Human Physiology 2nd Year Medical Lab Techniques PDF

9/25/2024 Human Physiology 2nd Year Medical Lab Techniques Dr. Athir K. Mohammed Lec 1 Body Fluids Dr. Athir K. Mohammed 1 Human Physiology: is the science that describes how organisms (or organ)...

9/25/2024 Human Physiology 2nd Year Medical Lab Techniques Dr. Athir K. Mohammed Lec 1 Body Fluids Dr. Athir K. Mohammed 1 Human Physiology: is the science that describes how organisms (or organ) FUNCTION and survive in continually changing environments Dr. Athir K. Mohammed 2 1  9/25/2024 Dr. Athir K. Mohammed 3 Dr. Athir K. Mohammed 4 2  9/25/2024 Cells exist in an extra-cellular fluid [ECF], sometimes called "Internal Environment“. From this fluid the cells take up oxygen & nutrients; into it, they discharge metabolic waste products. Solutions play a big role in physiology. Solution is a mixture; most abundant component called solvent (usually water in biology) and other components called solutes (ions, proteins, glucose and other nutrients, oxygen and CO2). Dr. Athir K. Mohammed 5 60% of body weight accounts 42 Liter.  Intracellular fluid:. =~ 28 L Extracellular fluid: =~ 14 L Interstitial fluid:. =~ 11 L Plasma: =~ 3 L Blood? Serum? Clot Does not clot Transcellular fluid: is another small compartment of specialized ECF (1-2 L) Dr. Athir K. Mohammed 6 3  9/25/2024 Factors affecting body fluids Normal TBW % depends on 3 main factors:  Age: (elderly < young)  Gender: ( < )  Degree of Obesity: (obese < non-obese) In addition to other factors; including: Water intake & output Climate Level of physical activity  Habits Dr. Athir K. Mohammed 7 body fluids Composition Boundaries between body fluid compartments are two: 1. Capillary walls: permeable to electrolyte but not protein. 2. Cell membranes: permeable to water but not electrolytes. Dr. Athir K. Mohammed 8 4  9/25/2024 Body fluids Composition ICF : ECF: C E K+ L Na+ L in addition to: HPO42- M Cl− E protein M HCO3− Mg2+ & B & R Ca2+ A Ca2+ N E Dr. Athir K. Mohammed 9 Regulating Electrolytes Sodium Potassium Calcium Magnesium Chloride Phosphate Bicarbonate Dr. Athir K. Mohammed 10 5  9/25/2024 Dr. Athir K. Mohammed 11 Na+: is a cation (= +ve ion) involved in generating action membrane potential of both: muscle cells (( muscle contraction)) & nerve cells ((nerve impulse conduction)) Also it makes major contribution to extracellular osmolarity ((water follows sodium by osmosis)). Dr. Athir K. Mohammed 12 6  9/25/2024 K+: maintaining the resting membrane potentials of excitable cells (muscle & nerve cells); So plays key role in nerve impulse conduction, muscle contraction and cardiac rhythm. Also it is a greatest contributor to intracellular osmolarity and cell volume Dr. Athir K. Mohammed 13 Ca2+: has the following functions: trigger muscle contraction; control secretion of hormones and neurotransmitters; essential factor in blood clotting; control metabolism & activates many cellular enzymes; &  strengthen the skeleton. Dr. Athir K. Mohammed 14 7  9/25/2024 So Muscle Contraction rely markedly on these three cations (Na+, K+ & Ca2+) Cl−: together with Na+ ; be the main anion (= ve ion) of the plasma and interstitial fluid & HCO3− & HPO42−: are anions that stabilize pH of body fluids H+ and OH−: are cations that determine the degree of acidity Dr. Athir K. Mohammed 15 Many Serious Medical Problems Involve Abnormalities of Salts & Water HyperKalemia: is the increase level of serum K+ above normal (> 5.5 mEq/L); caused by kidney disease & medical malpractice; can result in intestine cramps and muscle weakness progressing to paralysis, slowed heart conduction  cardiac arrest (asystole). Hypokalemia: is the decrease level of serum K+ below normal (< 3.5 mEq/L); caused by no oral intake of food and fluids; can stop nerve and muscle excitation  paralysis and respiratory arrest. Dr. Athir K. Mohammed 16 8  9/25/2024 HyperNatremia: is the increase level of serum Na+ above normal (> 145 mEq/L); Hyponatremia: is the decrease level of serum Na+ below normal (< 130 mEq/L); HyperCalcemia: (plasma Ca++ concentration above 11, 0 ml/dl) leads to heart dysrhythmias, and cardiac arrest Hypocalcemia (Ca++ concentration below 9, 0 mg/dl) leads to muscle spasm. If level is very low a person can go into tetanus and breathing will stop. Dr. Athir K. Mohammed 17 Dehydration: is the decrease of body water below normal  Blood becomes too viscous to circulate well  loss of temperature regulation  hyperthermia, death. Edema: the accumulation of fluid in the interstitial spaces. Development of edema: an imbalance between the filtration of fluid from the bloodstream and drainage via the lymph system. Dr. Athir K. Mohammed 18 9  9/25/2024 pH of common substances: Approximate Common Examples of Substances pH Stomach acid (HCl), Strong Acids 0-2 battery acid (H2SO4) Weak Acids 3-6 Lemon juice, vinegar, rain water Neutral 7 Pure water Weak Bases 8-11 Bicarbonate solution (HCO3−) Solutions of lye (NaOH), Strong Bases 12-14 oven cleaner (KOH) Dr. Athir K. Mohammed 19 Daily Intake of Water: Water is gained from three sources: 1) Ingestion of food } add ~ 2000 ml/day 2) Drink of water 3) Synthesis of water in the body as a result of oxidation of carbohydrates (add ~ 200 ml/day) Dr. Athir K. Mohammed 20 10  9/25/2024 Routes of water loss 1. Insensible Water Loss a) Breath (by lung) – obligatory water loss b) Cutaneous diffusion (by skin) – obligatory water loss This is through respiratory tract by evaporation and through the skin by diffusion. Both account for ~ 700 ml/ day. Loss through the skin occurs independently of sweating. It is increased when the cornified layer is lost (as occurs with extensive burns). Insensible water loss through the respiratory tract account ~ 350 ml/day. This loss increases as the temperature decreases. This explains the dry feeling in the respiratory passages in cold weather. Dr. Athir K. Mohammed 21 Routes of water loss 2. Sweat (by skin through sweat glands) – for releasing heat, varies significantly The amount of water lost by sweating is highly variable, depending on physical activity and environmental temperature. The volume of sweat normally is about 100 ml/day, but in very hot weather or during heavy exercise, water loss in sweat occasionally increases to 1 to 2 L/hour. This would rapidly deplete the body fluids if intake were not also increased by activating the thirst mechanism. Dr. Athir K. Mohammed 22 11  9/25/2024 Routes of water loss 3. Feces (by GIT) – obligatory water loss Only a small amount of water (100 ml/day) normally is lost in the feces. This can increase to several liters a day in people with severe diarrhea (e.g. cholera). For this reason, severe diarrhea can be life threatening if not corrected within a few days. Dr. Athir K. Mohammed 23 Routes of water loss 4. Urine (by kidney) – obligatory (unavoidable) and physiologically regulated. The remaining water loss from the body occurs in the urine excreted by the kidneys. Urine volume can be as low as 0.5 L/day in a dehydrated person or as high as 20 L/day in a person who has been drinking tremendous amounts of water. The kidneys take the task of adjusting the excretion rate of water and electrolytes to match precisely the intake of these substances, as well as compensating for excessive losses of fluids and electrolytes. Dr. Athir K. Mohammed 24 12  Human Physiology 2nd Year Medical Lab Techniques Dr. Athir K. Mohammed Lec 2 Cell; Structure & Function Levels of Organization Subatomic particles Atom System Chemical Molecule Macromolecule Organism Organelle Organ Cell Tissue 1  1st Chemical Level Atoms – made up of subatomic particles Molecules – 2 or more atoms Macromolecules – small molecules joined together – Carbohydrates, lipids, proteins, nucleic acids 3 2nd Cellular Level Macromolecules combine to form cells Basic structural and functional unit of the body 2  3rd Tissue Level Group of cells working together to perform a function 4 basic types – epithelial tissue – connective tissue – muscle tissue – nerve tissue 4th Organ Level 2 or more tissues joined together with a specific function and shape 3  5th System Level Related organs with a common function 11 systems e.g. : cardiovascular digestive nervous respiratory 6th Organism 4  Cell The basic structural and functional unit of the human body is the cell. There are ~ 100 trillion cells in the human body. (25% are RBCs) Differentiation is when cells specialize. As a result of differentiation, cells vary in size and shape due to their unique function. Two types of cells on earth Prokaryotic cells: are more primitive, small and without nucleus or organelles; like bacteria and blue-green algae. Eukaryotic cells: are more advanced, larger, and contain nucleus plus organelles; like animals, plants, fungi, and protozoa. In our body prokaryotic cells actually outnumber eukaryotic cells!! Intestinal Bacteria 5  Cell Parts Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Major parts include: Phospholipid bilayer Flagellum Nucleus Nucleus Nuclear envelope Nucleolus Chromatin Ribosomes Microtubules Basal body Cell membrane contains DNA Centrioles Rough Endoplasmic reticulum Cytoplasm Mitochondrion Smooth Endoplasmic reticulum cellular contents between plasma membrane & nucleus Microvilli Secretory Cell membrane vesicles Cilia Golgi apparatus selective barrier Microtubule Microtubules Lysosomes 11 Cell Membrane Selectively permeable Phospholipid bilayer Water-soluble “heads” form surfaces (hydrophilic) Water-insoluble “tails” form interior (hydrophobic) Permeable to lipid-soluble substances Cholesterol stabilizes the membrane Proteins: Receptors Pores, channels and carriers Enzymes Self-markers Carbohydrates as glycoprotein and glycolipid function in cell recognition. 6 Cell Membrane Functions: 1. Supporting and retaining the cytoplasm 2. Transport: being a selective barrier: Some molecules can cross the membrane without assistance, most cannot. Water, all non-polar (hydrophobic = lipid soluble) molecules and some small polar (hydrophilic = lipid insoluble) molecules can cross easily. 3. Communication (via receptors): Hormones and neurotransmitters affect on cell though its membrane 4. Recognition: The cell identify other cells and microorganisms though its membrane 7  Cell Nucleus Is the control center of the cell Nuclear envelope Porous double membrane Separates nucleoplasm from cytoplasm Nucleolus Dense collection of RNA and Nucleus Nuclear proteins envelope Site of ribosome production Nucleolus Chromatin Fibers of DNA and proteins Chromatin Stores information for synthesis of Nuclear pores proteins (a) Most cells contain 1 nucleus, but: Some liver cells have multiple nuclei (polyploidy) Muscle cells are very long and have hundreds of nuclei Mature red blood cell has lost its nucleus 8  Cytoplasm consists of a gelatinous solution (Cytosol) and contains microtubules and microfimaments (which serve as a cell's cytoskeleton) Organelles (literally 'little organs') are the content of the cytoplasim 17 Cytoplasm Microfilaments and microtubules Microtubules Thin rods and tubules Support cytoplasm Allows for movement of organells Give the cell its shape Inclusions Temporary nutrients and pigments Microfilaments 9  Organelles Endoplasmic Reticulum (ER) Connected, membrane-bound sacs, canals, and vesicles Transport system Rough ER Membranes Studded with ribosomes Membranes Smooth ER Lipid synthesis Added to proteins arriving from rough ER Ribosomes Break down of drugs (b) (c) Ribosomes Free floating or connected to ER Provide structural support and enzyme activity to amino acids to form protein (protein synthesis) Organelles Golgi apparatus synthesis (of substances likes Stack of flattened, phospholipids), packaging of membranous sacs materials for transport (in vesicles), Modifies, packages and production of lysosomes and delivers proteins Mitochondria Have a double-membrane: outer membrane & highly convoluted inner membrane with cristae important in ATP production. 1000 mitochondria small amounts of DNA 20 10  Organelles Lysosomes Membrane-enclosed spheres that contain powerful digestive enzymes digestion of phagocytosed materials or cell itself Peroxisomes Membranous sacs of oxidase enzymes & replicate by pinching in half Functions: Detoxify harmful substances Break down free radicals (highly reactive chemicals) 21 Organelles Centrosome Two rod-like centrioles Distributes chromosomes during cell division Centriole (cross-section) Centriole 22 (longitudinal section) (a) (b) a: © Don W. Fawcett/Visuals Unlimited 11  Organelles Cilia Short hair-like projections Propel substances on cell surface Cilia (single is cilium) are relatively short & numerous (e.g., those lining trachea). Flagellum Long tail-like projection Provides motility to sperm 23 Organelles Microvilli Projections of cell membrane that serve to increase surface area of a cell (which is important, for example, for cells that line the intestine) Sometimes confused with cilia, but much smaller (1 micron length) and with a different structure & different function. Vesicles Membranous sacs Store substances 24 12  Protein synthesis from DNA DNA- controlling protein synthesis in a cell. Transcription (Transcription of DNA sequences into mRNA called Codon) Translation (Translation of mRNA into polypeptides): mRNA (messenger RNA) then moves from the nucleus into the cytoplasm & is used to produce a protein in the presence of tRNA (transfer RNA), amino acids & a ribosome. 