Caps lecture notes- Midterm 2

composition of blood (L17)

Most of the blood is made of plasma (mostly water), then RBCs and then only a little WBCs and platelets

functions of blood (L17)

• Transport and protection:

  • Supply oxygen to tissues (haemoglobin)

  • Removal of waste (e.g. carbon dioxide)

  • Immunological functions (e.g. WBCs)

  • Coagulation (stop bleeding)

  • Messenger functions (e.g. hormone transport)

  • Maintains body temp. & acid-base balance

determination of hematocrit (L17)

• Hematocritt is the % of RBCs in blood 

• Blood volume is made up of:

  • Plasma 55-60% → water, proteins, nutrients, hormones etc.

  • Hematocrit (RBCs) 40-45%

  • Buffy coat (WBCs and platelets) <1%

• Blood volume = plasma volume + hematocrit

  • ~5.5L = 3L plasma (55%) + 2.5L hematocrit (45%)

functions of blood proteins (L17)

• Albumin: maintenance of oncotic pressure and transport 

• Lipoproteins: lipid transport 

• Glycoproteins: 

  • Transferrin → Fe³⁺ binding

• Coagulation factors: hemostasis

• Immunoglobulins: immunity

• Complement: immunity

structure and function of red blood cells (RBCs) (L17)

• Function only in peripheral blood stream

• Bind O₂ for delivery to tissues

• In exchanged, bind CO₂ for removal from tissues

• They have a unique discoid shape

  • Maximizes SA: ~140µm²

  • Important for gas exchange → the shape means hemoglobin (Hb) close to more areas of the membrane

  • Donut appearance under light microscope

• RBCs have a lifespan of ~120 days since they get damaged when going through tight spaces like capillaries 

• Structure 

  • Have a cell membrane and cell cytoplasm

  • The RBCs are malleable (squishy) so that multiple can flow through a venule and single RBCs can flow through capillaries

anemia and polycythemia (L17)

• Anemia: reduced capacity to carry oxygen

  • Not always due to reduced number of RBCs

  • Can be caused by iron deficiency (cannot bind oxygen to heme), pernicious (B12 deficiency) or hemorrhagic

• Polycythemia: too many circulating RBCs

  • Too viscous and can lead to blood clots and eventually strokes

how to identify the causes of anemia and polycythemia (L17)

• Medical history

• Physical exam

• Blood tests - commonly CBC

• Peripheral blood smear

• Oxygen saturation

• JAK2 mutation (polycythemia)

what is heme? (L17)

• Heme is an iron-containing molecule

• Critical component of proteins like hemoglobin

• Responsible for transport of oxygen and carbon dioxide

why do we care about iron in RBCs? (L17)

• Key component of hemoglobin (carries oxygen from lungs to tissues)

• Iron binds to heme

• Essential for bone marrow to produce new RBCs

• Iron-deficiency anemia= fatigue, weakness

iron metabolism (L17)

1. Absorption: Fe²⁺ absorbed through intestinal mucosa (duodenum)

2. Oxidation: ceruplasmin (oxidative enzyme) oxidizes Fe²⁺ to Fe³⁺ (ferric)

3. Transport: Fe³⁺ binds to and is transported through blood by transferrin 

4. Incorporation: in erythroblasts Fe³⁺ is reduced to Fe²⁺ and incorporated into heme, which is then incorporated into Hb

5. Storage: ferritin binds and stores excess iron (bone marrow and liver)

• High transferrin levels are likely bad since the body will keep pumping transferrin if no binding occurs

hemoglobin (Hb) synthesis (L17)

• Hb synthesis occurs in bone marrow, specifically, in erythoblasts and reticulocytes

• Adult Hb requires two parts:

  • Heme (iron-containing compound; non protein part of Hb)

  • Globins (proteins)

• Heme synthesis starts in the mitochondria → continues in the cytosol

• Globins (part of adult Hb) synthesis occurs on polyribosomes in cytosol

Hb synthesis in reticulocytes (L17)

• The reticulocyte is the stage of the RBC that still has some RNA (mostly ribosomal RNA) but has extruded its nucleus. So, hemoglobin synthesis continues into the reticulocyte stage, even though the nucleus is gone.

• Reticulocytes still contain residual ribosomal RNA (rRNA).

• This residual rRNA allows a small amount of protein synthesis (mostly hemoglobin) to continue after the cell has left the bone marrow.

