Circulatory System Overview

• The circulatory system transports oxygen, nutrients, hormones, white blood cells, and wastes, and also plays a role in thermoregulation, thus contributing to homeostasis.

Pressure and Resistance

• The systemic circuit has high pressure and high resistance.
• The pulmonary circuit has low pressure and low resistance.

Blood Volume Pumped

• On average, 70 mL of blood is pumped per beat.

Blood Flow Pathway

• Blood flows through the heart in this sequence: vena cava, right atrium, tricuspid valve, right ventricle, pulmonary semilunar valve, pulmonary artery, lungs, pulmonary vein, left atrium, mitral valve, left ventricle, aortic semilunar valve, and aorta.

AV Valve Backflow Prevention

• Backflow in atrioventricular (AV) valves is prevented by chordae tendineae, which are connected to papillary muscles on the ventricular walls.

Dual Pump

• The heart acts as a dual pump because both the left and right sides contract simultaneously, pumping blood for the pulmonary and systemic circuits.

Heart Valve Mechanism

• Heart valves open when pressure is greater behind the valve.
• Heart valves close when pressure is greater in front of the valve, ensuring one-way blood flow.

Cardiac Muscle Connection

• Cardiac muscle fibres are connected by intercalated discs.

Cardiac Muscle Similarities

• Cardiac muscle is similar to skeletal muscle in that it is striated, has sarcomeres, and contains troponin/tropomyosin.
• Cardiac muscle is similar to single-unit smooth muscle in that it exhibits involuntary contraction, has gap junctions, and its contractions are influenced by a pacemaker, the autonomic nervous system (ANS), hormones, and stretch..

Cardiac Muscle Cells

• Contractile cells make up 99% of cardiac muscle cells.
• Pacemaker/autorhythmic cells make up approximately 1% of the cardiac muscle cells.

Funny Channels

• Funny channels are voltage-gated channels in the heart that open when hyperpolarized.

Cardiac Muscle Action Potential Steps

• Initially the cell has resting potential of -90mV with Na+ and Ca2+ channels closed, as well as K+ rectifier channels open.
• Funny channels let in fast of Na+.
• The potential is returned to 0mV by transient K+ channels opening and K+ efflux.
• Ca2+ influx through L-type Ca2+ channels is electrically balanced by K+ efflux through K+ rectifier channels.
• The potential returns to -90mV as Ca2+ channels close and K+ channels stay open.

Refractory Period

• The heart has a longer refractory period to prevent tetanus, ensuring the chambers fill with blood for proper circulation.

Heart's Conduction System

• The sinoatrial (SA) node in the right atrium fires 70-80 times per minute; controlled by the ANS.
• The atrioventricular (AV) node on the left side of the right atrium fires 40-60 times per minute.
• The Bundle of His runs down the length of the interventricular septum, firing 20-40 times per minute.
• Purkinje fibers then send contractile signals to the ventricles.

Ventricular Fibrillation (V-Fib)

• The ventricles quiver instead of pumping.

AV Node Delay

• Action potentials are delayed at the AV node to allow the atria to contract and the ventricles to fill before contracting.

ECG Segments

• P wave: atrial depolarization
• PR segment: AV node delay
• QRS complex: ventricular depolarization, atrial repolarization
• ST segment: ventricular repolarization
• TP interval: time during which ventricles are relaxing and filling

ECG Measurements

• Heart rate is measured on an ECG by the R-R interval.

Diastole

• Cardiac muscles relax, and chambers fill with blood.

Systole

• Cardiac muscles contract, and chambers empty of blood.

Cardiac Cycle

• The cycle proceeds from diastole to atrial systole to ventricular systole and then back to diastole.

End Diastolic Volume (EDV)

• The volume of blood in the left ventricle before ventricular contraction.

End Systolic Volume (ESV)

• The volume of blood in the left ventricle after ventricular contraction.

Stroke Volume (SV)

• The amount of blood pumped per beat, measured by EDV - ESV.

