Week 1 Lectures Flashcards
Are RBCs and plasma proteins (i.e albumin) effective osmoles between plasma and ISF?
Yes
What is oncotic pressure
osmotic pressure exerted by proteins
Are blood vessels walls permeable to salt and water? What is the significance of this?
Yes–thus they do not create an osmotic gradient between intravascular and interstitial space
BUT vessels are not fully permeable to proteins therefore albumin stays in the plasma
in the end does the hydraulic/oncotic pressure balance favor retention in the plasma or net movement of fluid out?
balance results in slight net movement out–lymphatics return fluid to venous circulation
list causes of edema
CHALO (Capillary-Hydraulic–Albumin–Lymphatic–Oncotic)
- increased capillary permeability–may occur in sepsis or certain diseases
- increased hydraulic pressure–increased plasma volume due to primary sodium retention; venous obstruction; decreased arteriolar resistance (and thus increased volume moving into arterioles)
- decreased albumin–from protein loss, particularly in glomerular disease or reduced production
- lymphatic obstruction–more fluid trapped in interstitium
- increased interstitial oncotic pressure causes more fluid drawn into interstitium
describe the pathophysiology of edema
- -fluid moves out of the intravascular space and into the interstitial space
- -the issue with this is that the body is extremely protective against shock; as sodium and therefore water are extravasated, the baroreceptors pick this up
- -this results in the activation of the RAAS system and sodium is retained + vasoconstriction
- -the trouble with this is that even though sodium is retained for the purpose of restoring inravascular pressure, this does not solve the primary issue, which is whatever let more water get into the ISF anyway
- –in the case of hypoalbuminemia, the oncotic pressure is too low to keep fluid in the intravascular space
- -so even though the kidney is “doing the right thing”, water just keeps moving out of the intravascular space and into the interstitium
- -instead, the patients salt content remains high and thus their fluid load remains high as well
How is Na+ filtered in the golmerulus?
it is freely filtered
what is the concentration of the ultrafiltrate in the glomerulus compared to the blood?
they are the same (135-145 mmol/L)
What happens at the proximal tubule RE: Na+ and H2O reabsorption?
-65% of filtered Na+ and water are reabsorbed together
How is Na+ reabsorption accomplished in the proximal tubule once it has crossed into the cell (i.e how does it cross the basolateral membrane)?
Via Na+/K+ ATPase pump in the basolateral membrane
2 steps:
- Na+ moves across the apical (luminal) membrane from the lumen into the cell, down an electrochemical gradient established by the Na+/K+ ATPase pump
- Na+ moves across the basolateral membrane from the cell into the blood, against its electrochemical gradient, via the Na+/K+ ATPase pump
What else is reabsorbed in the PT?
small proteins that were filtered by the glomerulus (reabsorbed via endocytosis)
Describe the two mechanisms by which Na+ crosses the apical membrane (from lumen into cell) in EARLY proximal tubule
- Na+/H+ antiporter
- -Na+ entry coupled with H+ exit from cell; H+ secretion results in NaHCO3 reabsorption into blood - NA+/X- symporter–Na+ and X- both enter cell from lumen; X- crosses basolateral membrane into blood via passive transporter; X- = organic solute (glucose, aa’s, Pi, lactate); X- are almost completely removed from tubular fluid
What provides the driving force for reabsorption of H2O by osmosis in the early proximal tubule
reabsorption of NaHCO3 and NaX establishes a trans-tubular osmotic gradient that provides the driving force for passive reabsorption of H2O by osmisis
Because H2O is absorbed in excess of Cl- in the early segment of the PT, the Cl- concentration rises along the length of the segment
How does Na+ cross the apical membrane (from lumen into cell) in the LATE proximal tubule?
- coupled Na+/H+ and Cl-/HCO3- antiporters–Na+ entry coupled with H+ exit from cell; Cl- entry coupled with HCO3- exit from cell; H+ and HCO3- combine in the tubular fluid to form H2CO3 and reenter the cell
- paracellular reabsorption of Na+ and Cl- by passive diffusion– established a transcellular osmotic gradient that provides the driving force for the passive reabsorption of water by osmosis
driving force for both mechanisms is the Cl- gradient established in the EARLY proximal tubule
What does “paracellular reabsorption” refer to?
reabsorption through tight junction (rather than transcellularly through the cells lining the lumen of the PT)
Through which 2 pathways is water reabsorbed in the proximal tubule?
