Clinical Chemistry 2 Lesson 1 PDF - Body Water, Kidney Function, Edema

CLINICAL LESSON | 01 CHEMISTRY 2 Lecture | PRELIM | Batch 2024...

CLINICAL LESSON | 01 CHEMISTRY 2 Lecture | PRELIM | Batch 2024 BODY WATER REVIEW OF KIDNEY FUNCTION Most urea will be excreted NEPHRON is the a. Functional unit of kidneys Filtrate entering this part is b. Over 1 million per kidney close to its final composition c. Process about 1/4 of body’s blood supply at any given time to produce [about 95% of Na,Cl and at least 1 liter of urine/day 90% of water have been already reabsorbed from The amount of urine that being formed is greatly affected by the amount the original glomerular of fluid that person is taking filtrate] CLASSIFICATION OF NEPHRON Its function is to affect small adjustments to achieve electrolyte and acid-base homeostasis under hormonal control cause distal tubule to reabsorb more sodium and water which could of course increase the blood volume Aldosterone produced in the adrenal glands Secreted to increase blood flow/pressure, increase plasma sodium. Stimulates Na & Cl reabsorption and K/H excretion in the distal tubules CORTICAL JUXTAMEDULLARY ADH vast type Longer and extend deep to medulla converted to Found in the outer cortex would mediate the insertion of aquaporins into Specialized in concentration of the AVP nephron collecting ducts Primarily responsible for (Arginine urine (reabsorption & excretion) removal of waste products Vasopressin) and reabsorption of nutrients would be affecting the reabsorption process in the kidney Glomerulus Filtration produced by the hypothalamus; kept in the Tubules Reabsorption & secretion posterior *urine excretion – dependent on water intake ADH Affects water reabsorption by making non- NEPHRON (2 MAIN PARTS) permeable water parts like collecting tubules & 1. Renal corpuscle (Bowman’s capsule & glomerulus) ascending loop of Henle permeable to water. Water 2. Renal tubule (tubes) diffuses passively from lumen of tubules=concentrated urine NOTE!!! Nephrons perform three basic functions: 1. Glomerular filtration 2. Tubular reabsorption 3. Tubular secretion (NPNs) Blood enters our afferent arterial to the glomerulus (where there is filtration process to occur) Sizes with 60 daltons and above will not allow go through the filtration process. RBCs cannot pass through (big) *ADH and aldosterone also act on the collecting ducts to control Early morning urine – best specimen for RU reabsorption of water, sodium & chloride  CLINICAL LESSON | 01 CHEMISTRY 2 Lecture | PRELIM | Batch 2024 BODY WATER ION TRANSPORT PROCESSES The average body water constitutes around 40-75% of the total body Ion concentration within cells and plasma is maintained by energy- weight. consuming active transport processes and by diffusion or passive processes. The level declines with age (intracellular water). The estimated body water content according to body mass is: Active system that requires energy (ATP) to move ions transport across cellular membranes; Sodium-potassium pump BODY TYPE MALE FEMALE Lean 70% 60% passive movement of ions across a membrane and Normal 60% 50% is dependent on the size and charge of particles being Obese 50% 42% transported and on the nature of the membrane it is *Women and obese people have lower body water due to fat content Diffusion passing through. Fetus 100% The rate of diffusion of various ions also maybe Baby at birth 80% altered by physiologic and hormonal processes. Normal Adult 70% Elderly 50% NA-K ATPASE PUMP *The decline of TBW with age is due primarily to a decline in intracellular ATP in the active transport comes from the breakdown of ATP by water. ATPase-dependent ion pumps. Take note that the distribution of water in body compartments is IMPORTANCE OF BODY WATER controlled by maintaining the concentration of electrolytes and proteins Body water is important because it in those individual compartments. Biologic membranes are