Heart Sounds

• "Lub" is the sound of the closure of AV valves, low pitched.
• "Dup" is the sound of the closure of the semilunar valves, high pitched.

Murmur

• An abnormal heart sound.

Cardiac Output (CO)

• Volume of blood pumped by the heart per minute (CO = HR x SV in L/min).

Stroke Volume Factors

• Preload: amount of blood entering the heart from veins
• Afterload: resistance that needs to be overcome to eject blood from the heart
• Contractility of cardiac muscle

Frank-Starling Law of the Heart

• The more the heart fills with blood during diastole, the greater the force of contraction during systole.

Factors Influencing Afterload

• Blood pressure influences afterload.

Factors Influencing Contractility

• Sympathetic stimulation and exercise influence cardiac contractility.

Heart Rate (HR) vs. Heart Rhythm

• Heart rate is beats per minute.
• Heart rhythm is the regularity of beats or ECG waves.

Tachycardia vs. Bradycardia

• Tachycardia is a heart rate greater than 100 bpm.
• Bradycardia is a heart rate less than 60 bpm.

Normal Heart Rate

• The normal heart rate is 60-100 bpm.

Normal Blood Pressure

• The normal blood pressure is 120/80 mmHg.

Risk Factors for Primary Hypertension

• Genetics, excessive sodium intake, obesity, age, stress, smoking, alcohol, and caffeine.

Hypotension

• Blood pressure below 100/60 mmHg.

Circulatory Shock

• Any condition in which blood vessels are inadequately filled, and blood cannot circulate normally.
• Types: hypovolemic, cardiogenic, vasogenic, neurogenic.

Plasma

• The liquid part of blood, accounting for 55% of blood volume.

Plasma Proteins

• Albumins: most abundant, maintain oncotic pressure
• Globulins: transport iron, lipids, and hormones; also function as antibodies
• Fibrinogen: key factor in blood clotting

Erythrocytes

• Red blood cells (RBCs), carry oxygen on haemoglobin.
• Biconcave discs, lack nucleus and organelles, survive about 120 days.

Erythropoiesis

• Formation of new erythrocytes.
• Low oxygen carrying capacity sensed by kidneys, which secrete erythropoietin into blood, stimulating erythropoiesis in the bone marrow.

Hematocrit

• Percentage of blood volume occupied by red blood cells (normal: 45%).

Anaemia

• Below-normal oxygen carrying capacity of blood, low hematocrit (30%).
• Types: nutritional, aplastic, hemorrhagic, hemolytic.

Polycythaemia

• Hematocrit of 70%.

Universal Donor

• O negative.

Universal Recipient

• AB positive.

Leukocytes

• White blood cells (WBCs).
• Types: neutrophils, eosinophils, basophils, monocytes, lymphocytes.

Neutrophils

• Most abundant WBC, first defender, phagocytic specialist.

Eosinophils

• WBCs that increase in response to allergies and internal parasites.

Basophils

• Least abundant WBCs, synthesize and store histamine.

Lymphocytes

• WBCs that provide immune defense against specifically targeted pathogens.

Monocytes

• WBCs that leave the blood to enter tissues, transforming into macrophages.

Thrombocytes

• Platelets, involved in haemostasis (cell fragments shed from megakaryocytes).

Haemostasis

• Prevention of blood loss from a broken blood vessel.
• Steps: vascular spasm, platelet plug formation, blood coagulation.

Platelet Plug Formation

• Platelets adhere to exposed collagen at the injury site, release ADP and thromboxane A2, activate other platelets, and aggregate.
• Uninjured endothelium releases prostacyclin and nitric oxide, inhibiting aggregation and confining the platelet plug to the injury site.

Thrombus

• Formation of a blood clot in a healthy vein/artery.

Haemophilia

• Most common cause of excessive bleeding.
• Most sufferers lack the genetic ability to produce Factor VIII of the clotting cascade.