25 Protein synthesis from DNA 26 13  Movements Into and Out of the Cell Passive (Physical) Active (Physiological) Processes Processes Require no cellular Require cellular energy energy and include: and include: 1. Simple diffusion 1. Active transport 2. Facilitated diffusion 2. Endocytosis 3. Osmosis 3. Exocytosis 27 Simple Diffusion Movement of substances from regions of higher concentration to regions of lower concentration Oxygen, carbon dioxide and lipid-soluble substances Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Permeable Solute molecule membrane Water molecule A B A B A B (1) (2) (3) 28 Time 14  Diffusion Simple Diffusion The rate of diffusion is influenced by: concentration gradient cross-sectional area through which diffusion occurs distance through which diffusion occurs; temperature molecular weight of the substance. 30 15  Facilitated Diffusion Diffusion across a membrane with the help of a channel or carrier molecule Glucose and amino acids Region of higher concentration Transported substance Region of lower concentration Protein carrier molecule Cell membrane 31 Osmosis Movement of water through a selectively permeable membrane from regions of higher water concentration to regions of lower water concentration 16  When a solute is added to pure water, this reduces the concentration of water in the mixture. Thus, the higher the solute concentration, the lower the water concentration Osmosis and Osmotic Pressure Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Osmotic Pressure – ability of osmosis to generate enough pressure to move a volume of water Osmotic pressure increases as the concentration (a) of nonpermeable solutes increases Isotonic – same osmotic pressure Hypertonic – higher osmotic pressure (water loss) (b) Hypotonic – lower osmotic pressure (water gain) (c) © David M. Phillips/Visuals Unlimited 34 17 Effects of Different Solutions on Red Blood Cells Active Transport Carrier molecules transport substances across a membrane from regions of lower concentration to regions of higher concentration + expenditure of energy Sugar, Na + & K+ Carrier protein Binding site Region of higher concentration Cell membrane Region of lower Phospholipid concentration molecules Transported particle (a) Carrier protein with altered shape Cellular 36 energy (b) 18  Active Transport: Sodium-Potassium Pump Active transport mechanism Creates balance by “pumping” three (3) sodium (Na+) OUT and two (2) potassium (K+) INTO the cell 3:2 ratio 37 Active Transport 19  Endocytosis Cell engulfs a substance by forming a vesicle around the substance Three types: Pinocytosis – substance is mostly water Phagocytosis – substance is a solid Receptor-mediated endocytosis – requires the substance to bind to a membrane-bound receptor Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Cell Particle Phagocytized Vesicle membrane particle 39 Nucleus Nucleolus Exocytosis Reverse of endocytosis Substances in a vesicle fuse with cell membrane Contents released outside the cell Release of neurotransmitters from nerve cells Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Endoplasmic Golgi reticulum apparatus Nucleus 40 20  Saturation Both facilitated diffusion & active transport require the use of carriers that are specific to particular substances (that is, each type of carrier can 'carry' one type of substance); therefore both can exhibit saturation (movement across a membrane is limited by number of carriers & the speed with which they move materials). 41 Homeostasis 21  Homeostasis The maintenance of a relatively constant internal environment in an organism Human body has control systems; that depend on info about the changes (for any variable) in the internal environment; these data come from Receptors. Then the body response through the involved Organ System (one or more) by Effectors. 44 22  Homeostasis 1. Negative Feedback mechanism (corrects deviations) Receptors sense a deviation from normal range for a variable and effectors work to return it to normal again. e.g. Too hot, body sweats to lower body temp Too cold, we shiver Thyroid hormones 46 23  47 Homeostasis 2. Positive Feedback mechanism (intensifies response) Receptors sense that the body needs more power and the effectors respond by increasing or strengthening what is happening Ex. Child birth, increases strength of uterine contractions Hemostasis by platelets & clotting cascade 24 49 50 25 51 26  10/7/2024 Human Physiology Lec 3 : Blood (RBCs) Dr. Athir K. Mohammed Class: 2nd Year Medical Laboratory Techniques RBCs: is that part of extracellular fluid within the cardiovascular system  10/7/2024 Blood Components 5 liters (8% of total BW) 1. Formed elements (45%): 1. Red blood cells [RBCS] (Erythrocytes) 2. White blood cells [WBCS] (Leucocytes) 3. Platelets (Thrombocytes) Dr. Athir K. Mohammed Blood Components 2. Plasma (55%) : It is composed of : a) Water: about 97% of plasma is water, which form the intravascular component of the extracellular fluid. b) Plasma proteins : dissolved proteins that serve for different functions as follows: Dr. Athir K. Mohammed  10/7/2024 Blood Components  Albumin: the most numerous plasma proteins that serve mainly for transport of hormones, drugs, and biologically active substances. Plus buffering function and regulatory effect on blood volume (osmotic –oncotic- pressure) Dr. Athir K. Mohammed Blood Components  Globulin: that serves for immune functions  Fibrinogen: That serves for blood clotting and homeostasis.  Prothrombin: also serves for blood clotting and homeostasis All plasma proteins are produced in liver except one type; Gama globulin), which is produced by the plasma cells. Dr. Athir K. Mohammed  10/7/2024 Blood Components c) Organic materials: such as glucose , amino acids , and fat. d) Nonorganic materials: such as ions (sodium, potassium, calcium, chloride & bicarbonate) e) Others: hormones & blood gases. Dr. Athir K. Mohammed  Serum = plasma with clotting factors removed (i.e. serum has no clotting factors) Dr. Athir K. Mohammed  10/7/2024 Blood Functions: 1. Transportation: of  Oxygen from lungs to body cells  Carbon dioxide from body cells to lungs  Nutrients from GI tract to body cells  Nitrogenous wastes from body cells to kidneys  Hormones from glands to body cells Dr. Athir K. Mohammed Blood Functions: 2. Regulation (Maintenance of homeostasis): of  Body pH (by bicarbonate & blood proteins -albumin-)  Circulatory / interstitial fluid (by electrolytes &albumin )  Temperature (as in blushed skin) Dr. Athir K. Mohammed  10/7/2024 Blood Functions: 3. Protection: by  Clotting mechanism protects against blood loss (platelets and clotting proteins)  Immunity against many disease- causing agents (leukocytes, antibodies, complement proteins) Dr. Athir K. Mohammed Erythrocytes (RBCs) Dr. Athir K. Mohammed  10/7/2024 RBC Morphology & Characteristics:- 1. Biconcave discs. It can change its shape (molding) as it passes through capillaries which are of smaller diameter than that of RBC due to the excess cell membrane in relation to substances inside the RBC. Dr. Athir K. Mohammed RBC Morphology & Characteristics:-  Also allow RBC to form rouleaux inside narrow blood vessels Dr. Athir K. Mohammed  10/7/2024 RBC Morphology & Characteristics:- 2. Lack the nucleus (so called corpuscles rather than cells) and many organelles so RBC cannot reproduce.  (average lifespan ~ 120 days after they get destructed by hemolysis in the spleen).  They obtain energy via anaerobic glycolysis (they have no mitochondria). Dr. Athir K. Mohammed RBC Morphology & Characteristics:- 3. Transport Hemoglobin (each RBC has ~ 280 million Hb molecules) mainly for O2 transport. 4. Contain Carbonic Anhydrase Enzyme (for transport of carbon dioxide). Dr. Athir K. Mohammed  10/7/2024 Dr. Athir K. Mohammed RBC Count:-  Can be counted by counting chamber  In male ( ) =5.2 x 106 ± 300000/mm3; in female ( ) =4.7 x 106 ± 300000/mm3  In infant & old age it is much higher (due to hypoxia); also the number is increased in those living in high altitude (due to hypoxia).  It may be decreased in pregnancy (due to dilution of blood). Dr. Athir K. Mohammed  10/7/2024  PCV (or haematocrit value): represents the % of RBC in 100 cc of blood. Normally it is about 47% for males & 42% for females (± 5%). Hematocrit Dr. Athir K. Mohammed  Hb concentration: represents the amount of Hemoglobin in 100 cc of blood. Normally its average is ~ 14 g/dl in & 16 g/dl in (± 2g/dl). Remember>>>PCV represents the % of RBC in 100 cc of blood Dr. Athir K. Mohammed  10/7/2024 RBC Production Sites:-  RBC produced in different areas of the body, which vary according to age of subject:  In 1st trimester of pregnancy (first 3 months): Yolk sac  In 2nd trimester of pregnancy (second 3 m): Liver, spleen & lymph nodes  In 3rd trimester of pregnancy - 5 years of age: Bone marrow of all bones Dr. Athir K. Mohammed RBC Production Sites:-  In 5–20 years of age: Bone marrow of membranous bones and proximal part of long bones like tibia & femur; while the rest of bone marrow become fatty and can be reproductive on need  In 20 years & after: only Bone marrow of membranous bones; like vertebrae, iliac bone, sternum, ribs, and skull bones. Dr. Athir K. Mohammed  10/7/2024 Erythropoiesis:- Begins with a Hematopoietic Stem Cell (HSC)  Proerythroblast    Reticulocyte then Mature RBC Dr. Athir K. Mohammed RBC Genesis (Erythropoiesis):-  The body must produce about 2.5 million new RBCs every second  The rate is regulated by oxygen levels (tissue oxygenation):  Hypoxia (= decreased oxygen levels) is detected by cells in the kidneys kidney cells release the hormone erythropoietin into the blood  stimulates erythropoiesis in the bone marrow. Dr. Athir K. Mohammed  10/7/2024 RBC Genesis (Erythropoiesis):- Dr. Athir K. Mohammed Hemo globin (Hb) Molecule = Globin: 4 polypeptides = two alpha (α) chains & two beta (β) chains. + Each chain has a heme group (porphyrin ring with an iron in the center). Hb has 4 heme groups with 4 Iron Fe2+ that can bind max. to 4 O22- moelcules.  oxyhemoglobin Dr. Athir K. Mohammed  10/7/2024 Hemo globin  Also it can combine with carbon dioxide, but with less affinity.  Hb from dead RBCs is utilized (amino acids from globin & iron from heme) and excreted (bilirubin from porphyrin)  Hemolysis of RBCs  more Hb destruction  increase bilirubin in blood (jaundice). Dr. Athir K. Mohammed RBC Death  As RBCs get older, their membrane becomes less flexible and easily fragile.  When they pass through capillaries of spleen  hemolysis and phagoytosis by macrophage cells. Dr. Athir K. Mohammed  10/7/2024 1st Vitamin B12 (Cyanocobalamin) & 2nd Folic Acid  They are needed for DNA synthesis, so affect (nucleus division, growth & maturation) all rapidly growing tissues especilly bone marrow.  Their deficiency → decrease rate of RBC production & enlarged RBC (macrocyte) in megaloblastic anemia.  Daily requirement of vit.B12 = 5 µg; 1000x of this amount is stored in the liver so its deficiency in diet need 4-5 years to get Megaloblastic Anemia. Dr. Athir K. Mohammed 3rd Iron  The total body iron (Fe++) = 4 grams; 65% in Hb  The daily requirement of Fe in = 1 mg, & in = 2 mg (due to additional loss in menstrual cycle)  The old RBC (aged 4 months) will be destroyed in spleen & liver by macrophage  release Fe to be utilized again. , while bilirubin excreted by the biliary system.  Its deficiency  Iron deficiency anemia that is characterized by hypochromic microcytic blood film. Dr. Athir K. Mohammed  10/7/2024 Iron-Deficiency Anemia Dr. Athir K. Mohammed Regulation of RBC production:  RBC count should be with normal because:  If it decreases   tissue oxygenation.  If it increases   blood flow.  The basic mechanism for RBC regulation is tissue oxygenation.   O2 (hypoxia) as in anemia, lung disease, high altitude and cardiac failure) stimulate the release of erythropoietin hormone (90% from kidney & 10% from liver). Dr. Athir K. Mohammed  10/7/2024 Regulation of RBC production:  This hormone stimulates erythropoiesis so within 5 days new RBCs appear in circulation, this will continues till hypoxia disappear.  On stimulation of RBC formation, reticulocytes increase from 1% up to 30-50% of total number of RBC because no time for maturation of RBC.  reticulocytes  is a good indicator of a blood loss or hemolysis. Dr. Athir K. Mohammed Anemia  Deficiency of RBC &/or Hb; either due to: 1. Slow production: as in aplastic anemia, or 2. Rapid loss or destruction: as in blood loss and hemolytic anemia. Dr. Athir K. Mohammed  10/7/2024 I) Slow RBC production Anemia: 1. Aplastic anemia ‫فقر دم ﻻت س‬  Caused by damage of the bone marrow;  either by: 1. X-ray radiation, 2. Drugs like chloromphenicol or cytotoxic drugs, or 3. Bone marrow infiltration by myelofibrosis or leukemia.  Characterized by: Anemia, leucopenia ( infection) & thrombocytopenia ( bleeding). This decrease in all blood elements is called pancytopenia. Bone marrow aspirate shows fibrosis & decrease blast cells. Dr. Athir K. Mohammed 2. Megaloblastic anemia:  Caused by decrease Vit. B12, folic acid or intrinsic factor.  