Acid Base Balance

Objectives: Review buffers and respiratory control of acid-base balance Explain control of renal hydrogen sectretion and renal

reabsorption, production and excretion of HCO3

Acid base balance involves buffers w/c are substances that binds hydrogen or acid and base reversibly. Buffers are temporary binders of excess hydrogen ions or bicarbonate ions in the circulation.

Regulation of Acid-Base Balance involves the kidneys, lungs, and the buffers

HCO3 Buffer System

enzyme: carbonic anhydrase (available in red blood cells of kidneys and lungs)

take charge of binding of hydrogen ion in the systemic circulation

hydrogen is to be excreted and carbon dioxide is to be blown off carbonic acid: weak and volatile acid that can be buffered in 2

wayso can dissociate into water and carbon dioxide using

carbonic anhydrase. This process occur in the lungs.o can dissociate into hydrogen ion and

bicarbonate(reabsorbed in renal tubules). This process occur in the kidneys.

e.g HCl H + HCO3 H2CO3 H2O + CO2 (lungs)if we have a strong acid such as HCl, HCl dissociates and releases hydrogen ion. This hydrogen ion would bind with bicarbonate to form carbonic acid. Carbonic acid will proceed to form carbon dioxide and water. Carbon dioxide is blown off to the lungs increasing respiratory rate in an attempt to release excess carbon dioxide.

Sometimes it is difficult to differentiate patients with respiratory alkalosis and respiratory acidosis basing it only on their respiratory rate(RR). In respiratory alkalosis there is also an increase in RR but this is due to neurologic factors. Acidotic respiration also increase RR to decrease CO2

Increase in hydrogen ion concentration increase RR to blow off carbon dioxide to decrease partial pressure of CO2. If pCO2

is low there will be a negative feedback mechanism w/c will gradually decrease the concentration of hydrogen ions thereby decreasing RR. It autocorrects.

In alkalosis, the alveolus will decrease RR to conserve acid. Increasing pCO2 to bring back pH of body to normal.

Respiratory Center regulates removal of CO2 from the ECF acts within a few minutes to eliminate CO2, and therefore

H2CO3 from the body by increasing rate of respiration(during acidosis), lungs

remove CO2 from plasma by decreasing respiration(during alkalosis), lungs elevate pCO2

*the kidneys are the main controller of acid base balance but it takes longer time for them to compensate

Renal Control of Acid-Base Balance secretion of hydrogen reabsorption of filtered bicarbonate

o body conserve bicarbonate in order for it to react with hydrogen ions that are produced during cell metabolism

production of new bicarbonateo phosphate buffer systemo ammonia buffer system

Renal control kidneys role is to remove non volatile acids daily production of acids – 80 mEq are non volatile acids

(can’t be excreted by lungs) thus excretion is renal Kidneys prevent loss of bicarbonates that bind to extra acid to

buffer acid production Daily HCO3 filtered by kidneys: 4320 mEq (180 L/day x 24

mEq/L). All are reabsorbed back into the circulation to conserve this primary buffer system of the ECF.

bicarbonate just titrate the normal acid secretion, it takes care 4320 mEq/L of hydrogen ion in a 1:1 ratio

80 mEq/L excess must be excreted via the tubules

Balance Sheet of HCO3 and H+

Bicarbonate Hydrogen ions4320 mEq/L 4320 mEq/L + 80 mEq/L4320 mEq/L reabsorbed in tubular fluid

4400 mEq/L secreted in tubular fluid

alkalosis: there is excess of bicarbonate ion, kidney fail to reabsorb all the filtered HCO3, thus increasing excretion of HCO3 to bring back H+ to normal

acidosis: there is increase in H+, kidneys reabsorb all the filtered bicarbonate and produce new bicarbonate (from phosphate and ammonia buffer system) that is added back to the ECF to reduce H+ back to normal

Alkalosis is better controlled, because extra bicarbonate is just excreted. In acidosis, the kidneys reabsorb bicarbonates and at the same time produce new bicarbonates.