Blood Type Antigens

• A- has type A antigens
• A+ has type A and Rh antigens
• B- has type B antigens
• B+ has type B and Rh antigens
• AB- has type A and type B antigens
• AB+ has type A, type B, and Rh antigens
• O- has none
• O+ has Rh antigens

Blood Type Antibodies

• A has anti-B antibodies.
• B has anti-A antibodies.
• AB has no antibodies.
• O has anti-A and anti-B antibodies.
• Anti-Rh antibodies are not naturally occurring but can be made by Rh-negative individuals exposed to Rh-positive blood, causing issues with subsequent exposures.

Transfusion Reaction

• Tests are conducted to see if blood is compatible before transfusion, to ensure there is no agglutination (clumping) or haemolysis (rupture).

Blood Incompatibility

• Foreign blood is incompatible if it has antigens that correspond to the antibodies in the recipient's blood. For example, introducing type A blood with type A antigens to a type B person with anti-A antibodies.

Antibody Appearance

• Antibodies against foreign AB antigens appear in human plasma six months after birth.

Pathogen

• A disease-causing organism.

Bacteria as Pathogens

• Damage tissues by releasing enzymes or toxins.

Viruses as Pathogens

• Invade and damage host cells, using cell resources to reproduce.

Integument Main Functions

• External body defense, including thermoregulation, vitamin D synthesis, chemical defense secretions (e.g., oil and sweat), fluid balance, somatosensation, and providing a protective barrier.

Skin Absorption

• Fat-soluble (nonpolar) medications can be absorbed through the skin because they can penetrate cells.

Protective Functions of Integument

• Skin microbiome, secretions/enzymes that detoxify/kill some pathogens, melanin production for UV protection, and immune cells to protect against pathogens.

Epidermal Cells

• Keratinocytes, melanocytes, Langerhans cells, and Merkel cells.

Keratinocytes

• Most abundant, produce keratin and form outer layer; dead cells at the surface.

Melanocytes

• Produce melanin, the skin's pigment.

Langerhan's Cells

• Epidermal macrophages.

Merkel Cell

• Mechanosensory cell that detects light touch.

Exocrine Glands of Skin

• Sebaceous glands produce oily sebum to moisturize hair and skin.
• Apocrine sweat glands concentrated at the axillary and pubic region, secrete sweat into hair follicles and onto the skin surface.
• Eccrine sweat glands secrete sweat directly onto the skin through pores, located everywhere on the body.
• Hair follicles grow hair onto the skin surface.

Genitourinary System Defenses

• Acidic urine and vaginal secretions; sticky mucous traps pathogens.

Mucociliary Escalator

• Respiratory system defense with mucous trapping pathogens, cilia beat upwards and out.

Digestive System Defenses

• Enzymes in saliva, gastric acid, and gut-associated tissue.

Defenses of Eyes, Ears, Nostrils

• Eyelashes and tears; earwax; hairs and mucous.

Immune System Functions

• Pathogen defense, identification and destruction of abnormal cells, and removal of damaged or old cells.

Lymphoid Tissues

• Produce, store, or process leukocytes.

Innate vs. Adaptive Immune System

• Innate: rapid, non-specific, non-selective (naturally have it)
• Adaptive: specific, selective (due to vaccine or natural exposure)

Macrophage

• A type of WBC that surrounds/kills microorganisms, removes dead cells, and stimulates the action of other immune cells.

Innate Defenses

• Leukocytes, inflammation, interferons, and the complement system.

Recognition of Non-Self

• Immune cells have pattern recognition receptors (PRR) that bind to pathogen-associated molecular patterns (PAMPS) or damage-associated molecular patterns (DAMPS).

Natural Killer Cells

• Lymphocyte-like cells that nonspecifically destroy virus-infected and cancer cells by forming pores in target cell membranes and releasing cell-digesting proteins.

Dendritic Cells

• Reside in tissues, antigen-presenting cells that activate the adaptive immune response.

Mast Cells

• Leukocyte-like cells that reside in tissues and release histamine in response to injury or pathogens.

