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RENAL FUNCTION
AUB MEDTECH by Dr Sonnie P. Talavera
The Excretory System Organs:
Kidney
Ureter
Urinary bladder
Urethra
Kidney
Retroperitoneal bean-shaped organ in superior lumbar region
Extends from vertebral levels T12 superiorly and L3 inferiorly
Kidney Internal anatomy:
Cortex Superficial
Medulla deeper, consists mainly of pyramids
Pelvis formed by the union of 2 or major calyses
Major calyx is formed by the union of 2 or more minor calyses
A minor calyx receives urine from several renal papilla
Nephron
Structural and functional unit of the kidney
1 – 1.5 million for each kidney
2 Types of nephron
Cortical 85%
Juxtamedullary 15%- concentration of urine
Nephron Parts:
Glomerulus
a high pressure tuft of capillaries, with fenestrations or openings
Renal tubule
1. Glomerular or Bowman’s capsule
2. Proximal convoluted tubule (PCT)
3. Loop of Henle
4. Distal convoluted tubule (DCT)
Nephron
Layers of the Bowman’s capsule:
Outer parietal layer composed of simple squamous epithelium
Inner visceral layer composed of branching podocytes which cling to
the glomerulus.
branches of the octopus-like podocytes terminate into pedicels or foot processes; in between these are openings called filtration slits or slit pores
Renal Corpuscle
Renal or Malphigian corpuscle
glomerulus plus Bowman’s capsule
Juxtaglomerular apparatus
consists of juxtaglomerular cells of the afferent arteriole and the macula densa of the DCT
important in blood pressures regulation
Renal Physiology
Renal Physiology Mechanism of Urine formation
Renal blood flow
Glomerular filtration
Tubular reabsorption
Tubular secretion
Renal blood flow
Received 25% the pumped by the heart
Afferent arterioles
Efferent arterioles- smaller size
Peritubular arteries
Near PCT and DCT- immediate reabsorption
Vasa recta
loop of Henle in juxtamedullary nephron
Major exchange of water and salt between blood and medullary interstitium
Maintain osmotic gradient(salt concentration)
Renal Function This exchange maintains the osmotic gradient
[salt concentration ] in the medulla, which is necessary for renal concentration.
Based on average body size of 1.73 m2 of surface
total renal flow is approximately 1200 mL/min
total renal plasma flow ranges to 600 to 700 mL/min
Normal values for renal blood flow and renal function tests depend on body size
Glomerular filtration glomerulus consist of a coil of approximately eight capillary lobes
referred to the collectively as the capillary tuft
serves as noun selective filter of plasma substances with molecular weight of less than 70,000, several factors influence the actual filtration process. cellular structure of the capillary walls and Bowman’s
capsule, hydrostatic and oncotic pressures feedback mechanisms of the rennin angiotenisn-
aldosterone system. RAAS
Glomerular Filtration
This process involves passing the blood through layers of filtration barrier/membrane which includes the following:
Glomerular endothelial cell
Basement membrane
Epithelial cells of Bowmann’s capsule
The liquid that will result from filtration of blood is termed glomerular filtrate
Glomerular filtration Cellular Structure of the Glomerulus Capillary wall membrane
containing pores and are referred to as fenestrated that increase capillary permeability but do not allow the passage of large molecules and blood cells.
basement membrane [ basal lamina ]
visceral epithelium of Bowman’s capsule. filtration slits formed by the intertwining foot process
of the prodocytes of the inner layer of Bowman’s capsule.
Glomerular Pressure hydrostatic pressure smaller size of the efferent arteriole and the
glomerular capillaries enhances filtration
overcome the position of pressures from the fluid within Bowman’s capsule and the oncotic pressure of unfiltered plasma proteins in the glomerular capillaries.
Forces acting on Glomerular Filtration
Glomerular hydrostatic pressure Is the chief force pushing water and solutes across the
filtration membrane
Glomerular osmotic pressutre Opposes filtration; resulting from attractive forces
exerted by the proteins in the glomeruli
Capsular hydrostatic pressure Opposes filtration; force exerted by the fluid in the
Bowman’s capsule
Glomerular Pressure hydrostatic pressure
By increasing or decreasing the size of the afferent arterioles when blood pressure at relatively constant rate regardless of fluctuations in systemic blood pressure.