The intrinsic factor is glycoprotein produced by gastric mucosa: intrinsic factor bind Vit. B12 to prevent its digestion by GIT enzymes & bacteria. Dr. Athir K. Mohammed  10/7/2024 2. Megaloblastic anemia: intrinsic factor facilitate binding of Vit. B12 to receptors in ileum so increase its absorption. intrinsic factor is decreased by atrophic gastritis & gastrectomy  pernecious anemia. Megaloblastic anemia Characterized by: megalocytes & megaloblast cells, anisocytosis, poikelocytosis, dotted RBC, and tear drop RBC. Dr. Athir K. Mohammed I) Slow RBC production Anemia: 3) Iron deficiency anemia  Iron deficiency anemia develops when body stores of iron drop too low to support normal red blood cell (RBC) production.  Causes: Inadequate dietary iron, impaired iron absorption, or bleeding RBCs are microcytic and hypochromic in chronic cases Low serum iron and ferritin levels with an elevated total iron binding capacity (TIBC) are diagnostic of iron deficiency Dr. Athir K. Mohammed  10/7/2024 II) RBC loss/destruction Anemia: 1. Blood loss anemia:  Bleeding due to: trauma, peptic ulcer, haemorroid, etc…  In acute hemorrhage: plasma replaced within 3 days so get low concentration of RBC, then after 3-4 weeks regain normal RBC concentration; characterized by normochromic normocytic blood film.  In chronic hemorrhage: Body cannot absorb enough iron for Hb synthesis, so RBC cannot be replaced. So characterized by hypochromic microcytic anemia. Dr. Athir K. Mohammed II) RBC loss/destruction Anemia: 2. Hemolytic anemia: 1. Abnormality in RBC: likes hereditary spherocytosis. So get small, rigid, and easily fragile RBC hemolyzed during molding. 2. Abnormality in Hb: Sickle cell anemia (HbS) and thalassemia: abnormal Hb will be catalyzed or precipitate & rupture RBC. Dr. Athir K. Mohammed  10/7/2024 II) RBC loss/destruction Anemia: 2. Hemolytic anemia:  Sickle cell anemia : Dr. Athir K. Mohammed II) RBC loss/destruction Anemia: 2. Hemolytic anemia: 3. Abnormality of membrane: Favism = G6PD deficiency. If blood exposed to fava beans, aspirin or other drugs causing oxidization of membrane, it become rigid & ruptures. 4. Antibody-Antigen reaction on RBC membrane:  rupture of RBC as incompatible blood transfusion, Erythroblastosis fetalis, and Autoimmune hemolytic anemia. Dr. Athir K. Mohammed  10/7/2024 Polycythemia  Abnormal increased RBC count; two types: 1. Primary polycythemia: = Polycythemia vera: is tumor of stem cells, so increase all blood elements (RBC, WBC & platelets). RBC count 7-8 x 106/mm3 2. Secondary polycythemia: due to tissue hypoxia as in high altitude, lung diseases, and smoking  increase RBCs only to reach 6-7 x 106 /mm3 Dr. Athir K. Mohammed Polycythemia  Increase RBC count lead to increase viscosity of blood  decrease blood flow  bluish discoloration of skin (cyanosis) and may  thrombosis (e.g. deep vein thrombosis [DVT] or organ infarction) Dr. Athir K. Mohammed  10/16/2024 Human Physiology 2nd Year Med. Lab. Tech. Dr. Athir K. Mohammed MSc PhD. Physiology and Endocrinology Lec 4 White Blood Cells (leukocytes) Types & Count of (WBCs): 7000 (4500-11000/mm3) Leukocytosis X leukopenia I. Granulated (Granulocytes): its cytoplasm contains granules; also called polymorphnuclear –PMN- cells because of different shape of nucleus. 3 types according to their granules: 1  10/16/2024 Granulocytes: 1. Neutrophils = 62% (50-70%) contain neutrophilic granules.  (Neutrophila) in: inflammation & bacterial infection Granulocytes: 2. Eosinophils = 2.3% (1-4%) contain acidic granules (red).  (Eosinophila ) in: allergy & parasitic infection 2  10/16/2024 Granulocytes: 3. Basophils = 0.4% (0-0.5%) contain alkaline granules (blue). Function with mast cells to secrete heparin & histamine Types & Count of (WBCs): II. Agranulated (Agranulocytes): No granules in the cytoplasm. 2 types: 1. Monocytes = 5.3% (2-8%) large cytoplasm, kidney shape nucleus. Macrophages are the mature form of monocytes 3  10/16/2024 Agranulocytes: 2. Lymphocytes = 30% (20-40%) thin cytoplasm, round nucleus. Small & large lymphocytes T & B lymphocytes Never Let Monkeys Eat Bananas Eosinophil~2.5% E Neutrophil~60% L N Lymphocyte=30% B M Basophil=0.4% Monocyte~5% 4  10/16/2024 Genesis of leukocytes (Granulopoiesis): Granulocytes (neutophils, Eosinophils & basophils) & monocytes are formed only by bone marrow. Lymphocytes & plasma cells are partly formed by bone marrow but mostly by lymph glands, spleen, thymus & tonsils, that have stem cells come from bone marrow. 5  10/16/2024 Genesis of leukocytes (Granulopoiesis): Granulopoiesis stimulated by granulopoietin (colony stimulated factors: e.g. GM-CSF) released by activated macrophage (+ve feed back mechanism). It is inhibited by prostaglandin E & substance released by mature neutrophils (–ve feed back mechanism).. Life Span of WBC: Granulocytes: Normally, life span is 4-8 hours in the circulatory blood then 4-5 days in tissue. In infection, live for few hours only. Monocytes: Live for few hours in the circulatory blood then go to tissue and swell to form tissue macrophage that live months or years unless infection occur. 6  10/16/2024 Life Span of WBC: Lymphocytes: They circulate in blood, enter & drain through thoracic duct & lymph gland. They live for 100-300 days, some lymphocytes live for ever. Function of WBC: Neutrophils - phagocytosis (bacteria & cellular debris); very important in inflammation and bacterial infection. Eosinophils - stimulate inflammatory response against parasites & kill parasites. Also important in allergy. 7  10/16/2024 Function of WBC: Basophils - synthesize & store histamine (a substance released during allergy) & heparin (an anticoagulant). Function of WBC: Monocytes - phagocytosis (typically as macrophages in tissues of the liver -Kupffer cells-, spleen, lungs, & lymph nodes) Lymphocytes - specific immune system (including production of antibodies) increased (lymphocytosis) in viral infection. 8  10/16/2024 Neutrophils & Monocytes (Macroghages) 1. Margination: Sticking of WBC to capillary wall. Normally 3/5 of neutrophils & 3/4 of monocytes are sequestrated in the capillary due to their large size & stickiness of capillary. 2. Diapedesis: Squeezing the WBC through capillary walls even if WBC larger than pores. 3. Amoeboid motion: Neutrophils & macrophages move in the tissue by this mechanism up to 40 micron/min. 9  10/16/2024 Neutrophils & Monocytes (Macroghages) 4. Chemotaxis: On infection, a number of chemical substances released that stimulate neutrophils & monocytes movement to that area of infection. Chemotaxis depends on concentration gradient of chemical substance which is effective up to 100 micron away from site of inflammation. This is sufficient because no area of tissue is more than 50 micron distance from a nearby capillary. Neutrophils & Monocytes (Macroghages) 5. Phagocytosis: cell to be phagocytized by neutrophils & macrophages characterized by: 1) Rough surface. 