Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
648 Cards in this Set
- Front
- Back
|
What are the major regulatory functions of the kidney?
|
1. Total body water
2. Electrolyte balance 3. Acid-base balance 4. Mineral balance |
|
|
What is the major extracellular cation?
|
Sodium
|
|
|
What is the major extracellular anion?
|
Chloride
|
|
|
What is the major intracellular cation?
|
Potassium
|
|
|
What are the three main metabolic products that the kidney excretes?
|
1. Creatinine
2. Urea 3. End products of hemoglobin breakdown |
|
|
How do the kidneys function as an endocrine gland?
|
1. Erythropoietin
2. Renin 3. Active form of vitamin D [1,25-dihydroxyvitamin D3] 4. Gluconeogenesis |
|
|
How can you explain anemia in renal failure patients?
|
Reduced production of Epo leading to anemia.
|
|
|
(T/F) Most nephrons are juxtamedullary.
|
False - most nephrons are cortical [15% are juxtamedullary]
|
|
|
What is the capillary bed network associated with the cortical nephrons called?
|
Peritubular capillary beds
|
|
|
What is the capillary bed associated with the juxtamedullary nephrons called?
|
Vasa recta.
|
|
|
What is the main function of juxtamedullary nephrons?
|
Help create ion gradient to increase the concentration of urine.
|
|
|
List the division of the nephrons (8) in the renal system:
|
1. Proximal convoluted tubule (S1/S2)
2. S3 segment - pars recta 3. Descending loop of henle 4. Ascending loop of henle 5. Thick ascending loop [macula densa] 6. Distal convoluted tubule 7. Collecting duct [cortical] 8. Collecting duct [medullary] |
|
|
(T/F) 6-10 nephrons dump into one collecting duct.
|
True.
|
|
|
What percent of plasma is filtered into the Bowman's space?
|
20%
|
|
|
(T/F) The filtrate for the kidney contains protein.
|
False - filtrate does not contain cells nor protein [normally]
|
|
|
Where does the remaining 80% of the blood plasma that is not filtered go?
|
Efferent arteriole --> peritubular capilllaries or vasa recta
|
|
|
What are the three barrier layers during filtration?
|
1. Fenestrated endothelial layer
2. Glomerular basement membrane 3. Podocytes |
|
|
What does the fenestrated endothelial layer filter out?
|
Cells (RBCs)
|
|
|
What does the GBM filter?
|
Blocks large proteins.
|
|
|
What do podocytes filter? What is their other function?
|
Smaller proteins and other molecules
Maintain integrity of GBM by secreting matrix proteins. |
|
|
What are the three components of the juxtaglomerular apparatus?
|
1. Granular cells
2. Macula densa 3. Mesangial cells |
|
|
What is the function of granular cells?
|
Renin
|
|
|
What is the function of the macula densa?
|
Salt sensor
|
|
|
What are the two main functions of the JGA?
|
1. Salt/water balance
2. Blood pressure |
|
|
How do you calculate renal plasma flow from renal blood flow?
|
Based on the hematocrit level of the patient [RPF = (1-Hct)*RBF]
|
|
|
How is glomerular filtration rate related to renal plasma flow?
|
20% of the renal plasma flow.
|
|
|
(T/F) Secretion occurs more than reabsorption in the kidneys.
|
False -- reabsorption [over 99% reabsorbed]
|
|
|
When simplifying the renal system -- what is the input and what are the two outputs?
|
Input: renal blood flow
Output: venous blood flow + urine flow |
|
|
Name an example of a substance that is completely reabsorbed?
|
Glucose
|
|
|
What is an example of a substance that is only partially reabsorbed?
|
Urea
|
|
|
Name an example of a substance that is freely filtrated and also compeltely secreted?
|
Drugs [foreign substances]
|
|
|
(T/F) Water and sodium are mainly reabsorbed.
|
True.
|
|
|
What is the 4th renal process [outside of regulation, endocrine gland, and excretion]?
|
Metabolism [either for cells nutritional needs or to regulate acid-base balance]
|
|
|
Where does the majority of reabsorption occur in the nephron?
|
Proximal tubule.
|
|
|
Which portion of the nephron is sensitive to ADH and aldosterone?
|
Collecting duct
|
|
|
Which part of the nephron determines osmolarity of the urine by reabsorption of salt/water?
|
Loop of Henle.
|
|
|
What components of the kidney comprise 90-95% of the kidney weight?
|
Tubules and interstitium.
|
|
|
What occupies the majority of the other 5% of the kidney weight?
|
Glomeruli
|
|
|
(T/F) Premature babies have a higher likelihood of developing chronic renal disease and hypertension.
|
True -- born with fewer nephrons [linear relationship with birth weight]
|
|
|
What does the medullary papilla lead into?
|
The pelvis of the kidney [going to the ureter]
|
|
|
What are the four components of the kidney?
|
Glomeruli
Tubules Interstitium Blood vessels |
|
|
What vessel divides the medulla from the cortex?
|
Arcuate artery/vein
|
|
|
What is the order of branching of the vasculature of the kidney?
|
Renal artery --> Segmental --> Interlobar --> Arcuate --> Interlobular
|
|
|
What is the main constituent of the glomerular basement membrane?
|
Type IV Collagen.
|
|
|
Which alpha chains of Type IV collagen are in the adult human kidney?
|
Alpha 3,4,5.
|
|
|
Which alpha chains of Type IV collagen are in the fetal human kidney?
|
Alpha 1, 1, 2
|
|
|
What inherited disease is X-linked with a mutation in alpha 5 chain.
|
Alport's Syndrome [abnormally lamellated/split GBM]
|
|
|
Mutations in alpha 3 or alpha 4 chains can lead to what disease...
|
Thin basement membrane disease.
Usually does not progress to end-stage renal disease. |
|
|
What are the two main functions of mesangial cells?
|
Narrowing/dilation of glomerular capillaries
Mononuclear phagocyte system |
|
|
(T/F) There should be no more than ~3 mesangial cells per mesangial area.
|
True.
|
|
|
What autoimmune disorder can exhibit hypercellularity and inflammation of the mesangial cells?
|
Lupus.
|
|
|
Silver stain of the kidney can stain which components of the kidney?
|
Glomerular basement membrane
Mesangial area [due to collagen] |
|
|
What allows the repulsion of negatively charged particles from entering as filtrate?
|
Glycosialoprotein coat [negatively charged] -- surrounds podocytes/GBM/endothelial.
|
|
|
What is the purpose of the slit diaphragm?
|
Prevents small particles from entering [size 4x14 nm opening]
|
|
|
How is the slit diaphragm created?
|
Extracellular proteins from adjacent foot processes [podocytes] interact with each other and form the central bar for stability [zipper-like]
|
|
|
What are the 7 main proteins that contribute to the formation of the slit diaphragm?
|
1. Nephrin
2. Podocin 3. P-Cadherin 4. FAT 1 5. Neph1 6. Neph 2 7. CD2AP |
|
|
(T/F) Filtration barrier is just a size barrier.
|
False -- both size AND charge.
|
|
|
Where is the antigen for goodpasture's syndrome located?
|
Non-collagenous (NC1) portion of alpha chain 3.
|
|
|
What are the three layers of the GBM?
|
Lamina rara interna
Lamina densa Lamina rara externa |
|
|
Histologically speaking - if you see no basolateral folds nor microvilli - but the cells appear cuboidal -- what portion of the tubule are you looking at?
|
Collecting duct
|
|
|
Histologically speaking - if you see no basolateral folds nor microvilli and the cells appeared small/flattened -- what portion of the tubule are you looking at?
|
Loop of Henle
|
|
|
Histologically speaking -- if you see tall, columnar cells with a very small lumen, and dense microvilli -- what portion of the nephron are you looking at?
|
Proximal convoluted tubule.
|
|
|
What is the significance of the basolateral folds in the proximal convoluted tubule?
|
The base requires lots of pumps for Na+ since majority of reabsorption occurs in the proximal convoluted tubule [so more pumps to actively get the Na+ out of the cell so it can reabsorb more]
|
|
|
What is the difference between the S1/S2 segment and the S3 segment of the proximal convoluted tubule?
|
S3 = secretion, less prominent brush border and few basolateral foldings
S1/S2 = reabsorption, many infoldings and mitochondria. |
|
|
(T/F) The thin descending loop of Henle is water impermeable while the ascending limb is permeable.
|
False - it's the exact reverse.
|
|
|
The thick ascending limb of Henle produces a histologically distinct protein...
|
Tamm-Horsfall protein
|
|
|
What is the function of the Tamm-Horsfall protein?
|
Mucoprotein with antibactericidal activity to prevent spread of UTIs.
|
|
|
(T/F) The juxtoglomerular apparatus is located between the thick ascending loop of henle and the distal convoluted tubule.
|
True.
|
|
|
What shape do renin granules appear on electron microscopy?
|
Rhomboid!
|
|
|
(T/F) Proximal convoluted tubule has a higher N/C ratio than the distal convoluted tubule.
|
False -- distal is greater.
|
|
|
What are the two main types of collecting duct cells?
|
Principal cells
Intercalated cells |
|
|
What is the main function of principal cells and how do they appear?
|
Light cells.
