Human Physiology: Osmolality and Regulation

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Questions and Answers

What is the primary effect of increased plasma osmolality in the human body?

Stimulates thirst and ADH release (correct)

Reduces blood pressure

Increased skeletal muscle contraction

Decreased urine production

Which method is considered the preferred approach for determining osmolality?

Vapor pressure depression

Simple titration

Spectrophotometry

Freezing point depression (correct)

Which calculation is vital for determining calculated osmolality from plasma measurements?

BUN / 2.8 only

2(Na) - glucose/25 + BUN/4

1.86(Na) + glucose/18 + BUN (correct)

0.8(Na) + glucose/10 + BUN/5

What does a significant difference between measured and calculated osmolality indicate?

Presence of osmotically active substances Signup and view all the answers

What physiological mechanism triggers thirst and increases urine output regulation?

Changes in plasma osmolality Signup and view all the answers

Which condition is characterized by a deficiency of antidiuretic hormone (ADH) leading to decreased osmolality?

Diabetes Insipidus Signup and view all the answers

What is the normal range for serum osmolality in mOsm/Kg?

275-295 Signup and view all the answers

Which factor does NOT influence sodium concentration in the extracellular fluid?

Blood glucose levels Signup and view all the answers

What is the typical urine osmolality range measured over a 24-hour period in mOsm/Kg?

300-900 Signup and view all the answers

Which hormone stimulates the kidneys to conserve sodium based on changes in extracellular fluid volume and blood pressure?

Aldosterone Signup and view all the answers

What is the main role of chloride ions in the body?

Maintaining electrical neutrality Signup and view all the answers

How does the reabsorption of chloride in the kidneys occur?

Simultaneously with sodium Signup and view all the answers

What may indicate a case of hypochloremia?

Loss of gastric HCl Signup and view all the answers

Which method is used for measuring chloride levels in a specimen?

Amperometric/Coulometric titration Signup and view all the answers

What may cause hyperchloremia?

Congestive heart failure Signup and view all the answers

What is a potential consequence of low chloride levels?

Metabolic alkalosis Signup and view all the answers

Why is it necessary to collect fresh sweat for chloride measurement?

To ensure accuracy of Cl concentration Signup and view all the answers

What is the typical normal range for serum chloride levels in mEq/L?

100 - 110 Signup and view all the answers

Study Notes

Kidney Function

A nephron is a working unit of the kidney
Each kidney contains approximately one million nephrons
Blood flows into the glomerulus, and some fluid with dissolved substances is absorbed into the tubule
The fluid and substances needed by the body are returned to the blood in vessels alongside the tubule.
The tubule passes waste materials on to the bladder.

Renal Function Testing and Non-Protein Nitrogen Substances

Define terminologies applied in renal function tests
Define nonprotein nitrogenous (NPN) compounds
Discuss urea, creatinine, uric acid, creatinine clearance, and electrolytes
Discuss source, metabolism, and clinical significance of these substances.
Explain renal stones

Outline of Introduction

Definitions of important terminologies (concepts)
Anatomy and functions of the renal system
Renal threshold
Non-protein nitrogenous (NPN) compounds

Urea and BUN

NPN compounds present in the highest concentration in blood and urine
U = Urea
Blood Urea Nitrogen = BUN
Urea contains 2 nitrogen atoms: 28 g nitrogen/mole of urea
BUN x 2.14 = urea

Introduction (Urea Synthesis)

Liver removes toxic ammonia from circulation.
Converts it to nontoxic, water-soluble urea
Site of urea synthesis is the liver
Reactions leading to urea formation from ammonia are proposed by Krebs and Henseleit
Urea cycle is also called the Krebs-Henseleit cycle
Urea formation in the cycle occurs in five steps:
First reaction is not part of the urea cycle, but its product is essential for the continuation

Urea Synthesis (Continued)

