Term
What embryonic structures must fuse to ultimately become the adult kidney?
What structures does each component ultimately give rise to? |
|
Definition
Ureteric Bud and Metanephric Mesenchyme
1) Ureteric Bud (releases Wnt and binds GDNF)
- Renal pelvis
- Ureters
- Calcyces
- Collecting duct/tubules
2) Metanephric Mesenchyme (Reseases GDNF and binds WNT)
- PCT, DCT and LOH
- Renal corpuscles (except vessels) |
|
|
Term
| What does Hirschsprung disease have to do with embryonic renal development? |
|
Definition
Arises because of mutation in GNDF gene, which is produced in the metanephric mesenchyme and binds RET receptors on the Ureteric bud during development.
Mutation prevents proper innervation of intestine. |
|
|
Term
| What 2 genes are associated with congenital renal hypoplasia/dysplasia? |
|
Definition
PAX2/SALL1
Both are transcription factors that regulate GDNF signalling from the metanephric mesenchyme |
|
|
Term
How is GDNF expression limited to the sacral intermediate mesoderm during renal development?
What happens when this process is disrupted? |
|
Definition
SLIT/ROBO2 signaling (BMP 4 as well).
Mutations in ROBO2 signaling are associated with VUR (as well as EIA mutations) |
|
|
Term
| What is the molecular basis for the most common primary kidney tumor found in children? |
|
Definition
This is Wilm's Tumor
1) WT1 mutation prevents developmental arrest of metanephric precursor cells, thereby preventing proper metanephric differentiation
2) Resulting tumor is filled with arrested precursor cells. |
|
|
Term
| How do the bladder and urethra emerge embryologically? |
|
Definition
1) Cloaca splits into the Urogenital Sinus (UGS) and anorectal canal (4-7 weeks).
**at 7-8 weeks, cloacal membrane breaks down and UGS and ARC are exposed to amnion**
2) Cranial UGS becomes bladder and Caudal UGS becomes urethra
**UGS also becomes prostate and lower 1/3 of vagina** |
|
|
Term
| What artery impedes proper ascension of a horshoe kidney? |
|
Definition
Kidneys are fused at inferior poles and cannot ascend past the Inferior Mesenteric Artery.
This means that the kidneys cannot switch from metanephric to mesonephric circulation. |
|
|
Term
| What congenital malformation might give rise to a child with clubbed feet, craniofacial abnormalities and pulmonary hypoplasia. |
|
Definition
Renal Agenesis from RET or EYA1 mutations preventing proper Ureteric Bud development.
1) PE findings are consistent with Potter sequence
2) Would also see Oligohydramnios |
|
|
Term
| What is the pathological basis of PKD? |
|
Definition
Can be AR in children (polycistin) or AD in adults (PKD1 and PKD2).
1) Gene mutations disrupt proteins localized to non-motile cilia or ciliary basal bodies.
2) Non-motile cilia issues prevents regulation of cell polarity, cell cycle and Wnt signaling. |
|
|
Term
What are the normal values for each of the following?
1) RBF
2) RPF
3) GFR
4) FF |
|
Definition
1) 1200 ml/min or 180 L/day
2) 670 ml/min or about 95L/day
3) 100 (women) and 120 (men) ml/min
4) 0.18-0.22 |
|
|
Term
| How does Angiotensin 2 influence sodium reabsorption? |
|
Definition
Increases in low volume or "effective low volume" states, as well as low Na+ states.
1) Ang2 leads to efferent arteriolar constriction, which decreases RPF and increases GFR (initially).
2) Vasoconstriction increases DROP in hydrostatic pressure between the efferent arteriole and the peritubular capillaries.
3) Greater osmotic pressure:hydrostatic pressure in peritubular capillaries increases sodium reabsorption and water via "solvent drag" |
|
|
Term
What forms of autoregulation dominate in the context of low Na+ and normal BP?
What about when a patient is hypotensive or hypovolemic? |
|
Definition
1) Instrinsic autoregulation
- Myogenic, Ca2+ mediated regulation of afferent arteriole, causing contraction when vessel is stretched.
- Tubuloglomerular feedback in macular densa of cTAL, where How Cl- return causes renin release from JGA cells and causes contraction of the afferent arteriole via adenosine.
2) External neurohormonal regulation via RAAS |
|
|
Term
| What happens to the RAAS system during volume depletion? |
|
Definition
1) Low calcium levels lead to increased cAMP, which causes more renin release from JGA cells (e.g. more Ang2)
2) Ang2:AT1 binding causes
- PGE synthesis (type 1 medullary ECM cells)
- Aldosterone release from adrenal cortex.
- Decreased K+ (more secretion) because of aldosterone effect on principal cells of collecting duct. |
|
|
Term
| What makes inulin an ideal GFR substance? |
|
Definition
Same reason to use Creatinine clearance
1) freely filtered
2) not absorbed or secreted by tubules
3) not metabolized by kidneys |
|
|
Term
| What is the GFR of a 60 kg patient with a SCr of 1.2 mg/dL, a UCr of 100mg/ dL and a V of 1.2L/day? |
|
Definition
GFR= UCrV/SCr
= 1.2* 100/ 1.2= 100 L/day
- 100 * 1000 /1440= 70 ml/min. |
|
|
Term
| What are the major issues with using creatinine clearance to measure GFR clinically? |
|
Definition
1) 24h urine collection is not always reliable
Expected Cr per day (mg/kg/d)
Women= 15-25
Men= 20-30
Old= 10
children= 14.7 + (0.45Xage)
2) As GFR falls, rise in SCr is partially opposed by enhanced tubular secretion, which can overestimate GFR |
|
|
Term
| What are the limitations of using Serum Creatinine levels to estimate kidney function? |
|
Definition
1) Vary by age, gender, muscle mass ect.
2) Glomerular injury may not initially change GFR.
** Improve with Cockroft-Gault and MDRD formulas |
|
|
Term
| Use the Cockroft-Gault formula to predict the GFR of a 70 year old women who weight 50 kg with a SCr of 1.2 mg/dL. |
|
Definition
Remember, MRDR is more commonly used in practice
GFR=[(140-age)*weight in kg] / 72 * SCr
= (140-70)*50/ 72 * 1.2
= 350/86.4
= approximately 40 ml/min (VERY LOW) |
|
|
Term
| What are the limitations of using the Cockcroft Gault and MDRD formulas to estimate GFR, respectively? |
|
Definition
Use these to account for demographic differences missed by serum creatinine and to avoid 24h urine collection.
1) Cockcroft Gault will OVER estimate (used for dosing)
2) MDRD tends to UNDEResterimate |
|
|
Term
| In cases of AKI, what additional factors (other than GFR) does BUN help you assess? |
|
Definition
1) Dietary protein intake
2) Catabolism
3) Volume status
4) Renal perfusion |
|
|
Term
| What types of kidney stones are found in acidic/alkaline urine? |
|
Definition
1) Acidic
- Calcium oxylate (ethylene glycol)
- Uric acid (varied appearance)
- Cystine crystals (hexagons- always pathalogical)
2) Alkaline
- Uremic splitting in UTI with Triple stones (magnesium ammonium phosphate) that look like coffins
- Calcium carbonate crystals |
|
|
Term
What do each of the following urine sediments tell you about disease etiology?
1) Bland
2) Tubular cells with granular casts
3) RBC casts and hematuria
4) 4+ protein with fatty casts and oval fat bodies
5) WBC casts
6) Broad casts
7) Broad + Granular + RBC casts |
|
Definition
1) Pre-renal or Post-renal
2) ATN (most common cause of acute renal failure)
3) Nephritis (proliferative GN and renal vasculitis)
4) Nephrotic syndrome
5) Pyelonephritis of AIN
6) Chronic kidney failure
7) Telescoped urine found is ESRD |
|
|
Term
Which of the following hormones does not regulate ECF by altering Na excretion?
1) ANP
2) Aldosterone
3) Calcitrol
4) Angiotensin 2
5) ADH |
|
Definition
3) Calcitrol is the activated form of vitamin D (alpha-1 hydroxylase mediated cleavage) that inhibits PTH.
1) ANP is synthesized by atrial myocytes in response to stretch and stimulates sodium excretion by inhibiting the Na/K+ ATPase on the basolateral membrane of tubular epithelial cells.
**similar action to "third factors" from hypothalamus**
2) Aldosterone binds MR receptor and causes transcription of AIP genes that increase sodium channel expression in the distal nephron (NCC and ENaC). It also activates Na/K+ ATPase in the distal nephron
4) Angiotensin 2 increases Na+ reabsorption by causing aldosterone release, and causing efferent arteriole constriction (ultimately increases osmotic:hydrostatic gradient in peritubular capillaries).
5) ADH is released in response to increases in osmolality or volume depletion and leads to Aquaporin insertion in collecting duct (primary) and acts on Na/K/2Cl- in TAL and NCC and ENaC in distal nephron |
|
|
Term
| How does a decreased glomerual capillary flow rate influence sodium reabsorption? |
|
Definition
| Decreased flow rate increases the rate of rise in oncotic pressure in the peritubular capillaries, thereby increasing the amount of sodium that is reabsorbed. |
|
|
Term
| How is sodium reabsorbed in the proximal convoluted tubule? |
|
Definition
PCT= 65%- isoosmotic
-
1) Na+/H+ exchanger in apical membrane that derives energy from gradient produced by Na/K ATPase in basolateral membrane of tubular epithelial cell brings Na+ from the tubules into the the cell.
2) Na+ is then transported to the IT space via Na+/3HCO3- channels and Na/K ATPase in basolateral membrane
**Some sodium goes paracellularly with Cl-**
3) Once in IT space, Na+ either gets absorbed by peritubular capillaries via "solvent drag" (if oncotic pressure is high), or leaks back across tight junctions (RATE LIMITING STEP) |
|
|
Term
| How is sodium reabsorbed in the Loop of Henle? |
|
Definition
25-30% (50% of which is transcellular and 50% paracellular)
1) In thin loops, all transport is passive
2a) In TAL, Na+ enters apical membrane via Na/K/2Cl- transporter and exits basolateral membrane via Na/K ATPase (TRANSCELLULAR). Chloride exits via Cl- channels.
2b) In TAL, ROMK K+ channels in apical membrane create lumin (+) potential that drives paracellular transport of Na+, Mg2+ and Ca2+ into the IT space (PARACELLULAR)
**paracellular uses no energy!** |
|
|
Term
| How is sodium reabsorbed in the Distal Nephron? |
|
Definition
4-8% reabsorbed here (Aldosterone sensitive segment)
1) In early DCT, Na+ reabsorbed by Na,Cl co-transporter (thiazide sensitive)
2) In late DCT, Na+ reabsorbed by ENaC channel (K+ sparing sensitive)
**Mg2+ and Ca2+ are transported transcellularly** |
|
|
Term
| How does "effective volume depletion" in CHF influence renin release and what are the effects? |
|
Definition
1) Increased renin leads to increased Angiotensin 2 binding to AT1 receptor.
2a) increases Na+ reabsorption in proximal tubule by causing efferent arteriole constriction (ultimately increases osmotic:hydrostatic gradient in peritubular capillaries).
**also activates Na/H exchange**
2b) Increases Na+ reabsorption in distal nephron by causing aldosterone release (NCC and ENaC activation), and
3) Increased urea reabsorption (elevated BUN:creatinine) |
|
|
Term
| How is sodium reabsorption hormonally altered when peritibular capillary osmolality is high. |
|
Definition
ADH is released from posterior pituitary (driven by plasma osmolality and/or volume status)
1) ADH activates Na,K,2Cl- channel in TAL to increase Na/H2O reabsorption
2) ADH activates NCC and ENaC channels in distal nephron as well.