PT is highly permeable to water and it flows from the lumen into the blood via:
- transcellularly
- paracellularly (through tight junctions)
How much Na+ is reabsorbed in the loop of henle? Where?
25% approx (plus Cl- and K+)
Na+ mostly in the thick ascending but to lesser extent in other parts
How much water is reabsorbed in the loop of Henle? where?
about 15%
in the descending thin limb
Describe the 3 pathways by which Na+ is reabsorbed in the thick ascending limb of the loop of henle
*remember the Na+/K+ ATPase moves Na+ into the blood from the cell and thus sets up a concentration gradient along which Na+ can flow from the TAL
- Na+/K+/2Cl- symporter–uses the energy released by the downhill movement of Na+ and Cl- to move K+ uphill into the cell
- Na+/H+ antiporter–same as in early PT
- paracellular pathway–Na+ (and several other cations)
What is the significance of the TAL being impermeable to water?
reabsorption of NaCl and other solutes in the TAL thus reduces the osmolality of tubular fluid to less than 150mOsm/L
How much Na+ is reabsorbed in the distal tubule and collecting duct?
about 7% of filtered NaCl
About how much water is reabsorbed in the distal tubule and collecting duct? What does this depend on?
about 8-17%, depending on the concentration of ADH
Describe Na+ reabsorption in the early segments of the DT
- Na+ and Cl- enter the cell from the lumen via the Na+/Cl- symporter
- Na+ leaves the cell and goes into the blood via the Na+/K+ ATPase pump
- Cl- leaves by diffusion channels in the basolateral cell membrane and paracellularly
- impermeable to water
What are the 2 cells types relevant to Na+ reabsorption in the late DT and collecting duct?
- principal cells
2. intercalated cells
How do principal cells participate in Na+ reabsorption in the late DT/CD?
- reabsorb Na+ and H2O and secrete K+
- Na+ crosses apical membrane through diffusion through Na+ channels
- Na+ crosses the basolateral membrane via the Na+/K+ ATPase pump
How do intercalated cells participate in Na+ reabsorption in the late DT/CD?
- regulate acid/base balance by either (1) secreting H+ and reabsorbing HCO3- OR (2) secreting HCO3-
- reabsorb K+ (mech not understood)
Angiotensin II
- synthesis
- major stimulus
- site of action in nephron
- effect
- RAAS
- in response to increased renin
- PT
- increase NaCl and H2O reabsorption
Aldosterone
- synthesis
- major stimulus
- site of action in nephron
- effect
- synthesized by glomerulosa cells in the adrenal cortex
- in response to increased AT II and increased plasma K+
- TAL; DT/CD
- increases NaCl reabsorption; increases NaCl and water reabsorption
ANP
- synthesis
- major stimulus
- site of action in nephron
- effect
- secreted by cardiac atria
- in response to increased ECFV
- CD
- decreases NaCl and water reabsorption
Urodilatin
- synthesis
- major stimulus
- site of action in nephron
- effect
- secreted by DT and CD (not present in systemic circulation)
- in response to increased ECFV
- CD
- decreases NaCl and H2O reabsorption
Adrenalin/NA
- synthesis
- major stimulus
- site of action in nephron
- effect
- sympathetic nerves (adrenaline/NA) and adrenal medulla (adrenaline)
- in response to decreased ECFV (i.e bleeding)
- PT; TAL; DT/CD
- increases NaCl and water reabsorption; increases NaCl reabsorption; increases NaCl and water reabsorption
Dopamine
- synthesis
- major stimulus
- site of action in nephron
- effect
- released by dopaminergic nerves in the kidney, also synthesized by cells of PT (opposes action of adrenalin/NA)
- in response to increased ECFV
- PT
- decreases NaCl and H2O reabsorption
ADH
- synthesis
- major stimulus
- site of action in nephron
- effect
- secreted by posterior pituitary
- in response to increased Posm and/or decreased ECFV
- DT/CD
- increases water reabsorption
Where exactly in the hypothalamus is ADH made?
the supraoptic and paraventricular nuclei of the hypothalamus–>then packaged into granules and passed to posterior pituitary where is is released via exocytosis
What triggers ADH release?
detection of Posm > 280 mosmol/kg by osmoreceptors in the hypothalamus
What are some other stimuli that can result in ADH secretion?