ADH sensitive K+ secretion |
|
|
What is the main function of intercalated cells and how do they appear?
|
Dark cells
Acid-base balance |
|
|
Type A inercalated cells: ________ ::
Type B intercalated cells: _________ |
H+ secretion
HCO3- secretion |
|
|
(T/F) Majority of collecting duct cells are principal cells.
|
True -- 2/3 of cells.
|
|
|
(T/F) Medullary collecting ducts are less sensitive to ADH in comparison to cortical collecting ducts.
|
False -- more sensitive.
|
|
|
Ducts of Bellini are located ________ and appear as .....
|
Inner medullary collecting duct
Light, simple, cuboidal. |
|
|
What are the three components of the renal interstitium?
|
Peritubular capillaries
Interstitial cells Extracellular space |
|
|
List the following based on increasing relative interstitial space:
Cortex, medulla, papilla |
Cortex
Medulla Papilla |
|
|
What are the four functions of renal interstitium?
|
1. Tubular oxygen supply
2. Osmoregulation [with distal convoluted] 3. Immune cells [dendritic cells] 4. Some endocrine function |
|
|
Which vessels supply oxygen to the cortex?
|
Peritubular capillaries
|
|
|
Which vessels supply oxygen to the medulla?
|
Vasa recta
|
|
|
Red cell casts
|
Glomerulonephritis
|
|
|
Muddy brown casts
|
Acute tubular necrosis
|
|
|
Oval fat body
|
Heavy proteinuria
|
|
|
Narrow hyaline casts
|
Normal
|
|
|
Waxy casts
|
Renal damage [large dilated nephrons]
|
|
|
White blood cell casts
|
Pyelonephritis, glomerulonephritis, interstitial nephritis
|
|
|
Equation for clearance...
|
C = U*V/P
|
|
|
Why can inulin or creatinine be used for the assessment of GFR?
|
Substance is freely filtered and neither secreted nor reabsorbed by the renal tubules.
|
|
|
S_Cr = 1.0 mg/dL
|
Normal
|
|
|
S_Cr = 2.0 mg/dL
|
50% normal GFR
|
|
|
S_Cr = 4.0 mg/dL
|
25% of normal GFR
|
|
|
S_Cr = 8.0 mg/dL
|
12.5% of normal GFR
|
|
|
Why is the Cockcroft-Gault formula better than a simple Creatinine Clearance measurement?
|
Accounts for decline in muscle mass with age and differences between men/women.
|
|
|
(T/F) At steady state, creatinine production is independent of GFR.
|
True.
|
|
|
List the 5 factors that can affect serum creatinine measurements:
|
1. Severe exercise
2. Eating large amount of cooked meats 3. Renal failure (overestimate GFR) 4. Interference with creatinine measurement [ketones/drugs falsely elevate ] 5. Interference with tubular creatinine secretion [trimethoprim/cimetidine reduce secretion] |
|
|
What is the source of most urea?
|
Dietary proteins.
|
|
|
(T/F) Processes that increase proximal salt/water reabsorption can increase the BUN.
|
True.
|
|
|
Which radiologic investigation is best for visualizing polycystic kidney disease?
|
Renal ultrasound.
|
|
|
Which radiologic investigation is best for evaluating renal artery stenosis?
|
Renal arteriography.
|
|
|
Which imaging study can best visualize calcyes/pelvis/ureters of the kidney?
|
Excretory urography
|
|
|
(T/F) Excretory urography, renal arteriography, and CT are all contraindicated for those patients with contrast sensitivity or predisposition to acute tubular necrosis.
|
True.
|
|
|
Which radiographic study is most commonly used to study vesicoureteral reflux?
|
Cystography [voiding cystourethrography]
|
|
|
(T/F) Retrograde pyelography is contraindicated with patients with clotting abnormalities.
|
False -- antegrade.
|
|
|
Technetium glucoheptonate : anatomy of kidneys :: ortho-iodo hippurate :__________.
|
Renal function.
|
|
|
What is the gold standard for diagnosing a UTI?
|
Supra-pubic aspiration. [often used in infants]
|
|
|
Which method of urine collection is most frequently used?
|
Clean voided specimen.
|
|
|
Which method of urine collection is used if microbes want to be cultured?
|
Mid-stream specimen
|
|
|
If there is concern about contamination by vaginal flora -- what are urine specimen collection options?
|
Open-ended cathether.
|
|
|
For accurate measurement of chemical excretion rates and clearance -- which urine method collection is best?
|
24-hr timed urine collection.
|
|
|
What are the 9 things that can be tested via a urine dipstick?
|
pH
Specific gravity Ketones Glucose Protein Blood Leukocytes Nitrite Urobilinogen |
|
|
If a patient was treated in the ER recently to control bladder spasm -- what warning should (s)he receive?
|
Urine can turn bright red.
[use of pyridium] |
|
|
If you see bright orange urine what should you think?
|
Rifampin!
|
|
|
If the urine appears reddish brown but bleeding has been ruled out -- what is another possibility to consider?
|
Myoglobin
|
|
|
If you see milky urine what should you think?
|
Fat globules.
|
|
|
If you see hazy urine what should you think?
|
Mucus.
|
|
|
Atkins diet can cause what changes to urine?
What other pathologies can cause this same change? |
Fruity-smelling urine due to increase in ketones in urine.
diabetes/starvation. |
|
|
(T/F) You utilize centrifuged urine to do the dipstick test.
|
False -- fresh, unspun, well-mixed urine.
|
|
|
What is "urine runover"?
|
Excess urine from the protein reagent [which is acid-based] runs over the square for pH thus falsely decreasing pH reading.
|
|
|
If there are phosphate crystals in the urine -- what could you anticipate the pH to be?
|
>6.5
|
|
|
If tehre are urate crystals in the urine what could you anticipate the pH to be?
|
4.5-6
|
|
|
What does the specific gravity estimate?
|
Osmolality [ESTIMATE]
|
|
|
(T/F) Dipstick is more sensitive to albumin in comparison to LMW proteins.
|
True.
|
|
|
What are three scenarios that can cause false positives on a proteinuria test?
|
Chlorohexidine [antiseptic]
Vaginal secretions pH > 6.5 |
|
|
What is the normal albumin in urine across a 24 hr period?
|
< 80 mg
|
|
|
What is the level of microalbuminuria?
|
30-300 mg / 24 hr
|
|
|
(T/F) > 3+ [level of proteinuria] generally indicates nephrotic syndrome.
|
True.
|
|
|
What four scenarios can cause false positives on a hematuria test?
|
1. Betadine
2. Bacterial peroxidases [UTI] 3. Excess ascorbic acid 4. Menstraution |
|
|
How long does it take enterobacteriacae to convert urinary nitrate to nitrite so that the dipstick becomes positive?
|
>4 hrs
|
|
|
Interstitial nephritis (analgesic abuse nephropathy) can cause what to appear on the urine dipstick...
|
Sterile pyuria [no bacteria]
|
|
|
When would you see crenated RBCs?
|
If you let the sample sit out for too long.
|
|
|
What constitutes the matrix in an RBC cast?
|
Tamm-Horsfall protein [located in the distal convoluted tubule]
|
|
|
Squamous cells on the urine microscopy can indicate...
|
Contamination
|
|
|
Renal tubular cells on microscopy can indicate....
|
Tubular damage
|
|
|
How do transitional cells differ from renal tubular cells on microscopy and what can they indicate...
|
Centrally located nucleus
Cystitis or carcinoma if sterile |
|
|
If you see granular casts you should think of...
|
Acute tubular necrosis.
|
|
|
Diamond like crystals that dissolve if KOH is added indicate...
|
Uric acid crystals
|
|
|
Calcium oxalate crystals are often associated with....
|
ETHYLENE GLYCOL INTOXICATION
[shine brightly in polarized light] |
|
|
Define the filtration fraction...
|
GFR/RPF
[% of renal plasma flow that actually enters the kidney] |
|
|
What is the normal filtration fraction number?
|
20%
|
|
|
How does RBF and RPF differ?
|
Renal blood flow is the entire content -- RBCs + plasma.
Renal plasma flow is simply the fluid (plasma) |
|
|
What are the three layers of the filtration barrier?
|
1. Endothelial cells
2. GBM 3. Podocytes |
|
|
What are the two factors that limit filtration across the glomerulus?
|
1. Charge
2. Radius Negative = poorly filtered Large = poorly filtered |
|
|
(T/F) Proteinuria indicates glomerular damage.
|
False, can indicate BOTH glomerular OR tubular damage.
|
|
|
Renal blood flow is mainly determined by two factors...
|
1. Mean pressure in renal artery
2. Contractile state of afferent/efferent arterioles (resistance) |
|
|
Which component of the "typical" Starling equation is not included when discussing the GFR?
|
oncotic pressure of bowman's space b/c no albumin is filtered
|
|
|
What is the equation for GFR using Starling forces as your terms?
|
GFR = K_f * (P_GC - P_BS - pi_GC)
K_f = filtration coefficient GC = capillary BS = bowman's space |
|
|
What is the main cause of decreased filtration as the plasma flows from afferent to efferent arteriole?
|
Increased capillary oncotic pressure [as opposed to decreased hydrostatic pressure in systemic capillaries]
|
|
|
What are the five main differences between systemic and glomerular capillaries?
|
1. Higher renal hydrostatic pressure and little decrease along capillary length
2. Higher hydrostatic pressures in Bowman's space (compared to interstitium. 3. Zero oncotic pressure in Bowman's space. 4. Rise in plasma capillary oncotic pressure along capillary length. 5. Higher K_f due to higher surface area and increased permeability (thus much greater filtration). |
|
|
(T/F) Contraction of mesangial cells lead to an increased K_f.
|
False -- decrease due to decreased surface area on capillaries.
|
|
|
What change can you expect in the GFR based on a patient with severe GI bleeding?
|
Decreased GFR due to hypotension (reduced renal arterial pressure).
|
|
|
If you constrict BOTH afferent and efferent arterioles -- what happens to the GFR?
|
GFR remains the same , however renal blood flow is reduced.
|
|
|
(T/F) The hydrostatic pressure of Bowman's space can be controlled physiologically.
|
False.
|
|
|
Explain how an increased flow will increase the GFR?
|
Increased flow is less efficient - less plasma gets out, the increased volume remaining in the capillary lowers oncotic pressure and thus there is less of a drop-off for the filtration forces and GFR increases.
|
|
|
What is the range of autoregulation for the GFR?
|
70-200 mm Hg
|
|
|
At what blood pressure level will there be a GFR of 0?
|
<40-50 mm Hg
|
|
|
How does autoregulation occur?
|
Tubuloglomerular feedback mechanism --
salt sensor of macula densa -- if increased NaCl detected indicates higher GFR -- if swells from Na+ -- then signals constriction of afferent arteriole. |
|
|
What are the 3 basic renal functions?
|
1. Filtration
2. Reabsorption 3. Secretion |
|
|
What are the four outputs of the body?
|
1. Kidneys
2. Sweat 3. GI 4. Insensible (skin/lungs) |
|
|
How do you calculate the filtered load?
|
FL = plasma levels * GFR
[mg/min] or [mol/min] |
|
|
How do you calculate the excretion rate? What are the units?
|
Excretion rate = urine plasma concentration * urine flow rate
[mg/min] or [mol/min] -- amt/unit time |
|
|
How is urine flow rate calculated?
|
24-hr urine sample calculated -- thus the volume collected over 24 hrs gives urine flow rate.
|
|
|
What is clearance?
|
The volume of plasma that would be cleared completely of the solute based on the excreted amt in the urine.
|
|
|
How is clearance calculated? What are the units?
|
C_x = U_x * V / P_x
Units = Volume/unit time |
|
|
Which substance can be used to estimate GFR?
|
Clearance of creatinine or inulin.
|
|
|
Which substance can be used to estimate RPF?
|
PAH (para-aminohippurate)
|
|
|
How is RBF calculated from RPF?
|
RBF = RPF / (1-Hct)
|
|
|
Give an example of a freely filtered, 100% reabsorbed substance?
|
Glucose.
|
|
|
Why is PAH used to estimate RBF?
|
It is 100% filtered and also highly secreted [so no substance remains in the blood once it exits the kidneys]
|
|
|
What is the expected GFR (in ml/min)?
|
125 ml/min.
|
|
|
What is the clearance of glucose?
|
Zero. [excreted load = 0]
|
|
|
At what glucose level is the kidney no longer able to handle the load? What is this concept referred to?
|
>375 mg/min (filtered load)
Tubular maximum capacity (transporters are maxed out) |
|
|
(T/F) Solutes that are reabsorbed are not considered to be cleared by the kidney.
|
True.
