Clinical Chemistry Kidney

• Conservation and elimination of water and electrolytes
• elimination of waste
• maintenance of acid-base balance
• retention of certain substances
• endocrine
• vitamin D activation

• upon dehydration (osmo-concentration), osmoreceptors stimulate ADH release
• ADH increases absorption of water at collecting duct, lowering the plasma osmolarity and decreasing the volume (concentrating) of urine.

• antidiuretic hormone.  Stimulated by osmoconcentration (dehydration), by osmoreceptors to concentrate urine and retain water.  
• Also stimulated by reduced blood volume, trauma, pain, and anxiety also stimulate ADH secretion

• renin-angiotensin pathway
• renin secreted by kidney in response to decrease in renal perfusion.
• renin acts on circulating angiotensinogen to form angiotensin I, activates to angiotensin II, causes secretion of aldosterone from adrenal cortex
• aldosterone reabsorbs Na in exchange for K and H
• retains water to expand blood volume and reestablish normal blood pressure.

• electrolyte conservation.
• renin secreted by kidney in response to decrease in renal perfusion.
• renin acts on circulating angiotensinogen to form angiotensin I, activates to angiotensin II, causes secretion of aldosterone from adrenal cortex
• aldosterone reabsorbs Na in exchange for K and H
• retains water to expand blood volume and reestablish normal blood pressure.

• secreted from adrenal cortex in response to angiotensin II.  
• reabsorbs Na in exchange for K and H.  
• retains water to expand blood volume and reestablishes normal BP

• renin-angiotensin-aldosterone-system
• low blood volume = kidneys secrete renin = angiotensinogen (liver) to angiotensin I = angiotensin I converted to angiotensin II by angiotensin converting enzyme (lungs) = angiontensin II constricts vessels = increased blood pressure.  
• angiotensin II causes secretion of aldosterone from adrenal cortex = resorption of Na and water = increases blood volume to increase blood pressure.

kidneys eliminate urea, creatinine, drugs, foreign substances.

• ingestion (meat adds acid, plants add base)
• production in cellular metabolism
• insufficient respiratory ventilation (increase in CO2, acid)
• vomiting (lose acid)
• diarrhea (lose base, either)
• renal insufficiency (usually acidosis)

• chemical buffering
• respiratory adjustment of blood CO2 concentration
• excretion of hydrogen or bicarbonate ions in the kidney

• increased acid in the blood (low pH) causes body to excrete H+ in urine and absorb bicarb
• increased base in the blood (high pH) causes body to secrete bicarb and absorb H+ ions

• If pH is too low kidneys secrete H+ ions in exchange for a cation (Na+) and reabsorb bicarb.  
• H+ ions can be captured in the form of ammonium, transported to kidneys and secreted into tubular fluid
• Causes reduced H+ concentration, increased bicarb, acidification of urine, lowers blood pH to normal.

• if pH is too high kidneys secrete alkaline urine to normalize pH of blood.  
• Increased filtration of bicarb by glomerulus
• increased secretion of bicarb into tubular lumen and H+ reabsorption

• reabsorbs Na, Ca, bicarb
• eliminates K, Phosphorus, H+

• kidney retains protein, glucose, vitamins, hormones and minerals.  Also water and critical nutrients.  
• kidney excretes BUN, creatinine, sulfate, phosphate, uric acid.

secretes renin and erythropoeitin.

secreted from kidneys, ultimately leads to aldosterone secretion, which leads to Na+ reabsorption and water retention

stimulates production of RBC

comes from diet or UV light shining on precurser in skin.

• calcitriol, coverted to this form in the liver and kidney, final conversion in kidney under influence of PTH (parathyroid hormone)
• Increases intestinal absorption of calcium.

activates vitamin D into calcitriol using PTH to increase intestinal absorption of calcium.