Interferon and its Mechanism of Action

• Protein released from a virus-infected cell, warns other cells to produce virus-blocking enzymes if infected.
• Mechanism: when a cell is infected, it releases interferon, which binds with receptors on uninvaded cells, and they produce inactive enzymes that activate to break down viral mRNA and inhibit viral protein synthesis upon infection, preventing multiplication.

Complement System

• A set of inactive proteins present in plasma that form membrane attack complexes (MAC) that punch holes in victim cells when activated, these "complement" antibodies by killing antibody-tagged foreign cells.

Inflammation

• Nonspecific response to tissue injury (pathogen, chemical, heat, mechanical).
• Brings leukocytes and plasma proteins to injured area, characterized by localized pain, swelling, redness, and warmth.

Inflammatory Response

• Leukocytes recognize damage and release cytokines, prostaglandins, and histamine to enhance the immune response.
• Leukocytes (neutrophils, monocytes, natural killer cells) are attracted to the area by chemotaxins released from cytokines.
• Destruction of the pathogen, clearing of the area (pus may accumulate), and tissue repair (new cells, scarring).

Cytokine Key Functions

• Cytokines act as chemotaxins to attract leukocytes, decrease plasma iron concentration, induce fever, and stimulate the release of immune proteins.

Increased Capillary Permeability

• Histamine increases capillary permeability.

Inflammation Symptoms

• Increased blood flow causes symptoms of inflammation.

Inflammatory Conditions

• Named by body part, ending in "-itis".

Risk Factors of Chronic Inflammation

• Age, obesity, diet (sugars, sat. fats), smoking, environmental factors, and stress.

Anti-Inflammatory Nutrients

• Omega-3 fats are thought to have anti-inflammatory properties.

Communication Between Immune Systems

• The innate system secretes cytokines and presents antigens (often with dendritic cells) to activate the adaptive system.
• The adaptive system sends signals to recruit more leukocytes.

Antigen

• Unique large foreign molecules that can trigger an immune response (usually proteins or large carbs found on or secreted from foreign invaders).

Adaptive Immunity Classes

• Antibody-mediated (destroy free-existing invaders like bacteria using B cells).
• Cell-mediated (attack body cells gone awry like virus-infected or cancerous cells using T cells).

B and T cells Specificity

• Achieved through billions of unique receptors developed as a fetus.

B Cell Activation

• B cells are activated by binding with antigens, forming clones.
• Clones differentiate into plasma cells (secrete antibodies) and dormant memory cells (respond to later encounters with the same antigen).

Plasma Cells

• Contain more rough endoplasmic reticulum (ER) to produce more antibodies.

Antibody

• Also known as immunoglobulins or gamma globulins, these are Y-shaped proteins that bind to antigens and mark them for destruction.

Antibody Structure

• A Y-shaped protein made of 4 interlinked polypeptide chains (2 light, 2 heavy).
• The tail portion (Fc) is unique for each subclass of antibody and determines antibody property.
• The 2 arms have identical antigen-binding sites specific to the antibody.

Antibody Subclasses

• IgM: B-cell surface receptor secreted in early stages of plasma cell response.
• IgG: most abundant, produced in large amounts when the body is exposed to the same antigen.
• IgE: helps protect against parasitic worms, mediates allergic reactions.
• IgA: found in digestive, respiratory, and genitourinary systems, also in milk and tears.
• IgD: present on the surface of many B cells, the function is uncertain.

Antibody Support Mechanisms

• Antibodies clump antigenic cells.
• A complement molecule binds with Fc, Fab binds to the invader, forming a membrane attack complex to make holes in the foreign cell and causing its lysis.
• An antibody binds Fc to the phagocyte, and Fab binds to the pathogen, keeping it stable as it's engulfed.
• An NK cell binds to Fc, and Fab binds to the pathogen, inducing lysis of the foreign cell.

T Lymphocytes

• Cytotoxic or killer T cells (CD8) destroy modified host cells (cancerous or viral).
• Helper T cells (CD4) secrete chemicals to amplify other immune cells, help activate B cells and killer T cells.
• Regulatory T cells suppress/regulate the immune response.

