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Measurement of body fluid volumes Dr. Hana MohamedElhassan Ahmed MBBS, MSc, MD University of Khartoum  Method Method used is indicator dilution method Base: inject a substance stay in only one compartment, then calculate the vol...

Measurement of body fluid volumes Dr. Hana MohamedElhassan Ahmed MBBS, MSc, MD University of Khartoum  Method Method used is indicator dilution method Base: inject a substance stay in only one compartment, then calculate the volume of fluid in which the substance is distributed (volume of distribution)  Example  if 1 milliliter of a solution containing 10 mg/ml of dye is dispersed into chamber B and the final concentration in the chamber is 0.01 milligram for each milliliter of fluid, the unknown volume of the chamber can be calculated as follows: Volume B = 1ml* 10 mg/ml/0.01mg/ml = 1000 ml  Criteria of the substance  This method can be used to measure the volume of virtually any compartment in the body as long as the substance is:  1.Non toxic  2.Mix evenly throughout the compartment being measured  3.Disperse only in the compartment being measured  4.Does not change (metabolized/excreted) in the body.If the indicator is metabolized or excreted, correction must be made for loss of the indicator from the body.  5.Easy to measure  6.Do not affect water distribution in other compartment  Several substances can be used to measure the volume of each of the different body fluids. DETERMINATION OF VOLUMES OF SPECIFIC BODY FLUID COMPARTMENTS Measurement of Total Body Water  Radioactive water (tritium, 3H2O) or heavy water (deuterium, 2H2O) can be used to measure total body water.  These forms of water mix with the total body water within a few hours after being injected into the blood, and the dilution principle can be used to calculate total body water.  Another substance that has been used to measure total body water is antipyrine or aminopyrine, which is very lipid soluble and can rapidly penetrate cell membranes and distribute itself uniformly throughout the intracellular and extracellular compartments Measurement of extracellular fluid  The volume of extracellular fluid can be estimated using any of several substances that disperse in the plasma and interstitial fluid but do not readily permeate the cell membrane.  Substances used:  Radioactive electrolytes (sodium, chloride &bromide):These easily penetrate the entire ECF and may escape into cells ,therefore they overestimate the ECF.  Radioactive thiocyanate  thiosulfate  Saccharides (inulin, mannitol & sucrose):These fail to penetrate the trans-cellular fluid ,therefore they underestimate the ECF. Measurement of plasma volume  Substance used:  serum albumin labeled with radioactive iodine [RISA]  Labelled macroglobulin  Evan's blue dye (which binds to plasma protein and stay in plasma)  The red cell volume  Volume occupied by all the circulating red cells in the body = total blood volume - plasma volume  It may also be measured independently by injecting tagged red blood cells and after mixing has occurred, measuring the fraction of the red cells that is tagged with radioactive chromium Cr isotope Measurement of Total Blood volume  If one knows the plasma volume and the haematocrit (ie, the percentage of the blood volume that is made up of cells)  40% in men  36% in women  How to measure blood volume?  1. blood volume can also be calculated using the following equation:  Total blood volume = plasma volume/1- Hematocrit  For example, if plasma volume is 3 litres and haematocrit is 0.40, total blood volume would be calculated as:  3 litres /1- 0.4 = 5 litres  Also the total blood volume can be calculated by:  plasma volume × (100/100-Hct)  Example: The hematocrit is 38 and the plasma volume 3500 mL.  The total blood volume= 3500 × 100=5645 ml 100-38  2. inject into the circulation red blood cells that have been labelled with radioactive material. After these mix in the circulation, the radioactivity of a mixed blood sample can be measured and the total blood volume can be calculated using the indicator dilution principle.  