3) ADH causes aquaporin insertion in the collecting duct membrane from H20 reabsorption |
|
|
Term
| How does aldosterone regulate sodium reabsorption in a hyperkalemic patient? |
|
Definition
Aldosterone is secreted by adrenal cortex in response to 1) High K+ or 2) AngII
1) Aldosterone binds MR receptor which up-regulates AIPs, which activate SGK
2) SGK phosphorylates NEDD4, inactivating it and preventing it from keeping ENaC channels away from the membrane surface
3) More ENaC means more sodium reabsorption and more K+ secretion from principal cells of collecting duct. |
|
|
Term
| How do ANP and dopamine regulate sodium handling? |
|
Definition
1) ANP released from atrial myocytes in response to stretch, increasing GFR and inhibiting basolateral Na/K ATPase in the medullary collecting duct (increase excretion).
2) Dopamine increases Na excretion by inhibiting Na/H and Na/K ATPase in proximal tubule, as well as inactivating ENaC in distal nephron. |
|
|
Term
| How is water distributed between the IC and EC compartments in the body? |
|
Definition
1/3 EC and 2/3 IC
of 1/3, 3/4 is IT and 1/4 is IV
60% of body weight in males and 50% in females |
|
|
Term
A patient presents with orthostatic hypotension, tachycardia, low JVP and dizziness.
The patient is excreted concentrated, hyponatremic urine.
What is the hormonal compensatory response that is occurring in this patient? |
|
Definition
This is volume depletion from the IV space
(IT space would be poor skin turgor and dry mucous membranes).
1) RAAS is activated by TGF in macula densa
- Increased Na+ reabsorption (water as well)
- Increased K+ and H+ secretion via aldosterone
2) ADH is released since baroreceptors in carotid sinus sense low volume/pressure.
- Increased Na/H20 reabsorption in TAL and distal nephron
3) SNS activated
- vasoconstriction, increased contractility |
|
|
Term
Which rare inherited syndromes are associated with each of the following?
1) Na,K,2Cl in TAL
2) NCC in early DCT
3) ENaC in late DCT
4) Cortisol
5) |
|
Definition
1) Bartter syndrome involves mutation in this channel leading to Na+ wasting, hypokalemia and hypotension (LOOP DIURETIC LIKE)
2)
- Gitelman is LOF mutation (Thiazide like) with hypotension and hypokalemia
- Gordon is GOF mutation in NCC or ROMK with hypertension and hyperkalemia
3)
- Pseudohypoaldosteronism Type 1 is AR disorder that involves ENaC defect (K+ sparing like) with hypotension and hyperkalemia.
- Liddle's syndrome is GOF mutation in ENaC leading to hypertension and hypokalemia with metabolic acidosis
4) Syndrome of apparent Mineralcorticoid excess due to mutation is 11b OHSD where cortisol is not broken down and remains active, producing hypokalemia, hypertension and low aldosterone levels. |
|
|
Term
How do you treat volume overload associated with each of the following?
1) CHF
2) Liver cirrhosis
3) Nephrotic syndrome |
|
Definition
All of these are low "effective circulating arterial blood volume" conditions.
Treat all with Diuretics and Sodium restriction
1) Inotropes
2) Liver transplant
3) Steroids, cyclophosphamide (mezna) and ACE-i |
|
|
Term
| How do cells compensate for hypoosomlar extra cellular fluid and hyperosmolar extra cellular fluid? |
|
Definition
1) Hyposomal ECF will cause cellular swelling, so cells dump out KCl
2) Hyperosmal ECF will cause cellular shrinkage, so cells make or take up (NaCl) osmoles |
|
|
Term
| How does urea transport in the distal nephron influence urine concentration? |
|
Definition
During states of active water reabsorption (ADH-mediated), urea is also reabsorbed and contributes to the osmolality of the medullary IT.
If medullary urea drops (cases of diabetes insipidus where water cannot be reabsorbed), urine CANNOT be concentrated. |
|
|
Term
| How is water removed from the interstitium after ADH-mediated reabsorption in the medullary collecting duct? |
|
Definition
Countercurrrent Exchanger
H20 removed by vasa recta |
|
|
Term
| How does ADH modulate tonicity? |
|
Definition
Peptide made in the supraoptic nucleus of the hypothalamus and released from the posterior pituitary.
1) Secreted in response to high EC osmolality or low body volume (prior to the onset of thirst at 300 Osm/Kg)
2) ADH binds to V2 receptors on tubular epithelial cells in the collecting duct, leading to cAMP-mediated aquaporin insertion in the apical membranes. |
|
|
Term
| How does "volume regulation" differ from "water regulation" in terms of hormonal mediators? |
|
Definition
Volume= Na + H20
- RAAS and SNS
Water= H20
- ADH and thirst |
|
|
Term
| How do the treatments for dehydration and volume depletion differ? |
|
Definition
Always correct VOLUME first
Dehydration is lack of free H20
- Free water repletion (slowly)
Volume depletion
- Isotonic replacement (more rapidly) |
|
|
Term
| How does Mannitol alter the kidney's ability to concentrate/dilute urine? |
|
Definition
Osmotic diuretic that cannot be reabsorbed by the tubules and prevents Na/H20 reabsorption as well.
This can cause hypertonic hyponatremia, since there will be a hypertonic EC, which will draw fluid out of the IC space and dilute the EC space. |
|
|
Term
| How does hypotonic hyponatremia develop? |
|
Definition
H2O intake > H2O excretion
1) HUGE water intake (psychogenic polydipsia) with normal excretion
2) Normal intake with impaired excretion (high ADH or low EABV)
Low-volume hyponatremia
Normal-volume hyponatremia (psychogenic polydipsia, GR deficiency, Hypothyroid, SIADH)
High-volume hyponatremia (CHF, nephrotic syndrome, cirrhosis) |
|
|
Term
| What are the most common causes of SIADH and how do you treat? |
|
Definition
Euvolemic hypotonic hyponatremia due to 1) Lung cancer, 2) Pulmonary disease, 3) CNS disorder or 4) Drugs
1) Hypertonic saline with Furosemide (if serious CNS symptoms) acutely (otherwise fluid restrict alone).
2) Fluid restriction chronically and may continue loop diuretic or add demeclocycline (ADH inhibitor in collecting duct). |
|
|
Term
What is the proper therapeutic management for each of the following disorders of tonicity?
1) Low volume hyponatremia
2) Euvolemic hyponatremia (Psychogenic or SIADH)
3) High volume hyponatremia (CHF, Cirrhosis, Nephrosis)
4) Low volume hypernatremia
5) Euvolemic hypernatremia (NDI or CDI)
6) High volume hypernatremia (iatrogenic) |
|
Definition
1-3 caused by Low EABV and/or high ADH
1) Isotonic saline
2) Water restriction
3) Water and salt restriction
4) Saline, then water (volume first)
5) Water replacement
6) Diuretics and H2O replacement |
|
|
Term
True or False.
Hypertonic states cannot occur if the thirst mechanism is intact, the patient has access to free water and can ingest sufficient quantities. |
|
Definition
|
|
Term
| Why is it critical to give water replacement slowly for cases of hypernatremia? |
|
Definition
Hypertonic ECF causes cellular shrinkage, which causes neurons to produce idiogenic osmoles to counter.
If you give water really fast, you will actually cause cerebral EDEMA!
This is the opposite of treating hyponatremia, where you must raise Na slowly to avoid CPM, because of cellular swelling that has been compensated for by KCl dumping. |
|
|
Term
| What are the major causes of euvolemic hypernatremia, how can you distinguish between them and how can you treat them? |
|
Definition
This means volume status is fine, but sodium is high.
Give dDAVP and see if there is a response (means CDI), and give SLOW water replacement for BOTH.
1) Central Diabetes Insipidus
- Reduced ADH secretion
- Treat with dDAVP
2) Nephrogenic Diabetes insipidus
- Collecting duct can't respond to ADH
- Thiazide diuretics
- Amiloride for Lithium-induced cases. |
|
|
Term
| What are the most common causes of high-volume hypernatremia and how should you treat? |
|
Definition
Iatrogenic (NaHCO3 or Hypertonic saline).
Diuretic FIRST and Free Water replacement
- Consider dialysis if renal failure is severe |
|
|
Term
| What disorder of tonicity might you see in conditions of osmotic diuresis (Mannitol or hyperglycemia)? |
|
Definition
Low volume hypernatremia
Restore volume with saline and then give free water. |
|
|
Term
| How would you calculate a free water deficit for free water replacement therapy? |
|
Definition
TBWnormal X (Pna normal/Pna present)
FWD= (weight)(0.6 or 0.5) X (140/x) |
|
|
Term
| What is the action of loop/high ceiling diuretics and how are they most commonly used? |
|
Definition
Inhibit Na,K,2CL- transporter in TAL, leading to increased sodium delivery to distal nephron (this can cause K+ wasting and H+ excretion).
Very effective at treating acute pulmonary edema and CHF due to their brisk naturesis and increase in venous capacitance.
Also used in nephrotic syndrome, cirrhosis (volume contraction is an issue here) and Hypercalcemia.
**Remember, K+ is recycled at this site by ROMK channel in the apical membrane to drive Ca2+/Mg2+/Na+ paracellular transport.
**Cl- is removed in the basolateral membrane via CLC-Kb channels** |
|
|
Term
How do K+ sparing diuretics work to inhibit sodium reabsorption?
Why are they most commonly prescribed? |
|
Definition
Amiloride and Triamterene inhibit ENaC in distal nephron, inhibiting the generation of a negative intraluminal potential for K+ excretion by principle cells of the collecting duct.
Generally prescribed in combination for their K+ sparing capability to treat HTN, Liddle's syndrome and NDI (lithium-induced cases)
WATCH OUT FOR HYPERKALEMIA
- renal stones and AIN are also issues |
|
|
Term
What diuretics can cause hypokalemia and how does this happen?
Why do they also cause tubular acidification? |
|
Definition
1) Loop and Thiazide diuretics are a problem, because they increase sodium delivery to the distal nephron, causing increased reabsorption by ENaC channels in principal cells, enhancing the luminal negative potential that drives K+ secretion.
2) Remember that Type A intercalated cells in the collecting duct secrete H+ into the tubular lumen (H+ ATPase), and also rely on this luminal negative potential. |
|
|
Term
What congenital disorder exerts similar effects to each of the following diuretics?
1) Loop
2) Thiazide
3) K+ sparing |
|
Definition
1) Loop= Na,K,2Cl in TAL= Bartter syndrome (hypotension and hypokalemia)
2) Thiazide= NCC in early DCT= Gitelman syndrome (hypotension and hypokalemia)
3) K+ sparing= ENaC in late DCT= Pseudohypoaldosteronism Type 1 (AR disorder with hypotension and hyperkalemia) |
|
|
Term
| Why are spironolactone and eplenerone called "K+ sparing"? |
|
Definition
They inhibit aldosterone, which binds mineralcorticoid receptors in the distal nephron and causes AIP expression.
Usually, AIP expression drives sodium reabsorption and Na/K ATPase stimulation in the principal cells of the collecting duct, which increases K+ excretion. When this process does not occur, you do not lose K+, but you prevent RAAS mediated sodium/water retention. |
|
|
Term
| Why prescribe a diuretic (most commonly)? |
|
Definition
| Generalized edema due to CHF, Cirrhosis of the liver or Nephrotic syndrome |
|
|
Term
A patient presents with Palmar Erythema, Jaundice, Hypoalbuminemia and Spider Angiomata.
Why might you see systemic edema in this patient? |
|
Definition
Liver Cirrhosis Signs.