• functional unit of kidney.  
• glomerulus
• proximal convoluted tubule
• loop of henle
• distal convoluted tubule
• collecting ducts

• semipermeable membrane in nephron that filters blood to retain cells and large proteins in vasculature.  
• Extrudes a fluid nearly identical to plasma in its electrolyte and water composition

• part of nephron
• reabsorbs filtered water and solutes like glucose from urinary filtrate.  
• Secretes endogenous waste products and exogenous drugs and toxins

• part of nephron
• creates osmotic concentration gradient in fluid surrounding it
• produces urine that is more concentrated than plasma so we need less water to survive
• Desert animals have a very efficient Loop of Henle

• part of nephron
• reabsorbs Na+, Cl- and divalent cations (Ca2+, Mg2+)
• dilution of tubular fluid

• secretes and absorbs to regulate acid and bicarb and control electrolyte and fluid balance
• processes regulated aldosterone and ADH

• antidiuretic hormone
• regulates collecting duct water permeability to determine final urine osmolarity

increases tubular reabsorption of Na+ and secretion of K+

• no ADH is secreted so collecting ducts remain impermeable to water.  
• No water is reabsorbed, so urine is dilute with a low specific gravity.

ADH is released from pituitary, making collecting ducts more permeable to water.  Water is reabsorbed, concentrated urine with high specific gravity is produced.

• inability of glomerulus to retain protein (goes out in urine)
• impaired reabsorption in tubules
• inability to eliminate waste
• inability to retain protein, hormones, vitamins, glucose
• inability to concentrate or dilute urine

urination

increased total volume of urine produced in 24 hours

• increased volume of water consumed in 24 hours.  
• Dog more than 90 ml/kg/day
• cat more than 45 ml/kg/day

little urine output

no urine output

difficult or painful urination/micturition

straining to urinate

increased frequency of urination (number of TIMES of urination)

• serum concentration of BUN and/or creatinine is increased.  
• Can be prerenal, renal or postrenal.  
• Usually lose 75% of nephrons before azotemia is visible in bloodwork

• term to describe the illness accompanying renal failure
• waste products are being retained in blood, causing anorexia and lethargy, and later decreased mental activity and coma.

• glomerular filtrate rate.  
• Quantity of glomerular filtrate made each minute in the nephronsof both kidneys
• usually measured by clearance of creatinine, which is constant.
• GFR is decreased when creatinine, BUN etc are increased.

part of plasma without proteins

• urinalysis and/or urine culture
• chemistry panel
• renal biopsy

• refractometer determines specific gravity.  
• Tells hydration status and if kidney is concentrating urine.
• Concentrated is greater than 1.030 in dog, greater than 1.035 in cat
• isosthenuric is stuck at 1.008-1.012
• dilute is less than 1.008.

urine specific gravity is less than 1.008

• dog > 1.030
• cat > 1.035

• urine specific gravity stuck at 1.008-1.012.  Body can't concentrate or dilute urine.
• Indicates chronic and acute renal diseases.
• Animals with decreased renal function may sit at 1.015 - 1.020, suggests renal insufficiency but not enough for azotemia

• decreased water intake in animals with normal renal function
• increase in fluid loss through sources other than urination
• increased excretion of urine solutes.  ,
• may occur in dehydration or shock

• kidneys cannot absorb water.  
• Seen with increased fluid intake or polydipsea or with iatrogenic fluid administration

• anemia (due to decrease in erythropoietin)
• BUN
• creatinine
• Phosphorus
• sodium
• potassium
• bicarbonate
• proteins
• calcium

• end product of amino acid breakdown from protein catabolism or metabolism of bacteria.  Ammonium is produced by protein catabolism/bacterial waste, goes to liver by portal circulation, hepatocytes convert to urea and excrete in kidneys and intestines.  
• glomerulus filtration determines how much BUN is reabsorbed
• Ruminants can re-use urea to make protein from non-protein nitrogen

ruminants can re-use urea to make protein from non-protein nitrogen

• blood urea nitrogen.
• Created by liver from ammonium, secreted by kidneys

• increased urine production
• low GFR
• renal disease
• reabsorption of formed urine in blood stream (rupture of bladder, third-spacing, etc.)