Major Histocompatibility Complex (MHC)

• Plasma-membrane-bound glycoproteins found on all cells, varying between individuals.
• MHC-1 class is found on all nucleated cells, and killer T cells bind to it and antigens from infected cells.
• MHC-2 is found on antigen-presenting immune cells, and helper T cells bind to it and antigens from infected cells.

Killer T Cell Action Mechanism

• A virus invades a host cell, and viral antigens are displayed on the host cell surface.
• A killer T cell binds with MHC-1 and viral antigens, releasing chemicals that destroy the attacked cell before the virus can enter the nucleus and replicate.

Memory Cells

• More ready for immediate action than original clone lymphocytes.
• Secondary response is quicker, more potent, and more long-lasting.

Active vs. Passive Immunity

• Active: production of antibodies as a result of exposure to an antigen (i.e., disease or vaccination).
• Passive: direct antibody transfer from another person or animal (i.e., pregnancy, breastfeeding, clinical administration).

Vaccine

• Weakened, dead, or parts of pathogens administered to activate an immune response.

Allergy and its cause

• Inappropriate specific immune response (hypersensitivity) to a normally harmless environmental substance.
• Cause: IgE inappropriately formed by B cells, inserts into mast cells and eosinophils and acts as receptors for allergens. When the allergen is contacted again, these cells release histamine, causing the allergic response.

Too Much Histamine

• Anaphylactic shock, a type of vasogenic shock.

External vs. Internal Respiration

• External respiration: exchange of CO2 and O2 in lungs (air and blood) at the alveoli.
• Internal respiration: exchange of CO2 and O2 in tissues (blood and tissues) with ECF.

Cellular Respiration

• Within the cells: food + O2 = CO2 + H20 + ATP (energy).

Respiratory Tract

• Mouth & nasal passages, pharynx, larynx, trachea, bronchi, bronchioles, terminal bronchioles, respiratory bronchioles, and alveoli.

Thoracic Cavity Cavities

• Pleural (lungs) and mediastinum (heart).

Conducting vs. Respiratory Portion

• Conducting moves air between atmosphere and lungs, and respiratory exchanges gas with blood.

Alveoli and Their Cells

• Thin-walled inflatable sacs adapted for gas exchange (large surface area, thin walls for efficient diffusion, rich capillary supply).
• Key cells: type I alveolar cells forming the alveolar wall and type II alveolar cells secreting pulmonary surfactant.
• Macrophages provide immune defense.

Boyle's/Marriotte's Law

• P1V1 = P2V2
• Volume up = pressure down
• Volume down = pressure up

Ventilation Mechanics

• Flow = change in pressure / resistance
• Air flows from HI to LO pressure
• Resistance inverse to radius (R proportional to 1/r^4)

Inspiration Mechanism

• The diaphragm contracts and flattens (main factor), and external intercostals open up the rib cage, increasing thoracic cavity volume, decreasing pressure, and allowing air to enter to equalize the pressure (active process).

Expiration Mechanism

• Passive diaphragm relaxation brings it up, decreasing thoracic cavity volume, increasing pressure, and allowing air to leave lungs to equalize pressure (mainly passive, can be active with contraction of internal intercostals and abdominal muscles).

Lung Compliance

• Ability of the alveoli to expand and fill with air.
• High: lungs can easily stretch and expand.
• Low: lungs are stiff and do not expand easily.
• Difficulty inhaling is a compliance issue.

Lung Recoil and Pressures

• Deflation of lungs occurs due to inward pressures promoting deflation (elastic recoil of alveolar stretch and surface tension where alveolar fluid is attracted to itself and pushes air out).

How Pulmonary Surfactant Prevents Alveolar Collapse

• Mixture of lipids and proteins, dispersing between water molecules in alveolar fluid and lowering surface tension.

How Transpulmonary Pressure Prevents Alveolar Collapse

• Lungs situated within the pleural sac of the pleural cavity, pleural pressure of intrapleural space always negative compared to alveoli, pulling them open.