Clearance based on urine excretion. |
|
|
Glucose : reabsorption-limited :: PAH : __________.
|
secretion-limited
|
|
|
(T/F) Sodium excretion can measure the dietary intake of sodium.
|
True.
|
|
|
What is the normal excretion load of sodium?
|
152-158 mmoles/day
|
|
|
What is normal renal plasma flow?
|
660 ml/min
|
|
|
What is normal renal blood flow?
|
1200 ml/min
|
|
|
If the clearance is less than that of inulin...
|
Substance is reabsorbed
|
|
|
If the clearance is greater than that of inulin...
|
Substance is secreted
|
|
|
If the clearance is equal to that of inulin....
|
Substance is only filtered
|
|
|
(T/F) RBF is 20-25% of cardiac output.
|
True.
|
|
|
(T/F) GFR is proportional to functional renal mass.
|
True.
|
|
|
How is fractional excretion calculated?
|
FE_x = C_x / C_In
In = inulin -- clinically creatinine is used x = substance of interest |
|
|
If FE > 1, what does that indicate?
|
Secretion has occurred (more of the plasma is cleared in comparison to what was originally filtered)
|
|
|
If FE < 1, what does that indicate?
|
Reabsorption has occurred (less of the plasma is cleared)
|
|
|
PAH underestimates RPF and
creatine ___________ GFR. (why?) |
overestimates - due to the small secretory component of creatinine.
|
|
|
(T/F) Plasma creatinine levels are inversely proportional to GFR.
|
True.
|
|
|
How is creatinine clinically used?
|
1. Measure clearance [24-hr urine required]
2. Measure GFR [only plasma creatinine levels required] |
|
|
If P_Cr levels are 2.0 in a male -- what can you say about the GFR rate?
|
GFR is halved.
|
|
|
What are the normals for creatinine in men and women?
|
0.8-1.3 in men
0.6-1.0 in women [due to less muscle mass] |
|
|
(T/F) 3 mesangial cells are typically grouped near each capillary.
|
True.
|
|
|
What are the three layers of the GBM?
|
1. Lamina rara interna
2. Lamina densa 3. Lamina rara externa |
|
|
What are the four clinical signs of glomerular hematuria?
|
1. Microscopic hematuria
2. Gross hematuria 3. Red blood cell casts 4. Dysmorphic RBCs [mickey mouse] |
|
|
What is considered nephrotic range proteinuria for adults?
|
>3.5 g/day
|
|
|
What is considered microalbuminuria?
|
Up to 300 mg/day
|
|
|
What is the normal range of proteinuria?
|
<100-150 mg/day
|
|
|
What are the four clinical criteria to dx nephrotic syndrome?
|
Hypoalbuminuria (<3.3 g/dL)
Edema Lipidemia (hyper) (>250 mg/dL) Proteinuria (>3.5 g/day) |
|
|
What are the three main manifestations of nephritic syndrome?
|
Hematuria
RBC Casts HTN [may see mild proteinuria] |
|
|
What is the gold standard in diagnosing glomerular disease?
|
Renal biopsy
|
|
|
What are the five indications for renal biopsy?
|
1. Proteinuria
2. Hematuria 3. Unexplained renal failure 4. Systemic disease w/renal involvement 5. Renal allograft dysfunction |
|
|
What are the six contraindications to renal biopsy?
|
1. Uncontrolled HTN
2. Hemorrhagic diathesis 3. Severe hydronephrosis 4. Polycystic kidney disease 5. Pyelonephritis/abscess 6. Renal artery aneurysm |
|
|
Silver stain in light microscopy is good for visualization of....
|
GBM
|
|
|
Trichrome stain in light microscopy is good for....
|
Detection of fibrinoid necrosis
(collagen = blue, necrosis = magenta) |
|
|
What are the different classifications the diseased kidney in terms of location?
|
Diffuse vs. focal [entire kidney]
Segmental vs. Global [within each glomerular tuft] |
|
|
What are the three different types of hypercellularity that can be seen?
|
1. Intracapillary [no lumen]
2. Extracapillary (in Bowman's capsule) [compresses lumen] 3. Mesangial [patent lumen] |
|
|
What is the definition of sclerosis in the kidney?
|
Accumulation of glomerular ECM [stains silver and PAS positive]
|
|
|
(T/F) IgD/IgE is not associated with any glomerular disease.
|
True.
|
|
|
Linear deposits of glomerular basement membrane on EM...
|
Goodpasture's.
|
|
|
Subepithelial, granular deposits causing nephritic syndrome...
|
Acute post-strep glomerulonephritis
|
|
|
GBM, granular deposits causing nephrotic syndrome...
|
Membranous nephropathy
|
|
|
Subendothelial granular deposits causing nephritic syndrome ...
|
Membranoproliferative GN.
(or lupus) |
|
|
What is the pathophysiology behind Alport syndrome?
|
Mutations in Col4A3-5 genes, thus preventing the proper production or assembly of the type IV collagen network [required for GBM]
|
|
|
What does the EM image for Alport Syndrome look like?
|
Lamellated glomerular basement membrane.
|
|
|
What is the normal protein excretion in adults?
|
<150 mg/24 hrs
|
|
|
What is the normal protein excretion in children?
|
< 100 mg/M2/24 hrs
[determined based on body surface area] |
|
|
(T/F) Nephrotic syndrome must indicate glomerular disease.
|
True.
Tubular disease typically not that HIGH of a proteinuria. |
|
|
What are the 8 causes of transient proteinuria listed?
|
1. Heavy exercise
2. Febrile/illness 3. Metabolic derangement (DKA) 4. CHF 5. Seizures 6. Sympathomimetic drugs 7. Abdominal operations 8. Cold/emotional stress |
|
|
What is orthostatic proteinuria?
|
Proteinuria while standing up but not while lying down -- said to be correlated with increased renal venous pressure or lymphatic pressures.
THIS IS A NORMAL VARIANT |
|
|
How can you confirm that you have a good 24-hr urine sample?
|
Creatinine 15-25 mg/kg/24 hr in men
Creatinine 10-22 mg/kg/24 hr in women |
|
|
To avoid the complications of a 24-hr urine sample, what can be utilized?
|
Spot protein/creatinine ratio --
Total protein excretion = U_p/U_Cr - 0.2 [kids] U_p/U_Cr [adults] |
|
|
(T/F) Magnitude of the persistent proteinuria is a direct indication of loss of function.
|
True, greater the proteinuria - the greater the renal dysfunction.
|
|
|
What are the two major constituents of proteins in the urine? [normal]
|
1. Albumin (40%)
2. Tamm-Horsfall protein (40%) -- released by tubular epithelium to prevent crystal formation and infections. |
|
|
What is a normal value on a spot urine test?
|
<0.2
|
|
|
What indicates nephrotic range proteinuria on the spot urine check?
|
>2.0
|
|
|
(T/F) Orthostatic proteinuria can be detected by a spot urine protein check.
|
False.
|
|
|
What are the limitations of the urine dipstick in relation to checking for proteinuria?
|
Only checks albumin
[can miss light chain proteins and myoglobin] |
|
|
Why is Comassie blue preferred over the sulfosalicylic acid test for urine protein levels?
|
Fewer false positives to radiocontrast agents or medications.
|
|
|
What is a limitation of the Comassie blue test?
|
Cannot detect small proteins with molecular weights <3,000.
|
|
|
What are the three main mechanisms of proteinuria?
|
1. Glomerular
2. Tubular 3. Overflow [orthostatic proteinuria] |
|
|
What macromolecules specifically allows for repulsion of negative charged particles?
|
Sialoproteins -- on endothelial and epithelial cells.
Proteoglycans -- on GBM. |
|
|
(T/F) Globular molecules filter more easily than linear molecules.
|
False -- globular molecules have greater restriction.
|
|
|
(T/F) Presence of IgGs in the urine indicates a more severe renal disease.
|
True.
|
|
|
Presence of Beta-2 microglobulin in the urine is strongly indicative of tubular dysfunction.
|
True.
|
|
|
What conditions can increase tubular secretion of proteins?
|
1. Renal calculi
2. Infection 3. Tumor |
|
|
(T/F) Orthostatic proteinuria can only be diagnosed upon resolution of proteinuria.
|
True.
|
|
|
(T/F) Nephrotoxic serum nephritis has the inability to repel anion charges.
|
True.
|
|
|
How does hemolytic uremic syndrome cause proteinuria and where in the nephron does it affect the kidneys?
|
Disrupts GBM/endothelial layers causing glomerular proteinuria.
|
|
|
Mesangial thickening/deposition leading to nephritic syndrome...
|
IgA Nephropathy
|
|
|
What is paraproteinemia?
|
Elevation of one specific monoclonal gammaglobulin -- seen in multiple myeloma
|
|
|
What is the epidemiology of orthostatic proteinuria?
|
Peak incident with adolescent growth spurt.