1) Chronic hepatocyte damage leads to fibrosis and compression of sinusoids and veins (sinusoidal and portal HTN)
2) Increased capillary hydrostatic pressure leads to net filtration into interstitial space (Ascites)
3) IV fluid falls and activates RAAS, which leads to sodium retention, K+ and H+ excretion Systemic edema. |
|
|
Term
| What are the 2 primary pathways that generate renal edema? |
|
Definition
1) Nephrotic (albumin loss)
- Low capillary oncotic pressure causes fluid to exit IV space and enter IT space.
2) Nephritic (glomerular)
- Reduced GFR causes increase Na retention and systemic edema |
|
|
Term
What do each of the following clinical descriptions indicate about the underlying etiology? How do you treat?
1) Severe edema without facial involvement or albumin loss
2) Mild edema with severe facial edema and hypoalbuminemia/proteinuria
3) Moderate edema with ascites and moderate hypoalbuminemia |
|
Definition
1) CHF- Probably use a loop diuretic or thiazide
2) Renal (Nephrotic/Nephritic)- Treat with Thiazide diuretic
3) Hepatic (cirrhosis)- Treat with Spironolactone |
|
|
Term
| Why is idiopathic edema such an issue? |
|
Definition
Cosmetic issue in pregnant women that causes many eating disorders.
Occurs in pregnant women because filtration overwhelms lymphatic drainage capacity and increased capillary permeability causes fluid to exit into the IT space. |
|
|
Term
|
Definition
Agents that cause WATER excretion, and not volume excretion.
1) Mannitol is an example (non-reabsorbed solute that pulls water out with it and can generate hypernatremia)
2) ADH inhibitors that prevent cAMP-dependent insertion of aquaporins into the collecting duct apical membranes. |
|
|
Term
| Why use a Thiazide diuretic in particular? |
|
Definition
Remember, these are NCC inhibitors with hypokalemia issues.
1) Best initial treatment for uncomplicated HTN.
2) Mainstay for NDI (along with Amiloride for lithium-induced)
3) Calcium nephrolithiasis |
|
|
Term
| With which diuretic class is hyponatremia a major concern? |
|
Definition
Thiazide diuretics because of
- decreased EFCV producing thirst and ADH secretion.
- Blockage of diluting segment of DCT prevents the kidney from excreting dilute urine and SUSTAINS the hyponatremia |
|
|
Term
| Why might you prescribe Spironolactone? What are the important SE to look out for? |
|
Definition
High aldosterone states
DRUG OF CHOICE for hepatic cirrhosis
1) Primary hyperaldosteronism
2) Refractory edema with secondary hyperaldosteronism
** look out for hyperkalemia, gynecomastia, gastritis and impotence** |
|
|
Term
What do each of the following do to a diuretics "ceiling dose"?
1) Increased Potency
2) Increased tubular transport
3) Decreased urinary protein binding |
|
Definition
ALL with decrease ceiling dose (takes less to get maximal effect)
LOOPs have highest cieling effects (least resistant) |
|
|
Term
| What contributes to increasing diuretic resistance? |
|
Definition
Diuretic Resistance= Lower ceiling effect
1) Noncompliance
2) NSAIDS (PGE inhibition decreases GFR and prevents tubular delivery).
3) Decreased tubular transport
4) Decreased RBF
5) ADH or RAAS changes
6) Distal nephron compensation
7) Diminished nephron responsiveness |
|
|
Term
| How can you prevent diuretic resistance? |
|
Definition
Resistance arises with distal compensation, when more ENaC channels are shuttled to the membrane in response to proximal channel inhibition.
1) Counseling for noncompliance
2) Continous infusion
3) Sequential blockage |
|
|
Term
| How is K+ secreted and reabsorbed in the distal nephron? |
|
Definition
1) Secreted from Principle cells
- ENaC brings sodium into the cell through the apical membrane, where it is then exchanged for K+ via the Na/K ATPase.
- K+ is also kicked out via ROMK (intraluminal + charge drives this)
2) Reabsorbed in Intercalated cells via H+/K+ ATPase in apical membrane and Na/K+ ATPase in basolateral membrane |
|
|
Term
| What are the 2 major factors that regulate distal tubular K+ handling? |
|
Definition
1) Distal tubular flow rate (and by extension, Na+ delivery)
- Increased DTF increases K+ secretion
2) Aldosterone
- Increases K+ excretion
**pH and luminal anion composition also regulates K+ handling** |
|
|
Term
| What are the 2 major factors that regulate distal tubular K+ handling? |
|
Definition
1) Distal tubular flow rate (and by extension, Na+ delivery)
- Increased DTF increases K+ secretion
2) Aldosterone
- Increases K+ excretion
**pH and luminal anion composition also regulates K+ handling** |
|
|
Term
| How does the kidney compensate for high K+ intake over time? |
|
Definition
1) At first, excretion is increased via aldosterone.
2) Over time, Na/K ATPase activity increases, as does Na+ and K+ transport in the apical membrane. Intercalated cells also take up less K+ |
|
|
Term
| What happens to K+ handling during intravascular volume depletion? |
|
Definition
| Decreased tubular flow rate (decreased secretion) and Increased Aldosterone (increased secretion) BALANCE |
|
|
Term
| What 3 chemical stimulate intracellular K+ uptake (internal balance) and when might you use them clinically? |
|
Definition
Might give insulin, beta agonists or synthetic aldosterone in Hyperkalemic states.
1) Insulin through Na/K+ ATPase stimulation (diabetics can have hyperkalemia)
2) Beta-2 adrenergic receptor stimulation in liver/muscle increases Na/K ATPase activity
3) Aldosterone- Minor effect intriincally, compared to extrinsically. |
|
|
Term
What happens to K+ handling under conditions of high serum bicarbonate?
What about with increased plasma tonicity? |
|
Definition
1) Alkalemia causes H+ to exit intracellular space and K+ is exchanged, entering cells and ultimately being excreted.
This is why Alkalemia is associated with hypokalemia.
2) Increased plasma tonicity causes K+ to enter EC space via solvent-drag (since water is being pulled out). |
|
|
Term
| What external factors cause chronic hyperkalemia? |
|
Definition
remember, external factors cause chronic hyperkalemia (internal factors cause acute hyperkalemia)
1) Excess intake
2) Decreased excretion (insufficiency)
3) Decreased distal tubular flow
4) Mineralcorticoid deficiency
5) Distal tubular dysfunction |
|
|
Term
| What internal factors cause acute hyperkalemia? |
|
Definition
1) Insulin deficiency (DM)
2) Beta-adrenergic blockage
3) Hypertonicity
4) Acidemia (especially Hyperchloremic)
5) Cell lysis |
|
|
Term
All of the following would generate a hyperkalemic state EXCEPT:
1) Aldosterone deficiency
2) Cell proliferation
3) Insulin deficiency
4) Hypertonic plasma
5) Acidemia |
|
Definition
| 2) proliferating cells take up K+ |
|
|
Term
True or False:
Hypokalemia causes decreased neuronal membrane excitability |
|
Definition
False!
Hypokalemia would cause a "hyperpolarized" membrane, which would actually increase the sensitivity of voltage-gated Na+ channels to generate AP.
HYPERkalemia causes cardiac toxicity and NM toxicity because of decreased excitability. |
|
|
Term
| How should you treat Hyperkalemia? |
|
Definition
1) Acutely control membrane potential with IV calcium (increase excitability).
2) Get it back into cells- give IV insulin, beta agonists and sodium bicarbonate to get K+ back into cells.
3) Increase elimination with loop/thiazide diuretics and IV saline
**Give hemodialysis if you see CNS symptoms and/or EKG changes (T wave exaggeration, QRS widening, ect). |
|
|
Term
Why do you see hypokalemia in the context of HTN and what are the major HTN hyperkalemic disorders??
How can it arise in normotensive individuals? |
|
Definition
HTN causes MR up-regulation, which leads to AIP expression and increased sodium reabsorption/K+ secretion
1) HyperReninemia from renal artery stenosis
2) Primary hyperaldosteronism (Conn's syndrome)
3) Cushing's disease (adrenal tumor and cortisol release)
4) Congenital adrenal hyperplasia
Normotensive
1) Osmotic diuresis
2) RTA
3) Vomiting and nasogastric lavage (metabolic acidosis)
4) Ureteral diversion |
|
|
Term
| Why does tubular acidification increase K+ secretion? How can it arise? |
|
Definition
1) H+ intercalated cells prevents K+ uptake from tubules.
2) Types 1, 2 and 4
- Type 1 is distal tubule acidification and involves failure of H+ secretion by intercalated cells, which prevents K+ reuptake (Hypokalemia)
- Type 2 is a proximal defect where HCO3- cannot be taken up from urinary space, thereby leading to acidemia. The decreased HCO3- uptake prevents Na/Cl reabsopriton and ultimately leads to hyperaldosteronism, which causes hypokalemia.
- Type 4 is an aldosterone deficiency and actually generates HYPERkalemia |
|
|
Term
| How does the bicarbonate buffering system resist changes in BODY pH when a strong acid is added? |
|
Definition
When a strong acid is added, the pH of the solution will be less than the pKa of HCO3-, so it will become protonated as carbonic acid.
Carbonic acid is stress broken into CO2 and H2O (CA) and CO2 is vented out of the lungs (increased respiration rate) |
|
|
Term
| How is volatile acid production managed by the respiratory system? |
|
Definition
1) Oxidative metabolism of nutrients produces CO2, which enters RBCs
2) Once in RBCs, CA-mediated carbonic acid production eventually yields H+ and HCO3- (when pO2 is low, H+ binds to Hb)
3) When RBC reaches pulmonary capillary, CO2 is released and excreted by lungs |
|
|
Term
| How is fixed acid excretion managed by the kidneys? |
|
Definition
1) Distal tubular acid secretion
2) Ammonium generation and excretion1 |
|
|
Term
| How is filtered HCO3- handled in the proximal tubule of the nephron? How is the energy for this exchange generated? |
|
Definition
All driven by Na/K ATPase
1) Na/H exchange leads to H+ secretion into the tubule, where it complexes with HCO3- and is rapidly converted to CO2 and H2O (CA mediated)
2) CO2 re-enters proximal tubule and complexes with H2O (CA mediated), eventually regenerating HCO3- and H+.
3) H+ is again secreted in exchange for Na+, but HCO3- passes with Na (Na+/3HCO3-) across the basolateral membrane and into the interstitial space. |
|
|
Term
What effect does each of the following have on HCO3- handling and acid-base balance in the proximal tubule?
1) Decreased intravascular volume
2) Chloride depletion
3) Acidemia
4) Hyperkalemia
5) High PCO2 |
|
Definition
1) RAAS activation increases H+ secretion from proximal tubule, leading to increased HCO3- uptake
2) Increase in Na:HCO3- coupled transport (seen in volume depletion usually)
3) Increased H+ secretion leads to increased HCO3- reabsorption (inhibited during alkalemia)
4) High K+ leads to increased H+ exchange in the collecting duct, which inhibits HCO3- reabsorption.
5) Hypercapnia leads to increased H+ secretion across PT and increased bicarbonate retention. |
|
|
Term
| How is filtered HCO3- handled in the distal tubule of the nephron? How is the energy for this exchange generated? |
|
Definition
1) K+ is excreted from principle cells via ROMK channels, thereby providing a driving force for H+ exchange in intercalated cells.
**Increased sodium reabsorption leads to increased H+ secretion and increased H+ reabsorption.
2) HCO3- is taken into the IT space via HCO3-/Cl exchangers in the basolateral membrane of intercalated cells. |
|
|
Term
| What is the effect of mineralocorticoids, urinary buffers and K+ on distal nephron H+ secretion? |
|
Definition
1) Mineralocorticoids lead to increased Na+ reabsorption in principle cells, and K+ secretion, which ultimately drives H+ secretion from intercalated cells.