A substance frequently used to label the red blood cells is radioactive chromium (51Cr), which binds tightly with the red blood cells Measurement of intracellular fluid  The intracellular volume cannot be measured directly. However, it can be calculated as: Intracellular volume = Total body water- Extracellular volume Measurement of interstitial fluid  Interstitial fluid=ECF-plasma volume  Water balance intake output ingestion 2100 metabolism 200 Insensible skin 350 Insensible lungs 350 Sweat 100 feces 100 urine 1400 total 2300 2300 Fluid Movement across Capillary Membrane Capillary wall Starling Forces  Starling forces  1- Capillary hydrostatic pressure (HPc)  It is the pressure of plasma acting on the lateral wall of the blood vessel  For filtration (from plasma to interstitial fluid)  = 35-37 mmHg at the arteriolar end of capillaries = 15-17 mmHg at the veniolar end of capillaries  2- Capillary oncotic pressure (OPc):  The osmotic pressure of plasma proteins (also known as colloid osmotic pressure or oncotic pressure)  It is exerted mainly by albumin  For absorption (from interstitial fluid to plasma)  = 25 mmHg throughout the capillaries (proteins are not filtered and therefore their oncotic pressure is not changed)  3- Interstitial fluid hydrostatic pressure HPISF:  Acts in the opposite side to HPC (i.e. against filtration)  4- Interstitial fluid oncotic pressure OPISF:  Acts in the opposite side to OPC (i.e. against absorption) Starling Forces Plasma Oncotic  about 80% of the pressure total colloid osmotic pressure of the plasma results from albumin  20% from the globulins,  and almost none from the fibrinogen  Filtration Process by which fluid is forced through a membrane because of pressure difference on the two sides  Starling Equation Filtration = Kf × NFP Kf = Filtration/NFP The capillary filtration coefficient (Kf) measure of the capacity of the capillary membranes to filter water for a given NFP and is usually expressed as ml/min per mm Hg determined by the number and size of the pores in each capillary as well as the number of capillaries in which blood is flowing  Filtration = Kf × (Pc – Pi) – (πc – πi) 1.The capillary hydrostatic pressure (Pc) which tends to force fluid outward through the capillary membrane. 2.The interstitial fluid hydrostatic pressure (Pi) which tends to force fluid inward 3.The capillary plasma colloid osmotic pressure (πc) which tends to cause osmosis of fluid inward 4.The interstitial fluid colloid osmotic pressure (πi) which tends to cause osmosis of fluid outward  The filtration pressure is calculated by subtracting the capillary oncotic pressure from the capillary hydrostatic pressure as follows: o At the arteriolar end= (35-25)= +10 mmHg (i.e. net filtration) o At the veniolar end= (15-25)= -10 mmHg (i.e. net absorption)  Factors That Can Increase Capillary Filtration Filtration = Kf × (Pc – Pi) – (πc – πi) any one of the following changes can increase the capillary filtration rate: 1. Increased capillary filtration coefficient 2. Increased capillary hydrostatic pressure. 3. Decreased plasma colloid osmotic pressure.  Interstitial fluid volume  Depends on 1. Starling forces 2. Filtration coefficient 3. Number of active capillaries 4. Lymph flow 5. Total ECF volume  About 90% of the filtered fluid at the arteriolar end of capillaries is absorbed back to the capillaries at their veniolar end; the remaining 10% of the filtered fluid is also absorbed but by the lymphatics.  The lymphatic vessels also absorb small amount of protein that may escape out of the plasma to the interstitium.  The lymphatics return this protein together with the 10% of the filtered fluid back to the circulation at the neck where the main lymphatic duct drains into the jugular vein. This keeps balance between filtration and absorption of fluid at the capillaries.  Disturbance of this balance between filtration and absorption may result in accumulation of fluid in the interstitium causing edema. Thanks Abnormalities in body fluids oedema Dr. Hana MohamedElhassan Ahmed MBBS, MSc, MD University of Khartoum  Edema or Oedema refers to the presence of excess fluid in the body tissues. In most instances, edema occurs mainly in the extracellular fluid compartment, but it can involve intracellular fluid as well.  