permeable to o is the solvent for all processes in the body; water but not to ions and proteins. Thus, the concentration of ions and o transports nutrients to cells; proteins at the either side of the membrane will influence the flow water o determines cell volume; removes waste products; across a membrane (known as osmoregulators). o acts as body cooling system (Sweating; thirst center is stimulated) o carries electrolytes and other substances. SOURCES OF BODY WATER 2 major compartments of total body water. These are: 1. OXIDATION OF FOOD – 400 mL is located within the cells and Fat Metabolism 110 ml/100 g intracellular Protein Metabolism 44 ml/100 g constitutes around 28 liters or 66% of TBW fluid or ICF CHO Metabolism 60 ml/100 g the total body water (70 kg = 42 L) extracellular contains around 14 liters or 33% of 2. DIET – 1,100 mL fluid or ECF the remaining water Drinks 1000 mL; 800-1300 mL Food 1000-1200 mL; 750-1200 mL *TBW = 0.6 X BODY WEIGHT ECF is subdivided into (a) intravascular ECF (plasma), interstitial cell fluid (surrounds the cells in the tissues) and the smallest ECF component is the Transcellular fluid (water contained within the epithelial-lined spaces). Transcellular fluid is separated from other fluids by a cellular barrier and consists of cerebrospinal, pleural, gastrointestinal, intraocular, peritoneal, and synovial fluids (Elgart, 2004). Loss of transcellular fluid can produce fluid and electrolyte disturbance. NOTE!!! ECF IS SUBDIVIDED INTO intravascular ECF Plasma (3 L); 1/4 interstitial cell fluid 10.5 L (3/4) smallest ECF component (0.5 L) water contained within the epithelial-lined spaces Transcellular fluid Consist of Cerebrospinal, Pleural and Gastrointestinal, intraocular, peritoneal and synovial fluid ROUTES OF WATER EXCRETION WATER DISTRIBUTION Skin 500 ml Body 70% Water Lungs 400 ml Blood 85% water Gut 100 ml Brain 80% water Kidneys 500 ml Muscles 75% water Cells 90% water Normal plasma contains as much 93%; remaining volume is occupied by lipids and proteins.  CLINICAL LESSON | 01 CHEMISTRY 2 Lecture | PRELIM | Batch 2024 DISORDERS OF WATER BALANCE Who are the susceptible in dehydration: Among the more common disorders involving an imbalance in the less able to conserve water because they cannot tell us if Infants water of body fluids are they are thirsty ⚫ water deficit (dehydration) less sensitivity of their thirst center bought about by of ⚫ water load (intoxication and edema) Elderly course advancing age and plus there will be a physical People disability that would make it difficult for them to take A. DEHYDRATION adequate fluids. PURE WATER LOSS OR DEFICIT. This can lead to increased osmolality. It will have a less effect on plasma or ECF volume because TREATMENT FOR DEHYDRATION the body easily compensates for the fluid loss by recruiting water from to replace the water lost and electrolytes (Oral Rehydration Salt) the ICF. Pure water loss lowers total body water, but the total body of o if only water is replaced, the extracellular fluid will become more sodium remains normal. dilute normal. *ICF goes out of the cell (cell crenation – shrink) o This may produce a condition of water intoxication Both water and electrolytes should be replaced deficiency condition that occurs when the output of water exceeds the intake. Thirst is the major defense against hyperosmolality, and hypernatremia as water is lost, the extracellular fluid becomes increasingly more brought about by dehydration. An example of effectiveness of thirst in concentrated, and water tends to leave cells by osmosis. preventing dehydration is seen in DI, where there is no AVP or no ability SIGNS OF DEHYDRATION to respond to the AVP in the circulation. In these patients, excretion may 1. Dry, chapped lips increase to 10L of urine/day, but because thirst persists, water intake 2. Headaches matches output and plasma sodium, therefore plasma osmolality 3. Dry skin remains normal. 