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