Intracellular Edema  Conditions cause intracellular swelling 1. Hyponatremia 2. depression of the metabolic systems of the tissues 3. lack of adequate nutrition to the cells.  For example, when blood flow to a tissue is decreased, the delivery of oxygen and nutrients is reduced.  Failure to maintain normal tissue metabolism, the cell membrane ionic pumps become depressed.  4. Intracellular edema also occur in inflamed tissues  Extracellular Edema  occurs when there is excess fluid accumulation in the interstitial spaces.  Filtration = Kf × (Pc – Pi) – (πc – πi)  There are two general causes of extracellular edema: 1. abnormal leakage of fluid from the plasma to the interstitial spaces across the capillaries, and 2. failure of the lymphatics to return fluid from the interstitium back into the blood. Summary of Causes of Extracellular Edema I. Increased capillary hydrostatic pressure A. Excessive kidney retention of salt and water 1. Acute or chronic kidney failure 2. Mineralocorticoid excess I. Increased capillary pressure B. High venous pressure and venous constriction 1. Heart failure 2. Venous obstruction 3. Failure of venous pumps (a) Paralysis of muscles (b) Immobilization of parts of the body (c) Failure of venous valves I. Increased capillary pressure C. Decreased arteriolar resistance 1. Excessive body heat 2. Insufficiency of sympathetic nervous system 3. Vasodilator drugs II. Decreased plasma proteins A. Failure to produce proteins 1. Serious protein or caloric malnutrition 2. Liver disease (e.g., cirrhosis) B. Malabsorption e.g. chronic pancreatitis II. Decreased plasma proteins C. Loss of proteins in urine (nephrotic syndrome) D. Loss of protein from denuded skin areas 1. Burns 2. Wounds III. Increased capillary permeability A. Immune reactions that cause release of histamine and other immune products B. Toxins C. Bacterial infections D. Vitamin deficiency, especially vitamin C E. Prolonged ischemia F. Burns  IV. Blockage of lymph return A. Cancer B. Infections (e.g., filaria nematodes) C. Surgery D. Congenital absence or abnormality of lymphatic vessels SUMMARY OF CAUSES OF EXTRACELLULAR EDEMA  A large number of conditions can cause fluid accumulation in the interstitial spaces by abnormal leaking of fluid from the capillaries or by preventing the lymphatics from returning fluid from the interstitium back to the circulation.  Through the following mechanisms:  I. Increased capillary pressure A. Excessive kidney retention of salt and water B. High venous pressure and venous constriction C. Decreased arteriolar resistance  II. Decreased plasma proteins  III. Increased capillary permeability  IV. Blockage of lymph return  Types of edema  Pitting edema 1. High capillary hydrostatic pressure 2. Low capillary oncotic pressure  Non pitting edema 1. Increased permeability 2. Lymphatic obstruction Pitting edema Non-pitting edema  FLUIDS IN THE “POTENTIAL SPACES” OF THE BODY  Some examples of “potential spaces” are the pleural cavity, pericardial cavity, peritoneal cavity, and synovial cavities, including both the joint cavities.  Fluid Is Exchanged Between the Capillaries and the Potential Spaces.  Each potential space is in reality a large tissue space. Consequently, fluid in the capillaries adjacent to the potential space diffuses not only into the interstitial fluid but also into the potential space.  Lymphatic Vessels Drain Protein from the Potential Spaces.  Edema Fluid in the Potential Spaces Is Called Effusion.  lymph blockage or any of the multiple abnormalities that can cause excessive capillary filtration can cause effusion in the same way that interstitial edema is caused.  The abdominal cavity is especially prone to collect effusion fluid, and in this instance, the effusion is called ascites.  The potential spaces can become seriously swollen when generalized edema is present. Also, injury or local infection in any one of the cavities often blocks the lymph drainage, causing isolated swelling in the cavity.  