4. Achy joints 5. Fatigue B. OVERHYDRATION/ WATER INTOXICATION takes place when there is excessive intake of water or excessive EFFECTS OF DEHYDRATION reabsorption of water (ex. SIADH, ectopic ADH secretion) ⚫severe hyperthermia may develop as the body temperature-regulating mechanism becomes less effective due to a lack of water needed for A. WATER INTOXICATION sweating. known as water poisoning or dilutional hyponatremia ⚫In severe cases, as waste products accumulate in the extracellular is potentially fatal disturbance in brain functions that results when the fluid, symptoms of cerebral disturbances, including mental confusion, normal delirium, and coma may develop. balance of electrolytes in the body is pushed outside safe limits by overhydration TYPES OF DEHYDRATION according to water & Na loss When the serum sodium level drops, the eyes begin to flutter and seizures occur WATER AND SODIUM LOSS As the extracellular fluid becomes hypotonic, water enters the cells This has a greater effect on ECF or plasma volume. Hypovolemia readily rapidly by osmosis. takes place especially in isotonic fluid loss. Coma resulting from swelling brain tissues may follow unless water intake is restricted and hypertonic salt solutions given. The types are: Water intoxication results from excessive intake of water or excessive 1. HYPERNATREMIC DEHYDRATION (HYPERNATREMIC) reabsorption of water seen in Syndrome of Inappropriate Water loss exceeds sodium loss. Antidiuretic Hormone Secretion (SIADH), ectopic ADH Secretion Cell Shrink (crenation) – cell becomes dysfunctional. (tumor, tissue growth) Ex. Water and food deprivation, excessive sweating, osmotic diuresis (diabetes); thirsty CAUSES OF SIADH Tumors 2. NORMONATREMIC DEHYDRATION (ISOTONIC DEHYDRATION) Pulmonary Disorders Water and dissolves electrolytes are lost in equal proportion. CNS Disorders This is the common form of dehydration Drugs Ex. Vomiting, diarrhea (acute) HIV NOTE!!! 3. HYPONATREMIC DEHYDRATION (HYPOTONIC DEHYDRATION) DIABETES INSIPIDUS SIADH Sodium loss exceeds water loss. High Urinary Output Low Urinary Output Cell Swell Low levels of ADH High levels of ADH Ex. Diuretic therapy, salt-wasting renal disease, adrenocortical Hypernatremia Hyponatremia insufficiency (aldosterone insufficiency); shock Dehydrated Over Hydrated Lose too much fluid Retain too much fluid NOTE!!! ECF concentration ICF concentration Excessive thirstiness BOTH WILL PRESENT WITH EXCESSIVE THIRST! DIABETES INSIPIDUS DIABETES MELLITUS Low ADH Normal ADH Normal Insulin Low Insulin  CLINICAL LESSON | 01 CHEMISTRY 2 Lecture | PRELIM | Batch 2024 B. EDEMA OSMOLALITY ⚫ is an abnormal accumulation of extracellular fluid within the Osmolality is the concentration of solute (mmol/L) per kilogram of interstitial spaces. solvent. mainly regulated by sodium and chloride (92%). CAUSES OF EDEMA Parameter to assess response of the hypothalamus. Hypoproteinemia result to decrease plasma osmotic pressure that Measured using osmometer. reduces the normal return of tissue fluid to the venule ends of Increase osmolality = decrease freezing point, temperature, vapor capillaries. pressure Tissue fluid consequently accumulates in the interstitial spaces Physiological responses triggered by ECF osmolality are ADH release resulting in edema. and stimulation of hypothalamic thirst center. Therefore, ECF volume is maintained by: Lymphatic obstruction o Renal excretion of sodium or glomerular filtration rate o may result from surgery or from parasitic infections of lymphatic o Aldosterone via the RAA system vessels. o Back pressure develops in the lymphatic vessels, interfering with Both the sensation of thirst and arginine vasopressin (AVP) secretion are the normal movement of tissue fluid into them. stimulated by hypothalamus in response to increased osmolality. In o proteins that the lymphatic circulation ordinarily removes response to thirst, more fluids is consumed, increasing