Synthesis of urea from ammonia is an energy-dependent process
Enzymes of urea cycle are present in mitochondria and cytosol
First two reactions of urea formation occur in mitochondria; remaining ones happen in cytosol

Urea Cycle

Third reaction: argininosuccinate is cleaved by argininosuccinase to form arginine and fumarate
Fifth reaction: ornithine and urea formation from arginine is the final step catalyzed by arginase.
The formed ornithine goes into mitochondria to re-start the urea cycle
The overall equation for urea formation is NH3 + HCO3 + aspartate + 4ATP → Urea + fumarate + 4ADP + 4Pi
Urea has no physiological function; it is transported to kidneys for excretion in urine
Protein catabolism makes 10-25 g of urea excreted per day, which is 80-90% of total nitrogen excreted per day.
Blood also contains some urea

Urea Formation Regulation

Formation of urea is regulated by the activity of carbamoyl phosphate synthetase-I.
N-acetylglutamate regulates the activity of this enzyme, and is an allosteric activator.
High protein intake results in increased N-acetylglutamate formation; thus, increasing urea formation
Starvation also increases urea synthesis due to increased protein breakdown

Blood Urea N (BUN)

BUN reference ranges
For adults (serum/plasma): 6-20 mg/dL
For newborns up to one week (serum/plasma): 3-25 mg/dl
For adults over 60 (serum/plasma): 8-23 mg/dL

Urea/BUN Clinical Significance

Plasma levels depend on diet, liver function, kidney function, and hydration status
Increased urea (BUN): azotemia or uremia, increased protein intake, decreased kidney function, dehydration)
Decreased urea (BUN): decreased protein intake, decreased liver function

Ammonia Toxicity and Metabolism

Ammonia is toxic to the central nervous system, particularly glial cells
Blood ammonia level must be within a normal range
Symptoms of ammonia intoxication include slurred speech, blurred vision, tremors, coma, and early death in severe cases.
Ammonia can cause brain toxicity by three ways:
Entry into brain leads to glutamate formation, depleting alpha-ketoglutarate
Brain utilizes ammonia for glutamine synthesis, depleting cellular ATP
Excess glutamate overstimulates nerve cells.

Causes of Ammonia Toxicity

Impaired hepatic function (carbon tetrachloride poisoning, heavy metal poisoning, viral infections)
Collateral communications between portal vein and systemic blood (cirrhosis)
Consumption of high-protein diets after gastrointestinal hemorrhage
Ammonia metabolism
Liver deaminates amino acids, producing urea
Brain can convert ammonia to glutamine.

Creatinine

Formation and excretion: derived spontaneously from creatine in muscle; production is constant; excreted by glomerular filtration, not reabsorbed or secreted by tubules.
Metabolism: Involves transformations with phosphocreatine, forming creatine then creatinine.
Reference ranges:
Serum: 0.6-1.1 mg/dL in adult males, 0.5-0.8 mg/dL in adult females, 0-0.6 mg/dL in children
Urine: 800-2000 mg/24 hr in adult males, 600-1800 mg/24 hr in adult females
Amniotic fluid: 1-2 mg/dL

Creatinine Clinical Significance

Endogenous substance
Constant daily production (variations <10% daily); proportional to muscle mass
Filtered by glomerulus
Not handled by tubules
Good test for GFR
Not affected by diet
Increased serum creatinine indicates renal disease (impaired renal function). 50-60% renal function loss before serum creatinine increases

BUN/Creatinine Ratio

Calculated: serum BUN (mg/dL) / serum creatinine (mg/dL)
Normal ratio: 10-20, with the majority around 12-16
Increased ratio: pre-renal conditions (CHF, shock, hemorrhage, dehydration), increased protein metabolism, increased protein catabolism
Decreased ratio: post-renal conditions (obstruction of urine flow), low protein diet, liver disease
Renal conditions causing low CrCl or ratio: acute renal failure, chronic renal failure, glomerulonephritis, tubular necrosis