• Once the reticulocyte enters the bloodstream, it gradually loses all RNA.

• At this point, it becomes a fully mature RBC, which cannot synthesize any new proteins because it has no nucleus and no RNA.

adult hemoglobin structure (L17)

• It’s made of four globin chains, each bound to a heme group that contains Fe²⁺ (iron)

• Most commonly 2𝛽and 2𝜶 chains → HbA

• They are proteins that surround and protect heme

• In adults, there are four globin types: α, β, δ, γ.

• There are further A subtypes 

  • Example: HbA1c of clinical significance

  • Glycosylated Hb

  • Meaning glucose from plasma attaches non-enzymatically to hemoglobin.

  • The fraction of hemoglobin that is glycated reflects the average plasma glucose over the past 2–3 months (lifespan of RBCs).

  • A1c < 7% is generally considered good glucose control in diabetes.

  • Not always an accurate measurement of diabetes

heme structure (L17)

• Non-protein part (porphyrin ring)

• Iron (Fe²⁺) inside 

• Iron reversibly binds O₂

  • Transports from lungs to tissues and picks up CO₂ on way back

• Covalently bound to globins

• In globins: iron-containing heme groups

• Veins are blood due to the absorbance of light

• Good to know:

  • CO₂ doesn’t compete for Fe²⁺ it bidns the Hb protein chains (globins) but CO competes fiercely (binds 250x better for Fe)

  • Will win and cause rapid O₂ starvation which is why carbon monoxide poisoning is so rapidly fatal

blood types (L17)

• RBCs have different surface antigens

  • A⁺ blood is type A blood that also has Rh** surface antigen

  • A^- blood is type A blood that does not have Rh** surface antigen

  • O^- blood is type O blood that does not have Rh** surface antigen

    • Universal donor

  • AB⁺ blood is a universal acceptor

• **Rh: protein on surface of RBCs → determines if a person is Rh⁺ or Rh^-

• Critical factor in blood transfusions

What would happen if type B- blood was given to a person with type A blood? (L17)

• The recipient's anti-B antibodies will recognize the B antigens on the donor RBCs. This will cause aggutination (clumping) of the donor RBCs.

• Note that the donor antibodies have little effect unless it’s a large transfusion because the antibodies get diluted.

what is bone marrow? (L18)

• Spongy tissue in medullary cavities of bone

• Location of new blood formation

• Very active tissue and has two types

  • red and yellow marrow

red marrow (L18)

Packed with dividing stem cells and precursors of mature blood cells

yellow marrow (L18)

• Inactive bone marrow; dominated by fat cells

• May be reactivated (i.e. extreme blood loss)

normal changes in location of bone marrow (L18)

• In adults, only in heads of femur and humerus (long bones) and sternum, ribs, cranium, pelvis, vertebrate (flat bones)

• Important to know red:yellow marrow ratio as it is and indicator of health

  • Typically 50:50 ratio where both exist

megakaryocytes and platelets (L18)

• Megakaryocytes live in bone marrow

• They are multi-nucleated (endomitosis without cytokinesis; up to seven duplications without cell division) and 30-150µm

• Platelets are cytoplasmic fragments that break off and enter the peripheral blood stream. They function in blood clotting. 

• There are 1000-5000 platelets per megakayocyte

characteristics of platelets (L18)

• Lifespan of around 10 days

• Disc shaped with a diameter of 2-3µm

• Pseudopodia allow for shape alteration and movement 

• No nucleus but have mitochondria, ribosomes

• Granules are found in platelets:

  • Alpha granules: coagulation factors, adhesion molecules

  • Dense granules: ADP, ATP, Ca²⁺

hemostasis overview (L18)

• Normal hemostatic response acts to arrest bleeding following injury to vascular tissue

• Four stages:

1. Blood vessel constricts (smooth muscle) - helps reduce immediate blood loss

2. Platelet clot - circulating platelets stick to damaged vessel and form a temporary platelet clot

3. Coagulation cascade - coagulation factors amplify clotting effects to stabilize plug 

4. Fibrin clot - fibrin joins the party to form a solid, stable clot (during further healing, tissue replaces this)

platelet plug formation (primary wound healing) (L18)

• In response to vessel wall injury, platelets adhere to the site of injury:

