  • Parasympathetic via vagus nerve

Contraction

• Systole = ventricular contraction
  • Closure of AV valves
  • Higher pressure
• Diastole = ventricles relaxed
  • Semilunar valves closed
  • Elasticity of arteries prevents pressure from falling
• Cardiac output:
  • $CO = HR \times SV$
  • Usually $= 5 \text{ L/min}$
• Stroke volume (SV) = blood pumped per heartbeat

Vasculature

• Blood goes away from heart in arteries (aorta is largest)
• Pressure in aorta much higher than in superior vena cava
• Major arteries branch off aorta → further division
• Then branch into arterioles → capillaries
• Venous side:
  • capillaries → venules → veins → vena cavae
• Blood vessels lined with endothelial cells:
  • Maintain vessels
  • Release chemicals that vasodilate/constrict
  • Allow WBC passage
  • Release chemicals for blood clots

Arteries

• Most contain oxygenated blood
• Muscular arteries = arterioles
• Highly muscular + elastic → resistance to blood flow
• Heart must generate lots of pressure to overcome resistance
• Elastic recoil maintains pressure

Capillaries

• Single endothelial cell layer
• RBCs move single file → diffusion can occur
• Interface between circulation and tissues
• Allow endocrine signals to reach tissues too
• Bruise = leaking of blood from capillaries into ISF

Veins

• Thin-walled + inelastic
• Transport blood to heart
• Venules connect capillaries to larger veins
• Veins stretch to accommodate blood:
  • ~ $3/4$ of blood is in veins
• Low smooth muscle → can stretch
• Total volume passing through either side of heart per unit time is same

Venous return + gravity

• Blood flow against gravity → more blood in vertical column
• High pressure in legs → veins have valves
• Varicose veins:
  • Failure of venous valves → pooled blood
• Pregnancy ↑ risk:
  • ↑ blood volume + compression of IVC by fetus

Skeletal muscle pump

• Skeletal muscle contraction squeezes veins → moves blood
• Why you should move → prevents blood clot formation
• Deep vein thrombosis (DVT) = clot in deep veins
  • Can dislodge → pulmonary embolus

Circulation pathway

• Deoxy blood:
  • vena cava → right atrium → valve → right ventricle
  • pulmonary valve → pulmonary arteries → lungs
  • pulmonary venules → pulmonary veins
• Oxy blood:
  • left atrium → mitral valve → left ventricle
  • aortic valve → aorta
• Blood usually passes through one capillary bed
• Portal system has two capillary beds
  • Hepatic portal:
    • hepatic portal vein → bed in liver
  • Hypophyseal portal:
    • bed in anterior pituitary → paracrine secretion → release hormones
  • Renal portal:
    • leaving glomerulus through efferent arteriole → goes to nephron

Composition

• Blood is $55\%$ liquid and $45\%$ cells

Plasma

• Liquid portion
• Mix of nutrients, salts, respiratory gases, hormones, blood proteins
• Serum = plasma without clotting factors
  • Preferred because lacks clotting factors + fibrinogen

Cellular portion

• Erythrocytes, leukocytes, platelets
• Formed from hematopoietic stem cells

Erythrocytes (RBCs)

• Specialized for O₂ transport
• ~250 mil Hb per RBC, each Hb binds 4 O₂
• Each RBC carries ~1 billion O₂ molecules (as written)
• Biconcave:
  • ↑ surface area
  • Helps movement through capillaries
• Mature RBC has no nucleus → more room for Hb
• RBC doesn’t consume O₂ it carries:
  • Uses glycolysis for ATP
• Lifespan ~120 days → then phagocytized (senescent RBCs)
• Hb = hemoglobin
• Hematocrit = % RBCs
• Hb ranges:
  • Males: 13.5–17.5 g/dL
  • Females: 12–15 g/dL
• Hematocrit ranges:
  • Males: 41–53%
  • Females: 36–46%

Leukocytes (WBCs)

• < $1\%$ of blood volume
• $4{,}500$ – $11{,}000$ per µL
• Defend against foreign invaders
• Granular leukocytes:
  • Cytoplasmic granules visible on microscopy
  • Toxic compounds released via exocytosis
  • Inflammation, allergies, pus, bacteria destruction
• Agranulocytes:
  • Lymphocytes + monocytes

Lymphocytes

• Specific immune response
• Primary responders
• Help body learn from experience
• Vaccines train immune cells via exposure to weakened pathogen
• B-cells mature in bone marrow, T-cells mature in thymus

Monocytes

• Phagocytize foreign matter
• Become tissue macrophages after leaving blood
• Tissue-specific names:
  • Microglia (CNS)
  • Langerhans cells (skin)
  • Osteoclasts (bone)

Thrombocytes (platelets)

• Cell fragments/shards from megakaryocytes (bone marrow)
• Assist in blood clotting
• Present in high concentration

Hematopoiesis

• Blood cell + platelet production
• Triggered by hormones, growth factors, cytokines
• Erythropoietin:
  • Secreted by kidney
  • Stimulates RBC development
• Thrombopoietin:
  • Secreted by liver + kidney
  • Stimulates platelet development