Acid-Base Balance

Buffers

lungs kidneys

Secretion of H+ ions for each HCO3 reabsorbed, there must be a H+ secreted proximal tubule : 80 to 90% HCO3 reabsorbed, H+ secreted thick ascending limb : 10% HCO3 reabsorbed, H+ secreted distal tubule, collecting duct : reabsorb the rest (fine tuning)

4320 mEq/day bicarbonate is filtered by the glomerulus, 80% -90%(85%) is brought back to circulation and equal to that is 80-90% of hydrogen ion secreted in the proximal tubule. In the thick ascending limb 10% of bicarbonate are reabsorbed, and 10% of hydrogen ions are secreted

intercalated cells are present in the late distal and the collecting tubule. if the circulation detects that there is more hydrogen ions than that of bicarbonates the body secretes more hydrogen ions than bicarbonates. This is the reason for acidic urine.

in the proximal tubule(tubular cells):diffusion of CO2 towards the cell (w/c come from the tubule or as a product of metabolism) When CO2 enter it combines w/ water and w/ help of carbonic anhydarase to form carbonic acid

carbonic acid freely dissociates into bicarbonate ion and hydrogen ion. And since bicarbonate is to be reabsorb it follows ultrafiltration or bulk flow to enter peritubular capillaries.

hydrogen leave the cell using Na-H+ counter transporter. This protein transpoter is powered by Na-K ATPase pump w/c create the negative luminal charge to let Na enter

hydrogen then binds with the bicarbonate that is present in the tubule to form carbonic acid. This carbonic acid dissociates again into CO2 and H+

Secretion of H+

late distal and collecting tubules have intercalated cells secretion of H+ is by primary active transport by HATPase in luminal side of intercalated cells to form maximally acidic urine

in the late distal tubule, there is the presence of HATPase transporter in the luminal membrane that take care of fine tuning of amount of acid to be excreted in urine every day.

when decreased pH in interstitial cells and increased acids in the interstitial cells is detected, HATPase will be facilated. Aldosterone also facilitate the activity of HATPase pump.

in the distal tubule, there is no longer bicarbonate ion in w/c the hydrogen ion will bind to so that the extra hydrogen will be excreted in urine. Hydrogen then becomes concentrated.

H+ can be increased 900 fold in the distal tubules decreases the tubular fluid to pH of 4.5 aldosterone stimulates secretion of H+

oversecretion of alsoterone causes excessive secretion of H+

into tubular fluid, thus consequently increased HCO3 added to the blood (causing metabolic alkalosis)

Other Buffers in Tubular fluid phosphate buffer system ammonia buffer system

Phosphate Buffer System important in tubular fluids because:

1. phosphate usually becomes concentrated in the tubules, thereby increasing the buffering power of the PO4 system

2. the tubular fluid usually has a considerably lower pH than the ECF, bringing the operating range of the buffer closer to the pK (6.8)

any excess in H+ can combine with HPO4= and other tubular

buffers to form H2PO4- excretes as sodium salt (NaH2PO4)

there is net gain of HCO3 generated in the tubular cells for replenishment of ECF stores of HCO3

Na-K ATPase pump at the basolateral side of the membrane is the source of energy

CO2 enters the cell to combine with water to form carbonic acid. Carbonic acid dissociates to bicarbonate ion and hydrogen ion. Hydrogen that is secreted in the lumen combine with phosphate buffer, w/c is for excretion, so that hydrogen and the phosphate buffer come out as a phosphate salt

Ammonia Buffer System composed of NH3 and NH4

glutamine (from liver) delivered to the kidneys is transported into the epithelial cells of the proximal tubule, thick ascending limb and distal tubule

glutamine is metabolized to ultimately form 2NH4+ and two

HCO3-

NH4+ is secreted into the lumen, via counter transport with

sodium, HCO3 reabsorbed (new bicarbonate)

when glutamine is metabolized it dissociates into 2 NH4+ and 2

bicarbonate ions. The 2 bicarbonate ions is reabsorbed to serve as a replenishment for bicarbonates used in the body.

the 2 NH4+ will be exchange with Na-NH4

+ . NH4+ combine with

Cl- and is excreted as ammonium chloride. It gives the ammoniacal odor of urine. The more ammoniacal smelling the urine the more acidotic is the person.

NH3 combine with hydrogen ion to form NH4. NH4

combine with Cl- to form ammonium chloride (excreted).

Acid –Base DisorderspH H pCO2 HCO3

Normal 7.4 40 nEq/L 40mmHg 24 mEq/LRespiratory AcidosisRespiratory AlkalosisMetabolic AcidosisMetabolic Alkalosis

in respiratory aciodsis : main problem is the increase in acid that is to be blown off so teh partial pressure of Co2 is increased. The tendency of the lungs is to hyperventilate and there would be a slight increase in bicarbonate level.

in respiratory alkalosis: main problem is the decrease in partial pressure of CO2. There would be slight decrease in HCO3

in metabolic acidosis : main problem is the loss of bicarbonate. pCO2 can be low or sometimes not affected. Compensation of the kidney is the production of new bicarbonate through the buffer system.

in metabolic alkalosis: main problem is increased bicarbonate. The compensation of the kidneys is to excrete excess bicarbonate ions.