- decreased ECFV
- AT II
- hypoxia
- hypercapnia
- adrenaline
- cortisol
- sex steroids
- pain
- trauma
- psychogenic stimuli
How does ADH act?
binds to V2 receptors on CD cells and stimulates adenyl cyclase–>this raises cCAMP levels and causes intracellular vesicles containing water channels (AQP2) to fuse with the apical membrane
also binds V1 receptors on vascular smooth muscle cells, causing vasoconstriction and enhancing the effect of aldosterone on Na+ reabsorption in the DT (normal physiological concentrations of ADH are not enough to bind V1 receptors)
where is the JGA located in relation to the sections of the nephron?
in the distal tubule, approximately between the early and late distal tubule
What is the key to producing concentrated or dilute urine?
the presence of ADH
How does the kidney/nephron produce hypo-osmotic urine? (dilute the urine)
to do this, nephron must reabsorb solute from the tubular fluid and not allow water reabsorption to occur–this occurs in the ascending limb of the LoH and in the DT and CD in the ABSENCE OF ADH
- proximal tubule reabsorbs isoosmotic fluid with respect to plasma–this fluid enters the descending limb of the LoH
- the descending limb is permeable to water, less so to solute–as the fluid descends deeper into the medulla, it encounters an increasingly osmotic medullary interstitium–thus water is reabsorbed due to the osmotic gradient in this region
- the fluid then travels to the thin ascending limb–impermeable to water, permeable to NaCl and urea—NaCl is passively reabsorbed, urea diffuses passively into the tubule (volume of tubular fluid remains unchanged in the thin ascending limb, but NaCl decreases and urea increases. More NaCl leaves than urea enters tubular fluid and thus the fluid becomes slightly less concentrated that the surrounding interstitial fluid)
- moves to the thick ascending limb–this is impermeable to water and urea–only permeable to NaCl–NaCl = ACTIVELY reabsorbed from tubular fluid, which dilutes the tubular fluid
- fluid leaving thick ascending limb is hypo-osmotic relative to the plasma
- in the DT and cortical CD, NaCl is actively reabsorbed (impermeable to urea)–in ABSENCE of ADH, the DT/CD are impermeable to water and thus further dilution of tubular fluid occurs with the active reabsorption of NaCl
- in the medullary CD, NaCl is actively reabsorbed–slightly permeable to water and urea even in absence of ADH–overall causes FURTHER dilution
- urine can be diluted as much as 50 mosm/kg H2O
How does the kidney/nephron generate hyperosmotic urine
in presence of ADH
- steps until the DT and cortical CD are the same as when you are generating hypo-osmotic urine
- remember that the NaCl reabsorbed in the ascending limbs accumulates in the medullary interstitium, and is crucial for the production for hyper-osmotic urine–>this NaCl provides the driving force for water reabsorption by the medullary CD–> COUNTERCURRENT MULTIPLICATION
- in the DT and cortical CD, the fluid reaching these areas is hypo-osmotic w respect to surrounding interstitial fluid
- ADH increases water permeability of the last half of the DT and CD–> water diffuses out of the tubular lumen and thus tubule fluid osmolality increases
- although the fluid at this poin has the same osmolality that entered the descending thin limb, its composition has changed–less NaCl, more urea and other solutes
- At the medullary CD, the interstitial osmolality continues to increase as you go down into the medulla–in PRESENCE of ADH, the medullary CD is permeable to water–>tubular fluid becomes increasingly concentrated
- ADH also causes increased permeability to urea in the last part of the medullary CD–urea diffuses out of the tubule lumen
- urea can be concentrated to about 1200 mosmol/kg H2O–high concentreations of urea and other nonreabsorbed solutes
What are the two major classes of membrane transport proteins in the kidney?
- transporters/carriers–>bind a specific solute–>conformational change–>transfer solute
- channels–>interact with solute more weakly–>aqueous pores that allow specific solutes (usually inorganic ions of appropriate size and charge) to pass thru–>faster than transporters/carriers
What is primary active transport
linked to ATP hydrolysis (i.e Na+/K+ ATPase
What is secondary active reabsorption?
