CoverModule 1.0. Homeostasis, Membranes, Electrophysiology and ANS (Essay Questions)1.1. Homeostasis1.1.1. Homeostasis Defined1.1.2. Homeostatic Control Systems1.1.3. Feedback Response Loop1.2. Cell Transport; Water & Solutes1.2.1. Fluid Compartments1.2.2. Osmosis1.2.3. Diffusion of Solutes1.2.4. Active Transport1.2.5. Bulk Transport1.3. Electrophysiology1.3.1. Ions and Cell Membranes1.3.2. Membrane Potentials1.3.3. Graded Potential1.3.4. Action Potentials1.3.5. Refractory Periods1.3.6. Propagation of an Action Potential1.4. THE SYNAPSE1.5. THE AUTONOMIC NERVOUS SYSTEM1.5.1. Organization of the Nervous System1.5.2. Structural Organization of the ANS1.5.3. The SNS and the PNS1.5.4. The Enteric Nervous System1.5.5. Physiology of the ANS1.5.6. Neurotransmitters of the ANS1.5.7. Receptors of the ANS1.5.8. Actions of the Autonomic Nervous System1.5.9. Table of Actions for the SNS and PNS and Some Common DrugsModule 2.0. Skeletal Muscle and Special Senses2.1. Structural Organization of Skeletal Muscle2.2.1. Neuromuscular Junction, Excitation-Contraction Coupling2.2.2. Muscle Contractures and Cramps2.3. Whole Muscle Contraction, Fiber Type, Fatigue and Muscle Pharmacology2.3.1. Motor Units2.3.2. Factors that Influence the Force of Contraction2.3.3. Energy Source for Muscle Contraction2.3.4. Skeletal Muscle Fiber Types2.3.5. Fatigue2.3.6. Muscle Pharmacology2.4. Smooth Muscle2.4.1. Smooth Muscle Contraction2.5. Control of Body Movement2.5.1. Voluntary Control of Muscle2.5.2. Reflexes2.6. Taste and Smell2.6.1. Taste2.6.2. The Sense of Smell2.7. Vision2.7.1. Structure of the Eye2.7.2. Focusing Light on the Retina2.7.3. Converting Light to Action Potentials2.7.4. The Retina2.7.5. Phototransduction2.7.6. Receptive Fields2.8. Hearing and Equilibrium2.8.1. The Nature of Sound2.8.2. The Hearing Apparatus2.8.3. Sound Vibrations to Action Potentials2.8.4. The Sense of Balance and EquilibriumModule 3.0. Cardiovascular System3.1. Structure of the Heart3.1.1. Chambers and Circulation3.2. Cardiac Cell Action Potentials3.2.1. Action Potentials in Cardiac Muscle Cells3.2.2. Action Potentials in Cardiac Autorhythmic cells3.2.3. Cellular Mechanisms of Inotropy and Chronotropy3.3. Electrophysiology of Heart Muscle3.3.1. Heart Conduction System3.3.2. Electrocardiogram (ECG)3.3.3. Abnormal ECG - Current of Injury3.4. The Cardiac Cycle3.4.1. Cardiac cycle3.4.2. Cardiac Measurements and Pressure Volume Loops3.5. Blood vessels and Blood Pressure3.5.1. Arteries and Veins3.5.2. Capillaries3.5.3. Blood Pressure Regulation and Shock3.5.4. Capillary Exchange3.5.5. Myogenic and Paracrine Regulation of Vasoconstriction and Vasodilation3.6. Blood3.6.1. Composition of Blood3.6.2. Hematopoeisis3.6.3. Breaking Down Red Blood Cells3.6.4. HemostasisModule 4.0. Urinary and Respiratory Systems4.1. Function and Structure of the Kidney4.1.1. Urinary System Function4.1.2. Functional Anatomy of the Urinary System4.1.3. The Nephron: Functional Unit of the Kidney4.1.4. The Renal Corpuscle: Bowman's Capsule4.2. Physiology of Urine Production4.2.1. Filtration4.2.2. Renal Clearance4.2.3. Tubular Reabsorption4.2.4. Urine Concentration and Dilution4.2.5. Hormonal Regulation of Urine Production4.3. Acid/Base Balance4.3.1. Buffers4.3.2. Acid/Base Disturbances4.4. The Respiratory System4.4.1. Respiratory System Structure and Function4.4.2. Respiratory Membrane4.4.3. Respiratory pressures and Inspriation/Expiration4.4.4. Alveoli and Surfactant4.4.5. Pneumothorax4.5. Gas Exchange and Transport4.5.1. Gas Laws4.5.2. Partial Pressure Gradients in the Lung4.5.3. Alveolar Gas Equation4.5.4. Oxygen and Carbon Dioxide Transport in the Blood4.5.5. Alveolar Ventilation4.5.6. Ventilation/Perfusion Ratio4.6. Chronic Bronchitis and Emphysema4.6.1. Respiratory Control by the Medulla Oblongata4.6.2. Chemicals that Regulate VentilationModule 5.0. Digestive, Endocrine and Reproductive Systems5.1. Functional Anatomy of the Digestive System5.1.1. Layers of the Digestive Tract5.1.2. Enteric Nervous System5.1.3. Organs of the Digestive System5.2. Digestion5.2.1. Carbohydrates5.2.2. Proteins5.2.3. Lipids5.2.4. Lipoproteins5.3. Regulation of Digestive Secretions5.4. Endocrine System5.4.1. Overview of the Endocrine System5.4.2. Hormone Receptors5.4.3. Hormones of the Body5.4.4. Other Hormones: Melatonin and Pheromones5.5. The Hypothalamus and Pituitary Gland5.5.1. Structure and Function of the Hypothalamus and Pituitary Gland5.5.2. The Posterior Pituitary5.5.3. The Anterior Pituitary5.5.4. Growth Hormone5.5.5. Prolactin5.5.6. Thyroid Hormones5.5.7. Adrenal Hormones5.6. Pancreas5.6.1. Insulin and Glucagon5.6.2. Diabetes Mellitus5.7. Reproductive System Anatomy5.7.1. Female Reproductive Anatomy5.7.2. Male Reproductive Anatomy5.7.3. Sexual Development at Puberty5.7.4. Male Reproductive Endocrine Axis5.7.5. Spermatogenesis5.7.6. Female Reproductive System: Oogenesis5.7.7. Ovulation and Fertilization5.7.8. The Ovarian Cycle5.7.9. The Uterine Cycle5.7.10. PregnancyAppendix A. GenderAppendix B. The Placebo EffectB.2.1. The Placebo EffectB.2.2. Examples of the Placebo EffectB.2.3. How do Placebos Work?B.2.4. Are Placebos Ethical?B.2.5. How do we validate actual effectiveness of placebosB.2.6. Tips for evaluating scientific evidenceB.2.7. What about Faith Healings
4.2.2