**Deficiency may therefore produce acidemia**
2) Urinary buffers titrate secreted H+ ion and there presence leads to more secretion. Deficiencies inhibit secretion.
3) Hypokalemia will increase H+ secretion, via H+/K+ ATPase exchange in the intercalated cells. This is why hypokalemia is associated with alkalemia. |
|
|
Term
| Why is ammoniogensis in the proximal tubule stimulated by hypokalemia and acidemia? |
|
Definition
1) Hypokalemia leads to increased exchange of K+ for H+ in the IT space via H+/K+ ATPase, which increases the intracellular H+ concentration and ultimately acidify the urine.
Urine acidification increases NH4+ synthesis from glutamine, which also generates HCO3-, which is reabsorbed.
2) Acidemia leads will also lead to increased K+ exchange for H+, raising intracellular H+ concentrations and ultimately acidifying the urine.
The resulting HCO3- reabsorption will counter the acidemia |
|
|
Term
| How is ammonium buffering achieved in the nephron? |
|
Definition
Stimulated by Hypokalemia and Acidemia
1) 2NH4+ is synthesized from glutamine in the proximal tubule, producing 2HCO3- in the process, which are reabsorbed into the IT space.
2) NH4+ is secreted as either NH4 or NH3 and H+ and continues in the tubules as NH4+ until it reaches the TAL, where is it reabsorbed via the Na,K,2Cl transporter (in place of K+)
3) In IT space, small amount of NH4 becomes NH3 and H+, and NH3 (NOT NH4) can diffuse across the collecting duct.
4) NH3 that enters collecting duct can then buffer H+ and become "trapped" |
|
|
Term
| What is the relationship between ammonium excretion and bicarbonate reabsorption? |
|
Definition
Every molecule of NH4+ that is excreted means that 1 HCO3- is reabsorbed.
This is why NH4+ production is stimulated by
1) Hypokalemia
2) Acidemia |
|
|
Term
Patient's serum pH is 7.34.
[Na]= 140 mM
[Cl]= 100 mM
[HCO3]= 18mM
pCO2= 34mM
What is this condition? |
|
Definition
High AG metabolic acidosis with respiratory compensation.
pH is acidemia.
Bicarbonate is low (23-28 is normal), but pCO2 is normal
pCO2 is also low (38-42 is normal)
[AG]= 140 - 100- 18= 22 (high- normal is 10)
PCO2= 1.5 (18) +8 +/- 2= 34-38 (so compensation is appropriate) |
|
|
Term
| What are the causes of high AG metabolic acidosis? |
|
Definition
MUD PILES
1) Methanol
2) Uremia
3) DKA
4) Paraldehyde
5) Iron/ Isoniazide
6) Lactic acidosis
7) Ethylene glycol
8) Salicylate |
|
|
Term
| How do you determine whether respiratory compensation for metabolic acidosis is appropriate, or whether you are dealing with multiple acid-base disorders? |
|
Definition
Winter's formula
pCO2= 1.5 X tCO2 + 8 +/- 2 |
|
|
Term
| What are the major causes of Hypercholoremic metabolic acidosis? |
|
Definition
Serum HCO3- is decreased, but Cl- is increased (no AG) HARD UP
1) Hyperalimentation (eat a lot)
2) Acetazolamide and other CA inhibitors (used to
3) RTA
4) Diarrhea
5) Uretoenteric fistula
6) Pancreatic cyst |
|
|
Term
| What are the 3 renal tubular acidoses that can produce hypercholoremic metabolic acidosis? |
|
Definition
1) Type 1 (classic hypokelmic)- Impaired H+ secretion in intercalated cells with
2) Type 2 (proximal hypokalemic)- failed HCO3- uptake
(impaired H+ secretion and lowered threshold for HCO3- reabsorption- "you start wasting sooner")
3) Type 4 (Hyperkalemic)- Hypoaldosteronism leading to hyperkalemia, which decreases ammonium secretion, so you can't get rid of acid.
**Can also be due to voltage-edependent defect in H+ ion secretion.** |
|
|
Term
| How can you distinguish between renal and non-renal causes of hyperchloremic metabolic acidosis? |
|
Definition
Remember, this is HARD UP
Hyperalimentation, Acetazolamide, RTA, Diarhea, Ureterenteric redirection, Pancreatic cyst
Use the Urinary acid gap (Na + K - Cl)
- If >= 0, you are dealing with renal issue
- if <-, it is a non-renal issue |
|
|
Term
How should you treat a diabetic patient with serum pH of 7.0?
They are 70 kg, and their current tCO2 is 19. You want tCO2 to be 22 (not quite normal but closer) |
|
Definition
Diabetic KA with pH< 7.1 should be given insulin (if DM is poorly controlled) and ALKALI replacement to prevent myocardial risk (anything under 7.1 needs replacement)
HCO3 dose= 0.5 X TBW X ([HCO3]desired - [HCO3]actual)
= 0.5 (70) X (22-19)= 105 mmol |
|
|
Term
| Describe the generation and maintenance of a metabolic alkylosis. |
|
Definition
Remember, this is HIGH HCO3- with a compensation of rising pCO2 (breathe slower).
1) Generated by alkali gain or acid loss (hypokalemia and mineralcorticoid excess)
2) Maintained by impaired renal bicarbonate excretion resulting from Decreasd GFR, increased proximal tubular reclamation or Increased H+ secretion |
|
|
Term
| How can urinary chloride help you diagnose a cause of metabolic alkylosis? |
|
Definition
If <20 mmol/L, you are volume depleted
If >2- mmolL, it is excess aldosterone or Bartter's syndrome. |
|
|
Term
| How can you treat a patient with metabolic alkylosis? |
|
Definition
Depends on saline responsiveness.
1) If saline-responsive, expanded IV volume with decrease HCO3- reabsorption (can give KCl if Hypokalemicc)
2) If not responsive, you should treat mineralcorticoid excess (sprinolactone) or potassium wasting with K+ repletion. |
|
|
Term
| If a patient with a pH of 7.4 has HCO3- of 20 and a pCO2 of 20, what does that tell you? |
|
Definition
Bicarbonate is low (normal is 23-28), and pCO2 is also low (normal is 38-42).
HOWEVER< pH is normal. You are therefore dealing with a mixed disorder (compensation is NEVER complete).
This is metabolic acidosis with respiratory alkalosis. |
|
|
Term
| Why might treatment with acetazolamide cause hyperchloremic metabolic acidosis? |
|
Definition
Acetazolamide is a CA-i that acts in the proximal tubule. It prevents HCO3- re-uptake and is used to treat moderate metabolic alkalosis.
However, if you give too much, you will prevent H+ secretion to the point of alkalosis. However, Cl- will increase to the degree that HCO3- decreases, so there is a normal AG of 10. |
|
|
Term
What are the normal ranges for each of the following?
1) BUN
2) Creatinine
3) Na
4) K
5) Cl
6) tCO2
7) arterial pH
8) pCO2 |
|
Definition
1) 10-20 mg/dl
2) 0.6-1.2 mg/dl
3) 135-145
4) 3.5-5
5) 95-105
6) 23-28
7) 7.37-7.43
8) 38-42 mmHg |
|
|
Term
44 year old african american male presents with severe headache and retinal hemorrhages.
His BP is 160/120
What would you see on a gross/microscopic histological preparation section of his kidney? |
|
Definition
Malignant hypertension
Grossly appears flee bitten
Microscopically you see onion-skinning of capillaries (spared in benign HTN) |
|
|
Term
| What are the 3 common thrombotic diseases that affect the kidney? |
|
Definition
1) DIC from septicemia
2) Thrombotic Thrombocytopenic Purpura
3) HUS (oral contraceptives, E. coli, breast cancer) |
|
|
Term
| What is a common and concerning complication of chronic drug-induced interstitial nephritis |
|
Definition
Remember, chronic IN is oxidative damage and acutev IN is type 1 hypersensitivity (eosinophils against backdrop of edema)
Transition Cell Carcinoma! usually from smoking |
|
|
Term
What organisms commonly cause UTIs by colonizing catheter lumens?
What about urothelial cells? |
|
Definition
Proteus, Providencia (MOST COMMON) adhere to catheters
DONT TREAT WITH ANTIBIOTICS
E. coli adhere to urothelial cells |
|
|
Term
You obtain an isolated bacterial count of 10^2 CFU from the urinary tract of an asymptomatic patient.
What do you do? |
|
Definition
| ONLY treat if they are pregnant (Strep B hemolytic risk of infant meningitis) or about to undergo urologic surgery |
|
|
Term
Patient presents with dysuria, pyuria (15 leukocytes/mm ^3), but bacterial CFU < 10^2.
What is going on and how do you treat? |
|
Definition
| Sounds like Urethritis due to Chlamydia or Gonorrhoeae. |
|
|
Term
Woman with normal GU tract presents with increased frequency, urgency , dysuria and suprapubic pain.
Bacteria are found (10 ^ 4 CFU/ml)
UA comes back and is LE positive and nitrite positive
What do you do? |
|
Definition
Uncomplicated Cystitis (almost always E. coli).
Usually don't culture
Treat symptoms (1/3 will actually resolve spontaneously) with Nitrofurantoin (5 days), Fosfomycin (1 dose but $$$) or Bactrim (3 days) |
|
|
Term
| How should you deal with a case of acute pyelonephritis? |
|
Definition
1) Culture Urine
2) Start Ceftriaxone and maybe add Gentomycin (amino glycoside) if needed
If in man or child (or recurrent in woman) get IVP and MRI to look for abscess/obstruction |
|
|
Term
What is the most common cause of relapsing UTI in males?
What are the common organisms and how do you treat? |
|
Definition
Chronic bacterial prostatitis from E.coli, Proteus or Providencia
Give Cipro or Bactrim (poor Ab penetration of nitro drug) |
|
|
Term
| Under what conditions should you treat asymptomatic candiduria? |
|
Definition
Fluconazole
1) Fungus ball
2) Neutropenia
3) Renal t/x
4) Urologic procedure in 2-3 days |
|
|
Term
| Why is sterile pyuria such a concern? |
|
Definition
Could be urethritis from Chlamidia but could be TB!
Get a skin PPD, Image and multiple urine samples (LOOK FURTHER) |
|
|
Term
| What is the typical differential for diagnosing AKI? |
|
Definition
1) Pre-renal
- Drugs
- Low CO
2) Renal
- ATN (tubular cells and granular casts)
- AIN (eosinophils, WBCs, RBCs)
- AGN (RBC and RBC cast)
- Vascular (none or RBC- eosinophil if atheroembolic)
- Intralobular obstruction (crystals or Bence-jones proteins)
3) Post-renal
- Prostate |
|
|
Term
Patient presents with hypotension, tachycardia, orthostatic HTN and poor skin turgor.
They have a history of hepatic cirrhosis and labs come back with BUN:creatinine of 22:1.
Urine sediment is bland.
How do you treat? |
|
Definition
Pre-renal azotemia secondary to liver disease.
STOP diuretics, ACE-i and NSAIDs and correct volume deficit |
|
|
Term
Patient presents with painful suprapubic mass, increased urinary frequency and urgency.
Biopsy shows dilated renal collecting system (Hydronephrosis).
Post-void residual bladder volume is significantly elevated.
BUN:Creatinine is 20:1
What do you do? |
|
Definition
| Post-renal azotemia- get rid of obstruction and watch for post-obstructive diuresis (watch volume status) |
|
|
Term
| What are the 4 phases of acute ischemic tubular necrosis pathogenesis? |
|
Definition
ATN is most common intrinsic AKI and occurs by ischemia or nephrotoxicity
1) Initiation (Acute ischemic event)
2) Extension (Initiating event stops but endothelial injury, vasoconstriction and inflammation continue to do damage)
3) Maintenance (Initiation of tubular repair with chronic inflammation)
4) Recovery (recovery of GFR) |
|
|
Term
Patient who recently began taking amphoterecin B for a candida infection presents complaining of difficulty urinating.