2 or more substances interact with a specific membrane protein, does not require ATP
What is secondary active secretion?
counter-transport
i.e Na+/H+ exchanger on apical side
Name a diuretic that works in the Proximal Convoluted Tubule
Carbonic Anhydrase Inhibitor
Where do Carbonic Anhydrase Inhibitors work?
the PCT
Name 5 types of diuretics
- carbonic anhydrase inhibitorys
- loop diuretics
- thiazide diuretics
- K+ sparing diuretics
- osmotic diuretics
- V2 antagonist
Name a carbonic anhydrase inhibitor
Acetazolamide
What type of drug is Acetazolamide
a carbonic anhydrase inhibitor (diuretic)
MOA of carbonic anhydrase inhibitors
Inhibit Na+ and HCO3- reabsorption by inhibiting carbonic anhydrase (CA)
- in the lumen of the tubule, CA reversibly catalyzes the conversion of H2CO3 to CO2 and H2O, a critical step in the reabsorption of HCO3-
- CO2 crosses the PT membrane, reacting with H2O inside the cell
- CA in the cytoplasm of PT cells catalyze the reformation of H2CO3
- H2CO3 dissociates into HCO3- and H+–HCO3- is transported into the interstitium and H+ is recycled back into the lumen of the nephron in exchange for Na+
Name a diuretic that works in the loop of henle
Loop diuretics
Name a loop diuretic
furosemide
Where does furosemide work and what type of drug is it?
works in the loop of henle
it is a loop diuretic
MOA of loop diuretics/furosemide
inhibits the Na+/K+/2Cl- co-transporter in the thick ascending limb o the LoH
- less Na+, K+ and Cl- ions are reabsorbed from the lumen of the tubule
- reduction in the electrochemical gradient abolished the paracellular transport of Ca2+ and Mg2+ ions
- Normally, the gradient is set up by the channels which allow K+ ions to move back into the lumen and Cl- ions to move into the interstitium
- the +/- gradient allows Ca2+ and Mg2+ ions to move downstream, towards the -ve charge in the interstitium
- extra Na+ in the lumen is reabsorbed downstream in exchange for intracellular H+ and K+–results in hypokalemia and metabolic alkalosis
Name a diuretic that works in the DCT
Thiazide diuretics
Name a thiazide diuretic
Hydrochlorothiazide
Where does hydrochlorothiazide work, and what type of drug is it?
in the DCT of the nephron
it is a thiazide diuretic
MOA of thiazide diuretics/hydrochlorothiazide
inhibits the Na+/Cl- co-transporter in the DCT
- less Na+ and Cl- are reabsorbed from the lumen of the tubule
- extra Na+ in the lumen is reabsorbed downstream in exchange for H+ and K+–hypokalemia and metabolic alkalosis
- Ca2+ in the lumen is reabsorbed by a poorly understood mechanism–hypercalcemia
Name a diuretic that works in the collecting duct of the nephron
K+ sparing diuretics (aldosterone antagonists)
K+ sparing diuretics (ENaC blockers)
Name a K+ sparing diuretic (aldosterone antagonist)
Spironolactone
What type of drug is spironolactone and where does it act
K+ sparing diuretic (aldosterone antagonist)
in the Collecting Duct
MOA of K+ sparing diuretics (aldosterone antagonists) /spironolactone
acts as an antagonist at the mineralocorticoid receptor (MR) for aldosterone
- normally, the MR-aldosterone complex translocates to the nucleus where it acts on DNA to increase the expression of epithelial Na+ channels (ENac) and Na+/K+ ATPase pumps on the luminal and basolateral membranes, respectively
- Blocking the MR thus reduces the Na+ reabsorption, producing natriuresis and diuresis
- reducing the basolateral concentration of Na+/K+ ATPase also causes a reduction in the excretion of K+ (therefore sparing it)
Name a K+ sparing diuretic (ENaC blocker)
Triamterene, amiloride
Where do triamterene and amiloride work? What type of drug are they?