Glomerular Pressure hydrostatic pressure blood pressure drops
dilation of the afferent arterioles and constriction of the afferent arterioles when prevent as marked decrease in blood flowing through the kidney
increase in blood pressure
constriction of the afferent arterioles to provent overfiltration or damage to the glomerulus.
Renin-Angiotensin –Aldosterone System responds to the changes in blood pressure
and plasma sodium content that
monitored by the juxta glomerular apparatus,
juxtaglomerular cells in the afferent arteriole
macula densa of the distal convoluted tubules.
RAAS Low plasma sodium
---decrease water retention
--- decrease overall blood volume and blood pressure.
--- Inc . Renin ( juxtaglomerular cells)
---reacts angiotensinogen to produce the angiotensin I (blood)
RAAS --- reacts with angiotensin converting enzyme
[ ACE ] changes is to angiotension II(lungs)
---. vasodilation of the afferent arterioles , and constriction of the efferent arterioles
--- stimulating reabsorption of sodium (proximal convoluted tubules)
---release of aldosterone (adrenal cortex) and antidiuretic hormone ADH (hypothalamus)
Renin-Angiotensin –Aldosterone System glomerular mechanisms, every minute
approximately 120mL of water-containing low molecular weight substances.
Analysis of the fluid as it leaves the glomerulus shows the filtrate to have a specific gravity 1.010 and confirms that is chemically an ultrafiltrate of plasma.
Renal Clearance
General Clearance Formula in mL/min =
Urine substance in mg/dL x Volume in mL/min Serum substance in mg/dL
Clearance in mL/min/std. surface area =
Urine substance x Urine Volume x 1.73m2 Serum Substance A
Renal Clearance
Creatinine Clearance = denotes GFR
Urine Creat in mg/dL x Urine Volume in mL/min Serum Creat in mg/dL
Urine Creat x Urine Volume x 1.73m2 Serum Creat 1440 A
Where 1440 = number of minutes/24 hrs
1.73m2 = BSA of an average normal person
A = BSA from a normogram
Renal Clearance
Estimated Creatinine Clearance
Cockcroft & Gault (1976) with correction for age and
weight; results reported in mL/min
Males = (140-age) x Weight in kg
(72 x Serum Creat in mg/dL)
Females = (140-age) x Weight in kg
(0.85 x Serum Creat in mg/dL)
NV males 90-139 females 80-125
slight impairment 52--62.5 -- moderate impairment 28 – 42
mild impairment 42–52 -- severe impairment < 28
Renal Clearance
Renal Failure Index (RFI) =
Urine Na in mEq/L x Serum Creatinine in mg/dL Urine Creatinine in mg/dL
Interpretation
RFI <= 1: prerenal azotemia
RFI =1-3: less definitive but usually indicates tubular necrosis
RFI >= 3: acute tubular necrosis
Tubular Re-absorption The process of returning needed substances from the
filtrate in the tubules to the capillary blood.
Can be active or passive depending upon the substance to be reabsorbed
The PCT is the most active segment of the tubule in this process; most of the nutrients, 80% of water and Na ions, and the bulk of actively transported ions are reabsorbed here
Re-absorption of additional Na ions and water occur in the distal convulated tubule (DCT) and collecting tubule (CT) and is controlled by aldosterone and (antidiuretic hormone) ADH respectively
Tubular Reabsorption The body cannot lose 120mL of water-
containing essential substances every minutE
PCT cellular transport mechanism--- reabsorbing essential substances and water.
Tubular Reabsorption Reabsorption Mechanism
For active transport to occur the substance to be reabsorbed must combine with a carrier protein contained in the membranes of the renal tubular cells
Active transport is responsible for the rebsorption of glucose, amino acids, and salts in the proximal convoluted tubul, chloride in the ascending loop of Henle, and sodium in the distal convoluted tbule.
