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• Nephrons are the functional units of the kidneys and there are over 1 million per kidney.
• The kidneys process about 1/4 of the body's blood supply at any given time.
• This process results in producing at least 1 liter of urine per day.
• The amount of urine formed is greatly affected by the amount of fluid intake.

Classification of Nephrons

• Cortical Nephrons are prevalent in the outer cortex and primarily handle waste removal and nutrient reabsorption.
• Juxtamedullary Nephrons extend deeper into the medulla and specialize in urine concentration.
• Urine excretion relies on water intake.

Nephron Components and Function

• Nephrons have 2 main parts: the renal corpuscle (Bowman's capsule & glomerulus) & the renal tubule.
• Nephrons perform three basic functions: glomerular filtration, tubular reabsorption, and tubular secretion (NPNs).
• During glomerular filtration, blood enters the glomerulus via the afferent arteriole: filtration occurs.
• Substances above 60 daltons are unable to go through the filtration process.
• Red blood cells cannot pass through due to their size
• Early morning urine is the best specimen for routine urine analysis

Body Water Overview

• Total body water constitutes 40-75% of total body weight, decreasing with age because of lower intracellular water.
• Lean individuals have higher body water content than obese individuals.

Body Water % by Type

• Lean males average 70%
• Normal males average 60%
• Obese males average 50%
• Lean females average 60%
• Normal females average 50%
• Obese females average 42%
• Fetuses are 100%
• Babies at birth are 80%
• Normal adults are 70%
• Elderly people are 50% water.

Importance of Body Water

• Body water is important because it’s a solvent, transports nutrients, determines cell volume and removes waste, acts as a cooling system, & carries electrolytes.
• The 2 major compartments of water are intracellular fluid (ICF) and extracellular fluid (ECF).
• Intracellular fluid constitutes 28 liters or 66% of total body water, while extracellular fluid contains 14 liters or 33%.
• TBW = 0.6 X BODY WEIGHT
• ECF consists of intravascular fluid (plasma), interstitial cell fluid, & transcellular fluid.

Body Water Distribution

• Intravascular ECF (plasma) makes up about 1/4 of ECF at 3L
• Interstitial cell fluid makes up about 3/4 of ECF at 10.5L.
• Transcellular fluid is the smallest ECF component at 0.5 L.

Water Distribution Details

• Blood is 85%
• Brain is 80%
• Muscles are 75%
• Cells are 90% water.
• Normal plasma is 93% water, with lipids and proteins occupying the remaining volume.

Ion Transport Processes

• Ion concentration is maintained via active transport and passive diffusion
• Active transport requires energy (ATP) and a sodium-potassium pump
• Passive movement is dependent on particle size, charge, and membrane nature.
• Distribution of water is controlled by electrolyte and protein concentrations.
• Membranes are permeable to water, not ions/proteins, affecting water flow (osmoregulation)
• ATP in active transport comes from the breakdown of ATP by ATPase-dependent ion pumps.

Sources of Body Water

• Oxidation of food contributes about 400 mL.
• Fat metabolism yields 110 ml/100 g
• Protein metabolism yields 44 ml/100 g
• CHO metabolism yields 60 ml/100 g
• Diet contributes about 1,100 mL
• Drinks contribute 1000 mL (800-1300mL)
• Food contributes 1000-1200 mL (750-1200mL)

Average Intake/Output

• Average intake per day: 2500 ml which consists of:
  • 10% Metabolism
  • 30% Foods
  • 60% Beverages
• Average output per day: 2500 ml which consists of:
  • 4% Feces
  • 8% Sweat
  • 28% Insensible loss (skin & lungs)
  • 60% Urine

Routes of Water Excretion

• Skin: 500 ml
• Lungs: 400 ml
• Gut: 100 ml
• Kidneys: 900 ml

Disorders of Water Balance

• Common disorders include water deficit (dehydration) and water load (intoxication/edema).

Dehydration Types

• Pure water loss leads to increased osmolality, less effect on plasma volume.
• Deficiency occurs when water output exceeds intake.
• As water is lost, extracellular fluid becomes concentrated, causing water to leave cells by osmosis.
• Water and sodium loss has a greater effect on plasma volume.

Signs of Dehydration

• Dry/chapped lips
• Headaches
• Dry skin
• Achy joints
• Fatigue

Effects of Dehydration

• Severe cases can cause hyperthermia due to the lack of sweat required for cooling and may cause confusion, delirium, and coma by waste accumulation in ECF.

Types of Dehydration (Water and Sodium Loss)

• Hypernatremic: Water loss exceeds sodium loss. Cells shrink (crenation)
• Normonatremic: Water and electrolytes(Na) are lost in equal proportion - common form
• Hyponatremic: Sodium loss exceeds water loss resulting is cell swell
• Oral Rehydration Salt replaces the water & electrolytes that were lost during dehydration

Who is Susceptible to Dehydration?

