Renal SystemNephrology

Pete A. Gutierrez MD, MMS, PA-CMiami Dade College Physician Assistant Program

March 2009

GFR = UV/P An Elevated >20:1 Bun/Cr. Ratio indicates

wither pre-renal azotemia Alkalemia increase in blood calcium level

can lead to diffuse paresthesias/numbness and muscle spasm.

Formation of carbonic acid and dissociation into HCO3 and CO2.

Nephrology

Anion Gap◦ Anion Gap normal is 12 ◦ Formula is AG = Na –(HCO3+CL) ◦ The anions in blood include HCO3, Cl, Phosphate,

Sulfate, Albumin, and organic acids.◦ The Cations include NA, K, Ca, Mg.◦ Metabolic acidosis occurs with overproduction of

lactic acid or ketoacids.◦ It can also occur with HCO3 wasting or renal

tubular acidosis or diarrhea.◦ Underexcretion of acid (renal Failure) and also in

poisonings by agents that are metabolized to acids.

Nephrology

Causes of increased anion gap metabolic acidosis:◦ Severe CRF decreased acid especially NH4

◦ Ketoacidosis diabetic, alcoholic, starvation

◦ Lactic acidosis drugs, circulatory compromise

◦ Rhabdomyolysis

◦ Poisoning salicylates, methanol, ethylene glycol

Nephrology

Causes of normal anion gap acidosis:

◦ Renal tubular acidosis

◦ Diarrhea

◦ Carbonic anhydrase inhibitors

Nephrology

Patients who drink methanol produce formaldehyde and formic acid resulting in a high anion gap acidosis.

Ethylene glycol (Antifreeze) forms glycolic acid and oxalic acid resulting in a high anion gap acidosis and calcium oxalate crystals in the urine.

Patients drinking isopropyl alcohol can have significant ketosis without acidosis because isopropyl alcohol breaks down to acetone.

So a patient arriving with stuporous and fruity smell on his breath and has normal chemistry except high ketones.

Nephrology

These test should be preformed on a patient who comes in with high anion gap acidosis:◦ Urine + serum ketones levels ◦ Lactic acid level◦ And the osmolar gap.◦ The osmolar gap is the different between

measured and calculated osmolarity. Calculated osmolatity is: Osm = 2(NA) + BUN/2.8 + glucose/18 Normal osmolar gap is < 10. If >20 think of intoxication with any one of the

alcohols.

Nephrology

Metabolic Alkalosis: Usually results from volume contraction

caused by diuretics or vomiting which causes a lost of HCL.

Treatment requires KCL, and NaCl.

Nephrology

Acid base Status PH PCO2 PO2 Status

Example 7.56 20 90 Alkalosis Hyperve 7.56 20 50 Alk Asthma 7.44 20 90 Chronic CNS 7.43 30 60 as above COPD 7.24 60 80 Acidosis Sedative 7.16 70 50 Acidosis Hypoxia 7.44 60 90 Alkalosis HCO3

Nephrology

Normal Osmolality is usually 282+ or – 2 mosm/kg H2O.

If glucose and Bun are normal just use the (NA) x 2 to see if it is normal

Low Na is the most common electrolyte abnormality:◦ Isotonic◦ Hypertonic◦ Hypotonic

Nephrology

Isotonic hyponatremia occurs when protein or lipids displace sodium as in multiple myeloma (MM) and p

hyperlipidemia. There is an increased osmolar gap. The measured serum osmolality is normal while the calculated osmolality is low because of the low NA,

Hypertonic both glucose an mannitol cause an osmotic shift of water out of cells which dilutes plasma NA remember that for each 100 mg/dl increase in glucose, sodium concentrations decreases by 1.6.

Nephrology

Hypotonic: The hypo tonicity cause intracellular

swelling which may result in neuromuscular excitability, seizures and coma.

Usually when the NA goes below 120 the sodium level decreases slowly the cells re-equilibrate and do not swell enough to cause these symptoms.

The hypotonic group is further subdivide by volume status: Low-High-Normal

Nephrology

The low-volume is the group of patients that have lost both water and Na, but more Na than water this is normally caused by the use of diuretics, GI loses (Vomiting and Diarrhea) and adrenal insufficiency. In adrenal insufficiency, low aldosterone caused decreased active NA reapsortion which results in NA and water wasting, with high K and a mild metabolic acidosis.

Nephrology

Hypotonic High: These people usually have low output CHF

or hypoalbuminemia (From Cirrhosis) they retain water and NA but usually more water than NA so they have normal or even elevated total body NA.

Often these patients have edema and JVD. Normal treatment is restriction of water and

NA. (Used loop diuretics).