His labs come back and you see BUN is 50 and creatinine is 10. His Fractional Na excretion is 0.05 and his urine sediment contains "muddy brown" casts. The urine is isothenuric.
What is the pathophysiology of this condition and how do you manage it? |
|
Definition
Acute Tubular Necrosis secondary to nephrotoxic drug use.
**Fractional sodium excretion and urine sediment rule out pre-renal cause**
1) Nephrotoxicity causes loss of normal tubular cell morphology, with loss of polarity of membrane transport proteins.
- Epithelial cells undergo necrosis and apoptosis, and dead cells are sloughed off (can create obstruction).
- Renal vasoconstriction, tubular obstruction and filtrate back-leak cause decrease in GFR and renal failure
2) REMOVE offending drug. No pharmacological options, but usually reversible and can add hemodialysis in severe cases. |
|
|
Term
Patient who recently began taking furosemide for his HTN presents with fever, rash and oliguria.
On histology you find a lymphocytic infiltrate with eosinophilia and interstitial edema.
His urine contains WBC casts, neutrophils, low-grade proteinuria and eosinophils.
What is the pathophysiology of this condition and how do you manage it? |
|
Definition
Classic AIN from drug (loop diuretic in this case).
Remove underlying trigger and it should get better. |
|
|
Term
You find biconcave, needle-shaped clefts within blood vessels on histology.
What is the pathophysiology/treatment? |
|
Definition
AKI due to atheroembolic embolism of cholesterol from aorta to arterioles of kidney.
No specific treatment, but deal with volume status, acidosis and hyperkalemia as needed. |
|
|
Term
| What are the most important prognostic indicators of CKD at the population level? |
|
Definition
1) Reduction in eGFR (<60 is stages 3-5) and is "current speed"
**preferred to serum creatinine because of variation with muscle mass**
2) Proteinuria/Albuminuria is strongest indicator of prognosis and is "how hard you are pressing the break" |
|
|
Term
| What is the most important non-modifiable risk factor for CKD and why is it often overlooked in clinical practice? |
|
Definition
AGE!
Since creatinine levels decrease with age (less muscle mass), changes in GFR are often missed (65 y/o man with 1.0 Cr actually has eGFR of <60!)
CKD tends to be asymptomatic as well! |
|
|
Term
| How can you prevent the development of glomerular HTN is CKD? |
|
Definition
ACE inhibitor! Afferent dilation increases hydrostatic pressure in glomeruli and ACE-i counters this effect.
1) Remember, CKD is loss of nephron mass with hyper-filtration in remaining nephrons, leading to hypertrophy and glomerular growth (Endothelial injury, proliferation and fibrosis)
2) Nephron loss leads to increased AngII signaling |
|
|
Term
| Why might you stop an ACE-i in treating CKD? |
|
Definition
NOT because of low GFR!
if side effects are bad- Hyperkalemia, Cough (switch to ARB), or Creatinine spike. |
|
|
Term
| What is the most worrisome cause of death in a patient with CKD who has a GFR of 40? |
|
Definition
CVD!
when GFR<45, CVD risk is substantial so deal with it!
ACE-i, aspirin, exercise, statins, ect. |
|
|
Term
| What should you do for a patient with uremic frost and 1/2 and 1/2 nail beds that is resistant to pharmacological therapy? |
|
Definition
|
|
Term
| What happens to Creatinine, nitrogenous waste, sodium, water and potassium handling in CKD? |
|
Definition
1) Serum creatinine is pumped up in order to maintain normal filtration/excretion with decreased GFR
2) Urea is similar to Creatinine, but less directly related.
3) Fraction excretion increases and more sensitive to changes
4) Decreased fractional reabsorption per nephron to maintain excretion and urine is isothenuric
5) Fractional excretion increases (Increased distal tubular flow AND aldosterone) |
|
|
Term
| Why do you see metabolic acidosis in CKD? |
|
Definition
See early Hyperchloremia and later AG acidosis
1) NH4+ excretion is reduced because of fewer functional nephrons (remember, it is driven by hypokalemia and acidemia)
2) minor feature is proximal bicarbonate wasting |
|
|
Term
| What are the 3 most important complications of CKD? |
|
Definition
1) Anemia- decreased EPO synthesis by kidney and less RBC production in bone marrow (ESA use carries MAJOR risks)
2) Platelet dysfunction- Bleeding due to retention of uremic toxin
3) Mineral and Bone disease (secondary hyperparathyroidism)
- As GFR falls below 30, Phosphatemia, Hypocalciuria and low Calcitrol lead to Increased PTH, which breaks down bone
1) Osteitis fibrosa in adults (turnover gone crazy), 2) Rickets in children and 3), Adynamic bone disease (no turnover) |
|
|
Term
A young women presents with mild hematuria but no RBC casts are present. She has no other clinical symptoms, but was worried about seeing the blood in her urine.
What should you do? |
|
Definition
Sounds Asymptomatic Hematuria.
It is likely to be of extra-glomerular origin, BUT, if it is glomerular, ddx includes
1) Hereditary Nephritis (Alport syndrome)
2) IgA Nephropathy
3) thin basement membrane disease. |
|
|
Term
A young man presents wit difficulty hearing, significant proteinuria and his BP is 150/90.
On LM you see focal, segmental glomerulosclerosis with interstitial fibrosis and foam cells, but no GBM staining with antibody against alpha 5 collagen IV. On EM, GBM are thickened.
What is going on? |
|
Definition
Alport Syndrome.
Usually X-linked (can be AR or AD) mutation in alpha 5 type IV collagen leading to abnormal GBM assembly.
NOT an inflammatory condition. |
|
|
Term
A young child presents with massive edema and a case of bacterial peritonitis. He is normotensive and is concentrating urine effectively.
His urine contains fat bodies, fatty casts and 3+ proteinuria.
You order a renal biopsy.
What do you see on LM/IF/EM and how do you treat? |
|
Definition
This sounds like minimal change disease, a non-proliferative glomerulopathy producing nephrotic syndrome (MOST common cause in children)
LM and IF will be normal, but EM will show fusion of podocyte foot processes.
Treat with steroids and cyclophosphamide if needed. |
|
|
Term
A young, hypertensive, african american male presents with a nephrotic urine sediment.
You order a renal biopsy. What do you see on LM/IF/EM and how do you treat? |
|
Definition
Sounds like FSGS, the most common primary renal disease of African americans.
LM: focal segmental glomerulosclerosis with hyaline insudates
IF: IG and C3 in sclerotic areas
EM: no immune deposits
Try steroids, but may add immune-modulating agents and ACE-i for hypertension. |
|
|
Term
A 45 year old Caucasian male presents with HTN and a nephrotic urine sediment.
On pathology, you see
LM: chickened capillary wall, epimembranous spiking and train tracking with silver stain.
What do you see on EM and how do you treat? |
|
Definition
LM findings are consistent with Membranous GN, the most common primary nephrotic syndrome.
On EM you should see SUP-EPITHELIAL deposits.
1/3 rule of treatment , and treatment is debated (maybe try cyclophosphamide) |
|
|
Term
| What is the most common cause of nephrotic syndrome in adults and what are the characteristic pathological findings? |
|
Definition
Diabetic Nephropathy with Nodular Glomerulosclerosis (or Diffuse glomerulosclerosis)
Control blood glucose (Insulin), BP (ACE-i), Lipidemia (Statin) and smoking along with dietary protein restriction. |
|
|
Term
| If you see positive congo-red staining and green birifringence in a renal biopsy taken from a patient with nephrotic urine sediment, what do you expect to see on EM? |
|
Definition
Amyloidosis will show small non-branching fibrils 7.5-10 nm wide on EM.
Remember Amyloid AL is IG and Amyloid AA is inflammation. |
|
|
Term
| How can you usually tell if proteinuria is tubular or glomerular in origin? |
|
Definition
1) Isothenuric urine with orthostatic proteinuria suggests tubular cause (<3 g/day)
2) Gross proteinuria with concentrated urine, hyperlipidemia and HTN suggests glomerular origin. |
|
|
Term
| What is the most likely cause of isolated hematuria? |
|
Definition
Most likely extraglomerular!
Look out for cancer, until proven otherwise!
If glomerular, could be thin membrane disease, IgA GN or Alport's syndrome. |
|
|
Term
| Who should be worked up for microscopic hematuria? |
|
Definition
Remember, it is most likely not glomerular.
If they are hemodynamically stable, forget it, EXCEPT in CHILDREN or suspicious cases. |
|
|
Term
| What are the most important kidney stones found in acid and alkaline urines, respectively? |
|
Definition
1) ACID (Alkalinize urine with K+ citrate and solubilize with Tiopronin)
- Calcium Oxylate (ethylene glycol poisoning)
- Uric acid crystals
- Cystine crystals (genetic AR with hexagonal crystals in kids)
2) Base
- Struvite, Mg/NH4/PO4 crystals (Proteus)
- Calcium phosphate |
|
|
Term
A patient presents with colicky flank pain and hematuria.
What test should you order and how might you treat? |
|
Definition
Get a CT (sounds like kidney stone).
No matter what, restrict mineral intake, give them fluids and educate them.
If acid crystal, you can alkalize urine with K+ citrate or Thiazide diuretic (Penicillamine is toxic)
Can try an alpha blocker as wel |
|
|
Term
| What medications have been key in controlling the progressive of HTN in the last decade? |
|
Definition
ACE-i/ARB
HTN is second leading cause of ESRD! |
|
|
Term
| What is the basic pathophysiological basis of primary HTN? |
|
Definition
1) Initially, volume expansion increases CO (salt mediated)
- reset pressure natiuresis makes it more difficult to secrete salt)
- ouabain-like hormone deficiency prevents excretion
- Renin heterogenity (some cells release too much)
- Nephron loss
- SNS activation
2) Chronically, TPR increases and CO returns to normal
- RAAS/Endothelin/TGFb and decreased NO leads to vessel structural alteration and stiffening. |
|
|
Term
True or False:
DBP is a more powerful indicator of MI risk in HTN than SBP? |
|
Definition
False!
The opposite is true. |
|
|
Term
| What are the key elements of taking an accurate blood pressure? |
|
Definition
1) Listen with bell, not diaphragm
2) Take 2 or more times.
3) Have arm on heart level with patient seated upright and feet on the floor.
4) Don't let them smoke or drink caffeine 30 minutes before and make sure cuff fits. |
|
|
Term
| What are the 4 major organ systems that suffer significant consequences from prolonged HTN? |
|
Definition
1) Cardiac- LVH, CHF and LV dysfunction (look at systolic BP!)
2) Cerebrovascular- TIA/CVA (anti-hypertensives work here)
3) Peripheral vasculature- atherosclerosis and diminished circulation (claudication)
4) Renal- Proteinuria, creatinine excess, microalbuminuria
- First RVR increases between 20-30
- Functional and structural disturbances in vasculature between 30-40
- Decrease in filtration and sustained rise in FF with proteinuria between 40-50
- Nephrosclerosis and Glomerulosclerosis with critical decrease in renal mass after 50, SOMETIMES progressing to ESRD> |
|
|
Term
| What are the most important non-proliferative glomerular diseases? |
|
Definition
1) Alport's (isolated hematuria)
Nephrotic
2) Minimal change
3) FSGS
4) MGN
5) DN
6) Amyloidosis
7) Myeloma |
|
|
Term
What is the most common cause of primary acute nephritic syndrome?
What do you see on pathology and how do you treat? |
|
Definition
IgA nephropathy, presenting with hematuria, mild proteinuria and flu-like symptoms.