More common in taller individuals and women. |
|
|
What is the appropriate follow up to a patient with orthostatic proteinuria?
|
Annual evaluation for 5 yrs to r/o other pathological conditions.
|
|
|
Assign the following to either hereditary or acquired tubular necrosis:
1. cystinosis 2. Sarcoidosis 3. Fanconi 4. pyelonephritis 5. myoglobulinuria |
1. hereditary
2. acquired 3. hereditary 4. acquired 5. acquired |
|
|
How can a protein electrophoresis help distinguish glomerular vs. tubular disorders?
|
Glomerular -- increased albumin
Tubular -- increased small molecular weight proteins. |
|
|
(T/F) Penicillamine overuse can cause glomerular proteinuria.
|
True - nephrotic syndrome -- membranous GN (nephropathy)
|
|
|
What is the most common cause of nephrotic syndrome in children?
|
Minimal change disease.
|
|
|
What are the five complications of nephrotic syndrome?
|
1. Hypothyroidism
2. Vitamin D deficiency 3. Hypercoagulability 4. Anemia 5. Increased infections AH HIV |
|
|
What is the first plan for a child presenting with nephrotic syndrome?
|
Begin a trial of corticosteroids (12 weeks at least), if unresponsive only then complete a renal bx.
|
|
|
For children with MCD - if they begin to show steroid dependence, what can be used?
|
Cytotoxic agents [cyclophosphamide]
or calcineurin inhibitors (tacrolimus or cyclosporine) |
|
|
What is involved in the supportive care of nephrotic syndrome?
|
1. Control of edema
2. ABx prophylaxis 3. Good nutrition 4. Immunization |
|
|
(T/F) Progression to renal insufficiency is a good indication that the family history is Alport's syndrome and NOT benign familial hematuria.
|
True.
|
|
|
(T/F) H-S purpura can cause proteinuria.
|
True [sometimes to the level of nephrotic syndrome]
|
|
|
Why is facial edema more common as a clinical sign of nephrotic syndrome in babies?
|
They lie on their backs more often, thus the fluid accumulates in the upper body in comparison to adults which typically present with pedal edema.
|
|
|
What changes in urine can you anticipate with dehydration?
|
Increased protein levels [across the board] -- due to the lower amount of water [so increased concentration]
|
|
|
What are the four factors promoting IC deposition in the kidneys?
|
1. High blood flow
2. High hydrostatic pressure 3. High ultrafiltration coefficient 4. Large fenestrae |
|
|
IgG3 tends to deposit...
|
subendothelial [larger]
|
|
|
IgG4 tends to deposit..
|
subepithelial [smaller] - can disaggregate/agreggate easily
|
|
|
(T/F) IgG4 activates complement.
|
False -- IgG3 [subendothelial] -- bloodstream access.
|
|
|
(T/F) Immune complexes are formed in ANCA+ glomerular disease.
|
No -- attack the neutrophils -- so no IC formation.
|
|
|
What are the four ways to control progression of diabetic nephropathy?
|
1. Control sugar
2. HTN control 3. ACEi 4. Dietary protein restriction |
|
|
What is stage I diabetic nephropathy characterized by?
|
Hyperfiltration/hypertrophy [early stages post DM begins]
|
|
|
What is stage II diabetic nephropathy characterized by?
|
K-@ lesions, thickened GBM, hyalinosis --
2 yrs post onset of DM. |
|
|
What is stage III diabetic nephropathy characterized by?
|
Microalbuminuria -- 10-15 yrs post onset of DM.
|
|
|
What is stage IV diabetic nephropathy characterized by?
|
Proteinuria [>300 mg/day] -- 5-10 yrs after stage III.
|
|
|
What is ablative nephropathy?
|
Chronically overworked nephrons [if other kidney tissue is non-functional]
appears similar to kidney tissue of ESRD [sclerosis of glomeruli and tubulointerstitium] |
|
|
Rapidly progressive GN is typically associated with what histology upon bx?
|
Crescents!
|
|
|
What are the four components of the clinical presentation of nephritic syndrome?
|
1. hematuria/proteinuria
2. edema 3. azotemia/oliguria 4. HTN |
|
|
Give an example of an ATP dependent transport mechanism in the kidneys?
|
Na+/K+ ATPase pump
|
|
|
How does Na+ play a role in facilitated diffusion?
|
Na+ gradient establishes the energy gradient that another solute can utilize to be driven against its gradient.
|
|
|
(T/F) In order for net reabsorption or secretion to occur, the transport properties of the apical and basolateral membranes are the same.
|
False, different.
|
|
|
What is the paracellular transport?
|
When the electrical and chemical gradient promotes solute movement across tight junctions.
|
|
|
Give 6 examples of solutes that move via paracellular transport?
|
1. Sodium
2. Chloride 3. Magnesium 4. Urea 5. Potassium 6. Calcium |
|
|
What are the four main steps of salt and water transport in the kidneys?
|
1. Basolateral Na/K ATPase
2. Sodium enters the cell 3. Chloride follows Na+ in 4. Starling forces drive water/solutes in |
|
|
What is osmotic diuresis?
|
higher amount of osmoles in the filtrate leading to pull of water into the tubular lumen rather than out.
|
|
|
GLUT: basolateral :: ______ : apical
Which imposes the limit for T_m? |
SGLT
SGLT |
|
|
Why does chloride reabsorption occur in conjunction with sodium?
|
To maintain electroneutrality.
|
|
|
What is the critical component of transcellular water reabsorption throughout the kidney?
|
Aquaporins in the apical membrane are critical for water reabsorption.
|
|
|
What percentage of the filtrate is reabsorbed by the proximal tubule?
|
60-65%
|
|
|
(T/F) Reabsorption is iso-osmotic in the proximal tubule.
|
True.
|
|
|
What is the mechanism of action of ouabain?
|
Specific inhibitor of Na+-K+ ATPase
|
|
|
What helps create the gradient for sodium reabsorption to occur at the apical surface?
|
Na+-K+ ATPase
|
|
|
What helps create the gradient for H+ secretion at the apical surface?
|
Bicarb reabsorption mechanism
|
|
|
(T/F) Bicarbonate is coupled with Na+ reabsorption at the basolateral surface in the proximal tubule.
|
True.
|
|
|
What is the main mechanism of action for reabsorption of phosphate, amino acids, etc. in the proximal tubule?
|
Co-transport with Na+ -- utilize the Na+ gradient as the energy to drive it in.
|
|
|
Where is final urine osmolality determined?
|
Distal tubular segments
|
|
|
Why do glomerular capillaries favor filtration while peritubular capillaries favor uptake?
|
Difference in hydraulic pressure -- there is a drop-off for peritubular capillaries while glomerular capillaries (afferent/efferent) maintain the same hydraulic pressure.
|
|
|
What defines the beginning of the distal nephron?
|
Loop of Henle
|
|
|
Why is the ascending limb of Henle's loop called the diluting segment?
|
Reabsorbs salt, but not water -- thus dilutes the filtrate
[via Na-K-2Cl symporter] |
|
|
What is the role of K+ in the Na-K-2Cl symporter?
|
K+ is passively in, but recycled back out via apical channels to allow continued activity of Na-K-Cl.
|
|
|
Ascending loop : diluting :: descending loop : _________
|
Concentrating -- only reabsorbs water [not salts]
|
|
|
What is the role of the distal convoluted tubule?
|
Reabsorbs salt, not water
|
|
|
Which transporter has a major role in the distal convoluted tubule?
|
Na-Cl cotransporter
[this is what's blocked by thiazide diuretics] |
|
|
How does Na+ help calcium absorption mechanisms?
|
In the distal convoluted tubule ...
Ca+ channels controlled by PTH at apical surface -- at the basolateral surface the Na-Ca |
|
|
Intercalated cells predominate in the....
|
Medullary collecting ducts
|
|
|
What are the major transport functions of the principals cells of the cortical collecting duct?
|
Na+ reabsorption
K+ secretion |
|
|
What are the transport functions of the Type A intercalated cells?
|
K+ reabsorption
H+ secretion |
|
|
What are the transport functions of the Type B intercalated cells?
|
Cl- reabsorption
HCO3- secretion [H+ reabsorption] |
|
|
(T/F) Water reabsorption dominates in the medullary collecting duct.
|
True.
Cortical -- reabsorbs both salt/water. |
|
|
Why does increased Na+ reabsorption lead to greater K+ excretion?
|
Sodium reabsorbs through ENaC channels which is then pumped out using the Na-K ATPase basolateral pump and therefore K+ builds in the cell and is subsequently secreted.
|
|
|
What hormone controls ENaC channels?
|
Aldosterone.
|
|
|
What is the obligatory water loss by the kidneys? [with no H20 Intake]
|
440 mL/day
|
|
|
What is the normal urine osmolality?
|
600-800 mOsm/kg
|
|
|
Where is the interstitial osmolarity the highest?
|
Medulla.
|
|
|
What is urea?
|
End product of protein metabolism produced by the liver.
|
|
|
What allows for the generation and maintenance of the medullary gradient?
|
1. Ascending limb reabsorption of NaCl
2. Urea handling 3. Vasa recta follows tubular osmolarity (no "washing out") |
|
|
How does proximal tubule secretion work?
|
Via OCT and OATs [organic anion/cation transporters]
|
|
|
Why are OCT/OATs important for diuretics?
|
This secretion mechanism is how the drug gains access to the luminal surface.
|
|
|
What is the mechanism of chlorothiazide and hydrochlorothiazide?
|
Inhibit Na-Cl transporters in the distal convoluted tubule.
|
|
|
What is the clinical use of thiazide diuretics?
|
Vasodilation and diuretic in ESSENTIAL HTN [first line]
|
|
|
What are the SEVEN side effects of thiazide diuretics?
|
1. Decrease excretion of Ca++
2. Hypokalemia 3. Digoxin toxicity 4. Increased LDL 5. Decreased insulin secretion 6. Decreased uric acid excretion (gout) 7. Sulfonamides (allergic) |
|
|
If a patient has osteoporosis - which drug would you prefer to give -- chlorthalidone or furosemide?
|
Chlorthalidone -- thiazide diuretic increases Ca++ reabsorption [loop diuretics can lead to loss of Ca++]
|
|
|
What is the main difference between chlorthalidone and chlorothiazide?
|
Chlorthalidone has a longer duration of action.
|
|
|
What is the mechanism of action of furosemide, ethacrynic acid, bumetanide, torsemide?
|
Binds Cl- site on the Na-K-2Cl symporter to block reabsorption.
|
|
|
What are the clinical uses of the loop diuretics?
|
1. Refractory to thiazides
2. Severe edema [pulmonary/cerebral] 3. Forced diuresis in poisonings |
|
|
What are the FIVE side effects of loop diuretics?
|
1. Gout (decreased uric acid excretion)
2. Hypocalcemia 3. Severe hypokalemia 4. Dehydration 5. Auditory nerve damage |
|
|
How does NSAID use affect thiazide and loop diuretics?
|
Reduces efficacy
|
|
|
List the two classes of K+ sparing diuretics?
|
1. Aldosterone antagonists
2. Inhibitors of Na+ transport in distal/collecting duct |
|
|
How do drugs like spironolactone and eplerenone work?
|
Block aldosterone receptor [thus blocking the Na-K ATPase induction in basolateral level]
|
|
|
If you want to avoid the side effect of gynecomastia in the use of aldosterone antagonists - which one will you use?
|
Eplerenone [less affinity for steroid receptors]
|
|
|
What are the side-effects of aldosterone antagonists?
|
1. Hyperkalemia
2. Bind to other steroid receptors |
|
|
What is the clinical use of spironolactone?
|
Used in conjunction with a thiazide or loop diuretic to prevent K+ loss
|
|
|
How does amiloride and triamterene work?
|
Blocks ENaC channels [prevent Na+ from reaching intracellular area]
|
|
|
What is the function of acetazolamide?
|
Inhibits reabsorption of HCO3- by blocking carbonic anhydrase.
|
|
|
How is ethanol a diuretic?
|
Inhibit ADH.
|
|
|
What is the clinical use of mannitol as a osmotic diuretic?
|
1. Post trauma to maintain urine flow
2. decrease CSF/intraocular pressure |
|
|
What are the clinical uses of acetazolamide?
|
1. Mountain sickness (decreased synthesis of CSF)
2. Open angle glaucoma (decreased production of aqueous humor) 3. Epilepsy (alters brain pH) 4. Alkalinizes urine |
|
|
What is the most critical side effect of a K+ sparing diuretic?
|
Hyperkalemia
|
|
|
What is the difference between hypertensive emergency and urgency?
|
Emergency includes acute end-organ failure, while urgency is only a severely high blood pressure.