• Von Willebrand Factor (vWF) = exposed collagen fibres in vascular wall

• Activated platelets undergo conformational change (pseudopodia formation) and release alpha and dense granules → ADP and fibrinogen initiate platelet aggregation

• ADP causes the release of thromboxane A₂ from activated platelets → it is a potent vasoconstrictor and potentiates platelet aggregation

• Results in the formation of an unstable platelet plug

• Plug may be sufficient in small injuries

• Plug is localized due to ADP-induced prostacyclin (released by endothelial cells; inhibits platelet activation) and NO release (inhibits adhesion, aggregation of platelets)

platelet plug formation (L18)

• The overall aim of the coagulation cascade is to create a stable fibrin clot to complete the seal.

• This requires thrombin production (dependent on three enzyme complexes)

• Thrombin acts on fibrinogen (factor I) to promote clot formation

• Important that clotting is localized which is done by a network of amplification and negative feedback loops

• Extrinsic and intrinsic pathways

  • The intrinsic pathway is activated by factors in the blood, while the extrinsic pathway is activated by tissue factors

  • Both pathways cause an activation of factor X which leads to the common pathway and ends with converting fibrinogen into fibrin which forms a stable blood clot.

anticoagulation  (L18)

• We know clots aren’t permanent, but how do we get rid of them? → fibrinolysis

  • Driven by an enzyme called plasmin

  • Plasmin is formed from its inactive precursor plasminogen with plasminogen activators

  • Main two:

    • Tissue-tyope plasminogen activator (tPA) 

    • Urokinase-type plasminogen activator (uPA)

  • Once plasmin is activated it cleaves fibrin which breaks down the clot and it is cleared from the body.

disorders of hemostasis (L18)

1. Platelet abnormalities 

   1. Thrombocytopenia - too few platelets; bleeding, bruising, slow clotting

   2. Thromobocytosis - too many platelets; increased blood clot risk

   3. Hemophilia - inherited deficiency of specific clotting factors; injury can result in uncontrolled bleeding

      1. Type A- deficiency of factor VIII

      2. Type B - deficiency of factor IX

2. Von Willebrand disease 

   1. Inherited disorder of platelet adhesion (deficiencies in factor VIII and vWF)

   2. Injury leads to increased bleeding

3. Latrogenic coagulopathy

   1. Problems with bleeding or clotting caysed by medical interventions

   2. Eg. use of anticoagulants or antiplatelet medications

what is granulopoiesis (leukopoiesis)? (L18)

• Development of white blood cells in bone marrow 

• Neutrophils, eosinophils and basophils

• Granulocyte macrophage colony stimulating factor (GM-CSF)

  • Secreted by immune cells to stimulate production of more immune cells, especially granulocytes (and monocytes)

leukocytes (L18)

• Leukocytes = white blood cells (WBCs)

• Mobile units of immune system

• Recognize and destroy or enutralize foreign materials

• two types: granulocytes and agranulocytes

granulocytes (L18)

• polymorphonuclear (PMNs) - specific granules in cytoplasm:

  • Neutrophils- phagocytose e.g. bacteria and fungi= first responders

  • Eosinophils- fight parasitic infections and mediate allergic reactions

  • Basophils- allergic responses (histamine), parasitic infections

agranulocytes (L18)

• mononuclear- lack specific granules:

  • Monocytes- phagocytose viruses, bacteria, fungi → enter tissues and become macrophages (‘housekeepers’)

  • Lymphocytes- B and T cells= immune functions 

complete blood count CBC (L18)

• Leukocytes are least numerous blood cells in blood → ~ 1 WBC for every 700 RBCs 

• This is not because fewer WBCs are produced but because WBCs are only in transit while in the blood.

• Never Let Monkeys Eat Bananas

  • Neutrophils

  • Lymphocytes

  • Monocytes

  • Eosinophils

  • Basophils

  • Neutrophils are the most abundant whereas the least is basophils in the blood

neutrophils (L18)

• Granulocyte= contain granules

• 3-5 lobed nucleus (>5 is abnormal development)

• Cytoplasm filled with pale-staining granules (hence ‘neut-’)

• First defenders against bacterial infections (will be elevated on CDC if infection occurs)

• Phagocytosis of bacteria, release web of neutrophil extracellular traps (NETs) that contain bacteria killing chemicals

• Thus, they can kill intracellularly (phagocytosis) and extracellularly (NETs)