Tubular Re-absorption PCT
is the most active segment of the tubule in this process
most of the nutrients, 80% of water and Na ions, and the bulk of actively transported ions are reabsorbed here
Tubular Re-absorption Re-absorption of additional Na ions and
water occur in the distal convulated tubule (DCT) and collecting tubule (CT)
controlled by aldosterone and (antidiuretic hormone) ADH respectively
ACTION OF THE RAAS Dilation of the afferent arteriole and constriction
of the efferent arteriole Stimulation of sodium reabsorption in the
proximal convoluted tubule Triggers the adrenal cortex to release the sodium
retaining hormone, aldosterone, to cause reabsorption of sodium and excretion of potassium in the distal convoluted tubule and collecting duct
Triggers release of anti-diuretic hormone by the hypothalm8us to simulate water re-absorption in the collecting duct
TUBULAR REABSORPTION Passive re-absorption of water takes place in all
parts of the nephron except the ascending loop of Henle
Urea is passively reabsorbed in the proximal convoluted tubule and the ascending loop of Henle
passive reabsorption of sodium accompanies the active transport of chloride in the ascending loop filtrate concentration exceeds the maximal
reabsorptive capacity [ tm ] of the tubules, and the substance begins appearing in the urine.
The plasma concentration as which active transport stop is termed the renal threshold
glucose, the renal threshold 160 to 180mg/dl
Tubular Concentration begins in the descending and ascending
loops of Henle(high osmotic gradient of the renal medulla). Water is removed by osmosis in the descending
loop of Henle sodium and chloride are reabsorbed in the
ascending loop selective reabsorption process is called the
countercurrent mechanism maintain the osmotic gradient of the medulla.
Tubular Concentration prevent dilution of the medullary
interstium by the water reabsorbed from the descending loop.
concentration of the filtrate( ascending loop)--- low due to reabsorption of salt not water
Tubular Concentration Collecting Duct concentration
final concentration of the filtrate
re-absorption of waters distal convoluted tubule and collecting duct depends on the ff
osmotic gradient in the medulla
hormone vasopressin [ antidiuretic hormone [ ADH]
promotes a low volume concentrated urines.
Tubular Secretion Is a means of adding substances to the filtrate
from the blood or the tubule cells
Can be passive or passive
Tubular Secretion Important
1. eliminating urea, excess ions and drugs
1. maintaining the acid-base balance of the blood
inc body hydration--- dec ADH--- inc urine volume
dec body hydration --- inc ADH --- dec urine volume
Tubular Secretion substances are removed from the gloremural
filtrate and returned to the blood
passage of substances from the blood in the peritibular capillaries to the tubular filtrate
major site is the proximal convoluted tubule.
Acid-Base Balance maintain the normal blood pH of 7.4
blood must buffer and eliminate the excess acid formed by dietary intake and body metabolism
buffering capacity of the bloods depends on bicarbonate [ HCO-] ions that is returned to the blood
secretion of hydrogen ions combine with the filtrate causes return of bicarbonate ion to the plasma
100% reabsorption of filtered bicarbonate --- proximal convoluted tubule hydrogen ion combines with a filtered phosphate ions hydrogen ion is accomplished through their reaction with
ammonia, in the proximal convoluted tubule ammonia is produced from the breakdown of the amino acid glutamine.
Metabolic acidosis or renal tubular acidosis
Glomerular Filtration Tests measure the filtering capacity of the
glomeruli
clearance test, rate at which the kidneys are able to remove a filtratable substance from the blood.
Stability the substance in urine during a possible 24-hour collection period consistency of the plasma level
substances availability to the body
availability of test for analysis of the substance.
Clearance Tests A presents the use of urea as a test substance
from glomerular filtration has been replaced by the measurement of other substances including
Creatinine
Inulin
beta 2 microglobulin
cystatin C
radioisotopes
Inulin Clearance Inulin, a polymer of fructose extremely stable substance that is not reabsorbed or
secreted by the tubules exogenous-- not a normal body constituent infused constant rate throughout the testing period
a test that requires an infused substance is termed an exogeneous procedure
seldom the method of choice if suitable test substance is already present in the body.
inulin was the original reference method for clearance test, it is currently not used for glomerular filtration testing.