>220/120 = BP definition |
|
|
All hypertensive drugs have one common side effect which is...
|
hypotension
|
|
|
Which drugs function as an alpha-2 agonist, and how does this reduce HTN?
|
alpha-methyl dopa and clonidine
reduce the release of NE - thus inhibiting sympathetic outflow |
|
|
(T/F) Alpha-methyl dopa is a pro-drug that is metabolized to alpha-methyl NE which inhibits the alpha-2 receptors.
|
True.
|
|
|
What are the side effects of alpha-methyl dopa?
|
Drowsiness
Depression Impaired ejaculation Orthostatic hypertension Preeclampsia |
|
|
Sudden withdrawal from clonidine can lead to ....
|
hypertensive crisis
|
|
|
What are the off-label uses for clonidine? [5 total]
|
1. Tourette's syndrome
2. opiate withdrawal 3. ADD 4. insomnia 5. neuropathic pain [fibromyalgia] |
|
|
What is the mechanism of action for alpha-methyl tyrosine?
|
Inhibits tyrosine hydroxylase to prevent formation of NE, and epinephrine
|
|
|
Aside from HTN, what can alpha-methyl tyrosine be used for?
|
Pheochromocytoma
|
|
|
What is the mechanism of action of mecamylamine?
|
Blocks nicotinic cholinergic receptors -- thus total block of both sympathetic and parasympathetic outflow.
|
|
|
What is the clinical use of mecamylamine or trimethaphan camsylate?
|
Temporary basis for severe HTN.
|
|
|
What are the side effects for mecamylamine?
|
Orthostatic HTN
constipation tremors/convulsions (@ high doses) |
|
|
How do reserpine and guanethidine reduce HTN?
|
Reserpine inhibits incorporation of NE/DA into vesicles while guanethidine replaces NE in vesicles ==> reduced sympathetic outflow.
|
|
|
What is a major difference in the location of action between reserpine and guanethidine?
|
Guanethidine only acts peripherally - does NOT enter the CNS.
|
|
|
Mechanism of action of "Osins" [prazosin, terazosin]
|
Alpha-one receptor blockers
Alpha One Site INhibitors |
|
|
What are the side effects of alpha-1 blockers?
|
Orthostatic hypotension
Nasal congestion First pass effect [sudden fall in BP on first dosing] |
|
|
What can be used to treat BPH?
|
Afluzosin
Tamsulosin (Flomax) |
|
|
What are off-label uses for alpha-1 blockers?
|
PTSD
|
|
|
How does propranolol differ from metoprolol and atenolol?
|
Blocks both beta-1 and beta-2 receptors, while meto/atenolol are more Beta-1 selective blockers.
|
|
|
What is the clinical use of beta-blockers?
|
used in conjunction with powerful vasodilators for HTN
|
|
|
What are three off-label uses for propranolol?
|
1. Stage fright
2. PTSD 3. Migraine headaches |
|
|
What are the side effects of propranolol?
|
1. Can induce asthma
2. Bradycardia 3. Depression |
|
|
Why is a more selective Beta-1 blocker preferred?
|
Fewer CNS side effects
|
|
|
What is the clinical use of labetolol?
|
HTN during pregnancy
Blocks alpha 1, beta 1, and beta 2 receptors. |
|
|
What is the mechanism of action of losartan (Cozaar)?
|
AII receptor blocker [prevents vasoconstriction]
|
|
|
(T/F) Losartan can be given to pregnant women.
|
False, side effect of fetal abnormalities.
|
|
|
What is the mechanism of action of diazoxide and minoxidil? And what is their clinical use?
|
Opens K+ channels --> vasodilation
Minoxidil -- IV for severely refractory patients Diazoxide -- IV for HTN emergency |
|
|
What is the mechanism of action of nitroprusside and hydralazine?
|
Increases cGMP levels --> vasodilation
|
|
|
What are side effects of minoxidil?
|
Fluid retention (edema, pericardial effusion)
Hypertrichosis |
|
|
What are the side effects for diazoxide?
|
Since it is a thiazide analog -- diuretic effects and decreases insulin secretion when given orally.
|
|
|
Hydralazine is typically used in combination with...
|
Isosorbide dinitrate
|
|
|
What is a side effect of hydralazine?
|
Causes a lupus-like syndrome.
|
|
|
What is a very critical side effect of nitroprusside?
|
Cyanide poisoning [in the presence of light can be converted to cyanide]
|
|
|
What is the drug of choice in hypertensive emergencies?
|
Nitroprusside
|
|
|
How do nicardipine and amlodipine work?
|
Ca++ channel blockers directly at the smooth muscle of vessels [causing vasodilation]
|
|
|
How do the -PRILS work?
|
ACE inhibitors reducing AII levels preventing vasoconstriction.
|
|
|
What are the side effects of ACEi's?
|
Dry cough
Angioedema Fetal damage |
|
|
What is the mechanism of action of aliskiren?
|
Renin inhibitor.
|
|
|
What is the mechanism of action of fenoldapam?
|
Peripheral D1 (dopamine) receptor activator causing vasodilation.
|
|
|
What is the clinical use of fenoldapam?
|
IV during HTN emergencies
|
|
|
Total Body Water
|
60% of body weight
|
|
|
ICF
|
40% of body weight
2/3 of total body water |
|
|
ECF
|
20% of body weight
1/3 of total body water |
|
|
Interstitial Fluid
|
15% of body weight
|
|
|
Plasma
|
5% of body weight
|
|
|
(T/F) An obese person will have a lower total body water than the calculated total body water.
|
True
Fat contains less water compared to other tissue. |
|
|
What is the range of excretion of the kidneys for fluid?
|
440 mL to 15-20 L/day
|
|
|
Identify the component altered for water balance in the following people:
1. Burn patients 2. Heavy exercise 3. Vomiting/Diarrhea 4. Heat |
1. Insensible losses increase
2. Insensible losses/sweat increases 3. GI losses increase 4. Sweat increases |
|
|
Given the following information, calculate the total osmoles in the ICF:
40 kg person Measured osmolarity = 280 mOsm/L |
0.4 * 40 * 280 = 4,480
|
|
|
Assuming total osmoles = 800, and you ingest 100 mmoles of NaCl -- what will be your new ICF volume and osmolarity? (Assume total body water = 20 L, weight = 33.333 kg)
|
(800 + 200) / 20 = 50 mOsm/L
((2/3)*800)/50 = 10.67 L ECF = 20-10.67 = 9.33 L |
|
|
If isotonic saline is ingested - what changes will be expected in the ECF/ICF/TBW?
|
ICF same volume/osmolarity
ECF increased volume/same osmolarity TBW increased volume/same osmolarity |
|
|
What are the four quantities the kidney must regulate in salt/water balance?
|
1. SAlt balance
2. Water balance 3. Salt/water ratio 4. Blood pressure |
|
|
Name the organ that produces the following signaling molecules:
1. Aldosterone 2. Renin 3. Angiotensinogen 4. ACE |
1. Adrenal glands
2. Kidneys (granular cells) 3. Liver 4. Lungs and endothelial cells |
|
|
What are the effects of AII?
|
Potent vasoconstriction
Induces aldosterone release Proximal tubule Na+ reabsorption [stimulates of Na-H+ antiporter] |
|
|
What are the three inputs to the granular cells?
|
1. Mechanical stress [blood pressure], reduced BP leads to increased renin
2. Beta-adrenergic receptors -- increased sympathetic stimulation leads to increased renin 3. Macula dense sense high salt leads to inhibition of renin secretion. |
|
|
How is macula densa a salt sensor?
|
Na-K-Cl symporter -- high intracellular ions then cause cell swelling and depolarization of the membrane -- thus send a signal to REDUCE renin release.
|
|
|
How does the kidney signal for increased natriuresis and diuresis when high blood pressure occurs?
|
1. Endocytosis of Na-H antiporter
2. Backleak of peritubular capillaries reduces reabsorption 3. Decreased basolateral Na-K ATPase pump |
|
|
(T/F) Increased afferent renal arteriolar pressure directly increases secretion of renin.
|
True.
|
|
|
What mediates the mechanism of autoregulation from the JGA?
|
Prostaglandin release for vasoconstriction of afferent arteriole.
|
|
|
What are the three intra-renal mechanisms to control blood pressure?
|
1. Autoregulation
2. Tubulo-glomerular feedback 3. Glomerulo-tubular feedback |
|
|
What is the purpose of the glomerulo-tubular feedback mechanism?
|
In light of an increased GFR, must maintain Na+ reabsorption to keep the ratio about the same -- 65%
|
|
|
Because we are land-dwelling animals we require independent regulation of salt and water via these four independent mechanisms:
|
1. aldosterone
2. natriuretic peptides 3. antidiuretic hormone 4. miscellaneous hormones |
|
|
What is the mechanism of action of aldosterone?
|
Stimulation of ENaC via increasing transcription factor [in the nucleus]
|
|
|
The TWO major stimulators of aldosterone secretion are:
|
1. High plasma potassium
2. Angiotensin II |
|
|
What stimulates release of natriuretic peptides?
|
Volume expansion
Brain natriuretic and atrial natriuretic peptide [synthesized in teh heart] |
|
|
What are the three effects of natriuretic peptides?
|
1. Decreased renin
2. Decreased Na+ reabsorption 3. Relaxation of afferent arteriole |
|
|
When ADH levels get low -- what happens in the distal nephron?
|
endocytosis of aquaporin 2 pores through clathrin-coated vesicles.
|
|
|
How does ADH signal increased aquaporin 2 water pores?
|
1. V2 receptor
2. Increased cAMP 3. PKA activated that implants aquaporin 2 on apical surface. |
|
|
What are the two main input signals for ADH release?
|
1. High osmolarity [osmoreceptors]
2. Low BP [baroreceptors] |
|
|
Where is ADH synthesized?
|
Hypothalamic neurons -- supraoptic and paraventricular nuclei which terminates into the posterior pituitary.
|
|
|
What are the three stimulators of thirst sensation ...
