FUNCTIONS OF THE URINARY SYSTEM
• EXCRETION – kidneys are the major excretory organs of the body
• BLOOD VOLUME CONTROL – regulating the volume
... [Show More] of water removed from the blood to produce urine
ADH – ARGININE (VASOPRESSIN) encourages or influences permeability the glomerular structures to water
ADH – released from the Hypothalamus that regulates thirst of the body
VASOPRESSIN – to press a vessel (vasoconstriction); encourages water retention and reabsorption in the DLH, DCT, and Collecting Duct
Manner of Transport: PASSIVE DIFFUSION
COLLECTING DUCT – influences final concentration of urine filtrate
• ION CONCENTRATION REGULATION – the release of Hydrogen Ions, Reabsorption of Bicarbonate Ions.
BICARBONATE part of Carbonic Acid (HCO3) and Bicarbonate (H2CO3) Buffer System
BLOOD BUFFER SYSTEM – prevents rapid fluctuations of pH of the given environment; resists excessive changes of the pH
CARBONIC ACID 1 Hydrogen ion; when comes in contact with Kidney, it removes H+ released in urinary excreta and the bicarbonate must be retained
o If it fails to liberate the H+ ions, Carbonic Acid, as an acid itself can contribute to extremely low pH (acid) of the blood circulation and to the buffer system itself
RENAL TUBULAR ACIDOSIS (METABOLIC ACIDOSIS) excessive amounts of H+ ions in the blood circulation and increased levels of bicarbonate in the urine sample
o Blood pH levels will be low with high urine pH levels (abnormally expelling bicarbonate)
o ↑ H+ ions = ↓ blood pH, ↑ urine pH
↑ urine pH – caused by Bicarbonate
o ↓ H+ ions = ↑ blood pH, ↓ urine pH
o ↑Bicarbonate = defective tubular reabsorption functions of the nephrons
o Absence of Bicarbonate in the urine is NORMAL
o H+ ions should be secreted
• pH REGULATION – kidneys work with the lungs to buffer the acidity or alkalinity of the blood
• RED BLOOD CELL CONCENTRATION – kidneys are the source of EPO
EPO hormone that stimulates production of RBCs in the Red Marrow
CHRONIC KIDNEY DISEASE decreased EPO, diminishing rate of Hematopoiesis – causing Anemia of Chronic Kidney Disease
• VITAMIN D SYNTHESIS – kidneys, along with skin and liver participates in Vitamin D production
ERGOCALCIFEROL by synthesized form in the kidney
RENAL FUNCTIONS
A. Renal Blood Flow
B. Glomerular Filtration
C. Tubular Reabsorption
D. Tubular Secretion
• RENAL FUNCTION – each kidney contains approximately 1 to 1.5 million nephrons
• NEPHRONS – are the basic structural and functional unit of the kidneys
2 TYPES:
o CORTICAL NEPHRONS – comprises the 85% of the total number of nephrons in the kidney; located at the surface; with shorter Loops of Henle; Primary function is the removal of metabolites and reabsorption of the nutrients
o JUXTAMEDULLARY NEPHRONS - have longer Loops of Henle that extend deep into the medulla of the kidney; Primary function is to the concentration of the urine
ORDER OF RENAL BLOOD FLOW
1. RENAL ARTERY
2. AFFERENT ARTERIOLES → carries oxygen-rich blood that delivers oxygen from the arterioles to the glomerulus
3. GLOMERULUS → filtering unit of the nephron
4. EFFERENT ARTERIOLES → carries oxygen-deficient blood because the glomerulus have already consumed the oxygen component of the blood
5. PERITUBULAR CAPILLARIES
6. VASA RECTA
7. RENAL VEIN
• TOTAL RENAL BLOOD FLOW = 1200ML/MIN
• TOTAL RENAL PLASMA FLOW = 600 ML/MIN
ORDER OF URINE FORMATION
1. GLOMERULUS → non-selective filter, where essentials are reabsorbed
2. PROXIMAL CONVOLUTED TUBULE → where 65% of these metabolites are reabsorbed (Salt, Water, Amino Acid, Glucose, and Urea)
o UREA → major organic constituent
o CHLORIDE → major inorganic constituent; SODIUM → 2nd major; POTASSIUM → 3rd major
3. DESCENDING LOOP OF HENLE → permeable to water
4. ASCENDING LOOP OF HENLE → impermeable to water
5. DISTAL CONVOLUTED TUBULE
6. COLLECTING DUCT
7. CALYX
8. RENAL PELVIS
GLOMERULAR FILTRATION
• Influenced by the cellular structures of the capillary walls and Bowman’s capsule, Hydrostatic and Oncotic pressures and the Renin-Angiotenisn-Aldosterone System