LM- normal with focal segmental endocapillary and mesangial proliferation.
IF- IgA!
EM- Sub-ENDOTHELIAL deposits
No known treatment (maybe fish oil)
20 year renal survival is 50-70% |
|
|
Term
A child presents with acute onset gross hematuria 10 days after having a sore throat. His urine looks like "coca cola", and he has edema and HTN.
There is 2 g/day proteinuria and decreased serum complement.
You get a biopsy and see enlarged, hyper-cellular glomeruli tufts and capillaries filled with leukocytes. You also see "lumpy bumpy" pattern of IgG and C3 expression on IF, and Sub-epithelial deposits on EM that look like flames.
How do you treat this patient? What is the pathogenesis? |
|
Definition
Post- infectious glomerulonephritis
Diffuse endocapillary proliferative and exudative glomerulonephritis.
1) Treatment is supportive and includes
- Sodium restriction
- BP control
2) Pathogeneiss
- Ab response against group A beta-hemolytic that deposit in sup-epithelial space and may cross react with glomerular epitopes, causing IL-6 mediated inflammation.
**Usually, renal biopsy is not needed, and serology (Strep ASO titer) is sufficient for diagnosis. |
|
|
Term
| What glomerular diseases involve sub-endothelial and sub-epithelial deposits on EM? What about mesangial? |
|
Definition
1) Sub-endothelial
- Type 1 MPGN (mesangocapillary) like Cryoglobulinemia
- Mesangial-subendothelial SLE
2) Sub-epithelial
- Post-infectious GN (lumpy bumpy)
- MGN (epithelial spiking)
- Membranous SLE
3) Mesangial (1 and 2 also have mesangial involvment)
- IgA GN |
|
|
Term
What type of injury is caused by Cryoglobulinemia?
What are its defining pathological features? |
|
Definition
Type 1 MPGN in context of hep C
Mesangiocapillary glomerulonephritis
1) Tram tracking (NOT train tracking seen in MGN)
2) Sub-endothelial deposits (NOT epimembranous spiking in MGN) |
|
|
Term
| What form of glomerular disease is associated with dense deposits on EM in renal transplant patients? |
|
Definition
Type II MPGN due to C3 nephritic factor autoantibody against factor H and I
Associated with partial lipodystrophy! |
|
|
Term
What are the 2 principle patterns of immune complex deposition seen in young women who have "full house" staining under IF of a renal specimen and "Tubuloreticular inclusions" consisting of epithelial cells under EM.
How do you treat? |
|
Definition
SLE- treat class IV with immunosuppressants like Cyclosporin and Rituximab.
1) Mesangial-subendothelial: pre-formed immune complexes start it mesangium and then spread to sub-ENDOTHELIAL space.
2) Membranous- small complexes that become Sub-EPITHELIAL |
|
|
Term
| If you see crescentic glomerular lesions on pathology, what should be on your ddx? How do you treat each of these conditions? |
|
Definition
RPGN has 3 types.
Type 1
- Goodpasture's anti-GBM GN with linear IgG staining (treat with Plasmapheresis, steroids and cyclophosphamide)
Type II
- SLE (steroid and cyclophosphamide) or Cryoglobulinemic GN (Type 1 MPGN)
Type III (Pauci-immune proliferative and necrotizing GN)
- Wegener's (C-ANCA)
- Microscopic Polyangiitis (P-ANCA)
**Steroids and cyclophosphamide**
**NO immune deposits** |
|
|
Term
What glomerular disease is associated with each of the following pathological features?
1) IF: lumpy bumpy; EM: Subepdi, hump, flame-like
2) Nodular Sclerosis and KW lesions
3) Silver stain: Thick BM, epimembranous spikes and train tracks
4) IF: Linear deposits
5) IF: minimal immune deposits with nephritic sediment
6) Segmental sclerosis in african american males with HTN
7) Normal glomeruli with fused foot processes on EM
8) EM; small non-branching fibrils
9) Mesangial IgA deposits
10) Double contour of GM, tram tracks and subendothelial deposits
11) IF: "full house" |
|
Definition
1) Proliferative GN= Acute Post-infectious GN
2) Non-proliferative nephrotic- Diabetes nephropathy
3) MGN
4) Type 1 RPGN- Goodpastures
5) Type 3 RPGN- Pauci immune- Wegeners/Polyarteritis
6) Non-proliferative FSGS
7) Minimal change
8) Amyloidosis
9) IgA nephropathy (primary GN)
10) Type 1 MPGN like cryoglobulinemia
11) Lupus (mesangio-subepithelial or membranous) |
|
|
Term
| What are the 3 types of RPGN and what should you do if you detect any of them? |
|
Definition
Biopsy and therapy immediately!
- Steroid and cyclophosphamide
1) Goodpastures
2) Immune complex- SLE, Cryo, Post-infectious
3) Pauci-immune- Wegener's, Microscopic polyangiitis |
|
|
Term
| Which glomerulonephritis syndromes involve complement depletion? |
|
Definition
COMPS
1) Cryoglobulinemia (Type 1 MPGN)
2) AtherOembolic disease
3) MPGN
4) Post-infectious
5) SLE |
|
|
Term
What disease might cause you to see massive glomeruli on LM, with huge sub-epithelial immune deposits on EM and a nephrotic sediment?
How should these patients be treated? |
|
Definition
Post-infectious GN
Post-infectious and IgA nephritis tend to get better on their own, just manage with Na+ restriction and BP control with an ACE-i. |
|
|
Term
| What are the major types of membranoproliferative glomerulonephritis? |
|
Definition
Type 1- Mesangiocapillary disease (Cryoglobulinemia) with subendothelial deposits, tram tracking.
Type 2- Dense deposit disease (C3 nephritic factor) with subendothelial deposits |
|
|
Term
| How do you treat the proliferative glomerulopathies commonly associated with Nephritic urine sediments? |
|
Definition
1) Post-infectious, IgA glomerulopathy
- Salt restriction and BP management and maybe steroids
2) SLE, MPGN, RPGN
- Steroids and Cyclophoshamide
- SLE also gets immunomodulators |
|
|
Term
| How would you manage a patient with chronic glomerulonephritis? |
|
Definition
Etiology will be impossible to identify.
1) BP management with Ace-i
2) Lipid management with Statin
3) Edema management with diuretic (maybe)
4) Stop smoking. |
|
|
Term
A young asian american patient with a h/x of recent respiratory infection presents with gross hematuria and a nephrotic urine sediment?
What do you think it is and what is on your ddx? |
|
Definition
Most nephrotic syndromes can present with gross hematuria, and Post-infectious and IgA should be at the top of your list given the respiratory symptoms.
Other possibilities include MPGN, SLE.
Since it is a young asian american, I would choose IgA, so get a biopsy and look for mesangial expansion with IgA immune deposits.
Will get better on its own most likely, but may try steroids. |
|
|
Term
A young asian american patient with a h/x of recent respiratory infection presents with gross hematuria and a nephrotic urine sediment?
What do you think it is and what is on your ddx? |
|
Definition
Most nephrotic syndromes can present with gross hematuria, and Post-infectious and IgA should be at the top of your list given the respiratory symptoms.
Other possibilities include MPGN, SLE.
Since it is a young asian american, I would choose IgA, so get a biopsy and look for mesangial expansion with IgA immune deposits.
Will get better on its own most likely, but may try steroids. |
|
|
Term
| What are the indications for Dialysis/renal replacement? |
|
Definition
AEIOU
1) Acidosis
2) Electrolyte abnormalities with EKG changes
(hyperkalemia)
3) Intoxications
4) Overload with salt/water that is refractory to diuretics causing CHF and edema
5) Uremic symptoms like pericarditis, vomiting, anorexia |
|
|
Term
| What are the indications for Dialysis/renal replacement? |
|
Definition
AEIOU
1) Acidosis
2) Electrolyte abnormalities with EKG changes
(hyperkalemia)
3) Intoxications
4) Overload with salt/water that is refractory to diuretics causing CHF and edema
5) Uremic symptoms like pericarditis, vomiting, anorexia |
|
|
Term
| How are solutes and solvents removed in hemodialysis? |
|
Definition
1) Solutes are removed by Diffusion
- Low MW are flow rate dependent
- High MW are pore-size and SA dependent
**Remember, diasylate and blood flow in opposite directions for countercurrent exchange**
2) Solvents are removed by Hyper-filtration
- Increased resistance to flow that blood faces as it leaves the dialyzer increases hydrostatic pressure differential
- Water will "Drag" solutes with it. |
|
|
Term
| What are the benefits of using synthetic vs. native AV fistulas for vascular access in hemodialysis? |
|
Definition
Remember, AEIOU indications (acidosis, electrolytes, intoxication, overdose of salt/water, uremia)
1) Synthetic fistulas have a short "maturation period" (native fistulas need 6-8 weeks to mature and 6-12 months before use), but are prone to INFECTION and last SHORTER.
2) Native fistulas take a long time to mature, but they don't get infected and they last longer.
**If neither is possible, and immediate treatment is needed, use a Catheter**. |
|
|
Term
| What are the major acute/chronic complications of starting Hemodialysis? |
|
Definition
ACUTE
1) Hypotension (give normal saline)
2) Cramps (saline or muscle relaxant)
3) Nausea and vomiting (dysequilibrium syndrome- changing uremia too fast)
CHRONIC
1) Malnutrition (low serum albuminin confirms)
2) Hypertension
3) Hyperlipidemia
4) Pruritis
5) Mortality from CVD |
|
|
Term
| How does solute and solvent removal occur in peritoneal dialysis? |
|
Definition
1) Solute removal occurs by diffusion (REMEMBER, lactate is in the solution here instead of bicarbonate, to prevent ppt)
2) Solvent by Ultrafiltration acting via osmosis (increase glucose to increase hydrostatic pressure driving exchange) |
|
|
Term
What are the advantages/disadvantages of using Peritoneal dialysis in place of Hemodialysis
Why use CAPD vs. CCPD? |
|
Definition
Basically, it is easier to manage and gentler, but less efficient and carries significant infection risk. WIthin peritoneal dialysis, CAPD has higher infection risk, but it more effective. CCPD is safer, but less effective.
1) Peritoneal Advantages
- Fewer hemodynamic effects (good for HEART disease)
- Patient freedom
- Continuous infusion prevents dysequilibrium
- Antibiotic administration is easy and diet is more manageable.
2) Peritoneal disadvantage
- Gentle but inefficient
- INFECTION
- Requires compulsiveness and intellect
- Peritoneal disease limits use
3) CAPD has long dwell times, but requires manual changing. CCPD has short dwell times, but is automatic. |
|
|
Term
A patient with CKD presents with a GFR of 18 ml/min.
What do you need to find out before placing them on a transplant list? |
|
Definition
Once on, its 3-5 years of waiting.
1) Cardiac health (leading cause of death post-transplant is cardiac)
2) Malignancy
3) ID
4) HLA-typing
5) Social issues |
|
|
Term
Under what conditions of HTN are each of the following drugs first-line choices?
1) Thiazide diuretics
2) K-sparing diuretics
3) Beta blockers
4) Alpha blockers
5) ACE-i
6) CCBs |
|
Definition
1) Elderly patients, African american and mild HF when cost is a concern.
2) In combination
- Amiloride is good for lithium- induced NDI
- Spironolactone + Ace-inihibitor for severe heart failure
3) Selective, with low lipid solubilitiy (ATENOLOL)
- AP, MI, arrythmia
4) HTN from BPH
5) High-renin HTN. Give ARB if cough arises
6) Not 1st line |
|
|
Term
| What is the anti-hypertensive agent of choice in a hypertensive emergency with cardiac/cns/renal involvement? |
|
Definition
Need to reduce BP by 30% or to 105 DBP in minutes-1 hour
IV sodium nitroprusside (not for severe renal/liver disease), but great for cardiac |
|
|
Term
How should HTN be controlled in each of the following populations?