|
1. Low blood volume
2. High AII 3. Increased osmolarity |
|
|
(T/F) Sweat is hypo-osmotic.
|
True.
|
|
|
How much K+ is excreted daily?
|
Equivalent to daily intake [typically ~100 mmoles/day]
|
|
|
98% of the body stores of K+ are located....
|
in the ICF compartment
|
|
|
What is the major regulator of K+ excretion?
|
Kidneys -- handle 92% of K+ dietary intake
|
|
|
What are the three main factors that increase K+ movement from the ECF to the ICF:
|
1. pH [alkalosis]
2. Insulin 3. Epinephrine |
|
|
How does an increased osmolality lead to K+ exit from the cells?
|
Increased osmoles pull water out of the cell - with the pull of water, leads to solvent drag and K+ exits as well.
|
|
|
Hyperkalemia leads to increased _______ while hypokalemia leads to increased __________. [neurologic]
|
Depolarizations
Hyperpolarizations |
|
|
List the following as either increasing or decreasing ECF K+ levels:
1. Acidosis 2. Insulin 3. Alkalosis 4. Tissue damage/trauma 5. Exercise 6. Beta-blockers |
1. Increase
2. Decrease 3. Decrease 4. Increase 5. Increase 6. Increase |
|
|
K+ < 3.7 mM
|
Hypokalemia
|
|
|
K+ > 5.3 mM
|
Hyperkalemia
|
|
|
Which regions of the nephron are primarily responsible for altering K+ secretion?
|
Aldosterone:
1. Principals cells [collecting duct] 2. Distal convoluted tubule 3. TALH [minor] - Na-K-2Cl symporter |
|
|
What are the three main physiological regulators of K+ secretion?
|
1. Plasma [K+] levels
2. Tubular [Na+] levels 3. Aldosterone levels |
|
|
What are the modes of action of aldosterone?
|
1. Stimulate Na-K ATPase
2. + on ENaC 3. Open apical K+ channels |
|
|
What two things promote and what one thing inhibits the release of aldosterone [physiologically]?
|
1. Increased Plasma [K+]
2. AII 1. ANF |
|
|
(T/F) Reabsorption of K+ by intercalated Type A cells is constant regardless of potassium load.
|
True.
|
|
|
What are the two ways that diuretics [thiazides] cause K+ wasting?
|
1. Increased Na+ delivery in tubule of collecting duct
2. Increased urine flow simulates low tubular K+, thus promoting K+ secretion. |
|
|
(T/F) Acidosis inhibits Na-K ATPase pump thus further exacerbating the hyperkalemia. Alkalosis - the opposite occurs.
|
True.
|
|
|
How are proteins handled by the kidney?
|
1. Bind to receptor
2. Endocytosed 3. Lysed to amino acids 4. Reasbsorbed into interstitium |
|
|
Megalin and cubulin
|
Receptors in the proximal tubule used to bind proteins -- loss of function results in proteinuria
|
|
|
How are peptides handled by the kidney?
|
1. Peptidases on lumen
2. Amino acids reasborbed using amino acid transporter |
|
|
How are organic nutrients transported?
|
Active transport across a specific transporter [Tm-limited]
In conjunction with sodium uptake |
|
|
(T/F) OCT and OATs help bring anions and cations back into the interstitium in the S3 PCT.
|
False, they help SECRETE anions/cations.
S3 PCT part is true. |
|
|
(T/F) Anions are exchanged for Na+ when secreted into the tubule.
|
True.
|
|
|
(T/F) Cations are exchanged for H+ when secreted into the tubule.
|
True.
|
|
|
Explain how urea is recycled in the nephron.
|
Reabsorbed in the collecting duct and secreted into the loop of henle via UT transporters.
|
|
|
(T/F) Over 50% of urea filtered is excreted.
|
True.
|
|
|
LD-50
|
Dose at which 50% of test group die.
|
|
|
ED-50
|
Dose at which 50% of test group begin seeing benefits of medication.
|
|
|
TI
|
Therapeutic Index
LD50 / ED50 or TD50 |
|
|
What is margin of safety?
|
LD1 / ED99
Want this higher -- hard to overdose on medication |
|
|
What is TLV?
|
Threshold limit values
ceiling values -- can NEVER go above this level time weighted averages -- spend equal time above/below this limit |
|
|
What is the difference between TLV and PEL?
|
PEL = permissible exposure limit
PEL = legal ramifications, TLV = actual level of physical effects. |
|
|
Bioaccumulation
|
Accumulation of toxic compound in tissue of organism [i.e. fat] over time.
|
|
|
Biomagnification
|
Increased toxicity due to predator-prey relationships in the environment
|
|
|
What are the four things that can affect a toxicological response?
|
1. Supra-addition/Potentiation
2. Physiochemical characteristics [stability] 3. Route of administration 4. Metabolism (detox vs. bioactivate) |
|
|
What are the four general approaches to managing a poisoned patient?
|
1. ABCD
-- airway, breathing, circ, sugar [if obtunded] 2. Decontamination 3. Increased elimination 4. Antidote |
|
|
Mechanism of action of cyanide poisoning....
|
Inhibit cytochrome oxidase to reduce aerobic metabolism and phosphorylation
|
|
|
Clinical symptoms of cyanide poisoning...
|
1. Flush appearance
2. Dizziness/confusion/anxiety 3. Death within 10 minutes |
|
|
Treatment of cyanide poisoning...
|
Stabilize
Amyl nitrites + thiosulfate |
|
|
Mechanism of action of aflatoxin (mycotoxin) poisoning...
|
Bioactivation to epoxide that covalently binds to cell macromolecules
Reduces hepatic glycogen stores and increases hepatic lipids --> liver damage/hepatocellular carcinoma |
|
|
Clinical symptoms of mycotoxin poisoning...
|
1. Nausea/vomiting
2. GI bleeding 3. Jaundice [liver damage] 4. hepatocellular carcinoma |
|
|
Treatment of mycotoxin poisoning...
|
Stabilize and treat shock (acute)
|
|
|
(T/F) Post 24 hrs, tx of acetaminophen poisoning is futile.
|
True.
|
|
|
What is the best time frame to treat acetaminophen poisoning?
|
Within 15-24 hrs [N-acetyl cysteine]
|
|
|
What is the purpose of the nomogram?
|
Helps determine plasma level of acetaminophen based on hrs since ingestion
Also helps determine likelihood of liver damage. |
|
|
Clinical symptoms of acetaminophen poisoning...
|
Jaundice
N/V, anorexia, abdominal pain Elevation of liver enzymes |
|
|
Mechanism of acetaminophen poisoning...
|
Depletion of glutathione conjugation enzyme
Remains highly toxic to liver cells -- lipid peroxidation |
|
|
Treatment of acetaminophen poisoning...
|
1. Ipecac [w/in an hour]
2. N-acetyl cysteine 3. Monitor levels |
|
|
How does EtOH affect acetaminophen levels?
|
EtOH induce Cyp2e1 -- thus can cause overdose at therapeutic levels. [body overloaded with NAPQI reactive metabolite and depletes glutathione]
|
|
|
What is a chelator?
|
Organic compound with 2 or more electronegative groups that form stable covalent-coordinate bonds with cationic metal ions.
|
|
|
What are the EIGHT ideal characteristics of a chelating agent?
|
1. Nontoxic
2. Water soluble 3. Resistant to biotransformation 4. Reach storage site 5. Functions at physiological pH 6. Complex has lower toxicity 7. Lower affinity for Calcium 8. Lower affinity for endogenous ligands |
|
|
Symptoms of iron poisoning...
|
1. V/D (bloody)
2. May show improvement over 12 hrs 3. Abrupt relapse |
|
|
Mechanism of toxicity of iron poisoning...
|
Direct mucosal injury
Cellular dysfunction causing metabolic acidosis and liver necrosis |
|
|
Treatment of iron poisoning...
|
Treat shock
Deferoxamine (if serum Fe > TIBC) |
|
|
Symptoms of lead poisoning...
|
1. Projectile vomiting/diarrhea
2. Basophilic stippling 3. Personality changes 4. Lead line on gums 5. Peripheral neuropathy 6. Increased aminolevulinic acid and coporphyrin [disruption of RBC synthesis] |
|
|
Mechanism of toxicity of lead poisoning...
|
1. Bind Sulfhydryl groups interfere w/enzymes
2. Impairs HgB synthesis 3. Demyelination of nerves |
|
|
Treatment of lead poisoning...
|
Maintain urinary output
Dimercaprol OR calcium EDTA |
|
|
Symptoms of ethylene glycol poisoning...
|
1. Increased osmolar gap
2. Intoxication 3. Hyperventilation 4. Renal failure |
|
|
Mechanism of toxicity of ethylene glycol...
|
Metabolized by alcohol dehydrogenase which produces toxic acids
Calcium oxalate crystals cause tissue injury |
|
|
Treatment of ethylene glycol poisoning...
|
1. Hemodialysis
2. Ethanol 3. Fomepizole [for kids] |
|
|
Symptoms of ricin poisoning...
|
1. GI irritation (3-4 hrs post ingestion)
2. Short remission may occur 3. Hemorrhagic gastritis 4. Tissue necrosis |
|
|
Mechanism of toxicity of ricin poisoning...
|
Dirsupts protein synthesis by binding 60S subunit
[lectin ricin] |
|
|
Treatment of ricin poisoning...
|
Charcoal [if recently ingested]
Treat fluid/electrolyte losses Antidote (if available) |
|
|
Normal ECF [H+]
|
40 nM
|
|
|
What are the four non-bicarbonate buffers?
|
1. Phosphates (organic/inorganic)
2. Proteins 3. Hemoglobin 4. Bone |
|
|
For every H+ buffered...
|
A bicarb is lost via CO2 in the lungs
|
|
|
What is the Henderson-Hasselbach equation?
|
pH = 6.1+ log [ (HCO3)/(0.03*PCo2) ]
|
|
|
What is the difference between volatile and non-volatile acid?
|
Volatile = production of CO2/day
Non-volatile = acid from metabolism |
|
|
What are the three defenses against H+ swings of the body?
|
1. Immediate chemical buffering
2. Respiratory control of CO2 3. Renal control of HCO3 |
|
|
What is the role of kidneys in acid-base balance?
|
1. Reabsorb HCO3
2. Form new HCO3 when needed |
|
|
Describe Bicarb reabsorption in the proximal tubule ...
|
Na-H antiporter provides H+ for....