Nephrology

Hypotonic (SIADH):◦ The normal volume patients usually have SIADH,

but this can also be caused by psychogenic polydipsia (rare) and even by diuretics, if there is sufficient water replacement.

◦ The serum uric acid and bun are low but this is dilusional.

◦ The most serious causes of SIADH are CNS disorders to include meningitis, lung disorders, and cancer especially small cell carcinoma.

◦ Also cancer of the duodenum and thymus and some drugs like cyclophosphamide, clofibrate, and vincristine.

Nephrology

Treatment of Hyponatremia:◦ If the patient is hypovolemic give 1-2 liters of

normal saline.◦ If the symptoms are severe to include seizures

give 3% saline, along with loop diuretics.◦ Give the 3% saline over 8-12 hours, to increase

the sodium by 10meg/lt.◦ The meq is calculated by multiplying the total

body water (60% of body weight eg 60 L in a 100 kg patient) by 10 which would equals 600 meq.

◦ Each liter of 3% saline has 512 meq of NA so about 1 liter could be given over 12 hours.

Nephrology

NEVER, Never, Never give hypertonic saline rapidly.

The correction should not exceed 1-2 mmol/hr.

If the patient has SIADH treat with fluid restriction and give Demeclocycline 900 mg/day.

Osmotic demyelination syndrome, central pontine myelinolysis so it is very important not to replenish the NA too quickly.

Nephrology

Hypernatremia:◦ This is fairly rare and only due to the patient not

been able to get to water or the thirst mechanism is defective.

◦ Unlike hyponatremia patients these patients are always hyperosmolar.

◦ The amount of water needed to treat a hypernatremic patient is calculated by multiplying the total body water (60% of weight in Kg), by the fractional difference between the patient NA and normal NA.

Nephrology

Diuretics:◦ Proximal convoluted tubule (PCT) 90% of the HCO3 is

reabsorbed here by means of several chemical changes. The reabsortion process is driven by H being secreted.

◦ A carbonic anhydrase inhibitor (acetazolamide (Diamox) causes diuresis with bicarbonate wasting resulting in a metabolic acidosis).

◦ Calcium is also absorbed in the proximal tubule.◦ When treating severe hyperclacemia normal saline is infused at

a high rate along with loop diuretics. ◦ The saline expands the volume and causes increased flow in

the proximal tubules that prevents calcium reabsorption and the greatly increase calcium load then delivered to the distal tubule overwhelms the distal tubules ability to adsorb calcium and its ability is also block by the loop diuretics

Nephrology

Loop of Henle:◦ As the tubular fluid progresses down the loop of Henle

free H2O is sucked out of the fluid following the osmotic gradient (The renal medulla is very hypertonic).

◦ At the base of the loop, the tubular fluid is maximally concentrated.

◦ In the ascending limb 25% of the filtered NaCl is actively reabsorbed .

◦ This increases the hyper tonicity of the medulla and causes H2O from the descending limb to effectively follow the NA out of the ascending limb.

◦ Blockage of this absorption of NA with loop diuretics results in diuresis.

Nephrology

The Kidney Tubule

Nephrology

The Distal Tubule:◦ This is where NA is actively reabsorbed and either

H in the form of salts (NH4 or phosphate salts) or K are then excreted.

◦ They flow back down the electrical gradient caused by the reasorption of NA.

◦ This used to be called the NA-K pump but actually it is the NA pump—K/H electrical excretion gradient.

◦ Aldosterone facilitate this transport and an K sparing diuretic like triamterene our spironolactone.

Nephrology:

Collecting Duct:◦ Is where ADH has its effect.◦ In the normal kidney the urine is very dilute by

the time is reaches the collecting duct.◦ ADH increases the permeability of the collecting

duct to water, allowing the free water to reabsorbed into the hypertonic renal medulla.

◦ There there is no ADH a very dilute urine is produced.

Nephrology:

Minerals:◦ K◦ Even slight hyperkalemia stimulates the release of

aldosterone which causes a normally function kidney to increased absorption of NA distally and there for increase excretion of K.

◦ Hyperkalemia is caused by decreased excretion (Drugs, renal failure, hypoaldosteronism such as Addison disease) increased production (trauma, tumor lysis) volume contraction in hospital more common.

◦ Drugs are probably the most common cause of increase K like ACE inhibitors and beta blockers.

Nephrology:

The cardiac effects of hyperkalemia are due to the large difference between intracellular and extracellular K levels.

Treatment can be done with glucose + Insulin.

Can also give the patient IV calcium in the form of Calcium Chloride 1 amp.