Pneumothorax

• Air entering pleural space, causing pleural pressure to equilibrate with atmospheric pressure and eliminating transpulmonary pressure gradient, thereby causing lung collapse.

Ventilation Cycle

• One inhalation + one exhalation.

Minute Volume (MV)

• Amount inhaled or exhaled per minute: MV = frequency x tidal volume (Vt).

Spirometer

• Air-filled drum in a water-filled chamber; measures volume of air breathed in and out over time on a graph known as a spirogram.

Respiratory Dysfunction Categories

• Obstructive: high compliance, low recoil
• Easy to inflate, hard to deflate
• ex. asthma, COPD
• Restrictive: low compliance, high recoil
• Hard to inflate, easy to deflate
• ex. pulmonary fibrosis, pneumonia

Alveolar Ventilation

• Amount of air exchanged between the atmosphere and the alveoli per minute, equal to (tidal volume - dead space) x respiratory rate
• *Not all air participates in exchange, as some is in the anatomic dead space

Hyperventilation vs. Hypoventilation

• Hyper: rapid and deep breathing, lowers pH;
• Hypo: shallow and/or slow breathing, raises pH

Gas Exchange

• Occurs at the pulmonary capillaries in the lungs and at the tissue capillaries, mechanism is simple diffusion of CO2 and O2 down their partial pressure gradients

Dalton's Law (Partial Pressure)

• The partial pressure exerted by a gas is directly proportional to the percentage of the gas in the mixture.

PO2 and PCO2 Process

• In lungs, PO2 decreases as it mixes with dead space air and O2 diffuses into capillaries; PCO2 increases as it mixes with dead space air and CO2 diffuses out of the capillaries.
• Gases equilibrate between alveoli and capillaries.

PO2 Abnormalities

• Hypoxemia: low O2 in arterial blood
• Hypoxia: insufficient O2 at the tissue/cell level
• Hyperoxia: above-normal cell O2 (only occurs when breathing supplemental O2)

PCO2 Abormalities

• Hypercapnia: excess CO2 in arterial blood
• Hypocapnia: below-normal arterial CO2 levels (due to hyperventilation)

O2 and CO2 Transport

• O2: bound to haemoglobin (98.5%)
• CO2: as bicarbonate (HCO3-) (80-90%)

Haemoglobin and O2 Transport

• Haemoglobin (Hb) is an iron-containing protein in erythrocytes that combines with oxygen to form oxyhaemoglobin (each Hb can carry 4 O2 molecules);
• O2 bound to Hb does not contribute to PO2, allowing the blood to carry more O2 (Hb acts as an O2 storage depot keeping PO2 low)

PO2 / Hb Saturation

• Alveoli: PO2 is 100 mmHg, and Hb saturation is 97.5% (highest)
• Tissues: PO2 is 40 mmHg, and Hb saturation is 75%

Anaemia

• Low erythrocyte levels in the blood, causing low O2 concentration in the blood

Rightward Shift Effect

• O2 release to metabolically active cells is favored, increased PCO2, [H+], and temperature, and 2,3-bisphosphoglycerate (made by RBCs when O2 low)

Exercise Effect

• Lower pH due to lactic acid buildup

Carbaminohaemoglobin

• Hb bound to CO2

Ventilation Control

• Ventilation muscles are skeletal and must be voluntarily stimulated by motor neurons to contract; respiratory center in medulla (brain stem) establishes rhythmic breathing pattern and adjusts ventilation to meet demands

Homeostatic Ventilation Control

• Variable: respiratory rate/depth (too much inflation)
• Detector: mechanoreceptors in lungs & chest wall, chemoreceptors in brain and carotid arteries
• Integrator: respiratory center in medulla
• Effector: ventilation muscles (inhibited)

Respiratory Chemoreceptors

• Located in the brain, peripheral receptors found on carotid bodies, detect PCO2, O2, H+ changes