Collecting Duct
K+ sparing diuretics (ENaC blockers)
MOA of K+ sparing diuretics (ENaC blockers)/Triamterene/Amiloride
- inhibit ENaC on the luminal membrane, preventing Na+ from moving from the tubular lumen into the cell
- This keeps Na+ in the lumen of the tubule, therefore facilitating natriuresis and diureses
- Reduced entry of Na+ into the cell also reduces the amount of Na+ that can be exchanged for K+ at the ATPase pump–with the Na+/K+ ATPase pump unable to exchange Na+ for K+, the K+ stays in the bloodstream (K+ sparing)
Where do osmotic diuretics act
operate throughout the renal tubule
Name an osmotic diuretic
Mannitol
What type of drug is mannitol?
osmotic diuretic
MOA of osmotic diuretics/mannitol
freely filtered and poorly reabsorbed inert chemicals that stay in the tubule and therefor pulling water into the tubule via an increase in oncotic pressure
limited use as a diuretic
mainly used for non-diuretic indications such as an increase in intracranial pressure
avoid if patient experiences renal failure and has a low GFR
Where do V2 antagonists work?
Collecting Duct
Name a V2 antagonist
Tolvaptan
MOA of V2 antagonists/Tolvaptan
Acts as a V2 receptor antagonist–therefore, prevents the recruitment of aquaporins at the collecting duct (blocks action of ADH)
promotes “water diuresis” with minimal impact on the electrolytes
future drug
Benefit for using carbonic anhydrase inhibitors
inhibiting production of CA means that it will also inhibit production of aqueous humor, which means it can be used for GLAUCOMA
it results in loss of HCO3-, treating metabolic alkalosis
also used to treat acute mountain sickness (mechanism unknown, but it is thought that CA may contribute to CSF production)
Adverse effects/disadvantages of Carbonic Anhydrase Inhibitors
works early in proximal tubule and so much Na+ is reabsorbed later making the drug less effective
side effects include metabolic acidosis, renal stones and hypokalemia
Benefits of K+ sparing diuretics
prevents compensatory loss of K+ in the DT and CD and thus conserves body K+
spironolactone has a short half life (1-2 hours) but has an active metabolite that has a half life of 16 hours
can be used to treat hyperaldosteronism (spironolactone)
may prevent aldosterone aided heart failure (they reduce all cause mortality)–(spironolactone)
available in fixed dose combinations with hydrochlorothiazide
adverse effects/disadvantages of K+ sparing diuretics
causes hyperkalemia, metabolic acidosis
spironolactone itself causes gynecomastia, mentural disorders, testicular atrophy, CV injury
Benefits of loop diuretics
“high ceiling” diuretics
work on apical side of the lumen (must be filtered or secreted by the PT to work–NSAIDS can inhibit this secretion)
used for edema, HTN and acute hypercalcemia
more potent than thiazides
adverse effects/disadvantages of loop diuretics
may reduce expected calcium and magnesium levels in the body (although some Ca2+ recovered later in nephron)
can cause alkalosis through loss of H+
is a sulfa drug–>allergies
SEs incldue electrolyte imblanaces, metabolis alkalosis, ototoxicity, hyperuricemia
they are bound to albumin, higher levels of albumin means there is less diuretic to work in the tubules
may cause much K+ loss
Benefits to thiazide diuretics
acts in the DT–less compensatory mechanisms of Na+ reabsorption happening after this
promote Ca2+ reabsorption (mechanism not understood but inhibit renal stone function formation)
acts as vasodilators and decreases BP
act at luminal side (in the tubules–must be secreted through PT)
may be used for HTN, edema, or nephrogenic diabetes insipidus
has a flat dose response curve
adverse events/diadvantages to thiazide diuretics
may cause alkalosis by excretion of H+ ions (secondary passive exchange)
may cause much K+ loss
looses magnesium as well
becomes ineffective ones creatinine clearance goes below 30-50mL/min (they need a FUNCTIONING KIDNEY to work)
is a sulfa drug–allergies
SE include electrolyte disturbances, metabolic alkalosis, impaired glucose tolerance, hyperlipidemia, hyperuricemia, impotency
What types of findings can be seen on a urinary dipstick?