Calcium Gluconate.

Nephrology:

Calcium regulation:◦ Regulation of calcium PTH and vitamin D

metabolites cause changes in the way the kidney, GI, and bone handle calcium.

◦ Calcium circulates in an inactive form bound form (usually albumin) and an active form, called also ionized/unbound form.

◦ With hypoalbuminemia only the bound form decreases.

◦ For each decrease in albumin of 1, the total calcium will decrease by .7

Nephrology:

Magnesium:◦ Hypomagnesaemia is rare and occurs from the

use of Mg-containing laxatives or antacids in renal failure patients and MgSO4.

◦ Symptoms begin with levels of >4-6 meq/l.◦ Symptoms level are sedation, muscle weakness,

and a loss of deep tendon reflexes and can progress to paralysis.

Nephrology:

Hyperphosphatemia:

◦ Acute increase is from acute tubular necrosis, IV solutions, and tumor lysis after chemotherapy.

◦ Chronic increase in parathyroidism.

◦ Hypophosphatemia: Think Alcohol if severe PO4< 1mg/dl it may cause

rhabdomyolisis as also can low K.

Nephrology:

Diuretics Medications:◦ Ethacrynic Acid◦ Furosemide (Lasix◦ Bumex◦ Carbonic Anhidrase Inhibitors◦ Triamterene◦ Zaroxylin◦ Mannitol◦ Diazyde◦ ACE

Nephrology:

HTN:

◦ Primary Hypertension: 95% of all hypertension is primary (1.e. essential idiopathic.) The systolic and diastolic blood pressure (DBP) define the stages of HTN: Stage I SBP 140-159 or DBP 90-99 Stage II SBP 160-179 or DBP 100-109 Stage III SBP>180 or DBP>110

Nephrology:

Urinary System:◦ Structures:

Urethra Urinary Bladder

◦ Ureters Kidneys Renal pelvis Mayor Calyces Minor Calyces Collecting Ducts Nephrons

Nephrology

Functions Include:◦ Formation of Urine◦ Urine Storage◦ Urine Elimination◦ Removing Wastes and foreign Substances◦ By:

Glomerular Filtration Tubular Reabsorption Tubular Secretion

Nephrology

The breakdown of proteins produces amino acids and the subsequent metabolism of amino acids produces nitrogenous wastes like ammonia.

The Ammonia is converted in the liver into less harmful Urea.

The body accumulates excess ions of sodium, chloride, potassium, hydrogen ions, sulfate and phosphate.

Nephrology

The role of the Urinary system is to maintain a balance of these products and to remove the excesses from the blood.

The urine consists of the metabolic waste of urea, excess water, excess ions, and toxic wasted that may have been consumed with food.

Nephrology

Function’s of the Urinary System:◦ Excretion/Reabsortion◦ Maintain blood volume and concentration ◦ pH regulation◦ Blood Pressure-Renin which helps adjust

filtration pressure.◦ Erythropoietin-A hormone that stimulates red

blood cell production◦ Vitamin D Production convert vitamin D to its

active form Calciferol.

Nephrology

The kidneys are paired organs that are reddish in color and resemble kidney beans in shape. They are the size of a closed fist.

They are located between the parietal peritoneum and the posterior wall of the abdomen also known as the retroperitoneal space.

The right kidney is slighly lower that the left. The average kidney measures about 11.25cm

long and 5.0 to 7.5 cm wide.

Nephrology

Near the center of the kidney is a notch called the Hilum through which the ureter leaves the kidney, and blood vessels, nerves, and lymph vessels also enter and exit the kidney’s.

Three layers of tissue surround each kidney:◦ The innermost is the renal capsule (serves as barrier

against infection)◦ The second layer is the adipose capsule (Protects the

kidney’s from blows, and hold the kidney’s in place).◦ The outermost layer is the renal fascia which is

connective tissue that anchors the kidney’s to their surroundings.

Nephrology

The Internal Anatomy of the Kidney’s:◦ A frontal section will reveal the outer area called

the cortex , and an inter area called the medulla.◦ Within the medulla there are 8-18 striated,

triangular structures called the renal pyramids.◦ The Nephrons are the functional units of the

kidney’s. They regulate the composition and volume of blood and form the urine.

Nephrology

The Minor calyxes surrounds the tip of each renal pyramid and joint to form the Major calyxes which them joint together to form the renal pelvis.

The functional unit of the kidney’s are the nephrons, which is a microscopic renal tubule which functions as a filter.

As we age the kidney’s decrease in size. At age twenty they weigh approximately 260 grams and by age 80 they weigh is approximately 200 grams.