Summary initial regulation of acid-base balance is through buffer

systems and respiratory function final regulation is exerted by the kidneys via changes in

hydrogen or bicarbonate levels respiratory imbalance is initiated by changes in CO2,

metabolic imbalance is due to bicarbonate changes compensatory mechanisms aim to return acid-base

parameters back to normal primary acid-base disorders are compensated by metabolic

changes, and vice-versa

Micturition, Diuretics and Kidney Diseases

fusion of collecting duct form the renal pyramid w/c drain into the renal calyses to the renall pelvis

from renal pelvis urine travels via peristalsis of the smooth muscles of the ureter to the urinary bladder

urinary bladder serves as a temporary storage site for urine. UB is made up of detrusor muscles w/c are interlaced with each other.

UB has 2 partso body: temporary storage site of urineo neck: continuous w/ urethra

bladder trigone: triangular structure

Urinary Bladder

a smooth muscle (detrusor muscle) chamber 2 parts

o body : where urine collectso neck : funnel-shaped extension of the body passing

inferiorly and anteriorly into the urogenital triangle and connecting with the urethra (lower part is called posterior urethra)

Trigone : small triangular area on the posterior wall of the bladder. The 2 ureters enter the bladder at the uppermost angles of the trigone.

Posterior urethra : lowermost apex of the trigone; 2-3 cm long; composed of detrusor muscle interlaced with large amount of elastic tissue called the internal sphincter (always tightly sealed)

internal sphincter : keeps bladder neck and posterior urethra empty of urine, prevents emptying of the bladder until the pressure in the main part of the bladder rises above a critical threshold

urogenital diaphragm : a layer of muscle called external sphincter, a voluntary skeletal muscle

o under voluntary control of the nervous systemo used to consciously prevent urination even when

involuntary controls are attempting to empty the bladder

innervations of UB: smooth muscles tend to stretch in response to increased amount of urine

stretch is detected by pelvic nerve (from S2 & S3). The pelvic nerve has a sensory component and motor component

sensory component detects stretch of urinary bladder and sends signal to sacral plexus

other component (motor) innervates the bladder neck (post. urethra) w/c also innervate the internal sphincter (both therefore are parasympathetic)

a separate nerve, the pudendal nerve, innervates the external sphincter. It is controlled by pons and cerebrum for conscious control of urination.

Micturition

process by which the urinary bladder empties when it becomes filled

2 main steps1. bladder fills progressively until the tension in the

walls rises above a threshold level (threshold is different from person to person)

2. a nervous reflex (micturition reflex) occurs or a conscious desire to urinate to empty the bladder (internal sphincter remains contracted until external sphincter dictates that one can urinate)

an autonomic spinal cord reflex, may be inhibited or facilitated by the cerebral cortex or brain stem

Uterosacral Reflex pain impulses cause sympathetic reflex back to the kidney to

constrict the renal arterioles, thus decreasing urine output from the kidney (e.g when ureter is blocked by a stone the ureters contracts forcefully in an attempt to bring down the stone to the bladder)

important for preventing excessive flow of fluid into the pelvis of the kidney with blocked ureter

Micturition Reflex micturition contractions : caused by stretch reflexes initiated

by the sensory stretch receptors in the bladder wall specially at the posterior urethra

micturition reflex is a single complete cycle of1. progressive and rapid increase of pressure2. a period of sustained pressure to the basal tone of

the bladder3. return of pressure to the basal tone of the bladder

if the bladder fills, there is contraction, then the body is able to adapt to it, and then the bladder fills a little further so on and so on....until one urinates

all of the urine in the urinary bladder is voided out (but 5-10 ml of urine can stay in bladder and these are the urine that lines the bladder wall)

if not all the urine are excreted, then there would be an increased likelihood for urinary tract infection

residual volume of urine : less than 5 ml

Voluntary urination

voluntary contraction of abdominal muscles increases pressure in the bladder w/c allows extra urine to enter the bladder neck and posterior urethra under pressure and eventually stretching the bladder walls

stimulation of stretch receptors would excite micturition reflex w/c simultaneously inhibits the external urethral sphincter