- glucose with or without ketones
- nitrites and/or WBC
- hematuria or proteinuria (isolated or concurrent)
How is glucose detected on urinary dipstick?
with Glucose detectin: enzymatic test (glucose oxidase)
How are ketones detected on urinary dipstick?
nitroprusside reaction detects ACETOACETATE and ACETONE–it does not detect beta hydroxybutarate
In what conditions will glucose be present in the urine
- Diabetes Mellitus–glucose concentration exceeds 10mmol/L in serum
- Renal glycosuria–renal tubular resporption defect
also: pancreatitis, pancreatic carcinoma, pheochromocytoma, Cushings, shock, burns, pain, steroids, hyperthyroidism, renal tubular disease
In what conditions will ketones be present in the urine?
- Diabetic ketoacidosis–diabetics without insulin cannot use glucose for fuel, so they start breaking down fats, which will produce ketones and lead to ketoacidosis–will have BOTH glucose and ketones in urine/blood
- fasting or starvation states
also, high fat diet, vomiting, diarrhea, hyperthyroidism, febrile state esp. in children, aspirin overdose
How are nitrites detected on urine dipstick?
Humans excrete nitrates, which are turned into nitrites by bacterial nitrite reductase
How are leukocytes detected on urine dipstick?
detects both lysed or intact leukocytes based on the presence of leukocyte esterase (an intracellular leukocyte enzyme)
In what condition are nitrites present in the urine?
bacteriuria
false negatives: enterococci, streptococci, staphylococci
in what conditions are leukocytes present in the urine?
inflammation (pyuria)
false negative results may occur in the presence of high urinary protein or ascorbic acid
–confirmatory test is microscopic analysis and culture
How is blood detected on urine dipstick analysis
test detects peroxidase-like activity associated with hemoglobin
how is proteinuria detected on urine dipstick
works on the principle that a change in protein concentration changes the ionic strength of the solution and leads to a color change in a pH sensitive dye in proportion to the ionic strength
normal is
In what conditions might you find blood in urine?
hematuria, hemoglobinuria, myoglobinuria
List possible causes/reasons for detection of blood (hematuria) on urine dipstick
- hematologic–coagulopathy, sickle hemoglobinopathy
- renal–(a) glomerular–primary glomerular disease, multisystem disease like systemic lupus and (b) nonglomerular–renal infarction, TB, pyelonephritis, tumor, trauma, polycystic kidney disease
- post renal–stones, tumor of ureter/bladder/urethra, cystitis, TB, prostatitis, urethritis, BPH
List the most common reasons for nontraumatic hematuria from most common to least
- kidney stones
- carcinoma of kidney or bladder
- urethritis
- UTI
- BPH
- glomerulonephritis
Why might there be protein detected on urine dipstick
- glomerular defect–lets by too much protein
- tubular defect–cant reabsorb proteins properly
- overflow proteinuria–Bence Jones protein
also: pyelonephritis, glomerulonephritis, glomerular sclerosis (diabetes), nephrotic syndrome, myelome, postural causes, preeclampsia, malignant HTN, CHF
what does hematuria + proteinuria indicate regarding cause of pathology?
indicates the hematuria is from a renal source i.e like glomerulonephritis
What are renal casts
- formed cylindrical structure organized in the nephron
- form following urine stasis (protein ppt)
- acid pH, high salt, reduce urine flow and protein contribute to formation
- appearance is determined by matrix (hyaline, granular, waxy) and trapped cellular constituents (rbcs, leukocytes, epithelial cells)
- ID may be difficult but importnat (because reflects underlying renal pathology)
what is an erythrocyte cast and what does it indicate pathologically
also known as RBC casts–they contain distinct RBCs
they indicate renal bleeding, glomerular injury
what are renal tubular epithelial casts and what do they indicate pathologically
they contain intact or necrotic epithelial cells
renal tubular injury (acute tubular necrosis)
what are coarse granular casts and what do they indicate pathologically
they are coarse refractile granules
they indicate cell degeneration and proteinuria
What are fine granular casts and what do they indicate pathologically
they are semitransparent
they are non specific in etiology
what are broad (waxy) casts and what do they indicate pathologically
wide width cast, formed in dilated tubules
indicate advanced renal disease
what are leukocyte casts and what do they indicate pathologically
contain segmented neutrophils
indicate pyelonephritis
what are hyaline casts and what do they indicate pathologically
nonspecific transparent cast
increase with exercise, dehydration and fever
what are fatty casts and what do they indicate pathologically
they are refractile droplets
lipiduria, NEPHRITIC syndrome
What are urine crystals?