HYDROSTATIC PRESSURE → force of water under the influence of gravity
ONCOTIC PRESSURE → osmotic pressure exerted by proteins (CHON)
RAAS SYSTEM → regulate salt and water concentration of the blood
GLOMERULUS
• The tuft of capillaries having approximately 8 coiled lobes of blood vessels enclosed in Bowman’s capsule
• It resembles a sieve and is a non-selective filter of plasma substances with molecular weight less than 70,000 Daltons
SHIELD OF NEGATIVITY
• The glomerulus has a negative shield that repels negatively charged substances (particularly ALBUMIN with approximately 66,300 Daltons of MW). Thereby, preventing ALBUMINURIA and PROTEIN WASTAGE
4g/day Heavy Proteinuria
1 – 4g/day Moderate Proteinuria
<1g Light Proteinuria
GLOMERULAR PRESSURE
• Hydrostatic Pressure resulting from the smaller size of Efferent arterioles & glomerular capillaries enhances Filtration
• Pressure is needed to overcome opposition of fluids within the Bowman’s Capsule and the Oncotic pressure of unfiltered plasma proteins in glomerular capillaries
JUXTAGLOMERULAR APPARATUS
• Self-regulating Apparatus
• Consists of Juxtaglomerular cells of the Afferent Arterioles and Macula Densa of the Distal Convoluted Tubule
• Maintains the glomerular blood pressure at a relatively constant rate regardless of fluctuations in systemic blood pressure
↓ BP = ↓ Blood circulation = ↓ Oxygen in the kidneys = ↓ Filtering capacity
• Makes sure that there is an adequate glomerular blood supply and normal glomerular blood pressure despite having fluctuations
• Has an AUTOREGULATORY MECHANISM by either increasing/decreasing the sizes of the afferent and efferent arterioles
AUTOREGALUTORY MECHANISM
SYSTEMIC BLOOD PRESSURE – HIGH
SYSTEMIC BLOOD PRESSURE – LOW
RENIN – ANGIOTENSIN – ALDOSTERONE SYSTEM (RAAS SYSTEM)
• Responds to the changes in Blood Pressure, Plasma Sodium concentration (monitored by the Juxtaglomerular Apparatus)
• RAAS will be triggered once the body experiences the cascade of lows
THE CASCADE OF LOWS
• Decrease in Plasma Sodium
• Decrease in H2O Retention
Low levels of Plasma Sodium and Water Retention, patients are most likely to be Dehydrated or Hypovolemic causing decreased Blood Pressure
In response to Dehydration, low BP, and low sodium, renin is released by the kidney to convert Angiotensin to Angiotensin I
Angiotensin I with the action of ACE, will then be converted to Angiotensin II
ANGIOTENSIN II encourage the release of Aldosterone that promotes Sodium Retention and ADH that promotes Water Retention
• Decrease in Blood Volume
• Decrease in Blood Pressure
ANGIOTENSIN II
• Corrects Renal Blood Flow
• Aldosterone and ADH are released
• Increased Na+ and H2O Reabsorption
• Increased Blood Volume
• Increase Blood Pressure
TAKE NOTE
• The filter is non-selective, therefore the only difference between the compositions of the filtrate and the plasma is the absence of plasma proteins or any protein bound substances and the cells
• Analysis of the fluid as it leaves the glomerulus shows the filtrate to have a specific gravity of 1.010 and confirms that it is chemically an ultrafiltrate of plasma
• 1.010 Isosthenuric Glomerular Specific Gravity
>1.010 suggests glomerular destruction (Hypersthenuric – perhaps salt or protein is mixed)
• This information provides a useful baseline for evaluating the renal mechanisms involved in converting the plasma ultrafiltrate into the final urinary product.
CELLULAR STRUCTURES OF THE GLOMERULUS
• The glomerulus has 3 glomerular filtration barrier cellular layers:
1. CAPILLARY WALL MEMBRANE – with Fenestrated endothelial cells (the cells having pores that increase capillary
permeability but do not allow the passage of large molecules and blood cells)
2. BASEMENT MEMBRANE
3. VISCERAL EPITHELIUM OF THE BOWMAN’S CAPSULE
TUBULAR REABSORPTION
• THE FIRST FUNCTION TO BE AFFECTED IN RENAL DISEASES
• CONCENTRATIONS TESTS assess tubular reabsorption
ACTIVE TRANSPORT PASSIVE TRANSPORT
Requires the carrier proteins contained in the membranes of the renal tubular epithelial cells. An energy requiring process in the form of ATP.