• increased urea production, increased BUN
• mild elevations caused by high protein diet, upper GI tract bleeding, disorders that increase catabolism (fevery, trauma, burns, starvation, exercise)

• caused by significant liver disease, lowering liver's ability to make urea
• shunts

• consequence of decreased renal perfusion.  
• Caused by shock, dehydration, heart failure, hypoadrenocorticism (Addison's), thrombosis of renal artery, massive blood loss
• Greater than 1.030 in dog, 1.035 in cat, 1.025 in horse and cow

• renal insufficiency or failure due to primary renal disease
• Increased BUN and creatinine with isosthenuric urine indicates that 75% of nephrons are nonfunctional

• results when urine outflow is obstructed, usually urolithiasis. 
• Also caused by neoplasms, anatomic abnormalities, herniation, damage to part of lower urinary tract.  
• Can lead to rapid development of acute renal failure.

• rupture or leakage of urine from the excretory pathways.  
• AKA post renal azotemia.
• Urine in abdomen

• Increased BUN due to reabsorption of urine
• rupture or leakage of urine from the excretory pathways.
• urine in abdomen

• formed from creatine degredation.  Found in skeletal muscle, part of muscle metabolism.  
• Not as effected by things other than kidneys, so kidney-specific.  
• Amount produced daily is pretty constant, excreted primarily by glomerular filtration.

• Any condition that alters glomerular filtrate rate will alter serum creatinine.  
• Prerenal, postrenal and renal causes may increase serum creatinine, postrenal associated with largest and most acute increase.

increased BUN and creatinine.  Indicates that 75% of nephrons are nonfunctional.  Can be prerenal, renal or postrenal (check specific gravity of urine).

• decreased GFR, increased BUN and Creatinine.  Dogs >1.030, cats >1.035, cattle/horses> 1.025
• May be evidence of dehydration, hypovolemia and shock.  
• With increased urea production, sign of GI hemorrhage.  Look for melena.

• increased BUN and creatinine, isosthenuric (1.008-1.012) urine.  
• Could be other UA changes, electrolyte changes or anemia.
• Suggestive of renal disease, acute or chronic.

• increased BUN and creatinine
• look for dysuria, enlarged or ruptured bladder, urine in abdomen
• check hydration status, USG depends on it and presence/absence of current renal disease

kidney disease

kidney disease

• excreted by glomerular filtration.  Absorbed with calcium.  Kidneys can't activate Vit D, so need more calcium, so get more phosphate but can't excrete it normally, so it builds up.
• more urine, more PTH, more phosphate excreted.
• Less urine, less GFR, less PTH, more phosphate in blood.
• Increased phosphate and normal calcium most common in d/c, increased phosphate decreased calcium next most common.  Horses have low phosphate and high calcium.
• Parathyroid hormone increases phosphate excretion, so increased PTH = decreased phosphate.

• parathyroid hormone.  
• Increases calcium resorption from bone, increases renal excretion of phosphorus, increases calcium and phosphorus absorption from intestine
• increases formation of calcitriol (activated Vit D) by liver and kidney

• renal secondary hyperparathyroidism
• Renal disease =less GFR=more P, less Ca=release of PTH. 
• More PTH=Ca and P resorption from bone, more phosphorus in urine and activation of vitamin D.
• Less GFR = more PTH = renal hyperparathyroidism.

• absorption of calcium mandible and maxilla
• bones become softened "rubber Jaw" syndrome
• jaws don't close properly, so drooling, eating trouble, tongue out
• fractures and displacement of teeth.

• dietary modification
• calcitriol supplementation
• phosphate binders
• management of underlying renal disease

• Kidneys not producing properly, decreases GFR, P increases, Ca decreases, PTH secreted, more Ca and P absorbed, not Vit D activated.  
• PTH can act as a uremic toxin, promoting nephrocalcinosis and progression of CRF.

• renal mineralization
• secondary hyperparathyroidism
• progression of renal disease

• primarily reabsorbed by kidney (100%)
• Na reabsorption coupled by aldosterone to K secretion.  
• increase Na presentation to distal tubule also can increase urinary K loss.  
• Hyponatremia causes chronic renal failure (large animals) and uroabdomen (bladder rupture)

• Excreted in kidney in exchange for Na
• Hyperkalemia causes post renal azotemia (obstruction) or Acute renal failure if oliguria or acidosis
• Hypokalemia causes CRF with polyuria, ARF with anorexia.  Cattle in RF have it (alkylosis), so do 30% of CRF cats.