Control of Micturition by Higher Centers Higher centers keep micturition reflex partially inhibited

except when micturition is desired the higher centers can prevent micturition, even if the

micturition reflex does occur, by continual tonic contractions of the external bladder sphincter until a convenient time presents itself

when it is time to urinate, the cortical centers can facilitate the sacral micturition centers to help initiate a micturition reflex and at the same time inhibit the external urinary sphincter so that urination can occur

located in pons (facilitative and inhibitory centers in the brain stem)

centers in the cerebral cortex : mainly inhibitory

Abnormalities in Urination atonic bladder automatic bladder uninhibited neurogenic bladder

Atonic Bladder caused by destruction of sensory nerve fibers (sacral plexus) instead of emptying periodically, the bladder fills to capacity

and overflows a few drops at a time through the urethra called overflow incontinence

causes of atonic bladdero crush injury to the sacral region of the spinal cordo syphilis (damage – constrictive fibrosis to the dorsal

root nerve fibers that enter the spinal cord – called tabes dorsalis) causing tabetic bladder

Automatic Bladder caused by spinal cord damage above sacral region micturition is no longer controlled by the brain unannounced bladder emptying occurs

Uninhibited Neurogenic Bladder caused by lack of inhibitory signals from the brain results in uncontrolled micturition, promotes frequent

urination due to damage to spinal cord or brain stem that interrupts

inhibitory signals

Voiding Disorder Clinical Feature

Detrusor overactivity (overactive bladder)

Urinary frequency, urgency, urge incontinence, nocturnal enuresisMost prevalent among girlsFrequent urine leakage onto the underpantsSquatting behaviour or Vincent curtsy sign

Giggle incontinence

Usually found in girlsUnpredictable and is associated with laughing and gigglingMay result to complete bladder emptying

Postvoid dripping Usually found in toilet trained girlsLeakage after voiding and on standingMay be a result of vasicovaginal reflux

Dysfunctional voiding

May manifest as daytime urinary symptoms, recurrent UTI’s, constipationInability to fully relax urinary sphincter or pelvic floor muscles during voiding

Voiding postponement Syndrome

Children postpone urination until overwhelmed with urgency forcing them to rush to the toiletLeakage occurs on the way to the toiletRelated to significant behavioural symptoms

Non-neurogenic Bladder (Hinman syndrome)

May present as UTI, poor bladder emptyingInconctinence,. no neurologic pathology identifiedMay involve bowel dysfunction with encopresis, constipation, fecal impaction

in infants the central control for urination is not yet fully developed...when the bladder is full the urine just come out

during toddler years (2 years), toilet training occurs, and is able to correlate it with central control

3-5 years old proper continence is achieved. The child should not be wetting the bed

Voiding Scoring System bedwetting intermittency : interval of urination urgency: urgency incontinence

72 hour bladder chart urine output should at least be 1cc/kilo/hr free flow (emptied) fractionated staccato

Uroflow-emg correlate the micturition reflex w/ the activity of the sphincter

Initial Management of Voiding D/O behavioural and cognitive approach

o child and caregiver must be educated on normal bladder and sphincter function

o constipation, if present, must be treatedo UTI’s must be treated, prophylaxis if needed

**if behavioural therapy fails: institute pharmacology

Medications: anticholinergic therapy

o parasympathetic medicated stimulation of muscarinic receptors in the bladder leads to detrusor over activity, thus anticholinergics are given to increase bladder compliance, decrease uninhibited detrusor contractions

o examples1. oxybutynin (Ditropan XL)- OD2. Tolterodine (Detrol)3. Trospium chloride (Sanctura)4. Solifenacin (vesicare)5. Darivenacin (enablex)6. Propiverine (Mictonorm) : ½ tablet BID

o these drugs relax smooth muscles

Urotherapy pelvic floor exercise neuromodulation

o suprapubic cutaneous nerve stimulationo cutaneous posterior tibial nerve stimulationo Strollers-Spleen 6 acupuncture or posterior tibial

nerve stimulation

DMSA renal scan photopenic defects in kidneys (to locate non-functional part

of kidney)

Vcug (voiding cycto-urocystography)

RENAL FAILUREMain Categories of Kidney Diseases

Acute Renal Failure : the kidneys abruptly stop working entirely or almost entirely but may eventually recover nearly normal function; decreased urine output decreased ability to excrete metabolic wastes and so the patient would manifest w/ metabolic acidosis, some degree of anemia and congestion)

