PHGY209 BLOOD Lecture 1 and 2 2024 PDF

BLOOD Melissa A. Vollrath McIntyre Rm. 1234 514.398.2410 [email protected] USCAs Body Fluids, Transport Mechanisms & Blood August 30 – September 20 Kalenga Lubembele [email protected] Jasmine Chen chia-yu.che...

BLOOD Melissa A. Vollrath McIntyre Rm. 1234 514.398.2410 [email protected] USCAs Body Fluids, Transport Mechanisms & Blood August 30 – September 20 Kalenga Lubembele [email protected] Jasmine Chen [email protected] Victoria Lu [email protected]  SUMMARY – past few lectures Homeostasis & the Milieu Interieur Body Fluid Compartments & Sub-Compartments Communication with the External Environment & within the Internal Environment GI tract skin plasma lungs kidneys ISF Capillary Wall Transport Mechanisms across the Cell Membrane Cell Membrane across the Capillary Wall ICF Blood – a highly dynamic tissue, part of the cardiovascular system - supporter of life – “lifeblood” - associated with emotions – “bad blood” - reflective of relationship – “blood brothers” Ancient Chinese Medicine – blood flow linked to energy flow Ancient Greece – advocated bleeding as treatment for disease Medieval Western Medicine – blood inhabited by good and evil spirits Modern Time – blood as a carrier of disease Blood Functions Transport Nutrients Respiratory Gasses Wastes Hormones Temperature Regulation Acid-Base Balance Normal pH range 7.35 - 7.45 Protection WBCs and Plasma Proteins  Whole Centrifuged Blood Blood 100 55% Plasma Buffy Layer WBCs, Platelets 45% Red Blood RBCs erythrocytes Cells Blood Contains ECF – Extracellular Fluid which is termed Plasma ICF – Intracellular Fluid fluid inside the Blood Cells Blood accounts for ~7% of Body Mass  Blood Volume Terminology Normal Blood Volume = NORMOVOLEMIA Lower Blood Volume = HYPOVOLEMIA Higher Blood Volume = HYPERVOLEMIA  Hematocrit (Ht) – a useful clinical index The percentage of Blood Volume occupied by Red Blood Cells 100% Ht = Height of Red Blood Cell column x 100 Height of whole blood column Normal Value: ~45%  Blood Volume ~7 % of Body Weight ~5 L in the 70 kg male If Hematocrit* is 45%, 100% Volume of blood occupied by RBCs = ~2.25 L Volume of blood occupied by Plasma = ~2.75L * % of blood volume occupied by RBCs  Composition of Plasma similar to ISF > 90% water Ions: Na+, K+, (Ca++, Mg++), Cl-, HCO3-, (PO4--) May be approximated by physiological saline 0.9 % NaCl Nutrients, Respiratory Gasses, Wastes Glucose, Amino Acids, Lipids, O2, CO2, Urea, Lactic Acid Proteins (colloids) = 7 % Albumins Globulins Fibrinogen Separating Plasma Proteins Differential Precipitation by Salts Sedimentation in Ultracentrifuge Immunological Characteristics Electrophoretic Mobility  Electrophoresis – fractionation method based on movement of charged particles along a voltage gradient The rate of migration is influenced by the number and distribution of charges and by the molecular weight, MW, of each protein Each protein migrates at its own characteristic rate + Apply Current Drop of plasma  Scan Fibrinogen Globulins Fibrinogen Albumin α1 α2 β φ γ + Stain Drop of plasma Serum* Electrophoretic Pattern Note absence of Fibrinogen (φ) peak * Serum is plasma with Fibrinogen, the clotting factor, removed  Origin of Plasma Proteins Liver Lymphoid Tissue α1, α2, β Albumin Globulins Gamma (γ) Globulin Fibrinogen  Plasma Protein Synthesis Except for gamma globulin, plasma proteins are synthesized in the LIVER So, when the liver is diseased, plasma protein levels decrease  Electrophoretic Pattern in Renal Disease Fibrinogen Albumin