Bicarb reaction in lumen to form CO2 CO2 easily permeates into cell Bicarb rxn occurs -- H+ is released to lumen, HCO3 is released back to blood using Na-HCO3 cotransporter |
|
|
(T/F) When reabsorbing HCO3 - there is no net H+ secretion and no new HCO3 produced.
|
True.
|
|
|
Describe bicarb reabsorption in the intercalated Type A cells...
|
CO2 + H20 to H and HCO3 using CA
H+ - ATPase and K-H ATPase pump hydrogen out Body accepts HCO3 via HCO3-Cl antiporter |
|
|
What two regions of the nephron are responsible for excretion of acid loads?
|
1. Intercalated Type A cell - Collecting duct
2. Proximal tubules |
|
|
How do Intercalated Type A cells secrete acid loads?
|
Instead of a HCO3 buffer -- there is a phosphate buffer in the lumen - thus when CA makes the H/HCO3 -- the HCO3 reabsorbed is NEW.
|
|
|
How do proximal tubules secrete acid loads?
|
Glutamine [intracellularly] breaks down into ammonium and bicarb -- the ammonium is secreted into the filtrate [proton equivalent] and the bicarb is reabsorbed -- both utilize sodium for reabsorption.
|
|
|
Which acid secretion mechanism has the greater regulatory influence?
|
Ammonia secretion in proximal tubules.
|
|
|
How do you calculate the new bicarb added to the body?
|
New bicarb =
Titratable acid + NH4 excreted - HCO3 excreted |
|
|
What are the two triggers for a renal response to initiate acid-base balance mechanisms?
|
1. Changes in PaCO2
2. Changes in arterial pH |
|
|
How does aldosterone help acidify the urine?
|
1. Stimulates Na+-H+ antiporter [PT]
2. Promotes H-ATPase [PT and CD, Type A] 3. Stimulates Na-HCO3 basolateral symporter [PT] |
|
|
What is the kidney's response in an acidosis?
|
Complete HCO3 reabsorb
Formation of new HCO3 Increased H+ secretion |
|
|
What is the kidney's response in an alkalosis?
|
Secrete HCO3
Retain H+ Decrease NH4+ excretion |
|
|
How do Type B intercalated cells secrete HCO3?
|
Reverse of Type A
HCO3/Cl- on apical surface -- Cl- in, HCO3 out At the basolateral surface, H-ATPase and H-K ATPase. |
|
|
Bacteriuria = infection
|
False -- could be colonization of distal urethra or contamination.
|
|
|
Infection of prostate
|
Prostatitis
|
|
|
Infection of bladder
|
Cystitis
|
|
|
Pyelonephritis
|
Infection of kidney
|
|
|
Pyuria
|
Presence of leukocytes in urine
|
|
|
What defines a LOWER urinary tract infection?
|
Bladder, prostate, or urethra infection.
|
|
|
What defines a UPPER urinary tract infection?
|
Kidneys and/or perinephric space
|
|
|
(T/F) Females are always at increased risk for UTIs.
|
False -- boys are at increased risk for first 6 months of life -- then girls increase in risk after this.
|
|
|
(T/F) Acute UTIs are rare in men under the age of 50.
|
True.
|
|
|
(T/F) Of the 5% of women that get bacteriuria - only 8% can clear their own bacteriuria.
|
False -- only 8% progress to have symptomatic infection.
|
|
|
(T/F) Half of the women with symptomatic infection have spontaneous resolution over 1-2 weeks.
|
True.
|
|
|
What are four risk factors that increase the likelihood of infection?
|
1. Pregnancy
2. Obstruction 3. Neurogenic bladder issues 4. VUR |
|
|
What is the most common bacteria to cause UTIs?
|
E. Coli -- 80%
|
|
|
Which two enterobacteriae can promote urolithiasis (struvite)?
|
Klebsiella
Proteus |
|
|
Which bacteria is associated with the healthcare setting?
|
Pseudomonas aeruginosa
|
|
|
Which bacteria causes approximately 10% of uncomplicated cystitis in sexually active females?
|
Staph. saphrophyticus
|
|
|
What are the two main situations that S. aureus can be isolated from a urine culture?
|
1. Spread of systemic infection to kidneys
2. instrument/catheter placement |
|
|
For nosocomial UTIs - what are the three main bacterial etiologies to initially suspect...
|
1. enterococcus
2. pseudomonas 3. s. aureus |
|
|
Elderly men with prostatic hypertrophy are at increased risk for...
|
Infxn with Enterococcus
|
|
|
(T/F) Lactobacilli, staph, strep,and diptheroids are all part of the normal flora.
|
True.
|
|
|
What are the three factors that can affect detection of an infection?
|
1. Antibiotic exposure
2. Contraceptive use 3. Other genital infections (STDs) |
|
|
Why is the urinary tract a harsh environment for bacteria? (3 factors)
|
1. consistent voiding/flushing
2. high urea concentration 3. osmolarity of urine |
|
|
What role do hemolysin, siderophores, and pili production have infection of urinary tract?
|
Virulence factors promoting infection.
|
|
|
(T/F) >10 neutrophils per high power field is abnormal.
|
True.
|
|
|
What is the cut-off for distinguishing between perineal contamination and actual UTI?
|
>= 100,000 colonies per mL
(>10^5) |
|
|
(T/F) One can r/o UTI as a cause if bacterial colony count is only 20,000 per mL.
|
False -- if symptomatic then should still be considered.
|
|
|
What are the six causes of sterile pyuria?
|
1. Previous administration of abx
2. Contamination from vaginal leukocytes 3. Chronic interstitial nephritis 4. Nephrolithiasis 5. Tumor 6. Infection of atypical organisms |
|
|
What are the three main atypical organisms that cna cause UTIs?
|
Chlamydia trachomatis
Ureaplasma urealyticum TB |
|
|
What are the cases where you ABSOLUTELY would TREAT an asymptomatic bacteriuria? (3)
|
1. Pregnancy
2. Men undergoing prostatic surgery 3. Patient about to undergo urological procedure |
|
|
What are the cases where there is RELATIVE indication for treating asymptomatic bacteriuria? (4)
|
1. Diabetes mellitus
2. Immunocompromised/suppressed 3. Kids with VUR 4. Struvite nephrolithiasis |
|
|
What is the first-line rx for women with a community-acquired UTI?
|
Bactrim - TMP-SMX.
|
|
|
When is fluoroquinolones used for UTIs?
|
If prevalence of E. coli resistance to TMP-SMX is >20%.
|
|
|
What is CRITICAL before administering fluoroquinolones to a woman?
|
EXCLUDE PREGNANCY!!!!
|
|
|
What is the length of therapy for uncomplicated cystitis in women?
|
3 days.
|
|
|
What is the use of pyridium in UTIs?
|
For women experiencing significant dysuria -- this is a urinary analgesic.
|
|
|
What is the empiric rx for complicated UTIs?
|
Fluoroquinolones.
|
|
|
What is the length of therapy for pyelonephritis or a complicated infection?
|
7-14 days.
|
|
|
When should you see improvement from UTI rx?
|
Within 24-48 hrs.
|
|
|
What is the recommended course of rx for men with bacterial prostatitis?
|
6 weeks.
|
|
|
If for some reason - the clinic does not have bactrim nor fluoroquinolone...what drug can you look to next for uncomplicated cystitis?
|
Nitrofurantoin.
|
|
|
What transporter is responsible for the bulk of Na+ reabsorption in the PT?
|
Na-H exchanger.
|
|
|
(T/F) Chloride is taken up by both transcellular and paracellular routes
|
True.
|
|
|
(T/F) Overall, the loop of Henle reabsorbs more salt than water back into the bloodstream
|
True (results in dilute urine)
|
|
|
Confirm the following is true:
Macula densa signals high salt (thus implying high flow/high BP) - releases less renin -- so less AII - causing dilation [more dilation of efferent than afferent] -- this then causes reduction in BP (due to reduced vasoconstriction) and maintenance of normal GFR rather than increased GFR in light of the pressure changes. |
Yes.
|
|
|
(T/F) 60-65% of filtered load of bicarbonate is reabsorbed in the PT.
|
False -- 80-90%
Other solutes are about 60-65% |
|
|
(T/F) Phosphate is the most important non-bicarbonate buffer.
|
True.
|
|
|
How do thiazides increase Ca+ reabsorption?
|
By blocking Na/Cl symport in the DCT -- it promotes the basolateral Na-Ca antiporter thus pushing Ca+ back into blood and Na+ into the cell.
|
|
|
Apical Ca+ reabsorption in the Distal Convoluted Tubule is controlled by ______.
|
PTH.
|
|
|
Why does the kidney want to increase Pi excretion in light of PTH stimulation?
|
Pi is released more during bone resorption and reabsorbed by gut more with activated Vit D
to prevent crystal formation in the body, the kidney must excrete the Pi. |
|
|
What is the mechanism by which PTH can increase Pi excretion in the kidneys?
|
Inhibits Na-PO4 co-transporter in the proximal tubule [thus reduced reabsorption].
|
|
|
Main mineral component of bone
|
Hydroxyapatite
|
|
|
Two major hormones controlling calcium and phosphate levels
|
1. Vit D [activated]
2. PTH |
|
|
(T/F) Hypocalcemia can lead to tetany due to loss of Calcium on extracellular membrane that usually prevents inappropriate depolarizations
|
True.
|
|
|
Bone matrix constituents
|
Hydroxyapatite + Type I Collagen
|
|
|
Osteoblasts
|
build bone
|
|
|
Osteoclasts
|
Resorption of bone
|
|
|
Osteocytes
|
Mechanotransduction of bone
|
|
|
(T/F) Cathepsins and H+ help degrade mineral on bone [secreted by osteoclasts]
|
True
|
|
|
What % of calcium is absorbed by the GI tract?
|
20%
|
|
|
Acidosis ______ Ca+ reabsorption, while alkalosis _______ Ca+ reabsorption.
|
Inhibits
Induces |
|
|
(T/F) Only a small amount of absorbed calcium reaches the kidneys for filtration
|
True, bone absorbs majority of Ca+
|
|
|
How do loop diuretics lead to reduced Ca+ reabsorption?
|
Stop reabsorption of cations thus affected electrochemical gradient which reduces the paracellular absorption of Ca+
|
|
|
What are the 3 effects of calcitriol [active Vit D]
|
1. stimulate intestinal reabsorption;
2. promote bone resorption; 3. increase reabsorption in kidney |
|
|
(T/F) High calcium stimulates PTH secretion
|
False, opposite
|
|
|
How does PTH increase Ca+ levels?
|
1. Upregulates Ca+ reabsorption in DCT,
2. Promotes Vit D activation (thus increasing gut reabsorption) 3. Increases bone resorption |
|
|
What is the purpose of calcitonin?
|
Thyroid hormone secreted that inhibits osteoclast activity thus helping reduce Ca+ levels [not involved in day-to-day homeostasis]
|
|
|
How is the opposing action of PTH and Vit D in light of PO4 balance critical?