• Infants are less able to conserve water and can not express thirst
• Elderly: less sensitive to their thirst center

Treatment for Dehydration

• Must replace both water and electrolytes (oral rehydration solution).
• Replacing only water may cause water intoxication.
• Thirst prevents hyperosmolality from dehydration.
• In diabetes insipidus, water intake matches output so plasma osmolality remains normal.

Overhydration/Water Intoxication

• Occurs with excessive water intake or reabsorption of water (ex. SIADH).
• Water intoxication, or dilutional hyponatremia, results when a normal balance of electrolytes is pushed outside safe limits by overhydration.
• Low serium sodium level will cause eyes to flutter and result in seizures.

How Overhydration Occurs

• Extracellular fluid becomes hypotonic, water enters cells rapidly by osmosis.
• Coma from swelling brain tissues may occur unless water intake is restricted
• Water intoxication results from excessive intake of water/reabsorption, seen in SIADH, ectopic ADH secretion (tumor).

Causes of SIADH

• Tumors
• Pulmonary Disorders
• CNS Disorders
• Drugs
• HIV

• Diabetes Insipidus: Low ADH, Normal Insulin
• Diabetes Mellitus: Normal ADH, Low Insulin

Edema

• Edema is an abnormal accumulation of extracellular fluid within the interstitial spaces.

Causes of Edema

• Hypoproteinemia reduces normal return of fluid to venule ends of capillaries.
• Tissue fluid accumulates in interstitial spaces.
• Lymphatic obstruction interferes with normal tissue fluid movement
• Proteins accumulate in interstitial spaces, increasing osmotic pressure.
• Increased venous pressure within in the liver and portal blood blocks outflow into the inferior vena cava.
• Fluid with high concentrations of protein is exuded into the peritoneal
• Abdominal fluid accumulates, distending the abdomen.
• Increased capillary permeability accompanies inflammation, releasing chemicals such as histamine from damaged cells.

Osmolality

• Osmolality measures solute concentration (mmol/L) per kilogram of solvent.
• Primarily regulated by sodium and chloride (92%).
• This parameter assesses hypothalamic response
• High osmolality will decrease freezing point, temperature, vapor pressure
• ECF volume is maintained by renal sodium excretion, glomerular filtration rate, aldosterone through the RAA system.
• Osmolality is measured using an osmometer
• Increased osmolality = decreased freezing point, temperature, vapor pressure

ECF Volume Regulation

• Thirst and arginine vasopressin (AVP) secretion are stimulated by the hypothalamus in response to increased osmolality
• AVP Increases water reabsorption in the kidneys
• Normal plasma osmolality requires response from osmoreceptors in the hypothalamus

Actions of AVP

• A 1% to 2% increase in osmolality causes AVP to increases fourfold
• AVP increases water reabsorption in the cortical/medullary collecting tubules.
• AVP has a half-life in circulation of only 15 to 20 mins
• Stimulants of AVP:
  • Decreased ECF volume
  • Increased ECF osmolality

Factors Affecting Blood Volume

• RAAS
• ANP
• GFR
• Volume Receptors

RAAS System

• Low Na+ levels stimulate Angiotensin II production.
• Decreased blood volume stimulates renin secretion, which converts angiotensinogen to angiotensin.
• ACE converts angiotensin 1 to angiotensin II.
• Angiotensin II results in vasoconstriction, increased blood pressure, and aldosterone secretion, which enhances retention of Na and water.

ANP Factors

• Increased sodium increases ANP to eliminate excess Na+.
• ANP is produced by the myocardial atria in response to volume expansion
• Volume receptors independent of osmolality stimulate the release of AVP

RAA System

• Hyponatremia, hypotension, & hyperkalemia stimulate juxtaglomerular (JG) cells in the kidneys to release renin.
• Renin converts angiotensinogen to angiotensin 1 (AI).
• AI is converted to angiotensin II (A II) ACE.
• A II stimulates the adrenal cortex to produce aldosterone.
• Aldosterone promotes retention of sodium and excretion of potassium in the kidneys

Plasma Osmolality

• Is important for hypothalamus response assessment
• Increase in osmolality will decrease the temperature and vapor pressure A. 2 Na + Glucose (mg) / 20 + BUN / 3 B. 1.86 Na + Glucose/ 18 + BUN / 2.8 +9

Osmolal Gap

• The measure osmolality minus the calculated osmolality attributed to other osmotically active compounds (ethanol, methanol, ethylene glycol, lactate, or β-hydroxybutyrate)

Abnormal Serum Osmolality

• Serum hyperosmolality: water loss, alcohol intoxication
• Serum hyposmolality: polydipsia, SIADH

Lab Assessment of Osmolality

• Sample should be urine or serum
• Methods should be based on colligative properties using osmometers
• Plasma is not recommended because anticoagulants can intervere
• Turbid serum//urine samples must be centrifuged before all assays can be done
• Osmometers should be measured at supercooled temperatures