Makes use of carrier substances Movement of molecules across a membrane as a result of differences in their concentrations or electrical potential on opposite sides of the membrane.
Relies on Passive Diffusion
ACTIVE TRANSPORT PASSIVE TRANSPORT
Substance Location Substance Location
Glucose, Amino Acid Salts PCT Water PCT, DLH, CD
Chloride ALH Urea PCT, ALH
Sodium PCT, DCT Sodium ALH
PROXIMAL CONVOLUTED TUBULE
• 65% of reabsorption of substances
• Reabsorbs Salts, Water, Amino Acids, Glucose, and Urea
RENAL THRESHOLD
• When plasma levels of a substance reach abnormally high, the filtrate concentration exceeds
the Maximal Reabsorption Capacity of the tubules, and the substance begins to appear in the urine
• RENAL THRESHOLD FOR GLUCOSE: 160 – 180 mg/dL
TUBULAR CONCENTRATION
• Begins in the Descending and Ascending Loop of Henle
• Water is removed by OSMOSIS in DLH
• Sodium and Chloride are reabsorbed in ALH
COUNTERCURRENT MECHANISM
• Prevents the overabsorption of water by maintaining the osmotic gradient of the medulla of the kidneys. It is essential for the final concentration of the filtrate when it reaches the collecting duct.
COLLECTING DUCT CONCENTRATION
• Influenced by the action of the VASOPRESSIN/ ANTI-DIURETIC HORMONE
• HIGH ADH increases the permeability of the capillaries allowing an increase in water reabsorption; ↑ Water Retention
• LOW ADH decreases or renders the collecting duct impermeable to water; ↓ Water Retention
• Therefore, the ADH value is determined by the body’s hydration status
• DIABETES INSIPIDUS problems in the ADH
TUBULAR SECRETION
• Secretion of waste products that aren’t filtered by the glomerulus
• Regulates the Acid-Base balances by secreting Hydrogen Ions
• Many foreign substances (ex. Medications) can’t be filtered by the glomerulus because they are protein-bound.
• Major Site of removal of these non-filtered substances is the PCT
ACID-BASE BALANCE
• 100% Bicarbonate is reabsorbed, and this occurs in the PCT
• PCT is also the site of Ammonia production from the breakdown of Glutamine
• Ammonia reacts with the Hydrogen ions to form the Ammonium ion
NH3 + H+ = NH4 (reversible reaction)
Endogenously, ammonia is produced by the liver due to urea metabolism
Upon long standing, this Ammonium ion will dissociate hydrogen ions, thus ammonia is retained in the urine, increasing the urine pH
• Bicarbonate is prevented to be excreted by secretion of Hydrogen ions by the renal tubular cells into the filtrate
METABOLIC ACIDOSIS/ RENAL TUBULAR ACIDOSIS
• Inability of the kidneys to produce acidic urine
• Excessive H+ in blood
• ↓ Blood pH = ↑ Urine pH (due to presence of Bicarbonate)
RENAL FUNCTION TESTS
GLOMERULAR FILTRATION TESTS
• Normal functioning is determined through Clearance tests
• It measures the ability of the kidneys to remove a filterable substance in the blood
• Substances tested must be neither reabsorbed nor secreted by the tubules
• The substance must be stable in urine during a 24-hour collection
CLEARANCE TESTS
1. Urea
2. Creatinine
3. Inulin
4. B2 microglobulin
5. Radioisotopes
6. Cystatin C
• Greatest Source of Error: Improper timing of collection
• ENDOGENOUS CLEARANCE – the substance is readily available in the body
UREA previously utilized in Endogenous testing but because of insufficient clearance assessment, it was replaced by Creatinine
CREATININE
• EXOGENOUS CLEARANCE – the substance is infused into the bloodstream
INULIN
CREATININE CLEARANCE
• Most common clearance test
• Creatinine is a waste product of muscle metabolism
• Produced enzymatically by Creatine Phosphokinase which links with ATP to produce ADP and Energy
• Test should begin and end with an empty bladder
• Sample should be refrigerated
• REFERENCE RANGES:
Males: 107 – 139 mL/min
Females: 87 – 107 mL/min
• Where:
1.73 = Constant Body Surface Area
A = BSA of the patient
Minutes = 1440 minutes
COCKGROFT AND GAULT FORMULA
• Estimated Glomerular Filtration Rate
• Results is multiplied to 0.85 if the patient is Female
• Variables to consider: Age, Gender, Serum Crea
• Formula taken from the National Kidney Foundation
INCREASED DECREASED
• High Cardiac Input increased BP, BC, GFR
• Pregnancy there are physiologic changes that results to Hyperplastic and Hypertrophic changes in the muscles in the body of a woman; enlarged extremities
• Burns damaged muscles
• Carbon Monoxide Poisoning • Impaired Kidney Function decreased GFR
• Shock and Dehydration decreased BV, BP, and GFR
• Hemorrhage contributing factor to Shock and Dehydration
• Congestive Heart Failure decelerates heartbeat
DISADVANTAGES OF CREATININE CLEARANCE
a) Some creatinine is secreted by the tubules. Secretion increases as blood levels rises.