• Act as scavengers to clean up debris, e.g. old RBCs, damaged tissue

eosinophils (L18)

• Granulocyte = contains granules

• Bi-lobed nucleus 

• Cytoplasm filled with pink-staining granules (hence ‘eosino-’)

• First defenders against parasites (e.g. worms)

basophils (L18)

• Granulocyte = contain granules

• Bi-lobed nucleus

• Nucleus obscured by the density of overlying granules

• Cyotplasm filled with blue-purplish-staining granules (hence ‘baso-’)

• Lowest cell count in CBCs often read as zero

• Involved in allergic responses (contain heparin and histamine) and bacteria, fungi and viruses  

flow of blood through the heart (L19)

• Deoxygenated blood returns from body via superior and inferior vena cavae 

• Enters the right atrium

• The right atrium contracts and pushes blood through tricuspid valve

• Enters the right ventricle

• The right ventricle contracts pushes blood through pulmonary valve into lungs

• In lungs blood picks up O₂ and releases CO₂

• O₂ rich blood returns through pulmonary veins 

• Enters the left atrium

• The left atrium contracts and pushes blood through mitral valve

• Enters the left ventricle

• The left ventricle contracts pushes blood through aortic valve 

• Enters the aorta and can go back to the body 

atrio-ventricular valves (L19)

• The tricupsid and mitral (bicuspid) valves

• Located between the atria and ventricles

• Tricuspid 

  • Between right atrium and right ventricle

  • Three cusps (anterior, septal and posterior)

  • At the base of each cusp anchored (chordae tendineae) to fibrous ring that surrounds orifice 

• Mitral (bicuspid)

  • Between left atrium and left ventricle

  • Regulates the blood flow between them

  • Two leaflets: anterior (aortic) and posterior (mural)

  • They are supported by two structures → chordae tendinae and papillary muscles

semilunar valves (L19)

• Pulmonary and aortic valves

• Located between ventricles and their corresponding artery

• Regulate blood flow of blood leaving the heart

• Pulmonary valve

  • Between the right ventricle and pulmonary artery

  • Three leaflets (anterior, left and right)

  • Attached to a touch, fibrous ring called annulus 

  • Main function: allow blood flow from right ventricles to pulmonary artery and prevent backflow into right ventricle

  • The leaflets overlap to ensure complete closure and prevent backflow of blood into the right ventricle

papillary muscles (L19)

• Small, cone-shaped muscles in ventricle

• Play crucial role in valve function: contract during systole (prevents AV valves from collapsing into atria, ensure one-way flow and prevent regurgitation)

chordae tendinae (L19)

• Functions with papillary muscles to prevent blood backflow

• Connect the papillary muscles to AV valve leaflets

• Prevents valve leaflets from being pushed back into the atria

what is the cardiac cycle? (L19)

• The cardiac cycle is the complete sequence of physiological events that occur in the heart, from one heartbeat to the next

• Systole = phase of chamber contraction

• Diastole = phase of chamber relaxation and filling

1. The atria contract

2. The ventricles contract (AV valve closes, semilunar valve opens, blood ejected into great vessels)

3. Atria relax

4. Ventricles relax (semilunar valve closes, AV valve opens)

• Note: valve are one-way = when they open, blood flows out/ when they are closed, no blood leaks back

• Note: we usually associate systole with ventricular systole - period of ventricular contraction which is time between AV valve closure and semilunar valve closure

“Lub Dub” heart sounds (L19)

• This sound is caused by the closing of heart valves during each cardiac cycle

• Lub= also known as S1 produced by closing of AV valves (mitral and tricuspid)

• Dub= also known as S2 produced by closing aortic and pulmonary valves as blood ejected from ventricles

• Abnormal heart sounds occur as a result of abnormal valve movements or abnormal cardiac movements. Can also occur in healthy people. 