the water content accumulate in the interstitial spaces, raising osmotic pressure of of ECF, therefore diluting the elevated solute (Na) levels and decreasing the interstitial fluid. This effect attracts still more fluid into the the osmolality of the plasma. AVP on the other hand, acts on cells of interstitial spaces. collecting ducts in the kidneys to increase water reabsorption. This is an example of negative feedback loop, as water is conserved, the osmolality Increase venous pressure within the liver and portal blood. decreases, which in turn shuts off AVP secretion. o This results when the outflow of blood from the liver into the inferior vena cava is blocked. To maintain a normal plasma osmolality, osmoreceptors in the o As result, fluid with a high concentration of protein is exuded hypothalamus respond quickly to small changes in osmolality. A 1% to from the surfaces of the liver and intestine into the peritoneal 2% increase in osmolality causes a fourfold increase in the circulating cavity. concentration of AVP, and 1% to 2% decrease in osmolality shuts off o This causes a rise in the osmotic pressure of the abdominal fluid, AVP production. AVP acts by increasing the reabsorption of water in the which, in turn, attracts more water into the peritoneal cavity by cortical and medullary collecting tubules but has a half-life in the osmosis. This condition, called ascites, distends the abdomen. circulation of only 15 to 20 minutes. It is quite painful Stimulants: Increased capillary permeability accompanying inflammation. 1. Decreased ECF volume o Inflammation is a response to tissue damage and usually 2. Increased ECF osmolality releases chemicals such as histamine from damaged cells. o Histamines causes vasodilation and increased capillary permeability, so that excess fluid leaks out of the capillary and enters the interstitial spaces. REGULATION OF BLOOD VOLUME FACTORS AFFECTING BLOOD VOLUME RAAS o Low Na+ (Angiotensin II to stimulate Aldosterone prod) o Stimuli are decreased blood vol, thus renin is secreted to convert angiotensinogen to angiotensin o ACE converts angiotensin 1 to angiotensin II. Angiotensin II *Thirst is more important in preventing water deficit. causes vasoconstriction, which quickly increases blood pressure, and secretion of aldosterone which increases retention of na and the water that accompanies the Na. RAA SYSTEM: NOTE!!! Hyponatremia, hypotension, and hyperkalemia stimulate ANP juxtaglomerular (JG) cells of the kidneys to release renin. o atrial natriuretic factor (heart – balance sodium in the blood) ↓ o Increased sodium – increase in ANP (to eliminate excess Na+) Renin (kidneys) converts angiotensinogen to angiotensin 1 (AI). o ANP is produced by the myocardial atria in response to volume ↓ expansion, promotes Na excretion. Volume receptors AI is converted to angiotensin ll (A ll) in by ACE (produced by the lungs) independent of osmolality stimulate the release of AVP, which ↓ conserves water by renal abosorption. A ll stimulates the adrenal cortex to produce aldosterone. ↓ Volume receptors independent of osmolality Aldosterone promotes retention of sodium and excretion of potassium in the kidneys GFR – GLOMERULAR FILTRATION RATE o GFR increases with vol expansion and decreases with volume depression. All other things equal o an increased plasma Na will increase urinary Na excretion and vice versa  CLINICAL LESSON | 01 CHEMISTRY 2 Lecture | PRELIM | Batch 2024 PLASMA OSMOLALITY is important because it is the parameter to assess the response of the hypothalamus. Osmolality can be measured on urine or serum specimens using an osmometer. An increase in osmolality decreases the freezing-point temperature and the vapor pressure. 𝐦𝐠 𝐦𝐠 𝐆𝐥𝐮𝐜𝐨𝐬𝐞 ( ) 𝐁𝐔𝐍 ( ) 𝐝𝐋 𝐝𝐋 A. 𝟐 𝐍𝐚 + + 𝟐𝟎 𝟑 𝐆𝐥𝐮𝐜𝐨𝐬𝐞 𝐁𝐔𝐍 B. 1.86 𝐍𝐚 + + + 𝟗 𝟏𝟖 𝟐.𝟖 Reference: Serum 275-295 mOsmol/kg 24 h Urine 300-900 mOsmol/kg Urine:serum ratio 1.0-3.0 Random urine 50-1200 mOsm/kg Osmolal gap