Chronic Renal Failure : there is progressive loss of function of more and more nephrons that gradually decrease overall kidney function (may begin with an acute type of renal failure and symptoms may not be as marked as the acute type and patient may not be symptomatic)

Acute Renal Failure (ARF)1. Pre renal ARF: problem comes from systemic circulation (blood supply or renal perfusion); 2. Intra renal ARF: problem is w/n the kidneys (glomerulus upto renal insterstitium)3. Post renal ARF: obstructive type (from ureter to urethra)

Risk Factors to renal failure:o may be cardiac, use of diuretics, volume depletion

(hemorrhage, internal bleeding), advancing age (less than 10% after 40 years old- # of nephron), postoperative, infection (pneumonia), proteinuria (changes in glomerular BM, change in negative charge), myeloma (production of abnormal WBC)

3 main categories of causes of ARF

1. ARF resulting from decreased blood supply to the kidneys (pre renal ARF)

blood flow should not decrease to 20-25% of normal to be reversible (1.1 liter of blood supply of kidneys supply the Na-K ATPase pump w/ oxygen and assures proper electrolyte regulation)

if for example the kidneys receive 600-800ml of blood the basolateral membrane is intact and there is still exchange of fluid and can still reabsorb water and salt. With this decrease in blood flow the kidneys can still recover.

Diving reflex: preferential distribution of blood in vital organs especially in the heart and the brain during uncorrected blood loss (severe hypotension and trauma) to sustain life. This would decrease blood flow in kidneys and would cause irreversible damage to the kidneys.

causes of Pre renal ARFa. intravascular volume depletion

o hemorrhage (trauma, surgery, postpartum, gastrointestinal)

o diarrhea, vomiting (electrolyte losses from vomiting Na & Cl; from stool Na, K, Cl and bicarbonate)

o burns (evaporation of fluid in the burned part)b. cardiac failure

o myocardial infarction (decrease delivery of blood)o valvular damage

c. primary renal hemodynamic abnormalities o renal artery stenosis, embolism, thrombosis of

renal artery or veino excessive blockade of prostaglandin synthesis

(aspirin)

d. peripheral vasodilation and resultant hypotensiono anaphylactic shock

o anesthesiao sepsis, severe infections

2. Intrarenal ARF abnormalities that originate within the kidney and the

abruptly diminish urine output fall into the general category of intrarenal ARF

divided into conditions that:a. injure the glomerular capillaries or other small renal

vesselsb. damage the renal tubular epitheliumc. cause damage to the renal interstitium

causes of intrarenal ARFa. small vessel and/or glumerular injury

o vasculitis (polyarteritis nodosa-in adults): inflammation of small BV (e.g Henoch Shönlein purpura - common in child)

o cholesterol embolio malignant hypertensiono acute glomerulonephritis (antigen-antibody

reaction)b. tubular epithelial injury (tubular necrosis)

o acute tubular necrosis due to ischemiao acute tubular necrosis due to toxins (heavy

metals, ethylene glycol, insecticides, poison mushrooms, carbon tetrachloride)*aminoglycosides : most nephrotoxic

c. renal interstial injuryo acute pyelonephritiso acute allergic interstitial nephritis

nephrotoxic substances proximal convoluted tubule (S1/S2 segments)

o aminoglycosideso cephaloridineo cadmium chlorideo potassium dichromate

glomerulio interferon-alpha (for severe viral infection)o goldo penicillamine

proximal straight tubule (S3 segment)o cisplatin (for leukemia)o mercuric chlorideo dichlorovinyl-L-cysteine

renal interstitiumo cephalosporinso cadmiumo NSAIDso ACE inhibitors

renal vesselso NSAIDso ACE inhibitorso Cyclosporine A

renal papillae phenacetin

*Outer and inner medullary duct: supplied by vasa recta w/c have a slow blood flow and that decreased oxygenation would compromise the vasa rectaGlomerular Filtration Rate

best estimate of the functional renal mass reflects severity of renal disease CREATININE =

urine creatinine x volumeplasma creatinine x 60 x hours of urine collection x 1.73/BSA

= ml/min/1.73m2 (BSA=body surface area) estimated creatinine clearance (for whose 24 hr urine

sample cannot be collected) Schwartz formula= k x height (cm) plasma creatinine

Cystatatin C protein produced by nucleated cells eliminated exclusively

from the circulation by glomerular filtration reciprocal serum values correlate linearly with GFR