• Physiological splitting of S2:

  • Normal separation of the second heart sound into two components

  • Aortic valve closure and pulmonary valve closure are not synchronized during inspiration 

  • Aortic valve closes slightly before pulmonic and this splits S2 into two distinct components

heart murmurs (L19)

• A sound heard as a result of turbulent flow in the heart

• Aortic stenosis 

  • Normal flow across a narrowed valve

• Mitral regurgitation

  • Across a valve which doesn’t close properly (backflow)

• Ventricular septal defect

  • Through a hole, from a high pressure chamber to low pressure chamber

three tunics of blood vessels (L20)

• Tunica intima (innermost)

  • Endothelium, basement membrane, connective tissue

• Tunica media (most variable layer- related to functions)

  • Smooth muscle, elastic fibres, connective tissue

• Tunica adventitia 

  • Loose connective tissue, blood vessels, nerves

Lumens of all vessels are lined by endothelial cells but capillaries are only composed of the endothelial layer and its basement membrane — they lack the media and adventitia. Why? (L20)

to allow for easier gas exchange

thickness of arteries and veins (L20)

There is a progressive thinning of vessel walls from artery → arteriole → capillary (where gas exchange occurs), then gradual thickening again from venule → vein as blood returns to the heart.

three arteries (L20)

• Large (elastic) arteries

  • Aorta, pulmonary arteries

  • Convey blood from heart to systemic circulation

  • High pressure vessels 

• Med (muscular) arteries

  • Most arteries

  • Distributing vessels

• Arterioles

  • Start of microcirculatory bed

  • Resistance vessels

  • Arterioles still have smooth muscle in their tunica media, unlike capillaries.

  • That smooth muscle lets arterioles constrict or dilate, controlling:

    • Blood flow into capillary beds

    • Blood pressure (they are called the “resistance vessels” of the circulation)

three veins (L20)

• Large veins eg. vena cava, femoral

• Med veins: most veins (contain 70% of blood); run with arteries

• Venules: receive blood from capillaries

  • Travel with arterioles

  • Venule lumens less regular in shape

  • Capacitance vessels (volume storage)

capillaries (L20)

• Wall is one endothelial cell thick

• Designed for easy and rapid exchanges between blood and tissues

• Pericytes wrap around endothelial cells:

  • Regulate blood flow

  • Phagocytes

  • Permeability of BBB

three types of capillaries (L20)

• Continuous:

  • Endothelial cells form a continuous, unbroken lining (tight junctions between cells)

  • Small gaps only at intercellular clefts where small molecules can pass

  • Surrounded by a complete basement membrane

  • Allow limited exchange — mainly small molecules like water, ions, and gases (O₂, CO₂)

  • Prevent loss of plasma proteins and blood cells

  • Found in tissues that require a tight barrier: Muscle, skin, lungsand central nervous system (CNS) → forms part of the blood-brain barrier

• Fenestrated:

  • Endothelial cells have fenestrations (pores) in their plasma membranes.

  • Pores may have thin diaphragms covering them.

  • The basement membrane is still continuous.

  • Allow more rapid exchange of water and small solutes (like glucose, hormones, ions).

  • Still retain large proteins and cells due to intact basement membrane.

  • Found in tissues with high exchange or filtration: Kidneys, small intestine (villi), endocrine glands and ciliary body of eye

• Sinusoid 

  • Have an incomplete basement membrane and intercellular gap

vascular endothelium (L20)

• Simple squamous epithelial cells (called epithelial cells)

• Crucial for vascular functions and homeostasis 

• Forms a thin, continuous inner lining of all blood vessels — arteries, veins, and capillaries (~60,000 miles total in the body!).

• Rests on a basement membrane.

• Serves as a selective barrier and an active regulator of blood flow, clotting, and vessel health — essential for maintaining vascular homeostasis

how do veins pump blood against gravity? (L20)

• Through valves

• Through surrounding skeletal muscles contraction

• Through tons of smooth muscle (media and adeventitia)

neural control of arteriolar diameter (L20)

• SNS:

  • Noradrenaline- vasoconstriction- through alpha-adrenergic receptor stimulation - increases vascular resistance

  • Adrenaline- vasoconstriction - how is not known

• PNS: insignificant

hormonal control of arteriolar diameter (L20)

• Hormones (released from endocrine glands) can cause vasoconstriction and vasodialation by interacting with receptors on smooth muscle cells lining arteriolar walls

• Constrictors: angiotensin II, arginine vasopressin (AVP)

• Dilator: atrial natriuretic peptide (ANP)

tissue metabolites of arteriolar diameter (L20)

• Produced by active tissues (e.g. increased activity during exercise) - act as vasodilators

• E.g. adenosine- potent vasodilator, CO₂- vasodilation, lactate (by-product of anaerobic metabolism)- vasodilation, oxygen- affects release of vasoactive substances

angina (chest pain) (L20)

• Angina occurs when ischemia (decreased oxygen) in the heart activates afferent pain pathways, sending signals to the brain that are perceived as chest pain. If blood flow is not restored, this can progress to a heart attack (myocardial infarction).