1) HF
2) Post-MI
3) CKD
4) Diabetes |
|
Definition
1) ACE-i (anything will work except CCB)
2) ACE-i or Beta blocker
3) ACE-i or ARB
4) Anything except aldosterone antagonist |
|
|
Term
Which of the following Nephron sites plays NO role in potassium handling in the kidney?
1) Collecting Tubule.
2) Distal convoluted tubule.
3) Medullary thick limb of the loop of Henle.
4) Thin descending limb of the loop of Henle.
5) Proximal Tubule. |
|
Definition
|
|
Term
Which of the following manifestations is NOT associated with hypokalemia?
1) A prominent U-wave on ECG
2) Decreased response to ADH
3) Cardiac arrhythmias
4) A peaked T-Wave
5) Increased ammoniagenesis in the proximal tubule. |
|
Definition
|
|
Term
Inhibition of brush border carbonic anhydrase in the proximal tubule would have what effect on proximal tubular transport?
1) Increased chloride transport from the lumen into the proximal tubule cells and blood.
2) An increase in serum pH (more alkaline).
3) Increased ammonium reabsorption.
4) No effect.
5) Increased sodium transport from the cell lumen into the proximal tubular cells. |
|
Definition
| 1) Chloride reabsorption would be increased since less bicarbonate would be available for sodium transport |
|
|
Term
Which of the following are NOT known to have an effect on proximal tubular reabsorption of bicarbonate?
1) Chloride depletion.
2) Volume depletion.
3) Antidiuretic hormone.
4) Decreased serum potassium.
5) Increased pCO2. |
|
Definition
| 3) ADH affects water and urea reabsoprtion in distal segments and has no effect on proximal tubular bicarbonate reabsorption. |
|
|
Term
An anion gap metabolic acidosis is associated with all of the following EXCEPT:
1) A patient with diabetes mellitus who has a glucose of 900 mg/dL (normal 80-120 mg/dL).
2) A patient with a BP of 80/50 mm Hg, a temperature of 38.3 C and blood cultures that are growing gram positive cocci in clusters.
3) A 53 year old Senator who has been on a drinking binge.
4) A depressed 25 year old man who took 100 aspirin.
5) An intern who ate old potato salad from a drug company sponsored lecture and lunch and developed severe diarrhea. |
|
Definition
| 5) This is Hyperchloemia (HARDUP) |
|
|
Term
Proximal renal tubular acidosis (Type II) is characterized by which one of the following statements?
1) A lowered threshold for bicarbonate reclamation.
2) An increased enymatic threshold for bicarbonate reabsorption.
3) An inability to properly reclaim bicarbonate at low plasma bicarbonate concentrations.
4) Proximal RTA is frequently complicated by HYPERkalemia
5) An increased back leak of hydrogen from the lumen of the tubule into the proximal tubule cell |
|
Definition
|
|
Term
Which of the following metabolic alkaloses would be corrected by volume expansion with isotonic saline?
1) Hyperaldosteronism.
2) Prolonged vomiting.
3) Metabolic alkalosis due to bicarbonate administration.
4) Metabolic alkalosis due to citrate administration.
5) Metabolic alkalosis due to hypokalemia. |
|
Definition
Vomiting is Chloride loss, so saline can do it.
Vomiting results in chloride and volume loss. Metabolic alkalosis develops due to increased sodium reabsorption with bicarbonate in the proximal tubule and increased sodium reabsorption in the collecting duct. In the latter case, alkalosis and hypokalemia would develop due to the increased excretion of K and H in response to increased luminal electronegativity caused by the increased sodium reabsorption. |
|
|
Term
A prisoner goes on a hunger strike for better prison food. He will take only water orally and refuses to take food. After 15 days he is too weak to resist and is taken to the prison infirmary. Blood work reveals a serum potassium of 2.5 mEq/L. What effect would hypokalemia have on the proximal tubular intracellular pH and ammoniagenesis in this cell?
1) Increased intracellular pH (alkaline) and decreased ammoniagenesis.
2) Decreased intracellular pH (acidic) and increased ammoniagenesis.
3) Increased intracellular pH (alkaline) and increased ammoniagenesis.
4) Decreased intracellular pH (acidic) and decreased ammoniagenesis.
5) No Effect |
|
Definition
|
|
Term
Which of the following are factors that predispose to urinary tract infection?
1) Obstruction to urine flow.
2) Diabetes mellitus
3) Inability to completely empty the bladder.
4) All of the above.
5) None of the above. |
|
Definition
|
|
Term
Which of the following statements regarding urinary tract tuberculosis is TRUE?
1) Urinary tract tuberculosis is an acute Illness that is clinically obvious within days of the initial pulmonary tuberculosis infection.
2) Antibiotic therapy is ineffective in treating genitourinary TB.
3) Genitourinary TB is considered to be an uncomplicated form of UTI.
4) Genitourinary TB is a rare site of extrapulmonary TB.
5) Standard treatment of genitourinary TB is isoniazid (INH) and a bacteriostatic antibiotic. |
|
Definition
|
|
Term
Which of the following statement(s) regarding the pathogenesis of UTI is/are TRUE?
1) The ability of bacteria to adhere to the uroepithelium is important in their ability to cause UTI.
2) High osmolality and low pH in the urine increases the risk of urinary tract infectiion.
3) Normal Bacterial flora are important in suppressing UTI incidence.
4) 1 and 3.
5) 1, 2 and 3. |
|
Definition
|
|
Term
Tubular fluid in the late proximal tubule would have which of the following characteristics compared to plasma?
1) A 20% higher sodium concentration than plasma.
2) A higher bicarbonate concentration.
3) An alkaline pH.
4) An acidic pH.
5) A higher glucose concentration |
|
Definition
| 4) Bicarbonate is avidly reabsorbed in the proximal tubule creating a more acidic enivronment. |
|
|
Term
In which of the following nephron segments is calcium reabsorption regulated by parathyroid hormone?
1) Medullary collecting duct.
2) Cortical collecting duct.
3) Distal convoluted tubule.
4) Thin ascending limb of the loop of Henle.
5) Thin descending limb of the loop of Henle. |
|
Definition
|
|
Term
Which of the following statements concerning acute tubular necrosis is TRUE?
1) Frequently associated with severe volume loss and hypotension.
2) Urine sediment typically shows no casts or other cells.
3) Can be rapidly corrected with an indwelling bladder catheter.
4) Acute tubular necrosis is frequently seen with drug allergies.
5) Acute tubular necrosis is rarely associated with contrast used for angiography. |
|
Definition
| 1) Ischemic or Drug-intoxication, but not allergy |
|
|
Term
Chronic kidney disease leads to the development of uremia. All of the following are signs or symptoms of uremia EXCEPT:
1) Decreased appetite (anorexia).
2) Dizziness.
3) Increased bruising.
4) muscle twitching (myoclonus.
5) Edema. |
|
Definition
|
|
Term
What part of the glomerulus removes immune complexes?
1) Capillary endothelial cells.
2) Visceral epithelial cells (podocytes).
3) Parietal epithelial cells.
4) Mesangial Cells.
5) Macula Densa cells. |
|
Definition
|
|
Term
Which of the following is NOT a common cause of gross hematuria? (gross hematuria is blood in the urine that is visible to the naked eye.)
1) Blunt trauma to the bladder.
2) Renal cell carcinoma.
3) Blunt injury to the kidney.
4) Kidney stone in the right renal pelvis.
5) Simple Cysts. |
|
Definition
|
|
Term
Essential hypertension is common in older patients but what secondary cause of hypertension should always be kept in mind in this population?
1) Pheochromocytoma
2) Use of street drugs.
3) Renovascular hypertension.
4) Sleep apnea.
5) Hyperthyroidism. |
|
Definition
| Correct: Absolutely right! As we age we have increased atherosclerosis increasing the risk of renovascular hypertension. |
|
|
Term
A 65 year old African American gentleman presents to your office for an upper respiratory infection. On examination his blood pressure is noted to be 145/95. The remainder of his physical exam is unremarkable. What should the physician do about the patient's blood pressure elevation?
1) The patient should be scheduled for a renal ultrasound to evaluate for renal artery stenosis.
2) The patient should be informed that his blood pressure is elevated and instructed on life style modifications.
3) The patient should be immediately admitted to Hospital.
4) The patient should be evaluated for renovascular hypertension.
5) The should be given prescriptions for diuretic and a beta-blocker |
|
Definition
| 2) Don't do much on 1 visit! |
|
|
Term
Complications with peritoneal dialysis include all of the following EXCEPT:
1) Excess urea removal.
2) Occlusion of the catheter due to fibrin.
3) Poor catheter drainage due to malposition.
4) Dialysate leakage around the catheter.
5) Infection associated with the catheter. |
|
Definition
| 1 is Correct: Small molecule clearances are limited with peritoneal dialysis due to lower blood and dialysate flow rates compared to hemodialysis. |
|
|
Term
The Joint National Commission on Hypertension recommends which of the following medications to be first line drugs for hypertension?
1) Dihydropyridines (nifedipine).
2) Angiotensin Converting Enzyme Inhibitors (enalapril).
3) Diuretics and Beta blockers.
4) Angiotensin receptor blockers.
5) Clonodine. |
|
Definition
|
|
Term
he following Case history pertains to Questions 1, 2 and 3
A 40 year old woman, who weighs 72 kg, is transferred to UPMC Presbyterian for evaluation of hyponatremia. Her past medical history is remarkable for chronic schizophrenia treated with trifluoperazine, an antipsychotic medication. She is chronically institutionalized and her serum sodium of 120 mEq/L was obtained as part of her routine blood work. She has no complaints and review of the records shows no other medications. On physical examination her blood pressure was 120/80 with a pulse of 80/minute both lying and standing. She had clear lungs, no neck vein distention, a normal heart and lung exam and no edema. While she was being examined she drank a large container of water and voided 1000 ml of clear urine that was sent for evaluation.
Labs
Serum
Na 120 mEq/L K 3.5 mEq/L
Cl 85 mEq/L
tCO2 25 mEq/L
glucose 80 mg/dl
BUN 3 mg/dl
Cr 1 mg/d
Urine
Specific gravity 1.001, no protein, blood or glucose
What is her calculated GFR? |
|
Definition
85
(100-40)(72)(0.85)/[72 x 1] |
|
|
Term
All of the following drugs may contribute to the development of hyperkalemia EXCEPT
1) Lisinopril
2) Propranolol
3) Nifedipine
4) Amiloride
5) Spirinolactone |
|
Definition
|
|
Term
In the human embryo, the mesonephric kidneys
1) give rise to the collecting system
2) do not contribute to kidney function in adults
3) may persist as pelvic kidneys
4) consist of a system of tubules that completely
5) disappear before birth
None of the above |
|
Definition
|
|
Term
Which of the following factors increases renal stone formation?
1) Low urine volume
2) Low urine osmolality
3) High urinary calcium excretion
4) A and C
5) All of the above |
|
Definition
| Renal stones form in low volumes of concentrated urine with high mineral compositions |
|
|
Term
Renal potassium excretion is increased by all of the following, EXCEPT:
1) Volume Expansion
2) Glucosuria
3) Bicarbonaturia
4) Aldosterone
5) Amiloride |
|
Definition
5
Glucosuria, serum HCO3-, Aldosterone and volume expansion cause increased potassium excretion |
|
|
Term
A female infant was born without a visible anal opening. Physical and radiographic examination indicated the presence of a fistula between the vagina and the rectum. What is the embryological basis for this condition?
1) An abnormal partitioning of the cloaca by the urorectal septum.