Renal Clearance

The concept of renal clearance is a very useful diagnostic tool in medicine. Clearance is a measurement that compares the rate that a substance is filtered back into the bloodstream with the rate at which the kidneys excrete the substance in the urine. The units for renal clearance are milliliters of plasma per minute. This represents the volume of plasma that is completely cleared of a particular substance per minute. For example, if 100 milliliters of filtrate enters the kidney tubules and all of the water is reabsorbed but none of a particular solute, we would say that the renal clearance for that solute is 100 ml/min. On the other hand, if 100 milliliters of filtrate enter the kidney tubules and all of the water is reabsorbed and one-half of a particular solute is reabsorbed, we would say that the renal clearance for the solute is 50 ml/min (i.e. one half of the filtered plasma is cleared of the solute). Each substance that is filtered has a specific clearance value. This value is a function of glomerular filtration, reabsorption, and in some cases, secretion (from the peritubular capillaries into the nephron). Measuring the difference between filtration and excretion allows us to see how the nephron is handling a particular substance in terms of filtration, reabsorption and/or secretion. Renal clearance can be measured by collecting urine over a given time and comparing the concentration of a given substance found in the urine with the concentration of the same substance found in the blood. Mathematically, the relationships for a given substance, say X, are expressed as:

Cx  Ux * V / Px

Where, Clearance (Cx) = the amount of plasma cleared of a substance (x) per minute;    Ux = the concentration of x in the urine; V= the urine flow rate (or Volume of Urine/time); and Px = the plasma concentrations of x.

As an example, consider that a substance is measured in the urine at a concentration of 100mg/ml, the urine flow rate is 1ml/min, and the plasma concentration is 1mg/ml. The clearance of this substance would be 100ml/min. This means that 100 ml of plasma are cleared of this substance per min. Note: Urine flow rate is computed by collecting all of the urine produced in a certain amount of time, say 60 minutes, and then dividing the volume collected by the time interval. If 60 ml were collected in 60 minutes the flow rate would be 60 ml divided by 60 minutes or 1 ml per minute.

We can also use the clearance equation to determine the glomerular filtration rate (GFR), but only if the substance meets a very strict set of criteria. For a clearance value to equal the GFR the substance must meet the following criteria:

  1. The substance must be small and non-charged. In other words, the substance must be freely filtered at the glomerulus with no impediment by the negatively charged membrane or the pore size of the filtration barrier.
  2. The substance must not be reabsorbed, secreted, degraded or produced by the nephron. Remember, we are trying to figure out the filtration rate, so the amount filtered must match that found in the urine.

Most substances in the body do not meet these strict criteria, as they are mostly reabsorbed, so their clearance rates will not tell us the GFR. However, the body does produce a substance called creatinine (a metabolic product of creatine) at a constant rate and creatinine meets the above criteria. Thus, determining the clearance of creatinine, by collection of urine through time, will give a good estimate of the GFR, which in turn gives us an overall view of kidney function. A healthy kidney should yield a clearance rate for creatinine and thus a GFR of 97 to 137 ml/min for a male, and 88 to 128 ml/min for a female. Thus, if we apply this concept of clearance and GFR to other substances processed by the kidneys we could use these values to determine:

The graph below illustrates typical renal clearance of various solutes. Inulin is a substance with the same clearance as creatinine and is an indicator of how well the kidney is filtering. Creatinine and Inulin are neither secreted nor absorbed, only filtered and excreted and therefore will indicate the GFR. Glucose is typically 100% reabsorbed, which means that none of it is excreted in the urine. This should make sense as glucose is our main source of energy and it would be inefficient to excrete it. However, if plasma glucose exceeds the threshold of 180mg/dL, the kidney will no longer be able to completely reabsorb all the filtered glucose, and some will be excreted with the urine (“glucosuria”).

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When this occurs we say that the renal threshold for that substance has been met. This is due to saturation of the glucose transport proteins in the proximal tubule and is what happens in diabetics who become severely hyperglycemic. Conversely, para-aminohippurate (PAH), is a non-harmful substance also used to test kidney function. Since PAH is both filtered and secreted by the kidneys, and 90% is removed from the blood on a single pass through the kidney, the clearance of PAH is often used to estimate renal blood flow (the amount of blood going through the kidneys per minute). Notice that like glucose reabsorption, the proteins responsible for PAH secretion in the DCT can also become saturated if the plasma concentration of PAH is too high. At this point, any additional PAH found in the urine would be due to increased filtration.

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