Creatinine clearance Waste product of muscle metabolism
Employed as test substance for GFR Glomerular filtration rate in clinical laboratory
Disadvantage Some are secreted in the tubule, thus secretion increase in in
blood level rise Chromogen in human blood reacts in chemical analysis Gentamycin, cephalosphorin and cimetidine inhibit tubular
secretion--- falsely low serum value Bacteria breakdown urinary craeatinine kept long in room temp Heavy meat diet can affect value during 24hour collection
It is not reliable indicator in patient suffering from muscle wasting
Creatinine clearance Procedure
Greatest error --- use of improperly timed urine specimen
GFR—ml/min (determine the number of ml of plasma from which clearance substance is completely removed during 1minute V—urine volume in ml /min
U--- urine creatinine concentration in mg/dl(U)
P--- plasma creatinine concentration in mg/dl(U)
C= UV or CP=UV P Example 24hr specimen 1440ml, serum creatinine
1mg/dl, urine creatinine 120mg/dl V= 1440m = 1ml/min __________________________ 60min x24 = 1440min C= 120mg/dl x 1ml/min = 120ml/min ___________________________ 1mg/dl
Average individual 1.73 m2 body surface has a plasma filtrate of 120ml
Normal clearance 120ml/min
Male 107- 139ml/min
Female 87- 107ml/min
Normal creatinine plasma 0.5- 1.5mg/dl
depends on size and muscle mass
Lower in older people
Adjustment for clearance test for body size
UV 1.73
C= ____ x ____
P A
A—actual body size
Log A= (0.425 x log weight) + (0.725 x log weight) - 2.144
Or it may be obtained from nomogram
Clinical Significance
Determine the number of functioning nephrons and functional capacity of nephron
Determine
Extent of nephron damage in renal disease
Monitor effectiveness of treatment
Determine feasibility of administering medicatioN
Calculated Glomerular Filtration Estimates
Provides estimates of GFR based on serum creatinine without urine creatinine
Creatinine clearance is not useful in diagnosing Early renal disease
Cockfort and Gault--- most frequently used formula
Used for document eligibility and evaluating patient placement on kidney transplant list
(140- age) (weight in kg)
C cf = _______________________
72 x serum creatinine mg/dl
The result are multiplied by 0.85 for female patient
There is a modification in the original formula substitute IDEAL BODY WEIGHT and ADJUSTED BODY WEIGHT.
IBD Male--
50kg + 2.3kg for each inch height over 60 inches
Female– 45.5kg + 2.3kg for each inch height over 60 inches
AjBW IBW + 0.3 (ABW- IBW)
Modification of Diet in Renal Disease MDRD
Ethnicity
BUN
Serum Albumin
GFR= 170 xserum cxreatinine x age x 0.822 (if patient is female)x 1.1880 (if patient is black) x BUN x serum Albumin
Note: that the calculation can be performed automatically byt instrument performing serum creatinine
125I-iothalamate
Provides glomerular filtration by measuring plasma disappearance of the rsadioactive material and enable visualization of filtration in one or both kidneys
125I-iothalamate
Provides glomerular filtration by measuring plasma disappearance of the rsadioactive material and enable visualization of filtration in one or both kidneys
B2microglobulin
Molecular weight 11,800---
dissociate from human leukocyte antigen at a constant rate and rapidly removed in the plasma by glomerular filtration
sensitive method—enzyme immunoassay EIA
more sensitiveindicator of decrease GFR
not reliable in patient with history of immunologic disorder or malignancy
cystatin C small protein with mol wt 13,359 produced in constant rate in all nucleated cell readily filtered by glomerulus and reabsorbed
and broken downby renal tubular cell immunoassay recommended pediatric DM patient Elderly critically ill patient
Tubular Re-absorption Ability to treabsorb essential salt and water that
has been not selectively filtered by glomerulus Also known as Concentration Test Ultrafiltrate—1.010 SG and urine has a higher
SG But urine concentration is largely determined by
body state of hydration and normal kidney only reabsorb water necessary to preserve adequate supply of body water
Fishberg Mtd
Pt are deprived of fluid for 24 hours
Mosenthal Mtd
Compared vo lume and SG of day and night urine sample
SG measurement is most useful as screening procedure ans quantitative measurement of renal concentrating ability is best assessed by OSMOMETRY
IMPORTANT
Pt with normal concentrating ability if deprived of fluid for 16hrs---1.025
Ff overnight water deprivation an osmolarity of 800mOsm or above--- NORMAL concentrating abilty
OSMOLARITY Specific gravity Depends on the number of particle present in
asolution and density of this particle Osmolarity Affected only the number of particle Urea MW60 Sodium MW23 Chloride MW 35.5
Osmole is define as 1 gram molecular weight of a substance divided by the number of particle into which it dissociates.