2) A persistence of the allantois.
3) A persistence of the urogenital sinus.
4) A deficiency in the hindgut endoderm.
5) An abnormal partitioning of the ureteric bud. |
|
Definition
| 1- Abnormal partitioning of cloaca by urorectal septum |
|
|
Term
| How does ethanol consumption alter hormonal regulation of tonicity? |
|
Definition
| Inhibits ADH, preventing water reabsorption and leading to free water excretion in a dilute urine. |
|
|
Term
Which of the following is not an EKG manifestation of hyperkalemia?
1) Prolongation of the PR interval
2) Widening of the QRS complex
3) ST-segment depression
4) Peaking of the T-wave
5) AV nodal block |
|
Definition
|
|
Term
The earliest pathologic finding/s seen on renal biopsies from diabetic patients is/are
1) Nodular intercapillary glomerulosclerosis (Kimmelstiel-Wilson nodule)
2) Subendothelial electron dense deposits.
3) Vascular afferent and efferent arteriolar hyalinosis
4) Glomerular basement membrane thickening and mesangial expansion
5) Interstitial fibrosis with papillary necrosis |
|
Definition
|
|
Term
Which of the following lifestyle modifications is NOT recommended for treating hypertension?
1) Regular aerobic exercise
2) A reduction in dietary potassium and calcium
hypertension.
3) Weight loss if overweight
4) Limiting ethanol intake to less than 15 ml a day
5) No added salt diet |
|
Definition
| 2 Correct: Not recommended. This would worsem |
|
|
Term
Which of the following is commonly associated with a nephritic-nephrotic presentation and low serum complement levels?
A) Membranous glomerulonephropathy.
B) IgA nephropathy.
C) Amyloidosis.
D) Cryoglobulinemia.
E) Wegener’s granulomatosis |
|
Definition
|
|
Term
Which are commonly associated with nephrotic syndrome?
A) Subepithelial immune complex deposits.
B) Podocyte foot process fusion.
C) Normal serum complement levels.
D) Deposits of non-branching fibrillary material measuring 8-10 nanometers in thickness.
E) All of the above |
|
Definition
|
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Term
3. Which autoantibody is associated with a pauci-immune form of crescentic glomerulonephritis and pulmonary vasculitis?
A) Anti-GBM antibody
B) Proteinase-3 antibody
C) Anti-nuclear antibody.
D) Anti-streptolysin-O antibody.
E) C3 nephritic factor. |
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Definition
| B- Wegener's has C-ANCA with PR3 |
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Term
Which disorder is associated with IgA predominant mesangial immune complex deposits and systemic small vessel vasculitis?
A) Hemolytic uremic syndrome.
B) Microscopic polyangiitis.
C) Henoch-Schönlein purpura.
D) Wegener’s granulomatosis.
E) Cryoglobulinemia |
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Definition
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Term
A patient with chronic hepatitis C viral infection presents with acute renal failure, proteinuria, hematuria, and hypocomplementemia. What is the kidney biopsy most likely to show?
A) Diffuse endocapillary proliferative glomerulonephritis with lumpy bumpy staining for IgG and C3 and large subepithelial hump-like immune complex deposits.
B) Crescentic glomerulonephritis with diffuse linear staining for IgG, and absence of electron dense deposits.
C) Membranoproliferative glomerulonephritis, type I, with hyaline thrombi, granular glomerular basement membrane and mesangial staining for IgG, IgM and C3, subendothelial and mesangial immune complex deposits and mesangial interposition.
D) Focal segmental proliferative glomerulonephritis, with full house immunofluorescence and mesangial and focal subendothelial immune complex deposits.
E) Membranoproliferative glomerulonephritis, type II (dense deposit disease), with C3 glomerular basement membrane and mesangial staining, electron dense thickening of the lamina densa and C3 nephritic factor |
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Definition
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Term
Which glomerular disorder has hyaline thrombi that frequently contain IgG, IgM and C3, occurring in association with hypocomplementemia?
A) Cryoglobulinemia.
B) Focal segmental glomerulosclerosis.
C) Diabetes.
D) Membranoproliferative glomerulonephritis, type II.
E) Cholesterol atheroembolic renal disease. |
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Definition
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Term
The smallest size barrier in the glomerular capillary wall is:
A) Lamina densa.
B) Type IV collagen suprastructure.
C) Endothelial cell fenestrations.
D) Heparan sulfate.
E) Podocyte filtration slit diaphragm. |
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Definition
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Term
The following is true regarding acute post-infectious glomerulonephritis:
A) Serum complement levels are normal.
B) Immune deposits disappear due to clearance of the antigen and resultant antibody excess.
C) Immune deposits are predominantly subendothelial.
D) Frequently associated with necrotizing lesions and glomerular
crescents.
E) Immunosuppressive therapy decreases the probability of
chronic renal injury. |
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Definition
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Term
Which of the following is most likely in a patient presenting with nephrotic syndrome?
A) A diffuse endocapillary proliferative glomerular disorder with neutrophil margination in the glomerular capillaries.
B) Thin basement membranes.
C) A non-proliferative glomerular disorder with injury to the podocyte foot processes.
D) A diffuse mesangial proliferative disorder with IgA predominant, mesangial limited, immune complex deposits.
E) Subendothelial immune complex deposits. |
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Definition
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Term
A 45-year-old man presents with acute renal failure and was found to have
new onset hypertension, edema and a nephritic urine sediment. Which
feature in a renal biopsy if identified in this patient is the best predictor of
chronic progressive renal disease?
A) Glomerular endocapillary proliferation.
B) Immune complex deposits.
C) Interstitial lymphocytic inflammation.
D) Cellular crescents.
E) Red blood cell casts. |
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Definition
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Term
Which of the following is most closely associated with a diffuse endocapillary proliferative glomerulonephritis, nephritic syndrome, seropositivity for ANA and hypocomplementemia ?
A) Amyloid deposits in the glomerular basement membrane.
B) Podocyte foot process fusion..
C) Subendothelial immune complex deposits.
D) Mesangial immune complex deposits.
E) Glomerular basement membrane spikes |
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Definition
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Term
Which property (properties) of immune complex deposits determine their
localization in the glomerular basement membrane?
A) Charge.
B) Size.
C) Shape.
D) Affinity of antigen and antibody.
E) All of the above. |
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Definition
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Term
) Determinant (s) of glomerular permeability to protein include:
A) Podocyte filtration slit diaphragm.
B) Type IV collagen suprastructure in the lamina densa.
C) Heparan sulfate negative charge.
D) Glycocalyx on surfaces of endothelial cell and podocyte.
E) All of the above. |
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Definition
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Term
A patient was found to have proteinuria and glucosuria on a dipstick.
Urine protein evaluation with protein quantitation and electrophoresis
performed on a 24-hour urine collection revealed a protein excretion of 2
grams, with most of the protein consisting of non-immunoglobulin,
non-albumin, low-molecular weight proteins. Serum protein evaluation and
serum glucose were normal, with no monoclonal immunoglobulin detected in the serum or urine. Which of the following is most likely?
A) Glomerular permeability defect.
B) Tubular reabsorption defect.
C) Overproduction of a low-molecular weight protein.
D) Lower urinary tract source due to a urinary tract infection.
E) Subclinical diabetes. |
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Definition
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Term
Which of the following histories is associated with acute / subacute renal failure, absence of seropositivity for autoantibodies, no detectable monoclonal immunoglobulin, variably depressed serum complement levels, inactive urinary sediment and intracellular needle-like crystalline inclusions in the lumina of small blood vessels in the kidney?
A) Lytic bone lesions.
B) Hepatitis C infection.
C) Recent cardiac catheterization with atheroembolization.
D) Recent beta-lactam antibiotic therapy.
E) Recent Streptococcal infection. |
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Definition
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Term
Which lesion is present in malignant hypertensive nephropathy but not in chronic benign hypertensive renal disease?
A) Hyaline arteriolar sclerosis.
B) Fibrinoid necrosis.
C) Vasculitis.
D) Glomerular basement membrane wrinkling.
E) Hyaline thrombi. |
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Definition
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Term
Adult polycystic kidney disease is associated with:
A) Renal failure early in the course of the disease.
B) Autosomal recessive disorder involving chromosome 16.
C) Cerebral berry aneurysms.
D) High rate of recurrence in transplanted kidneys.
E) Significantly increased risk of Wilm’s tumor. |
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Definition
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Term
A 60-year-old man presents with bone pain and acute renal failure. Bone marrow biopsy reveals increased numbers of plasma cells, with light chain restriction. Which of the following is most likely in the renal biopsy?
A) Endocapillary proliferative glomerulonephritis.
B) Acute tubulointerstitial nephritis.
C) Plasma cell neoplasm infiltrating renal interstitium.
D) Insoluble proteinaceous casts with cracking artifact and cellular reaction.
E) Deposition of fibrillar protein in glomeruli, blood vessels and interstitium |
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Definition
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Term
An 80-year-old woman presented to the hospital with gram-negative sepsis and was started on gentamicin. She developed acute renal failure.
Urinalysis revealed a high fractional excretion of sodium and granular casts were present in the urinary sediment. Which of the following is true
regarding the patient’s disorder?
A) Steroids accelerate renal recovery.
B) The disorder is most likely due to a hypersensitivity reaction to gentamicin.
C) The disorder is most likely due to septic embolization to the kidney.
D) Kidney biopsy reveals liquefactive necrosis in some patients.
E) Renal biopsy reveals coagulative necrosis in some patients. |
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Definition
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Term
Which of the following is true regarding acute tubulointerstitial nephritis:
A) Biopsy shows mixed inflammatory infiltrate with predominance of lymphocytes, with frequent tubular injury and normal glomeruli and blood vessels.
B) Disorder is usually progressive despite cessation of inciting agent.
C) Eosinophils are always present when disorder is due to an adverse drug reaction.
D) Immune complex deposits are usually present.
E) Urine sediment usually contains neutrophils. |
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Definition
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Term
Which of the following applies to acute pyelonephritis?
A) Frequently associated with renal failure.
B) Ascending form is usually associated with hematogenous infection and renal microabscesses.
C) Histology shows thyroidization type tubular atrophy.
D) Descending form is commonly associated with renal compound papillae.
E) Ascending form is frequently associated with vesicoureteral reflux. |
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Definition
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Term
What are the important histological features of each of the following?
1) Chronic Pyelonephritis
2) ATN
3) Atheroembolic Nephropathy
4) Chronic hypertension
5) AIN
6) Acute Pyelonephritis |
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Definition
1) Tubule and Interstitial fibrosis with lymphocytic infiltrate and Thyroidization of tubule centers.
2) Coagulation necrosis of tubule epithelium. Variable edema but not fibrosis.
3) Cholesterol clefts in medium-large arteries with histiocytes
4) Mural thickening and narrowing of vessels with intimal fibrosis and duplication of internal elastic lamina. Fibrotic interstitium and tubular atrophy.
5) Interstitial edema and mixed inflammatory infiltrate
6) Small asymmetric kidneys with hydronephrosis. Inflammatory cells are mostly polys. |
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Term
| What does urine analysis for AIN show? |
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Definition
2+ protein, RBCs, WBCs and eosinophils.
MIXED inflammatory infiltrate |
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Term
| What are the most common organisms found in ascending/descending UTI causing Pyelonephritis? |
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Definition
1) Ascending is E. coli
2) Descending/Hematogenous is Staph |
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Term
| What is the pathophysiological basis of Adult PKD? |
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Definition
Transplant!
Mutations in PKD1 (85%) or PKD2 (15%)
PKD1 is more severe, affecting a protein in distal tubular epithelial cells.
PKD2 affects calcium channel
Berry aneurysm comes from abnormal expression in vascular smooth muscle. |
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