The normal fluid pressure in most or all of the potential spaces in the non-edematous state is negative in the same way that this pressure is negative (sub-atmospheric) in loose subcutaneous tissue.  For instance, the interstitial fluid hydrostatic pressure is normally about -7 to -8 mm Hg in the pleural cavity, -3 to -5 mm Hg in the joint spaces, and -5 to -6 mm Hg in the pericardial cavity. Thanks  Autonomic Nervous System – I Introduction & Anatomic Organization By: Dr. Isra Hassan Bashir Siddique M.B.B.S., M.Sc. University of Khartoum (2020)  What is Autonomic Nervous System? The autonomic nervous system (ANS) is the part of the nervous system that is responsible for homeostasis. Except for skeletal muscle, innervation to all other organs is supplied by the ANS. 12/7/2020 Dr Isra Hassan Bashir  About ANS Nerve terminals are located in smooth muscle, cardiac muscle, and glands. Two anatomically distinct divisions: 1. sympathetic 2. Parasympathetic Some target organs are innervated by both divisions and others are controlled by only one. 12/7/2020 Dr Isra Hassan Bashir  ANATOMIC ORGANIZATION OF AUTONOMIC OUTFLOW 12/7/2020 Dr Isra Hassan Bashir  ANATOMIC ORGANIZATION OF AUTONOMIC OUTFLOW Cell bodies of the preganglionic neurons in the intermediolateral (IML) column of spinal cord & in motor nuclei of cranial nerves (10,9,7,3). Preganglionic axons: B fibers. Postganglionic axons: C fibers. A preganglionic axon diverges: 8-9 (diffuse). 12/7/2020 Dr Isra Hassan Bashir  SYMPATHETIC DIVISION Originate from the first thoracic to the third or fourth lumbar segments. (thoracolumbar) Exit via the ventral root with axons of α- and γ- motor neurons. Separate via the white rami communicans and project to sympathetic paravertebral ganglion. 12/7/2020 Dr Isra Hassan Bashir  Paravertebral Sympathetic Chain Paravertebral ganglia are located adjacent to each thoracic and upper lumbar spinal segment, EXTEND cervical and sacral. The ganglia are interconnected via the axons of preganglionic neurons. 12/7/2020 Dr Isra Hassan Bashir  Paravertebral Sympathetic Chain Together these ganglia and axons form the sympathetic chain. Right and Left. 12/7/2020 Dr Isra Hassan Bashir 12/7/2020 Dr Isra Hassan Bashir  Projection of Sympathetic Preganglionic and Postganglionic Fibers. 12/7/2020 Dr Isra Hassan Bashir Prevertebral (or collateral) Ganglia They are three: celiac, superior mesenteric, and inferior mesenteric ganglia. Close to the viscera. Preganglionic neurons ONLY pass through the paravertebral ganglion chain. 12/7/2020 Dr Isra Hassan Bashir  Termination of Sympathetic Outflow Postganglionic neurons leave the chain ganglia via the gray rami visceral targets communicans Postganglionic fibers from prevertebral ganglia 12/7/2020 Dr Isra Hassan Bashir General Scheme of Sympathetic Nerves The adrenal gland is exceptionally receiving preganglionic sympathetic neuron. 12/7/2020 Dr Isra Hassan Bashir  PARASYMPATHETIC DIVISION- Anatomic Arrangement Preganglionic neurons in cranial nerve nuclei (III, VII, IX, and X) and in the IML of the sacral spinal cord. Craniosacral Outflow 12/7/2020 Dr Isra Hassan Bashir  General Scheme of Parasympathetic Nerves 12/7/2020 Dr Isra Hassan Bashir  DESCENDING INPUTS TO AUTONOMIC PREGANGLIONIC NEURONS 12/7/2020 Dr Isra Hassan Bashir The End. 12/7/2020 Dr Isra Hassan Bashir  Autonomic Nervous System II CHEMICAL TRANSMISSION AT AUTONOMIC JUNCTIONS By: Dr. Isra Hassan Bashir Siddique M.B.B.S., M.Sc. University of Khartoum (2020)  Transmission is Chemical Transmission at the synaptic junctions* are chemically mediated. The principal transmitter agents involved are acetylcholine (Ach.) and norepinephrine (NE.) 12/7/2020 DR ISRA HASSAN BASHIR  Transmission at Synaptic Junctions 12/7/2020 DR ISRA HASSAN BASHIR  Cholinergic & Adrenergic Neurons Cholinergic Neurons: 1. all preganglionic autonomic neurons 2. all parasympathetic postganglionic neurons 3. sympathetic postganglionic neurons that enervate sweat glands 4. sympathetic postganglionic neurons that end on blood vessels in some skeletal muscles. Noradrenergic Neurons: Postganglionic sympathetic neurons. 