Glucose MW180 (180g /osmole)
NaCl MW58.5
Osmolal soln of glucose has 180g of glucose dissolved in 1 kg of solvent.
Osmolar soln of glucose has 180g of glucose dissolved in 1 liter of solvent.
But in clinical laboratory, practically use milliosmole mOsm
Colligative property of solute in a solvent soln
Lower freezing point
Higher boiling point
Increase osmotic pressure
Lower vapor pressure
Note: Number of the particle in a sample can be determined by comparing colligative property with that of pure water
Freezing Point Osmometer
1ST principle incorporated in clinical laboratory
Determine freezing point of soln by supercooling a sample by -27 C--- vibrated produces crystallization
1mol(1000mOsm) of an anionizing substance dissolved in 1kg of water is known to lower freezing point of 1.86C
Reference Std for Clinical Osmometer—known NaCl
Vapor Pressure Osmometer
Actualmeasurement of dew point (temp at which water vapor condenses to liquid)
Depression of dew point temp by solute parallels th dec in vapor pressure
Uses microsample of 0.01ml
Technical
Erroneuos result
Lipemic serum
Lactic acid
Ethanol esp for vapor pressure osmometer
Clinical significance
Evaluating concentrating ability
Monitor course of renal disease
Monitor fluid and electrolyte therapy
Evaluating secretion and renal response to ADH
Normal serum Osmolarity--- 275- 300mOsm
Vaue can range 50-1400mOsm
Normal random 1:1
Controlled fluid intake 3:1
Fluid intake and injection of ADH can differ DM from Diabetes Insipidus
If with ADH injection for Diabetes Insipidus--- failure to achieve 3:1 ratio mean the collecting duct does not have functionl receptor for ADH
Free Water Clearance
Deytermined by calculating OSMOLAR CLEARANCE
CmOsm= UmOsmV or CmOsm PmOsm=UmOsm V
PmOsm
Example
CmOsm= 600mOsmx 2 = 4
300mOsm
C H2O= 2- 4.0 = -2 free water (indicates how much water must be cleared each minute to produce urine of
the sameosmolarity as of plasma)
-2 --dehydration
0 ---no renal concentration or dilution
+2---excess water
Tubular Secretion
Renal Blood Flow Test
Bothe are closely related because the total renal blood flow through the nephron is measured by a substance that is secreted
Clinical Significant---impired tubular secretory ability and decrease renal blood flow
PAH p- aminohippuric acid test—most common
Principle same with clearance test
Measures exact amount of blood flowing through the kidney using a substance that is completely removed from the blood through the peritubular capillaries at PCT
Exogenous but meets criteria and loosely bound to plasma protein
CPAH(ml/min)= Umg/dl PAH x V ml /min urine
Pmg/dl PAH
PAH p- aminohippuric acid test—most common
Principle same with clearance test
Measures exact amount of blood flowing through the kidney using a substance that is completely removed from the blood through the peritubular capillaries at PCT
Exogenous but meets criteria and loosely bound to plasma protein
Effective Renal Plasma Flow 600-700ml/min
Effective Renal Blood Flow 1200ml/min
Effective—bec approximately 8% of renal blood flowdoes not come in contact with functional nephron
Nuclear Medicine—radioactive Hippurate
Titratable Acidity/ Urinary Ammonia
Acidity of urine depends
Tubular secretion of acid
Production and secretion of ammonia by DCT
Normal--- 70meq/day
titratable acid (H+)
hydrogen phosphate ion(H2PO4-)
ammonium ion (NH4+)
diurnal variation in urine acidity
alkaline tides appears shortly after arising and postprandiallyat approximately 2pm and 8pm
lowest pH at night
METABOLIC ACIDOSIS
Impaired secretion H+ by PCT and NH3+ by DCT
DEFECTIVE FUNCTION measures
Urine pH
Titratable acid
Urinary ammonia
Specimen --- fresh or -preserved urine collected with 2hours interval from patient primed with an acid load of oral ammonium chloride---and by titrating the amount of free H+----- TOTAL ACIDITY
Ammonium can be measured by difference of Titratable acid and Total acidity