• Post renal azotemia (obstruction) leads to acidosis, which brings K out of cell in exchange for H+.  
• Can get acute renal failure if oliguria or acidosis are also present

• CRF if polyuria
• ARF if anorexic
• Cattle in renal failure have alkylosis
• 30% of cats with renal failure are hypokalemic

reabsorbed by kidneys. In chronic renal disease, kidney can't reabsorb HCO3 so can't eliminate H+, leading to metabolic acidosis (not in cow)

• conserved at glomerulus, so glomerular disease=protein loss=hypoproteinemia and hypoalbuminemia.  
• Glomerularnephritis (GN)
• Amyloidosis
• chronic renal disease

deposition of protein with abnormal folding at glomerulus, leaves holes in filter, allows protein into urine and hypoproteinemia.

chronic immune stimuli (antigen-antibody) punch holes into glomerular filter.

• Qualitative assessment in urine analysis (1+, 2+, etc).  
• Quantitative assessment checks urine protein-creatinine ratio (UPC), because creatinine is constant.

• urine protein creatinine
• Concentration of urine increases protein and creatinine equally, so ratio is more diagnostic.
• healthy dog UPC<0.2
• questionable renal 0.2<UPC<0.5
• renal disease UPC>0.5
• Glomerular UPC > 5
• GN UPC > 10
• Amyloidosis UPC > 20

definitive diagnosis of kidney disease.

• Abrupt decline in kidney function
• Caused by toxic injury to kidney (antifreeze, grapes and raisins) that decrease blood flow and O2, caused by dehydration, hemorrhage, CHF, septic shock and heatstroke
• Infections like Leptospirosis
• Obstruction of kidney

• lethargy
• anorexia
• vomiting
• dehydration
• diarrhea
• anything wrong with urine (polyuria, oliguria, anuria)
• kidney large and painful

• azotemia
• isosthenuria (1.008-1.012)
• increased phosporus
• metabolic acidosis
• increased potassium
• active urine analysis sediment (casts, WBC, bacteria, glucose, crystals)

• IV fluids (carefully)
• discontinue any nephrotoxic drugs
• give antidote if possible (antifreeze)
• correct acid-base and electrolytes
• Antibiotics if infection
• oliguric or anuric promote increased urine volume (monitor in and out, titrate IV fluids, LRS, mannitol or dextrose for osmotic rate
• dialysis
• renal transplant

• animal goes into acute renal disease.
• dogs get 4-methylpyrazole (4-MP) or ethanol to inactivate alcohol dehydrogenase.  
• Cats get ethanol, competitive inhibitor.

• poor short term
• good long term if make it through acute crisis
• must get better or die.

• long term, low grade injury to kidneys, body compensates until 75% is losted by 
• Caused by viral, fungal, bacterial infection, parasites, toxic reactions to poisons or meds, cancer, amyloidosis, inflammation, trauma, congenital or inherited disorders, loss of blood flow to kidneys from vascular disease, immune mediated disease.

• develop gradually over weeks/months/years
• mild for most of azotemia
• lethargy, anorexia, weight loss, PUPD
• Uremic breath at end stage
• vomiting/diarrea
• dehydration
• ulceration of GI and oral
• renal secondary hyperparathyroidism (rubberjaw)
• small, irregular kidneys
• neuro signs (coma) 
• death

• azotemia
• isosthenuria
• non-regenerative anemia
• hyperphosphatemia
• acidosis due to not resorbing bicarb so no buffer
• hypercalcemia or hypocalcemia, often normo
• hypoalbuminemia
• proteinuria

• varies depending on stage.  
• dietary protein reduction
• phosphorus restricted diet and/or phosphate binders
• Fluid therapy (IV or SQ)
• Epogen (erythropoietin) if seeing clinical signs of anemia.
• Supportive treatment of complications (hypertension with ACE inhibitor or calcium channel blockers, acidosis with potassium citrate or sodium bicarb, bacterial UTI with abs, vomiting with famotidine, cerenia).  
• Poor long-term prognosis.

• illness accompanying kidney failure.  Azotemia with symptoms.  
• Nitrogenous waste builds up in body.  
• anorexia and lethargy early
• decreased mental activity and coma later