Other exogenous markers for GFR radionucleotides : 51-CrEDTA, Tc-DTPA, 125 I-iothalamate non radioactive contrast agent : iohexol

RIFLE CRITERIA FOR ACUTE RENAL INJURYGRF CRITERIA URINE OUTPUT

CRITERIARISK Serum creatinine x1.5

GRF decreased >25%UO < .5ml/kg/h

Hig

h se

nsiti

vity

INJURY Serum creatinine x2GFR decreased >50%

UO < .5ml/kg/h for 12 hours

FAILURE Serum creatinine x3 (or more than 4 mg)GFR decreased >75%

UO <.3ml/kg/h for 24 hr or no UO for 12 hours (oliguria)

Hig

h sp

ecifi

city

LOSS Persistent ARF (complete loss of kidney function >4 weeks)

ESKD End Stage Kidney Disease (> 3 months)

Chronic Renal Failure progressive and irreversible loss of large numbers of

functioning nephrons serious clinical symptoms often do not occur until the number

of functional nephrons falls to at least 70 to 75% below normal

some causes of chronic renal failureo metabolic disorders

diabetes mellitus (most common cause) obesity amyloidosis

o hypertensiono renal vascular disorders

atherosclerosis nephrosclerosis-hypertension

o immunologic disorders glumerolonephritis polyarteriritis nodosa lupus erythematosus

o infections pyelonephritis tuberculosis

o primary tubular disorders nephrotoxins (analgesics, heavy metals)

o urinary tract obstruction renal calculi hypertrophy of prostate urethral constriction (persistent urethral

valve-in newborn )o congenital disorders

polycystic disease (glomeruli has decreased in number)

congenital absence of kidney tissue (renal hypoplasia)

primary kidney disease (list above) cause decrease in number of nephrons and so the remaining nephrons will compensate increasing their work load but then they tire up

how do they tire up…..they hypertrophy increasing GFR and growth and so the tubules also vasodilate….arterial pressure

also increase because blood flow is shifted to the normal nephrons….. there is consumption of so much energy

renal and nephron scarring will occur ***** the only proven method of slowing down progressive loss of

kidney function is to lower arterial pressure and glomerular hydrostatic pressure

by using ACE inhitors of Angiotensin II antagonists ACE inhibitors prevent conversion of angitensin I to angiotensin

II thereby decreasing angiotensin II level to decrease vasoconstriction

Risk factors for ESRD (End Stage Renal Disease) Obesity : most important risk factor; multifactorial ; brings a

lot of work load to tissues of the body Diabetes: hyperfiltration of glucose load (Na-K ATPase tire up) Hypertension: increased pressure (wear and tear)

Other Effects of Renal Failure (opposite of functions of kidneys) Isosthenuria : inability to concentrate urine; increased water

in urine Uremia : high concentration of urea and NPN; with signs and

symptoms of renal failure Generalized edema Acidosis: decreased secretion oh H+ and decreased

reabsorption of bicarbonate High concentration of nonprotein nitrogens-urea, creatinine,

uric acid (azotemia): increased nitrogenous wastes but no symptoms

High concentration of phenols, sulfates, phosphates, potassium, guanidine bases

Anemia: decreased erythropoietin Osteomalacia: decreased calcitriol; hyperparathyroidism

5 Stages of Chronic Renal Kidney Disease Stage I = 90 or more ml/min/1.73 m2 (N) Stage II= 60-89 ml/min/1.73m2 (mild):treat primary cause Stage III = 30-59 ml/min/1.73 m2 (moderate): monitor Stage IV = 15-29 ml/min/1.73 m2 (severe): renal replacement Stage V = < 15 ml/min/1.73 m2 (end stage)

Nephrotic Syndrome : derangement of eprithelial cell of filtering membrane and so protein is excreted (2 grams per day in children, 3 grams per day in adults…results to edema)

Cushinoid fascie : due to treatment with prednisone (can also lead to buffalo hump, decrease growth rate etc)

Peritoneal Dialysis : use peritoneum to serve as diffusing membrane, to exchange nitrogenous wastes and the dialysis solution

Peritoneal Ambulatory Continuous Dialysis (PACD) : the patient can do normal work after dialysis(ambulatory), but dialysis should be done everyday (continuous)

Titer machine: automatic (even the patient is sleeping)

Hemodialysis machine : use “dialyzer” as the filtering membrane