Regulation of Urine Concentration and Volume Urine osmolarity ranges from 50-1200 mosm
The hyperosmolarity of the medullary fluid ensures that the urine reaching the DCT is dilute (hypo-osmolar)
Regulation of Urine Concentration and Volume In the absence of ADH
the dilute filtrate is allowed to pass the CT a dilute urine is formed
When blood levels of ADH rise the permeability of the DCT and CT to water
increases, more water is reabsorbed, less is left with filtrate
hence small volume of more concentrated urine is formed
Renal Clearance
is the rate at which the kidneys clear the plasma of a particular solute
Urinary Bladder A smooth, distensible muscular sac, lying
posterior to the pubic symphysis, which functions to store urine
Has two inlet (ureters) and one outlet (urethra) which form the vesical trigone
Fig. 18.17
The urinary bladder
Hollow pyramid shaped organ located in the pelvis
Lined with transitional epithelium With thick detrusor muscles Micturition reflex resulting from the
distension of the organ Impulses are transmitted to the sacral
parasympathetic segments to initiate urination
Urinary Bladder
Slide 15.21b
Trigone – three openings
Two from the ureters
One to the urethrea
Figure 15.6
Ureter 25 to 30 cm slender muscular tube that
conveys urine, through peristalsis, from the kidney to the urinary bladder
Ureter 3 Anatomical Constrictions of the Ureter where
stones can be arrested:
Ureteropelvic junction
Bifurcation of common iliac vessels near the pelvic brim
Vesico-ureteral junction
The Ureter Left and right
A long slender tube that propels urine from the kidney to the urinary bladder
With smooth muscles and transitional epithelium
With innervations from the sympathetic and parasympathetic
Urethra A thin walled muscular tube draining urine from the
urinary bladder to body exterior
With two sphincters that regulate the passage of urine:
Internal urethral sphincter located near the bladder, involuntary
External urethral sphincter located at the urogenital diaphragm level, voluntary
In females, the urethra is 3-4 cm long and conducts only urine; in male, 20 cm long and conducts both urine and semen
Urethra
Tube extending from the urinary bladder to the external urethral orifice 1 ½ inches in females
3 parts in Males 1. Prostatic urethra- most dilatable
2. Membranous urethra- least dilatable and shortest
3. Penile urethra- longest
Urethra Gender Differences
Slide 15.24b
Function
Females – only carries urine
Males – carries urine and is a passageway for sperm cells
Micturation Also called urination, a process of emptying the
bladder
Micturation reflex: Stretching of the bladder wall by the accumulating
urine (200mL and above)
Sensory impulses sent to the sacral segment of the spinal cord
Motor impulses conducted to the detrussor muscles via the parasympathetic nerves
Contraction of the detrussor muscles and relaxation of the sphincters urine results to voiding of urine
Renal Failure A very serious but uncommon problem
Kidneys are unable to do its physiologic functions such as concentrating urine, removing nitrogenous wastes from the blood, and maintaining electrolyte and pH balance of the body
Causes: drugs, toxic chemicals, infections, hypertension, DM, etc.
Fluids, Electrolytes and Acid Base Balance
Body Fluids The human body is 45% to 75% water. The
amount of body water depends on the following:
1. Age of the individual
2. Sex
3. Amount of adipose tissue
Total body water (TBW)
Total body water (TBW) is divided into compartments
Intracellular fluid (ICF)
Found within cells
25L, 40% of body weight
Total body water (TBW)
Extracellular fluid (ECF)
15 L, 20% of body weight
Subdivided into
interstitial fluid
intravascular fluid (or the plasma)
• Solutes dissolved in the body fluids are electrolytes and non electrolytes (e.g. proteins).
• Intracellularly, there are abundant potassium, magnesium, phosphates and proteins
• extracellularly, there are abundant sodium, chloride and bicarbonate.