• ECG will show ST depression

cardiac output (L21)

• Cardiac output= the volume of blood ejected from the heart every minute (units: mL/min)

• Heart rate= number of heart beats per minute

• Stroke volume= volume of blood ejected from left ventricle with each sytosolic contraction

• CO= heart rate (HR) x stroke volume (SV)

regulation of cardiac output (parasympathetic) (L21)

• Increased parasympathetic activity 

  • Negative feedback on heart rate and positive feedback on CO

  • HR decreases (slower heartbeat)

  • Filling time increases → more blood fills the ventricles between beats

  • Stroke volume (SV) can increase due to the Frank–Starling mechanism (the heart pumps what it receives — more filling = stronger contraction)

regulation of cardiac output (sympathetic) (L21)

• Increased sympathetic activity

  • Epinephrine

  • Positive feedback on HR, SV, venous control 

  • Increased end diastolic volume

  • Positive feedback on stroke volume

  • Positive feedback on CO

regulation of cardiac output (stroke volume) (L21)

• Sympathetic nerves (releasing NE)

• Acting on 𝛽1 receptors on cardiac muscle cells → increased intracellular calcium and increased stroke volume

• In ventricle this means increased calcium entry into the myocytes from outside cell and calcium release from intracellular stores → promote contraction of ventricle 

Frank Starling law of the heart (L21)

• States that the strength of contraction is related to initial length of cardiac muscle fibres

• The more stretched the muscle is initially, the stronger the contraction

• So what? Why is this important for the heart?

  • The initial length of the heart muscle before contraction is equivalent to how filled the heart is at the end of diastole, or the end of the diastolic volume

  • The strength of contraction is equivalent to the stroke volume during systole

  • Bottom line: if you increase ventricular end diastolic volume (or preload) you increase the stroke volume (within reason, the heart will pump what it receives)

pressure and resistance (L21)

• CO= cardiac output
  Blood pressure= CO x resistance

• CO= volume in vessels

• Resistance = diameter of vessels (systemic vascular resistance or SVR)

• So, what determines SVR?

  • Resistance is determined by the radius of the blood vessels

  • Resistance = 1/r⁴

    • Inversely proportional to the fourth power of the vessel’s radius

  • This means a small change in radius has a significant impact on resistance, because it is raised to the fourth power

  • E.g. if a blood vessels constricts to half of its original radius, the resistance to flow will increase 16 times

what causes vasoconstriction (ie. increased SVR)? (L21)

• Exposure to cold

• Stress

• Certain medications (e.g. decongestants, migraine medications, stimulants)

• Raynaud’s phenomenon: spasms in response to cold, stress, emotional upset

• Smoking, coffee, salty foods

what causes vasodilation (ie. decreased SVR)? (L21)

• Exercise (muscles require more oxygen and nutrients, vasodilation increases blood flow)

• Low oxygen levels (hypoxia)

• Increased body temp. (helps release heat through skin, aiding in cooling)

• Inflammation: deliver more oxygen and nutrients

vasoactive hormones (L21)

• Constrictors:

  • Angiotensin II

  • Arginine vasopressin

• Dilator:

  • Atrial natriuretic peptide (ANP)

afterload (L21)

• The pressure the ventricle must generate in order to eject cardiac output 

• Primarily determined by resistance in arteries

• Chronic high arterial BP is an example of high afterload

capillary hydrostatic pressure (L21)

pressure exerted by blood within a capillary, driving fluid out of the vessel and into surrounding tissues

capillary oncotic pressure (L21)

pressure exerted by proteins in the blood plasma that draws water from the interstitial space back into capillaries —> opposes hydrostatic pressure

no net movement (L21)

state where no overall movement of fluid, solutes across capillary wall, either in or out of the blood. Typically occurs when driving forces are balanced or opposed → equilibrium.

net filtration (L21)

process where fluid is pushed out of capillaries into surrounding tissues. Occurs due to differences between hydrostatic pressure (pressure of fluid w/in capillary) & osmotic pressure (pressure exerted by proteins in blood). Occurs when capillary hydrostatic pressure> blood colloid osmotic pressure. In most capillaries, more fluid is filtered out than is reabsorbed, leading to a net filtration

interstitial oncotic pressure (L21)