b) Chromogens present in plasma react in chemical analysis
c) Medications like Gentamicin, Cephalosporin, Cimetidine (TAGAMET) inhibit tubular secretion of
creatinine, thereby results to falsely decreased serum values.
d) Urinary Creatinine is broken down by bacteria, if specimen is not stored in refrigerated temperature.
e) Diet rich in meats consumed during collection of 24 hours’ urine sampling will influence the result. (If blood sample is drawn before collection period)
f) Not a reliable clearance test for patients with muscular degenerative diseases or to persons involved in heavy exercise or athletes supplementing with creatine
g) Accurate results depend on accurate completeness of Urine collection.
h) Must be corrected by body surface area unless normal is assumed. Must always be corrected for children.
INULIN CLEARANCE
• Gold Standard Clearance Test
• INULIN – a polymer of fructose. It is extremely stable substance that is not reabsorbed or secreted by the tubules
• It must be administered intravenously at a constant rate throughout the testing period
• NORMAL VALUES:
Males: 127 mL/min
Females: 118 mL/min
RADIOISOTOPES
• The use of 125I – Iothalamate Method of providing visualization of one or both kidneys and complete plasma disappearance of the material
• Measures the viability of a transplanted kidney
CYSTATIN C
• A small molecular weight protease inhibitor and is produced constantly by all nucleated cells
• Readily filtered by the glomerulus and reabsorbed and broken down by renal tubular cells (PCT)
• Presence in the urine denotes damage in the glomerulus
• Completely reabsorbed by the Proximal Convoluted Tubule, hence its presence in the urine denotes damage of the tubule
If the PCT fails to reabsorb Cystatin C, increasing Cystatin C concentration in the blood plasma of patients
• The Indirect Estimate of GFR (Because renal clearance of this substance cannot be measured)
• Not affected by muscle mass, age, diet, and gender
• Specimen of choice is SERUM or PLASMA (Fasting requirement aren’t needed)
• Increased Serum Cystatin C Acute and Chronic Renal Failure and Diabetic Nephropathy
• Patient Considerations: Infants, Newborns, Pediatric, Geriatric, Renal Transplant patients
CLINICAL SIGNIFICANCE OF CLEARANCE TEST
• GFR is determined not only by the number of functioning nephrons but also knowing the functional capacity of these nephrons
• GFR does not lie in detection of early renal diseases, instead, it is used to know the extent of nephron damage in a known renal disease
• Employed only when there is established initial findings
• To monitor the effectiveness of a treatment designed to prevent further nephron damage
If Creatinine levels are decreased, that is suggestive that there is a response in therapy glomerular functions are back to normal; ↓ Creatine levels in the blood and ↑ Creatinine levels in the urine
• And to determine the feasibility of administration of medications (which can build up into toxic levels in the blood if the GFR is markedly decreased)
TUBULAR REABSORPTION TESTS
• Concentration tests are used to evaluate reabsorption capacity of the tubules
1. SPECIFIC GRAVITY – Influenced by the number and density of particles in a solution
2. OSMOLARITY – influenced by the number of particles in the solution
• PRINCIPLE OF FREEZING POINT DEPRESSION:
1 Osm or 1000 mOsm/ kg of water will lower the freezing point of water by 1.86 Celsius
• Used to determine the Osmolarity of urine
OBSOLETE TESTS
1. FISHBERG TEST – patient is deprived of fluid for 24hrs then urine SG is measured. (SG should be ≥1.026)
2. MOSENTHAL TEST – compares the day and night urine volume and SG
TUBULAR SECRETION & RENAL BLOOD FLOW
1. PAH TEST – (P-aminohippuric acid)
2. PSP TEST – (Phenolsulfonaphthalein)
• With no nutritional value; non-essential
• All these substances aren’t normally absorbed by the glomerulus, but it is secreted entirely by the renal tubules
• Both PAH and PSP tests are dye tests, if the renal tubules retain these, it is suggestive that there is a defect in the renal tubular secretion
ACIDITY AND ALKALINITY OF URINE
• pH - Important in the identification of crystals and determination of unsatisfactory specimens
NOTE
• NEGATIVE TO TRACE concentration of bicarbonate in urine of healthy individuals [Show Less]