Note
Fluid exchanges
Fluid exchanges between these compartments are regulated by several forces
Hydrostatic pressure
refers to the pressure which tends to push fluid out of the intravascular compartment
Osmotic pressure
Refers to the pressure exerted by the solutes which tend to attract water
Fluid exchanges
Water intake must be equal to water output in order to maintain proper hydration.
Water intake depends upon the habit of the individual; but is typically 2500ml/day in adults
Sources of body water
Ingested fluids (60%)
e.g. drinking water, juices
Moist foods (30%)
Cellular metabolism (10%)
a.k.a. water of oxidation or metabolic water
Sources of body water
Water output, on the other hand occurs via several routes:
Exhaled through the lungs in the form of water vapor
Diffuses through the skin (28%)
Thru perspiration (8%)
Goes with feces (4%)
Goes with the urine (60%)
Disorders of water balance: Dehydration
occurs when water loss exceeds water intake
manifested as
Thirst
dry skin
decreased urine output.
Disorders of water balance: Edema
abnormal accumulation of fluid in the interstitial space
may be secondary to
increased hydrostatic pressure (e.g. congestive heart failure)
decreased in osmotic pressure (e.g. decreased plasma proteins)
lymphatic obstruction
Electrolyte Imbalance Electrolyte include salts, acids and bases; but
in this topic electrolyte balance pertains primarily to the salt balance in the body
Electrolyte Imbalance Salts are important in cellular functions
e.g. nerve excitability
secretory activity of the gland
controlling fluid movements
Electrolyte Imbalance Sources of salts:
Ingested food
Ingested fluid –
e.g. water and juices
Metabolism
Electrolyte Imbalance Routes of electrolyte losses:
Perspiration or sweat
Through the GIT in the form of feces of vomitus
Urine
Sodium salts
(NaCl, NaHCO3) account for 90-95% of all solutes in the ECF. exert the bulk of ECF osmotic pressure (280mosm of
the 300mosm/L) control water volume and distribution in the body.
Note: Remember, water follows salt; so, movement of
sodium salt is always linked to movement of water. Sodium-water balance is inseparably linked to blood pressure and blood volume. This entails a variety of regulatory mechanisms.
Renal Clearance
Functional Excretion of Sodium (FENa) Na Clearance x 100 or Creatinine
Clearance
Urine Na x Serum Creat x 100 Urine Creat x Serum Na
FE-Na < 1% FE-Na > 1%
• 10% of cases of
nonoliguric ATN
• pre-renal azotemia
• acute glomerulonephritis
• early acute urinary tract
obstruction
• early sepsis
• most cases of ATN
• after diuretic administration
• pre-existing chronic renal
failure
• diuresis due to mannitol,
glycosuria, bicarbonaturia
Serum Osmolality
In mOsm/kg H20 NV 275-300 2Na + BUN(mg/dl) + Glucose(mg/dl)
2.8 18 if glucose and BUN are in mmol/L, do not use the
factors (18 & 2.8) anymore
In mOsm/L (Na x 1.86) + (Glu x 0.056) + (BUN x 0.36) + 9
(1.86xNa) + Glucose(mg/dL)+BUN(mg/dL) + 9 18 2.8
in SI units = (1.86 x NA) + glucose in mmol/L + BUN in mmol/L + 9
Anion and Osmolal Gap
Anion gap =
Na – (HCO3 + Cl) NV: 10 + 2 or 8-16mEq/L
(Na + K) – (Cl + HC03) NV: 10-20
Osmolal gap =
mathematical difference between measured and calculated osmolality
NV: <10 in healthy persons (0-6)
Aldosterone
major controller
Responsible for 75-80% of sodium reabsorbed in the proximal convoluted tubule
Triggered by the rennin-angiotensin- aldosterone system
which is mediated by the juxtaglomerular
apparatus of the renal tubules
Aldosterone
Increased secretion is hyperaldosteronism
e.g. Cushing disease
Decreased secretion is hypoaldosteronism
e.g. Addison’s disease.