Interstitial oncotic pressure is the osmotic pressure created by proteins in the interstitial fluid (the fluid surrounding cells in tissues).

pulls water out of capillaries and into the interstitial fluid.

net reabsorption (L21)

overall movement of fluid from interstitial space back into capillaries. Driven by difference in osmotic and hydrostatic pressures, with osmostic pressure favouring the movement of fluid back into capillaries due to higher [protein] in blood.

table comparison of pressure types (L21)

Starling forces adjustment after hemorrhage (L21)

• Overall goal: Restore intravascular (blood) volume after blood loss.

  • Fluid moves from interstitial space → into capillaries (net reabsorption).

  • After hemorrahage Starling forces shift to favour the movement of fluid from the interstitial space into the capillaries to restore blood volume

• Initial and most significant change is a sharp drop in capillary hydrostatic pressure, which reduces the force of pushing fluid out of the capillaries

  • Hemorrhage → ↓ blood volume → ↓ capillary blood pressure.

  • This reduces the outward filtration force that normally pushes fluid out.

  • Result: Less filtration / more reabsorption into capillaries.

• Followed by a slower, but critical process where proteins move from the interstitium back into the plasma, increasing capillary oncotic pressure and further promoting fluid reabsoprtion. 

  • As plasma volume falls, plasma proteins become more concentrated.

  • Over time, proteins also move from interstitial fluid → plasma, further raising capillary oncotic pressure.

  • This increases the inward osmotic pull, enhancing reabsorption of interstitial fluid.

blood pressure (L22)

Blood pressure (BP)= pressure inside blood vessels or heart chambers relative to atmospheric pressureHow does your brain know what your BP is and what does it do about it?

How does your brain know what your BP is and what does it do about it? (L22)

Afferent nerves in medulla receive messages from baroreceptors (BP sensors) and send message back through efferent vessels to blood pressure controllers (baroreceptors)

BP cuff (L22)

• Inflate cuff around upper arm to stop blood flow, then slowly release air while listening for blood flow sounds through brachial artery

• Systolic pressure recorded first when first sound heard, then diastolic pressure recorded when sound disappears

What and where are baroreceptors? (L22)

• Stretch sensitive nerve endings that detect BP

• Increased BP means increased nerve impulses from baroreceptors, which tells brain to lower BP by slowing heart rate and dilating blood vessels

carotid sinus and aortic arch (L22)

• Carotid sinus: in common carotid artery 

  • (afferent nerve= glossopharyngeal nerve)

• Aortic arch: in arch of aorta 

  • (afferent nerve= vagus nerve)

mean arterial pressure (MAP) (L22)

• MAP related to systolic and diastolic pressures through a formula 

  • MAP= DBP +⅓ (SBP-DBP)

  • Common way is to add diastolic to one-third of pulse pressure (= difference between diastolic and systolic)

• Why care?

  • MAP represents average pressure in person’s arteries, indicating overall blood circulation and organ perfusion

  • High MAP: increased risk of cardiovascular disease

  • Low MAP: not enough oxygen to organs= shock, organ damage

Restoring BP after acute rise in arterial pressure (L22)

• What can cause this? → stroke or hypertensive emergencies

• BP≥180/120 → can lead to stroke, heart attack, kidney failure

• Needs rapid interventions

  • IV anti-hypertensive medications that aim to reduce BP slowly (if not done slowly → headache, chest pain, shortness of breath, confusion)

Restoring BP after acute fall in arterial pressure (L22)

• Can be caused by hemorrhage, heart failure, cardiac event

• Treatment depends on cause:

  • If hemorrhage then stop bleeding and restore blood volume with fluid resuscitation and potentially blood transfusion

  • If heart failure or cardiac event, focus on optimizing cardiac output with medications like vasopressors to increase BP

why do we breathe? (L23)

• Gas exchange

• Route for water loss and heat elimination

• Acid-base balance (altering amount of H⁺)

• Speech, singing and smell

• Defends against inhaled foreign matter (alveolar macrophages)

conducting structures (L23)

• Nasal cavity

• Nasopharynx, oropharynx, larynx

• Trachea

• Bronchi

• Bronchioles 

• These all function to warm and humidify air and to remove foreign particles

respiratory structures (L23)