Nephrology

The nephron begins as a double-walled globe known as the Bowman’s Glomerular Capsule. This is located in the cortex of the kidney’s

The right and left renal arteries transport one quarter of the total cardiac output directly to the kidney’s.

About 1200 ml of blood passes through the kidney’s every minute

Nephrology

Circulation:◦ Renal arteries◦ Interlobar arteries◦ Arcuate arteries ◦ Interlobular arteries◦ Afferent arteriole◦ Glomerular capillaries◦ Efferent arteriole◦ Peritubular capillaries◦ Interlobular veins◦ Arcuate veins◦ Interlobar veins◦ Renal vein

Nephrology

Physiology of the nephrons:◦ In glomerular filtration, the glomerulus filters

water and certain dissolved substances from the plasma of blood. (Positive charge ions of sodium, potassium, calcium and magnesium.

◦ Both kidney’s filter about 45 gallons of blood plasma per day.

◦ Most fluid gets reabsorbed in the renal tubules and reenters the plasma.

Nephrology

Tubular reabsorption:◦ The majority of the reabsorption occurs in the

proximal tubule. Active transport reabsorbs amino acids, glucose, creatinine, lactic acid, Uric acid, Citric acid, and Ascorbic acid.

◦ Osmosis reabsorbs water◦ Chloride ions and other negatively charge ions

are reabsorbed by electrochemical attraction.

Nephrology

Tubular Secretion:◦ The proximal convoluted tubule actively secretes

penicillin, creatinine and histamine into the tubular fluid.

◦ It also secretes Hydrogen Ions (H+) thus helping in the regulation of body pH.

◦ Urine consist of water and solutes that the kidneys either eliminate or retain in the body in order to maintain homeostasis.

Nephrology

Renal Test:◦ There should be no RBC’s in the urine, but if the

urine Dip is positive thinks always of Hemoglobinuria or Myoglobinuria.

◦ One common cause of Hemoglobinuria is red blood cells lysis.

◦ If you see RBC casts or crenated dysmorphic red blood cells indicate a renal origin and probable glomerulonephritis.

◦ If you see eosinophiluria think of drug induce interstitial nephritis.

Nephrology

There should very little proteins found in the urine less than <150mg.◦ Proteinuria is the best indicator of underlying

renal pathology.◦ More than 2.5-3.5 gm (or 40-50mg/kg/d) means

significant glomerular pathology.◦ A pathology called Myeloma often results in

Bence-Jones proteinuria. The Bence Jones proteins are light chains which are not picked up on a urine dipstick.

Nephrology

Transient Proteinuria is common in people during a febrile illness, also after strenuous exercise, and in patients with CHF and COPD. You should always check the urine when the situation as passed.

Benign orthostatic proteinuria is a condition in which the proteinuria reverts back to normal when the patient is supine.

Nephrology

Microalbuminuria is an indication of early diabetic nephropathy this is not picked up on the urine dipstick.

Later in the disease the condition turns into nephrotic syndrome.

Causes of false positive urine albumin on the dipstick include a very alkaline urine with a pH >8, and a very concentrated urine.

Nephrology

GFR-Glomerular Filtration Rate, Urine to plasma creatinine concentration X urine flow rate.

Medicines that increase GFR are cimetide, probenecid and trimethroprim sulfa TMP/SMX.

Acetone and cefoxitin interfere with the test for creatinine and may give falsely elevated results.

Nephrology

Creatinine is produce by muscle mass and the breakdown of muscle tissue.

Renal biopsy is used to diagnose causes of acute renal failure, nephrotic syndrome, and glomerulonephritis.

Nephrology

Fluid and Electrolytes:◦ Normal Osmolatity is usually 282+or – 2 mosm/kg

H2O. ◦ Osm = 2(Na) +Glucose/18+Bun/2.8

Nephrology

Urinary tract infection most common pathogens:◦ Gram-Negative bacteria◦ Klebsiella◦ Pseudomonas◦ Proteus ◦ Enterobacter◦ Escherichia coli

Nephrology

Disorders of the Urinary System:◦ Kidneys stones known as calculi are composed of the

precipitates of uric acid, magnesium or calcium phosphate, or calcium oxalate.

◦ Cystitis an inflammation of the urinary bladder ◦ Gout is a condition caused by high concentrations of

uric acid in the plasma. Uric acid crystals.◦ Glomerulonephritis is an inflammation of the

kidneys where the filtration membrane within the renal capsule is infected with bacteria. (Following streptococcal sore throat infection).

◦ Renal failure ◦ Hematuria, oliguria or polyuria.

Nephrology