Cardiovascular system baroreceptors
Found in the heart and the large vessels (aortic sinus, carotid sinus)
Provides information on the “fullness” or volume of the circulation
Stimulated when stretched
Antidiuretic hormone Responsible for reabsorbing water in the distal
segments of the kidney tubules
Factors that trigger release: decreased fluid intake, prolonged fever, excessive sweating, vomiting or diarrhea, severe blood loss, burns
Atrial natriuretic factor
Released by cells in the atria of the heart in response to increased BP
Effects:
systemic vasodilation
inhibits release of rennin, aldosterone and ADH
Others
Estrogen due to its chemical similarity to aldosterone, it
increases Na reabsorption
Progesterone blocks the effect of aldosterone; thereby, decreasing
Na reabsorption
Glucocorticoids such as cortisol and hydrocortisol exhibit aldosterone
like effect
Regulation of Potassium Balance Potassium (K) is the chief intracellular cation.
It is important in neuromuscular activity and protein
synthesis.
Relative ECF-ICF K+ concentration directly affects the resting membrane potential, a slight change has profound effects on the neurons and muscle cells.
Regulation of Potassium Balance Hyperkalemia
Increases excitability of the cells by increasing depolarization
e.g. cardiac arrhythmia
Hypokalemia Decreased K+ in the ECF, causes non
responsiveness of the cells to stimuli due to hyperpolarization
e.g. cardiac arrest
Regulation of Potassium Balance Factors that regulate blood levels of
potassium:
Intracellular level of K+ in the kidney tubules
Aldosterone
Blood pH
Regulation of other Ions Calcium (Ca) concentration is regulated primarily
by two hormones: Parathyroid hormone
which is secreted by the parathyroid glands increases blood Ca by targeting the bones, intestines and
kidneys
Calcitonin which is secreted by the parafollicular cells of the thyroid
gland decreases blood Ca by accelerating its deposition in the
bones and inhibiting bone resorption
Regulation of other Ions Magnesium
is stored in skeleton (majority), cardiac muscles, skeletal muscles, and the liver.
Excretion is increased in increased levels of aldosterone
Chloride is the major anion accompanying sodium under
physiologic and slightly alkaline pH.
However, in acidosis, chloride is replaced by bicarbonate ions.
Regulation of other Ions
The concentrations of most anions in the plasma, not mentioned in the text, are regulated primarily by their transport maximums (“overflow” mechanism)
Acid-Based Balance Acids
are proton (H+) donors
strong acids dissociate completely in a solution (e.g. HCl);
weak acids dissociate incompletely (e.g. H2CO3)
Bases
are protons acceptors
Acid-Based Balance The homeostatic pH of arterial blood ranges
from 7.35-7.45
higher than this range is alkalosis
lower is acidosis.
Acid-Based Balance Regulation achieved by regulating the H+ concentration of the body
fluids.
Chemical buffer system
Single or paired (weak acid + salt) sets of molecules that resists shifts in pH by releasing or binding H+
bicarbonate buffer system (important in both ECF and ICF) phosphate buffer system (important in ICF and urine) protein buffer system (most plentiful and powerful source both in
the plasma and in the cells) ammonia buffer system (act in the urine)
Acid-Based Balance Regulation Respiratory center in the brain stem
Eliminates volatile acids
Acidosis activates the respiratory center to increase respiratory rate and depth which eliminates CO2 and causes blood pH to rise.
Alkalosis depresses the respiratory center, resulting in CO2 retention and a fall in blood pH
Acid-Based Balance Regulation Renal mechanism Eliminates metabolic or fixed acids e.g.
phosphoric uric, and ketone bodies
Major long term mechanism for controlling acid-base balance, acts slowly but surely
Acts mainly by excreting H+ and conserving or generating new HCO3
Abnormalities of Acid-Base Balance
Respiratory acidosis
decrease in blood pH resulting from CO2 retention
e.g. drowning, coma
Abnormalities of Acid-Base Balance
Respiratory alkalosis
increase in blood pH resulting from rapid elimination of CO2 than its production
e. g. hyperventilation syndrome
Abnormalities of Acid-Base Balance
Metabolic acidosis
decrease in blood pH resulting from the accumulation of metabolic acids or rapid loss of H2CO3 in the urine
e.g. diabetic ketoacidosis, renal failure
Abnormalities of Acid-Base Balance
Metabolic alkalosis
increase in blood pH resulting from excessive H2CO3 levels in the blood or loss of acids
e.g. excessive intake of antacids, vomiting of gastric contents
CLINICAL CORRELATION
Recommended