• Respiratory bronchioles

• Pulmonary alveoli

• Alveolar ducts

• Alveolar sacs

• Alveoli 

• These all function in gas exchange

common micro-anatomical plan lungs (L23)

• Mucosa: respiratory epithelium, basement membrane 

• Submucosa: loose connective tissue containing seromucous glands 

• Adventitia: outer connective tissue layer, binds airways to adjacent structures (so lungs aren’t floating freely)

respiratory epithelium (L23)

Functions in protection (pathogens), mucociliary clearance, humidity and warming, gas exchange and immune defense

airway lining fluid (L23)

• Composed of two layers

  • Mucus layer: gel-like substance, 97% water, 3% solid

  • Pericilliary layer: low viscous fluid 

  • Catch foreign debris

• Note: mucus is produced by both goblet cells and seromucous glands

Muco-ciliary escalator (L23)

• Cilia provide coordinated sweeping motion that moves mucus and entrapped foreign materials to the larynx for expulsion 

Tracheobronchial tree (L23)

• Trachea splits into two bronchi

• Airway further divides around 23 times finally reaching 150-250 million alveoli in each lung

Trachea (L23)

• Contains

  • Mucosa: respiratory epithelium

  • Submucosa: seromucous glands

  • Cartilage: 16-20 rings, maintains patency of tube (prevents collapse)

  • Adventitia: loose connective tissue

• Note: the cartilage is not continuous so that the trachealis muscle can stretch and allow for swallowing 

main bronchi (L23)

• Contains

  • Mucosa: respiratory epithelium

  • Submucosa: seromucous glands

  • Cartilage: 16-20 rings, maintains patency of tube (prevents collapse)

  • Adventitia: loose connective tissue

intrapulmonary bronchi (L23)

• Lots of branching

• As they become smaller:

  • Decreased cartilage

  • Epithelial height reduced (need only one cell layer for easy gas exchange)

  • Smooth muscle becomes prominent

bronchioles (L23)

• Very small conducting airways

• No cartilage

• No submucosal glands

• Epithelial lining transitions:

  • Respiratory → simple columnar → simple cuboidal

• Goblet cells replaced by club cells

club cells (L23)

• Dome-shaped

• Make up 80% of cells lining bronchioles

• Lung protective functions:

  • Surfactant (reduce surface tension)

    • Respiratory distress syndrome in babies born without because lungs not developed enough

    • Treated with surfactant replacement 

  • Inflammation control

  • Enzymes to break down mucus

  • Antimicrobial lysozymes

respiratory bronchioles (L23)

• Transition point in respiratory system

  • From air conduction to gas exchange

• Initial segments are ciliated cuboidal

• Club cells persist in initial segments and become dominant in distal segments 

• Epithelial height is reduced

turbinates (L23)

• Also known as nasal conchae

• Tiny structures in the nose (bony projections)

• Help regulate airflow and roles in warming, humidifying and filtering air

pulmonary alveoli (L23)

• These are the terminal air spaces 

• Primary site for gas exchange

• Air brought into very close proximity to blood

• Structure:

  • Septae

  • Network of capillaries 

  • Alveolar macrophages 

• Type 1 pneumocytes:

  • Squamous cells

  • Large SA for gas exchange

  • Cover 95% of alveolar surface

• Type 2 pneumocytes:

  • Cuboidal cells

  • More numerous but only cover 5% of SA

  • Secrete surfactant

blood air barrier (L23)

• Minimal thickness

• Type 1 pneumocytes: thin

• Capillary endothelium: thin

• Allows for rapid gas exchange 

• Diffusion of oxygen from alveoli to capillaries and diffusion of carbon dioxide out of capillaries to alveoli. Across the epithelium

Oxygen transport in the blood (L23)

• Hemoglobin (protein) contains iron which readily binds to oxygen 

  • When this occurs it is called oxyhemoglobin

• Hemoglobin allows for vast majority (98%) of oxygen to be transported (faster than if it was dissolved in plasma)

• Hemoglobin facilitates oxygen transport

  • Hemoglobin binds with oxygen in lungs

  • Has 4 binding sites 

  • Oxygen binds and becomes oxyhemoglobin 

  • The partial pressure difference (higher in alveoli compared to blood) drives oxygen from the alveoli to blood