Blood antigens

• RBC surface proteins = antigens
• Immune system reacts to antigens
• Major: ABO antigens + Rh factor

ABO antigens

• 3 alleles:
  • A and B codominant
  • Can have one, both, or none
• AB = A + B
• O is recessive:
  • no A/B variant
  • homozygous recessive genotype
• Must match blood type
• Severe hemolysis can occur if blood is foreign
• O⁻ = universal donor (no A/B/Rh antigens to trigger reaction)
  • But O-type individuals make anti-A and anti-B antibodies
• AB = universal recipient (can take any type)
• Whole blood usually not transfused:
  • packed RBCs (no plasma) are given

Antibodies

• Made in response to antigens
• No antibodies unless exposed
• Rh⁻ person does not naturally have Rh antibodies
• Gut E. coli proteins match A/B-like antigens:
  • allows production of anti-A/anti-B antibodies prior to exposure

Rh factor

• Protein expressed on RBCs
• Several variants, but +/− refers to allele D presence
• Autosomal dominant inheritance
• Maternal-fetal medicine:
  • Rh⁻ mom + Rh⁺ fetus → sensitization → antibodies made
  • Subsequent Rh⁺ fetus → antibodies attack fetal RBCs
  • Erythroblastosis fetalis (can be fatal)
• ABO mismatch less concern (antigens can’t cross placenta)
• Rh IgG antibodies can cross placenta

Blood pressure

• Must be kept sufficiently high
• Force per unit area on vessel walls
• Measured with sphygmomanometers
• Normal: 90/60 and 120/80 (as written)
• Relationship:
  • $\Delta P = CO \times TPR$
• Arterioles and capillaries act like resistance
• Arterioles can constrict → ↓ flow, ↑ resistance
• Systemic capillary beds in parallel (except portals)

Regulation

• Baroreceptors regulate BP
• Too low BP:
  • ADH/vasopressin
  • Low perfusion to JG cells → renin → aldosterone → Na⁺ reabsorption → more water
• Too high BP:
  • ANP released

Gas and solute exchange

Oxygen

• Carried by Hb:
  • protein with 4 subunits + prosthetic heme
• Blood O₂ level measured by $P_{aO_2}$:
  • $= 70$ – $100$ mmHg
• O₂ saturation:
  • $>97\%$
• Cooperative binding:
  • O₂ binding increases affinity (easier for more O₂ to bind)
  • O₂ leaving decreases affinity (easier for more to leave)
• Affinity decreases as pH decreases
• During exercise:
  • $P_{aO_2} = 20$ mmHg (as written)
  • normally $40$ mmHg (as written)

CO₂

• Mostly as bicarbonate
• Carbonic anhydrase catalyzes conversion
• ↑ $[CO_2]$ → ↑ protons → ↓ pH
• Protons reduce Hb affinity for O₂ → right shift (Bohr effect)
• Trigger usually tied to O₂ demand
• Bicarbonate system also buffers

Left shift from

• Decreased $P_{aCO_2}$
• Decreased $[H^+]$
• Increased pH
• Decreased temp
• Decreased 2,3-BPG
• Fetal HbF has higher affinity than HbA
  • Fetal cells pull O₂ off maternal cells

Kidney + acidosis

• Kidneys account for some acidosis handling
• Renal tubular acidosis type I:
  • can’t excrete acid effectively
  • proton buildup, buffer shifts left

Nutrients, waste, and hormones

• Carbs + AAs absorbed into small intestine capillaries → hepatic portal system
• Fats absorbed in lacteals → enter via thoracic duct
• Fats packaged into lipoproteins (water soluble)
• Wastes enter blood down concentration gradients → capillaries → kidney filtration
• Hormones enter near organ via exocytosis → bloodstream
  • bind cell surface receptors or diffuse into cells

Fluid balance

• Hydrostatic pressure:
  • force of blood against vessel wall
• Osmotic pressure:
  • solutes draw water into blood
  • due to plasma proteins → oncotic pressure
• Arteriole end:
  • hydrostatic > oncotic → fluid moves out
• Venous/capillary end:
  • hydrostatic lower → draws water back in
• Starling forces balance fluid volumes
• Imbalance → edema (too much/little fluid)
• Some ISF taken into lymphatics
  • returns via thoracic duct

Coagulation

• Clots composed of coagulation factors + trapped blood cells
• Injury exposes underlying connective tissue:
  • collagen + tissue factor
• Exposed collagen signals injury:
  • platelets release contents + aggregate
• Coagulation factors released by liver
• Cascade:
  • Prothrombin → thrombin (from thromboplastin)
  • Thrombin converts fibrinogen → fibrin
  • Fibrin fibers cross-link → woven structure → clot/scab
• Thrombus formation when vessel injured
• Platelets attach to exposed matrix when endothelium disrupted
• Activates $\alpha_{IIb}/\beta_3$ integrin (as written)
• Forms dense network to plug injury
• Clot breakdown:
  • plasmin (from plasminogen)