2) Devoted from protective protein that is present in normal cell that repel phogcytosis. 3) Dead cell & foreign particles which are electrically changed. 4) Some cells are recognized by Ab adhere to it. 10  10/16/2024 Neutrophils & Monocytes (Macroghages) Neutrophils are mature WBC, can start phagocytosis immediately; up to 20 bacteria can be phagocytized before inactivation & death. Monocytes are immature, as they go to tissue to be swollen 5 times its diameter (80µ) & develop lysosomes to be macrophage. More powerful more than neutrophil (ingest up to 100 bacteria). Dead neutrophil, necrotic tissue, malarial parasite & even RBC can be engulfed by tissue macrophage so called scavenger cells. Neutrophils & Monocytes (Macroghages) Death of neutrophils & macrophage after phagocytosis:- Neutrophils continue to ingest & digest bacteria & foreign body till toxic substances of bacteria kill neutrophil. Macrophages also the same; but not always, since it can extrude the residual break down product so live to weeks, months or even years. Pus: is a collection of necrotic tissue, dead neutrophils, dead macrophages, and tissue fluid. 11  10/16/2024 WBC abnormalities: Agranulocytosis: Bone marrow stops production of WBC leading to Luekopenia; especially neutrophil numbers decreased (neutropenia); so get multiple infections which may be lethal. This bone marrow aplasia occurs by: -  Gamma rays irradiation.  Drugs (Cloromphenicol, thiouracil, barbiturates & chemicals) WBC abnormalities: Neutrophilia: Increased neutrophil numbers above normal; in inflammation & bacterial infection. Eosinophilia: Increased eosinophil numbers above normal; in allergic reaction & parasitic infection 12  10/16/2024 WBC abnormalities: Leukeimas: Is an uncontrolled production of WBC (so increase number of abnormal WBC) due to carcinogenic mutation of: 1. Myelogenous cells (leading to Myeloid Leukemia) or 2. Lymphogenous cells (leading to Lymphoid Leukemia). These two types are further divided into: Acute and Chronic. 13  10/16/2024 WBC abnormalities: Chronic Myeloid & Lymphoid Leukemia produce partially differentiated cells in slow progression. Acute Myeloid & Lymphoid Leukemia produce undifferentiated cells; which is more acute and cause death within months. 14  10/27/2024 Human Physiology LEC 5 PLATELETS & HEMOSTASIS BLOOD GROUPS & TRANSFUSION Dr. Athir K. Mohammed MSc. PhD. Physiology & Endocrinology 2nd Year Medical Laboratory Techniques PLATELETS :-  (Also called thrombocytes) are minute discs 1 to 4 micrometers in diameter.  They are formed in the bone marrow from megakaryocytes, which are extremely large cells of the hematopoietic series in the marrow. The megakaryocytes fragment (bud) into the minute platelets. 1  10/27/2024 PLATELETS Megakaryocytes are giant cells with multiple copies of DNA in the nucleus. The edges of the megakaryocyte break off to form cell fragments called platelets Platelets Endoplasmic Red blood cell reticulum (a) PLATELETS 2  10/27/2024 PLATELETS Resting platelet Activated platelet PLATELETS  The normal concentration of platelets is 150,000 - 400,000 /mm3.  Platelets have many functional characteristics of whole cells, even though they do not have nuclei and cannot reproduce.  Thrombopoietin: Regulator of platelet production. Produced by the liver and kidneys.  Levels are increased in thrombocytopenia, and reduced in thrombocytosis. It increases the no. & rate of maturation of the megakaryocytes. 3  10/27/2024 PLATELETS  It has a half life in the blood of 8 to 10 days, so that over several weeks its functional processes run out. Then it is eliminated from the circulation mainly by the tissue macrophage system, mainly in the spleen. PLATELETS FUNCTIONS ❖ It is essential for normal hemostasis with different functions 1-maintenance of vascular integrity by sealing minor endothelial deficiencies 2-Helping to arrest bleeding by formation of platelets plugs 3-Contributing membrane (lipid procoagulant) activity to asses secondary hemostasis 4  10/27/2024 PLATELETS FUNCTIONS 4-Promoting vascular healing through platelet derived growth factor (PDGF) 5-Its active in synthesis proteins ,carbohydrates and lips 6- It have the ability to phagocytize some particles 7- It can generate metabolic activities 8-It play role in synthesization of the major component of factor 8(VIII). Fibrine stabilizing factor HEMOSTASIS:  It is the prevention of blood loss; in the sequence of the following steps:- 1) Vascular spasm:  Injury of blood vessel will cause contraction of blood vessel to stop bleeding.  Contraction extended few cm & continues for minutes or hours till platelet plug & clot formation is ensured.  It affects small & large blood vessels. 5  10/27/2024 HEMOSTASIS: 2) Platelet plug formation:  Blood vessel injury  damaged endothelial cells or collagen fibers become in contact with platelets  swell & become sticky  aggregate to form platelet plug; but it is loose and can block only small holes. HEMOSTASIS:  Platelet plugs (not the clots) are important to prevent spontaneous hemorrhage under the skin & internal organ from the small holes in small blood vessels that usually occur spontaneously. 6  10/27/2024 HEMOSTASIS: 3)Blood Coagulation (Clotting):  In blood & tissue there are 400 different substances that affect coagulation.  Some promote it (procoagulant)—others inhibit it (anticoagulant).  In normal state, they are in balance; while in tissue damage, procoagulant > anticoagulant to form a clot.  Clot started within seconds ̶ minutes & completed within 3-6 min. Then (1/2 –1 hour) clot retraction will occur to close the hole completely. 7  10/27/2024 Red blood cells enmeshed in the insoluble strands of a fibrin clot Electron micrograph of a fibrin fiber 8  10/27/2024 SUBSTANCES IMPORTANT IN COAGULATION (CLOTTING):  Ca2+ ion is required for coagulation.  Ca2+ ion will impair blood clotting. In vivo Ca2+ ions rarely falls low enough to affect blood clotting since it will cause tetany & suffocation before affecting clotting. Ca2+ ions removal from blood is used to prevent clotting outside body (in vitro) by either: Deionization of Ca2+ ions using citrate ion or precipitation of Ca2+ ions by oxalate. SUBSTANCES IMPORTANT IN COAGULATION (CLOTTING): Fibrinogen is plasma clotting protein of concentration 100-700 mg/100ml; formed in the liver. By thrombin, fibrinogen converted to fibrin. The fibrin meshes envelope blood cells, platelets & plasma to form blood clot. Vit. K is important in coagulation, so its deficiency will increase bleeding e.g. neonate bleeding Clotting factors (by liver) are essential in coagulation e.g. factor 8 (VIII). 