- common, mostly not diagnostically significant
- usually form after voiding when urine is supersaturated with chemical constituents
- types depend on pH of urine
List types of acid urine crystal
- normal/common: URIC ACID, amorphous urates, sodium urate
- CYSTEIN (cysteinuria)
- cholesterol (rare, nephritic syndrome)
- leucine, tyrosine (rare, liver disease)
- bilirubin (liver disease)
- URIC ACID crystals
List the types of acid, neutral, to slightly alkaline crystals
CALCIUM OXALATE
list the types of alkaline urine crystals
- TRIPLE PHOSPHATE (ammonium Mg phosphate)
2. idinavir crystals (HIV patient)
What urinary crystals might you find in an HIV patient
idinavir crystals
What is a normal RBC count in urine
What diseases cause an increase in RBCs in urine
- variety of urinary tract diseases (prostatitis)
- dysmorphic = glomerular bleeding
what is normal WBC levels in urine?
what does an increased WBC count in urine mean
indicates urinary tract inflammatory and infectious disorders
what is the normal amount of renal tubular epithelial cells in urine
what do increased renal tubular cells in urine indicate
indicates tubular injury
what are oval fat bodies
lipid laden renal cells
what do oval fat bodies indicate pathologically when in urine
NEPHROTIC syndrome
what are transitional epithelial cells
large and oval with central nucleus
what do the presence of transitional epithelial cells in urine mean
inflammatory and malignant conditions
where do squamous epithelial cells in urine come from
from distal urinary tract and female genital tract
largest cells found in urine
are the presence of squamous epithelial cells in urine significant
not clinically
what are the major pathogenic mechanisms of glomerular disease? (list)
- immune mechanism–antibody mediated and cell mediated
- hemodynamic–hyperperfusion/hyperfiltration and ischemic
- podocyte injury
- polyanion loss
- metabolic–familial, acquired
Describe the immune mechanisms of glomerular disease
- antibody mediated–(a) immune complesex i.e post-infectious glomerular nephritis or (b) antibodies against the basement membrane i.e Goodpasture’s disease, rapidly progressive glomerular nephritis
- cell-mediated–possible T cell involvement in minimal change disease
In the antibody mediated mechanism of glomerular disease, where can antibodies deposit and how does this affect symptoms?
either:
1. in the subendothelial/mesangial (blood vessel) side–inflammation
- in the subepithelial (podocyte) side–no inflammation
Describe the hemodynamic mechanisms of glomerular disease
- hyperperfusion/hyperfiltration–increased pressure stretches podocytes causing damage
- ischemic–ischemia causes collagen deposition in bowman’s capsule and shrinkage of the glomerular tuft–i.e benign nephrosclerosis
describe podocyte injury as a mechanism of glomerular disease
mediated by mechanical, infection, chemical or metabolic causes
i.e focal segmental glomerulosclerosis
describe the polyanion loss mechanism of glomerular disease
loss of negative charge on basement membrane allowing the negatively charged albumin to move into bowman’s capsule–ie minimal change disease
describe metabolic mechanisms of glomerular disease
- familial–ie Fabry’s disease, cystinosis
- acquired–i.e diabetes mellitus; overstimulation of mesangial cells leads to an increase in matrix secretion and glycosylation of matrix component prevents degredation–thickened basement membrane prevents proper filtration
Normal urinalysis levels RE:
- clarity/turbidity
- pH
- specific gravity
- glucose
- ketones
- nitrites
- leukocyte esterase
- bilirubin
- RBCs
- WBCs
- protein
- squamous epithelial cells
- casts
- crystals
- bacteria
- yeast
- clear or cloudy
- 4.5-8
- 1.005-1.024
- less than 130 mg/d
- none
- negative
- negative
- negative
- less than 2-3 per hpf
- less than 2-5 per hpf
- less than 150 mg/d
- less than 15-20 per hpf
- 0-5 hyaline casts per hpf
- occasionally
- none
- none