α1 α2 β Φ γ Globulins  Electrophoretic Pattern in Bacterial Infection Fibrinogen Albumin α1 α2 β Φ γ Globulins  Plasma Protein Properties 7g% Molecular Protein Shape Weight Concentration kDa g% Albumin 69 4 Globulins 90-800 2.7 Fibrinogen 350 0.3  Plasma Proteins Play a major role in determining the distribution of fluid between the plasma and the ISF compartments by controlling transcapillary dynamics Interstitial Fluid Plasma Body Water Compartments Extracellular Fluid ECF P Intracellular Interstitial L Fluid Fluid A ICF ISF S M A Cell membrane Capillary Wall relatively impermeable freely permeable to H2O and ions to ions impermeable to proteins Water Distribution Extracellular Fluid ECF ISF =15% 5% 14L P Intracellular Interstitial L Fluid Fluid A ICF ISF S M A 10.5L 3.5L ICF = 40% of Body Mass ECF = 20% Body fluid – ionic composition ECF ECF Note: Plasma has more protein than ISF (7g/dl) ECF may be approximated by a 0.9% solution of NaCl = 300 mOsm 6.7 atmospheres or ~ 5100 mm Hg  Osmolarity of Extracellular Fluid 1 M solution of NaCl 58.5 g NaCl (23 + 35.5) L Na+ Cl- 0.9 g% NaCl = 9 g/L NaCl 9/58.5 = ~ 0.15 M Because NaCl dissociates into 2 ions its osmolarity = 2 x molarity ~ 0.3 Osm = ~ 300 mOsm 6.7 atmospheres or ~ 5100 mm Hg Characteristics of… ISF Plasma 0.9% NaCl 0.9% NaCl 300 mOsm 300 mOsm osmotic = 6.7 atm osmotic = 6.7 atmospheres pressure pressure = 5100 mm Hg capillary wall = 5100 mm Hg For a net flow of water between compartments, there has to be a difference in osmotic pressure  Only Non-Diffusible solutes contribute to the effective Osmotic Pressure of a solution Diffusible solutes do NOT contribute, because they become equally distributed on the 2 sides of the membrane Plasma Proteins are Non-Diffusible therefore, they can exert an osmotic effect This effect is known as the Colloidal Osmotic (Oncotic) Pressure (C.O.P.) of Plasma = 25 mm Hg ISF Plasma 0.9% NaCl 0.9% NaCl 300 mOsm 300 mOsm osmotic = 6.7 atm osmotic = 6.7 atmospheres pressure pressure = 5100 mm Hg = 5100 mm Hg Colloidal Osmotic Pressure (C.O.P.) or Oncotic Pressure due to plasma proteins = 25 mm Hg If the COP increases, more water will flow into plasma If the COP decreases, more water will flow into ISF  Major Role of Plasma Proteins Across the capillary wall there is NO protein diffusion, So, proteins make a major contribution to the Colloidal Osmotic Pressure  Transport across the Capillary Wall There are two major forms of fluid transport across the capillary wall – filtration and osmotic flow 1. The C.O.P. of plasma determines how much water will flow into or out of capillaries ISF Plasma Transport across the Capillary Wall BULK FLOW – flow of molecules subjected to a pressure difference Magnitude of bulk flow α hydrostatic pressure difference peas sieve_jpg FILTRATION – bulk flow across a porous membrane which acts as a “sieve” withholding some particles P1 > P2 P1 Capillary Porous wall membrane P2  Key Mechanisms for Transport Across Capillaries (Transcapillary Dynamics) ISF Plasma 1) Filtration – because fluid in the blood vessel is under pressure, it tends to “push out” fluid from inside the capillaries into ISF 2) Osmotic Flow – plasma proteins, tends to “pull in” or retain fluid inside the capillaries 1) and 2) = STARLING FORCES  Please Note DIFFUSION is responsible for the exchange of nutrients, gases, and wastes across the capillary wall The STARLING FORCES determine the distribution of ECF volume between the Plasma and ISF BLOOD Melissa A. Vollrath McIntyre Rm. 1234 514.398.2410 [email protected] USCAs: Kalenga Lubembele [email protected] Jasmine Chen [email protected] Victoria Lu [email protected]  SUMMARY BLOOD LECTURE #1 Blood Functions Blood Composition – Plasma – “Buffy Coat” (WBCs & Platelets) – RBCs Definition of Hematocrit Plasma Composition – Proteins (Groups, Separation, Characteristics, Origin) Plasma calculated osmolarity – 300 mOsm (0.9% NaCl) – role of ions (“diffusible”) Plasma Colloidal Osmotic (oncotic) Pressure (C.O.P.) – – “non-diffusible” Hydrostatic pressure - filtration The Starling Forces Key Mechanisms for Transport Across Capillaries Transcapillary Dynamics ISF Plasma 1) Filtration – because fluid in the blood vessel is under pressure, it tends to “push out” fluid from inside the capillaries into ISF 2) Osmotic Flow – plasma proteins, tends to “pull in” or retain fluid inside the capillaries 1) and 2) = STARLING FORCES Simplified Circulatory System HEART Capillary Bed – site where exchanges between plasma and ISF take place Starling’s Transcapillary Dynamics Capillary Interstitial Fluid Starling’s Transcapillary Dynamics Starling’s Transcapillary Dynamics C.O.P. = 25 mm Hg 15 mm Hg  Starling’s Transcapillary Dynamics C.O.P. = 25 mm Hg 35mmHg 15mmHg 10 mm Hg 10 mm Hg  SUMMARY: capillary exchanges a) Nutrients, wastes, O2, CO2 move by simple diffusion b) Starling’sTranscapillary Dynamics determine the distribution of ECF volume between Plasma and ISF Filtration – tends to “push out” the fluid from inside the capillaries Osmotic Flow – tends to “pull in” or retain fluid inside the capillaries  Starling’s Transcapillary Dynamics Net filtration Net absorption Exchanges filtration/absorption take place along the whole length of the capillary bed not just at the 2 ends  Excess Fluid ISF Blood stream Only ~ 90% of the fluid filtered out is reabsorbed back into capillaries 10% is drained from the tissues by lymphatic vessels Lymphatic System A network of blind-ended terminal tubules which coalesce to form larger lymphatic vessels, which converge to form large lymphatic ducts, which drain into the large veins in the chest  Lymphatic Vessels The walls of lymphatic vessels are made up of a single layer of endothelial cells They are highly permeable to all ISF constituents including proteins which may have leaked into the ISF from the plasma Lymphatic vs Blood Flow Volumes On a daily basis: Total Blood Flow 6,000L Volume filtered into ISF 20L Volume returned by absorption 17L Volume returned by lymph drainage 3L  Colloidal Osmotic Pressure C.O.P. ISF Plasma Osmotic Flow – Due to plasma proteins, tends to “pull in” or retain fluid inside the capillaries ISF Plasma Which proteins contribute the most to C.O.P.? The osmotic pressure of a solution depends on the NUMBER of osmotically active particles/unit volume NOT their configuration, size, or charge Each protein fraction exerts an osmotic pressure which is (i) directly related to its Concentration in the plasma (ii) inversely related to the Molecular Weight of that protein balance 1 kg 1 kg See full size See full imagesize image See full size image See full See full size size image image See full size image See full See full See full size size size image image image See full See full See full See full size size size size image image image image See full size image See full size image Steel Ball Feather You need MANY MORE feathers than steel balls!!!  Plasma Protein Properties Molecular Protein Shape Weight Conc’n COP kDa g% mm Hg Albumin 69 4 ~20 Globulins 90-800 2.7 ~5 Fibrinogen 350 0.3