9  10/27/2024 ANTICOAGULATION Heparin is the in vivo anticoagulant i.e. prevents clot formation inside the body.  Thrombus: Is a clot abnormally formed in blood vessel.  Embolus: Is a clot formed in blood vessel, then breaks away due to blood flow to be lodged in small blood vessel of distant organ e.g. from deep venous thrombosis (DVT) to pulmonary embolism (thromboembolism). 10  10/27/2024 ANTICOAGULANT FACTORS FOR CLINICAL USES: 1. Heparin:-  It inhibits blood coagulation both in vivo& in vitro.  (Heparin is the only anticoagulant present inside the body-in vivo-)  It is extracted from animal tissue, purified to be used in small amount.  Its action immediately increasing clotting time (up to 30 minutes) & continues for 3-4 hours, to be destroyed later on by heparinase enzyme. ANTICOAGULANT FACTORS FOR CLINICAL USES:  Mechanism of action of heparin: 1. Prevents activation of prothrombin to thrombin 2. Neutralizes action of thrombin on fibrinogen to form fibrin 3. Facilitates the action of antithrombin III 11  10/27/2024 ANTICOAGULANT FACTORS FOR CLINICAL USES: 2. Ethylene diamine tetra-acetic acid (EDTA):-  It is a chelating agent for Ca++. It forms insoluble calcium salts by chelati on.  It is used most frequently.  It preserves the staining and morphologic al characteristics of leukocytes and platelets. ANTICOAGULANT FACTORS FOR CLINICAL USES: 3. Oxalate salts:  A mixture of dry ammonium oxalate and potassium oxalate  Mode of action: It combines with calcium to form insoluble Ca-oxalate (Precipitate Ca++). 12  10/27/2024 ANTICOAGULANT FACTORS FOR CLINICAL USES: 4. Citrate salts:  Acid citrate dextrose (ACD) is prepared from disodium hydroge n citrate  Mode of action: It combines with Ca to form an insoluble Ca-citrate. (Deionize Ca++) BLOOD GROUPS:  RBC membrane contains a variety of Ag (agglutinogen). ABO and Rh systems are the most important Ag systems. There are so many less potent Ag that are important for legal purposes (not in transfusion); like type M, N, S, kell & others. 13  10/27/2024 ABO SYSTEM  Inthis system we have only 2 agglutinogens on RBC: A or B; but because of the way of inheritance we will get 4 blood groups A, B, AB & O.  In the plasma we have Antibodies (also 2 types) called agglutinin differs according to blood group;  Ab (anti-A or anti-B) found in plasma if its specific antigen (A or B) is not present on RBC surface. 14  10/27/2024 anti-A + A & anti-B + B  AGGLUTINATION [clumping of RBC]. This reaction is used to type blood.  O− is the universal donor because it has no Ag on RBC so no clumping if its blood pint is given.  AB+ is the universal recipient because it has no Ab in plasma so no clumping if he receives any pint of blood. 15  10/27/2024 BLOOD TYPING TEST  Determines blood type and compatibility 16  10/27/2024 ABO SYSTEM  Ab (anti-A or anti-B) found in plasma if its specific antigen (A or B) is not present on RBC surface.  At birth there is no agglutinin in infant plasma, but 2-8 months later it will develop.  They are mostly IgG & IgM produced by B- lymphocyte due to entrance of small amount of Ag (A & B) into the blood with food, bacteria or other means to sensitize immune system. ABO SYSTEM  Type O+ve blood is the most common blood type, followed by type A, then type B, and, the least common blood type is AB−ve.  In general, Rh+ve is much more common than Rh−ve This distribution differs in different populations. 17  10/27/2024 TRANSFUSION REACTION DUE TO MISMATCHED BLOOD GROUP: 1. Agglutination of the Donor RBC: By Ab-Ag reaction. Agglutination rarely affects recipient RBC (i.e. Ag) due to dilution of the donor plasma (i.e. Ab) by recipient plasma. 2. RBC Hemolysis: Lead to hemoglobinemia and hemoglobinuria. Hb precipitates in organs and cause its damage e.g. renal tubules. TRANSFUSION REACTION DUE TO MISMATCHED BLOOD GROUP: 3. Acute Renal Failure: It is lethal effect, started within few minutes & end within few hours.  Therefore,to prevent this fatal reaction, We should testing both donor blood (pint) & recipient blood for matching before any blood transfusion. This is done by: 1. Slide method ((Short method)) 2. Cross match (test tube method) ((Long method)) 18  10/27/2024 RH SYSTEM:  Inherited independent of ABO system  Rh+ve = Antigen (mainly D) present on RBC. Body with Rh+ve can not produce anti-D antibodies at any circumstances.  Rh−ve = No antigen. Anti-D (anti-Rh) Ab does not spontaneously formed in plasma as ABO system, but it develops after previous exposure to Rh+ve RBC. RH SYSTEM:  If Rh−ve person receive Rh+ve blood for the 1st time, no immediate reaction will occur, because he has no anti-D Ab and it needs 2-4 weeks for Ab formation.  Insubsequent transfusion of Rh+ve blood to the same person there will be severe transfusion reaction due to sensitization that occurs after the 1st transfusion. 19  10/27/2024 ERYTHROBLASTOSIS FETALIS (RH DISEASE):  It occurs only when an Rh−ve mother & Rh+ve father have an Rh+ve fetus. 1st baby will escape the disease. D antigen during labour will transfer from the 1st Rh+ve baby to the mother through the palcenta, and she will produce Anti-D antibodies later on, that will attack the 2nd and subsequent fetuses (if has Rh+ve blood) during pregnancy. ERYTHROBLASTOSIS FETALIS (RH DISEASE):  Hemolysis of RBC of fetus which can cause severe anemia or intrauterine death (IUD).  Treatment involves injection of antibodies (Anti-D) to the mother after the labour to get rid of Rh+ve fetal RBCs (This is a good example of passive immunization). This injection should be within 72 hours after birth of Rh positive baby. 20  11/2/2024 Human Physiology  Circulation : Pulmonary (lungs) & Lec 7 Heart Physiology Systemic (the rest of body) Dr. Athir K. Mohammed MSc PhD. Physiology and Endocrinology  Heart: hollow, muscular organ 4 chambers: 2 atria (right & left) & 2nd Year 2 ventricles (right & left) Med. Lab. Tech. 1  11/2/2024  Heart has 2 distinct Layers plus a Membrane: 1. Endocardium - innermost layer; epithelial tissue that lines the entire circulatory system (endothelium) & 2. Myocardium - thickest layer; consists of cardiac muscle. 3. It is surrounded by a thin, external membrane called Pericardium; with pericardial fluid in between. 2  11/2/2024  Because of gap junctions between  Cardiac muscle cells of two types: cardiac cells, if any cell is stimulated, then the impulse will spread to all cells. 