Creatinine Clearance (CrCl)

Renal clearance expresses the volume of blood cleared of a substance per unit of time (e.g., mL of substance per minute)
Substance used to monitor GFR must not be reabsorbed or secreted by the tubules; creatinine is commonly used
Specimen handling: timed 24-hour urine collection, measure urine creatinine and serum creatinine
Standard clearance formula: UV/P, where U is urine creatinine, V is urine volume, and P is serum creatinine
Corrected clearance is calculated using UV x 1.73/P, where A is body surface area (BSA) and 1.73 is a value often used representing the average BSA.

Estimated GFR (eGFR)

The National Kidney Foundation recommends eGFR calculation each time a serum creatinine is reported
eGFR predicts GFR values based on patient age, sex, body size, race and serum creatinine readings.
Timed urine collection is not needed for eGFR calculations.

Uric Acid

Uric acid is the end product of purine catabolism.
Purines are the important constituents of DNA and RNA, found in exogenous (ingested nucleic acids) and endogenous (tissue destruction) sources.
Excretion: 70% of Uric acid elimination through renal excretion. The remainder goes via Gastrointestinal tract for bacterial enzyme degradation.
Uric acid is Insoluble in plasma and mostly presents as monosodium urate.
At high concentrations (greater than 6.8 mg/dL), uric acid precipitates in joints and tissues, causing painful inflammation.

Uric Acid Clinical Significance

Uric acid measurements assess inherited disorders of purine metabolism, confirm gout diagnosis, monitor gout treatment, aid in diagnosing renal calculi, prevent uric acid nephropathy during chemotherapy treatment, and detect kidney dysfunction.
Normal values are 3.4–7 mg/dL in adult males and 2.5–6 mg/dL in females.

Gout

Gout is a disease predominantly in men, often diagnosed between 30 and 50 years old.
Gout causes inflammation of joints, due to precipitation of sodium urates.
Affected individuals are susceptible to the formation of Renal Calculi

Causes of Increased Uric Acid

Increased metabolism of cell nuclei (chemotherapy for leukemia, lymphoma, multiple myeloma)
Chronic renal disease
Purine-rich diet
Increased tissue catabolism (starvation)
Inherited disorders of purine metabolism (Lesch-Nyhan syndrome)
Toxemia of pregnancy and lactic acidosis
Drugs (salicylates and thiazides)

Causes of Decreased Uric Acid

Liver disease
Defective tubular reabsorption (Fanconi syndrome)
Chemotherapy with azathioprine or 6-mercaptopurine
Excessive allopurinol treatment

Electrolytes

Electrolytes are substances whose molecules dissociate into ions when in water.
Medically important electrolytes include sodium (Na+), potassium (K+), chloride (Cl-), and bicarbonate (HCO3-) (carbon dioxide in its ionic form)
Functions are to regulate volume, osmotic activity, myocardial rhythm, and contractility, enzyme activation, ion pump regulation, acid-base balance, blood coagulation, and neuromuscular excitability.
They are contained in intracellular fluids (ICF), and extracellular fluids (ECF), the latter being further broken down into intravascular (plasma) and interstitial fluids (ISF)
Regulation of electrolytes has to do with diet, kidney function (e.g., reabsorption), and hormonal systems (e.g. aldosterone)

Osmolality

The physical property of a solution, based on solute concentration
Water concentration is regulated via thirst and urine output
Thirst and urine output are regulated by plasma osmolality
Osmolality: solute concentration/kilogram of solvent
Osmolarity: solute concentrated/liter of solution
Determination: Freezing-point depression or vapor-pressure depression
Serum collection preferred for measurement of osmolality

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Description

Test your knowledge on the mechanisms of osmolality and its physiological effects in the human body. This quiz covers essential concepts such as thirst regulation, antidiuretic hormone deficiency, and sodium concentration influences. Perfect for students studying human physiology or biochemistry.