Chemical Factor of Chemoreceptors

• Increased H+ (increases along with PCO2) leads to increased ventilation

Respiratory Failure

• Apnea: transient interruption of ventilation
• Sleep apnea: caused by the relaxation of upper airway skeletal muscles (which also causes snoring) and decreased sensitivity of central receptors during sleep, stops the breath for a few seconds at a time
• Dyspnea: difficulty breathing or shortness of breath

Blood Flow

• Vasoconstriction in lungs or portion of lungs with low PO2 redirects blood to areas of rich (alveolar) oxygen supply

Kidneys Homeostatic Functions

• Water balance, electrolyte concentration, blood volume/pressure, acid-base balance, waste elimination, erythropoetin production, conversion of vitamin D to active form.

Water Excretion

• 500 mL must be excreted per day from the kidneys.

Urine Pathway

• Created in the kidneys, travels down ureters into the urinary bladder for storage until excretion through the urethra.

Bladder Infections

• Less distance between the bladder and the outside, that is, a shorter urethra.

Renal Structure

• Renal cortex, renal medulla, and renal pelvis.

Nephrons Function

• Functional units of the kidney (~1 million/kidney); receive blood supply, filter it and produce urine.

Nephron Types

• Cortical: 80% of nephrons responsible for most urine formation, lie in the outer cortex, and loops of Henle only slightly dip into the medulla.
• Juxtamedullary: 20% of nephrons establish an osmotic gradient that descends into the medulla, lie in the inner cortex, and loops of Henle go deep into the medulla, have a peritubular capillary system that forms hairpin loops called vasa recta.

Blood Path

• Afferent arteriole, glomerulus, Bowman's capsule (blood leaves glomerulus via efferent arteriole; the rest is the filtrate), proximal convoluted tubule, loop of Henle, distal tubule, collecting duct, and renal pelvis.

Plasma Filtration Rate

• 20% of plasma is filtered into Bowman's capsule.

Glomerular Filtration

• Non-specific process that filters non-protein solutes and fluid into Bowman's capsule, ~125 mL per minute (~180 L/day).
• All constituents except plasma proteins are at equal concentrations between plasma and glomerular filtrate.

Glomerular Filtration Rate (GFR)

• Amount of fluid filtered into Bowman's capsule per minute, key determinant is net filtration pressure.
• To increase GFR, also increase arterial blood pressure.

Net Filtration Pressure (NFP)

• NFP = glomerular capillary blood pressure minus (plasma-colloid osmotic pressure plus Bowman's capsule hydrostatic pressure).

Blood Pressure

• Fluid pressure exerted by blood within glomerular capillaries (major outward force producing glomerular filtration).

Osmotic Pressure

• Caused by the unequal distribution of proteins across the glomerular membrane, opposes filtration (inward force).

Hydrostatic Pressure

• Pressure exerted by fluid in the initial part of the tubule, opposes filtration (inward force).

GFR Autoregulation

• Prevent spontaneous changes in GFR, maintain it with typical daily blood pressure fluctuations.

Myogenic Mechanism

• Vasoconstriction/vasodilation of afferent arterioles (increased or decreased arterial blood pressure, respectively), which regulates GFR.

Tubuloglomerular Feedback (TGF)

• Increase in GFR causes an increase in Na+ filtered, sensed by macula densa of the juxtaglomerular apparatus (located near distal tubule), which sends signals to constrict the afferent arteriole, reducing GFR.

Sympathetic Control of GFR

• Long-term regulation of blood volume/pressure can override autoregulatory mechanisms.
• A decrease in arterial BP detected by baroreceptors in the aortic arch and carotid sinus causes increased sympathetic activity like generalized arteriolar vasoconstriction (causing an increase in cardiac output and total peripheral resistance, which themselves increase arterial blood pressure in the short term).
• Afferent arteriolar vasoconstriction decreases glomerular capillary blood pressure and decreases GFR, which decreases urine volume, increasing fluid/salt retention, and bringing arterial blood pressure back up in the long term.

Exercise Effect on Renal Blood Flow

• Reduced.