1. Contractile cells: that contract when stimulated. Most of the cells.  There are no gap junctions between atrium & ventricle. In addition, the atria 2. Autorhythmic cells: are self- & ventricles are separated by the stimulating (initiate the cardiac impulse) electrically nonconductive fibrous tissue. & transmit it to other cells. located in special areas (Conductive  Rt. & Lt. atria always function as a unit & System) the ventricles always function as another unit together. 3  11/2/2024 ❖Depolarization (contraction = systole) Conductive System of the heart is due to the inward diffusion of mainly calcium Ca++ (not sodium as in nerve cell 1. Sinoatrial (SA), or sinus, node membranes). 2. Atrioventricular (AV) node ❖Re-polarization (relaxation = 3. Atrioventricular (AV) bundle (His diastole) is due to the outward diffusion of potassium K+. bundle) 4. Right & left bundle branches ❖Ca++ or K+ are critical for cardiac muscle 5. Purkinje fibers 4 11/2/2024 5  11/2/2024 Different autorhythmic cells have different rhythms:  SA node has the highest or fastest  Sinus node: heart rate (HR) normally 60 - 100 beat per minute; (sinus rhythm) rhythm (sinus rhythm) and if HR100/min = tachycardia contraction for the entire heart. As a result, the SA node is commonly  AV node & AV bundle: 40–60/min referred to as the natural (called junctional rhythm) pacemaker. Its rate can reach up to  Bundle branches & Purkinje fibers: 200beat/min. 20/min–40/min(ventricular rhythm) 6  11/2/2024 Spread of cardiac excitation Electrocardiogram (ECG)  It represents the record of spread of electrical activity through the heart.  formed from: 1. P wave: by atrial depolarization (systole) 2. QRS complex: ventricular depolarization (systole) 3. T wave: by ventricular re-polarization (diastole) 7  11/2/2024  ECG is useful in diagnosing abnormal Mechanical vs Electrical Events of Cardiac heart rates, arrhythmias, and damage of cycle: heart muscle. ECG Electrical events Mechanical events Cardiac cycle has 2 phases: P wave atrial depolarization atrial systole Systole (contraction) QRS complex ventricular ventricular systole & depolarization Diastole ventricular T wave ventricular diastole (relaxation) re-polarization Atrial diastole occurs at the same time of ventricular systole 8  11/2/2024 Cardiac output Factors permit variation in cardiac output  volume of blood pumped into the aorta each minute by the heart 1) Changes in heart rate:  cardiac output (L/min) = Heart Rate ◦ Parasympathetic stimulation (as occur in (HR) x (stroke volume) SV vasovagal reflex)  HR ◦ Sympathetic stimulation (as occur in  typically about 5 liters per minute (which exercise or anxiety)   HR is about equal to total blood volume;), but Both (constituting autonomic nervous maximum may be as high as 25-35L/min. system) exert their effects through affecting  During rest; SA node. cardiac output = 70 b/min X 0.07 liters/b = 5 liters/min ◦ Hormones like adrenalin and thyroxin increased the HR, therefore increase CO. 9  11/2/2024 2) Regulation of Stroke Volume: b) Extrinsic control: related to amount of a) Intrinsic control: related to amount of sympathetic stimulation venous return (amount of blood returning to the heart via veins).  sympathetic stimulation   amount of venous return   strength of cardiac muscle contraction   ventricular end-diastolic volume   stroke volume  stretching of cardiac muscle   strength of cardiac contraction   stroke volume. This is called the Frank-Starling law of the heart. 10  11/2/2024  Athletes have more SV than non-athletes (because of stronger cardiac muscle); therefore their HR is much slower (bradycardia) to have a relatively same cardiac output.  Hypotension leads to less SV; therefore the heart increases its rate (tachycardia) to keep the cardiac output (to a certain limit) within the normal.  Heart Failure cause both SV and HR to decrease; therefore decrease the cardiac output. 11  11/2/2024 Heart Sounds Heart Sounds  1stsound – snap closing of the  two sets of valves: Atrioventricular valves Atrioventricular & Semilunar valves.  2nd sound – snap closing of the I/ Atrioventricular (AV) valves Semilunar valves located at the atrial-ventricular junctions 1) Bicuspid (mitral) valve – located  Heart Valves: The major function of on the left; constitute of 2 flaps heart valves is to prevent backflow 2) Tricuspid valve – located on the of blood. right; constitute of 3 flaps 12  11/2/2024 Heart Sounds  When the heart (ventricle) is relaxed, the AV valves are open.  When the heart contracts, the AV valves are closed to prevent blood pass backward from ventricles to atria. This produces first heart sound 13  11/2/2024 Heart Sounds II/ Semilunar valves – located at the bases of the large arteries issuing from the ventricles. 1)Pulmonary valve – guards the pulmonary trunk 2)Aortic valve – guards the entrance of the aorta 14  11/2/2024 Heart Sounds Heart Sounds  Abnormal heart sound is called  When the heart is relaxed, the murmur (swishing sound) which semilunar valves are closed to is result from: prevent blood pass backward to ventricles. This produces abnormal heart valve ( prolapse second heart sound or stenosis), VSD (ventricular septal defect) &  When the heart contracts the ASD (artial septal defect), or semilunar valves open. abnormal arteries. 15  11/2/2024 Coronary Circulation  The blood supply of the heart divided into the left and right coronary arteries and veins.  Thecoronary arteries deliver During Systole (of ventricles) AV valves (Mitral & Tricuspid) are Closed  1st heart sound blood when the heart is relaxed Meanwhile Aortic & Pulmonary Valves are Opened. During Diastole Semilunar valves (Aortic & Pulmonary) are Closed (during diastole)  2nd heart sound Meanwhile Mitral & Tricuspid Valves are Opened. 16  11/2/2024 Coronary Circulation  Ischemic Heart Disease (IHD): ‫قصور الشرايين التاجية‬ )‫(الذبحة الصدرية‬  Is the decrease of oxygen supply to the myocardium due to imbalance between oxygen supply and demand.  IHD result from obstructive atherosclerotic disease of coronary arteries. 17  11/2/2024 Coronary Circulation  Myocardial Infarction (MI): ‫إحتشاء العضلة القلبية‬  Is irreversible myocardial tissue damage (cell death) occurs after complete coronary artery occlusion that is previously affected by atherosclerosis. 18  11/2/2024 Coronary Circulation  Heart Failure (HF): ‫عجز القلب‬  Is the inability of the heart to eject or fill with blood to compensate with the requirements of the body.  Left HF cause edema in lung (can be fatal). Right HF cause edema in the body tissue (e.g. legs and abdomen) 19