12/7/2020 DR ISRA HASSAN BASHIR  CHOLINERGIC NEUROTRANSMISSION Acetylcholine does not circulate in the blood, effects are localized and of short duration. Enzyme for catabolism: acetylcholinesterase. 12/7/2020 DR ISRA HASSAN BASHIR  Cholinergic Synapse Notice: 1. Synthesis 2. Release 3. Receptors 4. Enzyme for Catabolism 5. Presynaptic Receptors 6. Suggested Locations? 12/7/2020 DR ISRA HASSAN BASHIR 12/7/2020 DR ISRA HASSAN BASHIR  Cholinergic Receptors 1. Nicotinic (Nn, Nm)*  acetylcholine-gated ion channel  Blocked by Hexamethonium (Nn), and D-tubocurare (Nm) 2. Muscarinic (M1, M2, M3*, M4, M5)  GPCR  Blocked by atropine 12/7/2020 DR ISRA HASSAN BASHIR  Nicotinic Acetylcholine Receptor 12/7/2020 DR ISRA HASSAN BASHIR  Autonomic Ganglia Potentials EPSP: acetylcholine on Nn Slow EPSP: acetylcholine on M1 12/7/2020 DR ISRA HASSAN BASHIR  NORADRENERGIC NEUROTANSMISSION Norepinephrine spreads farther and has a more prolonged action than acetylcholine. Norepinephrine is made from tyrosine. Some of the tyrosine is formed from phenylalanine, but most is of dietary origin. Phenylalanine hydroxylase is found primarily in the liver* 12/7/2020 DR ISRA HASSAN BASHIR  Catecholamines are synthesized from the amino acid tyrosine by a multi-step process. Rate Limiting Step* 12/7/2020 DR ISRA HASSAN BASHIR  Noradrenergic Synapse Notice: 1. Synthesis 2. Release 3. Receptors 4. Reuptake 5. Presynaptic Receptors 6. Suggested Locations? 12/7/2020 DR ISRA HASSAN BASHIR  Catabolism of Catecholamines Epinephrine and norepinephrine are catabolized by either: 1. Oxidation monoamine oxidase (MAO) 2. Methylation catechol - O – methyl transferase (COMT) Vanillylmandelic acid (VMA) is the most plentiful catecholamine metabolite in urine.* 12/7/2020 DR ISRA HASSAN BASHIR  α- & β-Adrenoceptors Epinephrine and norepinephrine act on α-and β- adrenergic receptors. Norepinephrine has greater affinity for α- Epinephrine has greater affinity for β- GPCR Multiple subtypes:  α 1A , α 1B , α 1D , α 2A , α 2B , α 2C β1,β2,β3 12/7/2020 DR ISRA HASSAN BASHIR  α- & β-Adrenoceptors (Cont.) Activation of α 1 -adrenoceptors is excitatory to the postsynaptic target. Activation of α 2 -adrenoceptors inhibits the postsynaptic target. Presynaptic α 2 - adrenoceptors are autoreceptors, inhibit further release of norepinephrine. Activation of β1-adrenoceptors is stimulatory. Activation of β2-adrenoceptors is inhibitory. 12/7/2020 DR ISRA HASSAN BASHIR Example Locations of α- & β-Adrenoceptors α 1: smooth muscle α2: pancreatic islets and nerve terminals β 1: heart & renal juxtaglomerular cells β 2: bronchial smooth muscle β 3: adipose tissue. 12/7/2020 DR ISRA HASSAN BASHIR NONADRENERGIC, NONCHOLINERGIC TRANSMITTERS Co-released with noradrenaline: adenosine triphosphate (ATP), neuropeptide Y (NPY), and galanin. Co-released with acetylcholine: Vasoactive intestinal polypeptide (VIP), nitric oxide (NO)?*, and substance P*. 12/7/2020 DR ISRA HASSAN BASHIR End. 12/7/2020 DR ISRA HASSAN BASHIR  RESPONSES OF EFFECTOR ORGANS TO AUTONOMIC NERVE IMPULSES By: Dr. Isra Hassan Bashir (MBBS), (M.Sc.) University of Khartoum Lecturer of Physiology 2020 12/8/2020 Dr Isra Hassan Bshir  GENERAL ACTION SYMPATHETIC PARASYMPATHETIC GENERALIZED LOCALISED FLIGHT OR FIGHT REST AND DIGEST 12/8/2020 Dr Isra Hassan Bshir  Radial muscle of iris & Sphincter muscle of iris Sphincter Radial muscle muscle 12/8/2020 Dr Isra Hassan Bshir  Ciliary muscle 12/8/2020 Dr Isra Hassan Bshir  Heart 12/8/2020 Dr Isra Hassan Bshir  Arterioles Skin & splanchnic vessels Skeletal muscle 12/8/2020 Dr Isra Hassan Bshir  Bronchial smooth muscle 12/8/2020 Dr Isra Hassan Bshir  Stomach& Intestine 12/8/2020 Dr Isra Hassan Bshir  Male Reproductive System 12/8/2020 Dr Isra Hassan Bshir  Urinary bladder Detrusor & Sphincter 12/8/2020 Dr Isra Hassan Bshir  Skin Pilomotor muscles Sweat Glands & Apocrine Glands 12/8/2020 Dr Isra Hassan Bshir  Salivary glands 12/8/2020 Dr Isra Hassan Bshir  Lacrimal glands 12/8/2020 Dr Isra Hassan Bshir  End 12/8/2020 Dr Isra Hassan Bshir