|
PTH decreases PO4 [by increasing PO4 excretion] thus preventing mineralization in the bone, Vit D increases PO4 reabsorption from both gut/kidneys
|
|
|
Why is all PO4 not reabsorbed in the PCT? How is this facilitated?
|
PO4 required in Type A Intercalated cells for forming new HCO3, Type IIa Na-PO4 transporters get saturated thus allowing PO4 to be made available distally
|
|
|
How does PTH decrease PO4 reabsorption in kidney?
|
Endocytosis of Na-PO4 transporters to reduce T_m
|
|
|
(T/F) Only 60% of PO4 is available for filtration
|
False; 90% of PO4 is filtered (only 10% bound to proteins); this contrasts with Ca+ (40% bound to proteins)
|
|
|
What is the major cause of secondary hyperparathyroidism?
|
Chronic kidney failure
|
|
|
Why does bone weakening occur mainly in secondary hyperparathyroidism?
|
Kidneys cannot appropriately respond to increases in PTH due to disease -- thus the bone must compensate for this by increasing resorption rates.
|
|
|
What are the four signs of primary hyperparathyroidism
|
1. High [PTH]
2. Hypercalcemia 3. Hypercalcuria 4. Hypophosphatemia |
|
|
What is the difference between pharmacokinetics and pharmacodynamics?
|
Pharmacokinetics -- different plasma concentration with same dose
Pharmacodynamics -- different response to the same plasma concentration |
|
|
What are three ways that intake of a drug is affected?
|
1. In vitro interaction [direct precipitation/inactivation with another drug - tetracyclines + sulfonamides]
2. Altered GI absorption [abx decrease gut flora, increase K+ --> increase response to anticoag] 3. Dermatomucosal absorption [i..e nicotine patches] |
|
|
What are two ways that drug interactions affect distribution?
|
1. Alteration of plasma protein binding [displacement reduces drug half life - salicylates displace warfarin/phenytoin]
2. Displacement from tissue binding site [i.e. quinidine displaces digoxin] |
|
|
(T/F) Inhibition of P-450 lasts longer than induction.
|
True.
|
|
|
What are three ways that excretion can be affected?
|
1. Competition for same transport system
2. Change in urinary pH 3. Use of diuretics to reduce toxicity |
|
|
How does Tamoxifen work as a partial agonist?
|
Antagonist overall of estrogen, but an agonist at the bone estrogen receptors.
|
|
|
What is wrong with consuming a lot of black licorice with use of digoxin?
|
Glycyrrhizic acid [in licorice] will decrease K+ ECF levels which leads to digoxin toxicity.
|
|
|
Why is grapefruit juice consumption not recommended for Ca+ channel blockers?
|
Furanocoumarins in grapefruit juice will decrease activity of cyp3a4 thus increasing toxicity of these blockers?
|
|
|
If you administer phenobarbitol in a patient on anti-coagulative therapy (warfarin) - what would you expect to see?
|
A decrease in PTT since phenobarbitol induces enzyme that increases warfarin metabolism.
|
|
|
Chronic alcohol use + acetaminophen
|
Cyp2e1 induction - thus more toxic metabolites are produced at therapeutic doses.
|
|
|
What is the mechanism of action of disulfiram?
|
Inhibits acetaldehyde dehydrogenase - so that a person feels the negative effects of ethanol consumption [used to treat alcoholics]
|
|
|
How does fomepizole work?
|
Inhibits alcohol dehydrogenase to prevent more metabolism of ethylene glycol [in poisonings]
|
|
|
What is the effect of quinidine on digoxin?
|
Quinidine increases levels of digoxin [displaced]
|
|
|
Why do clarithromycin and rifabutin interact?
|
Both are metabolized via cyp3a4 pathways -- thus increasing levels of both drugs and their metabolites in the blood.
|
|
|
Why does azithromycin + rifabutin not lead to any problems?
|
They do not share a common metabolic pathway.
|
|
|
Decline in GFR-more than 50% loss in less than 3 months
|
Rapidly progressive GN
|
|
|
Rate of GFR loss in Stage IV Diabetic Nephropathy?
|
10-12 mL/min/yr!!!
|
|
|
Anion gap formula
|
Na - Cl - HCO3
normal = 10-12 |
|
|
Calculated osmoles formula
|
2*Na + Glucose/18 + BUN/2.8
|
|
|
Compensation of metabolic acidosis
|
Decrease in pCo2
delta (CO2/HCO3) = 1-1.5 |
|
|
Compensation of metabolic alkalosis
|
Increase in pCo2
delta (CO2/HCO3) = 0.5-1.0 |
|
|
Urine AG formula
|
Na + K - Cl
estimates level of NH4+ [ability of kidneys to acidify urine] |
|
|
RTA and Urine AG
|
Positive Urine AG
|
|
|
Causes of Type I RTA
|
Autoimmune (SLE, Sjogren's, RA)
Typically acquired (ampho B, lithium carbonate, toluene) Kids -- Marfan's, Ehler Danlos, Medullary cystic disease |
|
|
Causes of Type II RTA
|
Fanconi, cystinosis
Multiple myeloma, chronic use of CA inhibitors |
|
|
Causes of Type IV RTA
|
Reduced aldosterone or resistance in tubule [renal insufficiency of diabetes mellitus]
Use of K+ sparing diuretics |
|
|
Type III RTA
|
Autosomal recessive
CA II deficiency severe form of Type I |
|
|
How do you know if you have a volume responsive metabolic alkalosis?
|
Urine Cl < 10 = responsive
Urine Cl > 20 = unresponsive |
|
|
Causes of SIADH (4)
|
1. Pulmonary disorders [asthma/abscess/pneumonia]
2. CNS disorders [tumors/trauma/meningitis] 3. Carcinomas [lungs/GI/lymphomas] 4. Anxiety/drugs |
|
|
FENa < 1%
|
Pre-renal ARF
|
|
|
BUN > 20:1
|
Pre-renal ARF
|
|
|
When is uremia most likely to occur?
|
Generally occurs when GFR < 15 - 20% of normal
|
|
|
Which kidney stones form in alkaline pH?
|
Struvites and calcium phosphate stones.
|
|
|
Which kidney stones form in acidic pH?
|
Uric acid, oxalate, and cystine crystals.
|
|
|
Which kidney stones form independent of pH?
|
Calcium oxalate
|
|
|
Six risk factors for stone formation?
|
1. Low Urine Volume
2. Hypercalcemia 3. Hyperoxaluria 4. High Na+ diet 5. High protein 6. Hyperuricosuria |
|
|
(T/F) Calcium stones are the most common and affect men more than women.
|
True.
|
|
|
(T/F) Cystine crystals are radiolucent.
|
False - radiodense.
Uric acid crystals are radiolucent. |
|
|
Inheritance of reflux nephropathy...
|
Autosomal dominant with variable penetrance
|
|
|
What are late complications of reflux nephropathy?
|
HTN
Ablative nephropathy/proteinuria |
|
|
X-linked nephrogenic DI
|
ADH receptor issue
|
|
|
Autosomal recessive nephrogenic DI
|
aquaporin mutation
|
|
|
Explain thiazide diuretic use in nephrogenic DI.
|
Slightly reduce volume status so proximal tubule will increase amt of reabsorption so less solute is lost.
|
|
|
Two conditions leading to nephrocalcinosis
|
1. Hypercalciuria
2. Hypocitraturia |
|
|
(T/F) Nephrocalcinosis is an issue in proximal tubular RTA (type II)
|
False, distal RTA.
proximal does not have hypocitraturia. |
|
|
Which is the most common RTA?
|
Type IV
|
|
|
What are three features of global collecting duct injury?
|
1. Type IV RTA
2. Nephrogenic DI 3. Progressive renal failure |
|
|
What is the problem in Bartter's Syndrome?
|
Problem with Na-K-2Cl transporter with secondary hyperaldosteronism from volume depletion.
|
|
|
Is Bartter's a volume responsive or unresponsive metabolic alkalosis?
|
Unresponsive -- there is an inherent problem - not an acute loss of volume as seen with diuretics or vomiting.
|
|
|
What are the five factors leading to stone formation?
|
1. High solute amount
2. Low solvent amount [low H20] 3. Favorable pH for stone formation 4. Nidation [uric acid allows calcium oxalate crystals to form] 5. Lack of inhibitors [i.e. tamm horsfall, citrate, magnesium] |
|
|
What is the most common cause of hypercalciuria?
|
Idiopathic -- specifically excessive absorption of Ca+ from the GI [rx: reduced Ca+ diet]
|
|
|
Why is Na+ consumption a part of a risk factor for nephrolithiasis?
|
Increase in Na+ (every 100 mmol) increases Ca+ in the urine (by 25 mg)
|
|
|
What is the rx for enteric hyperoxaluria as a risk factor for nephrolithiasis?
|
Oral calcium supplements to complex with oxalate in GI -- so that less is reabsorbed by gut.
|
|
|
Goal for urine output [kidney stones]
|
> 2 L/day
|
|
|
Goal for hypercalciuria [kidney stones]
|
< 4 mg/kg/day
|
|
|
Goal for hyperoxaluria [kidney stones]
|
< 45 mg/day
|
|
|
Goal for hypocitraturia [kidney stones]
|
> 350 mg/day
|
|
|
High protein diet goal [kidney stones]
|
Protein intake ~1 gm/kg
|
|
|
Hyperuricosuria goal [kidney stones]
|
< 750-800 mg/day
|
|
|
High sodium intake goal [kidney stones]
|
< 150 mmol/day in urine
|
|
|
(T/F) No evidence that smoking or caffeine intake is a cause of a HTN.
|
True -- EtOH is proven, smoking is a cause of CV disease.
|
|
|
(T/F) Low dietary calcium intake helps reduce risk of HTN.
|
False -- higher intake lowers BP.
High SERUM levels is a cause of HTN. |
|
|
What is the main work-up for HTN in a patient?
|
1. Serum creatinine [r/o kidney disease]
2. Urinalysis [r/o kidney disease] 3. Serum K+ [r/o mineralocorticoid excess] 4. Lipid profile/EKG to check for risk factors |
|
|
What is pseudo-HTN?
|
Increased cuff BP reading due to stiffness of arterial walls due to peripheral disease -- cross-confirm with intra-arterial measurement [invasive]
|
|
|
What is malignant HTN?
|
Subset of HTN-ive emergency with retinal papilledema, hemorrhages, and exudates.
|
|
|
What are the four most common causes of secondary HTN?
|
1. Chronic kidney disease
2. Renovascular HTN 3. Obstructive sleep apnea 4. Primary hyperaldosteronism |
|
|
What is the classic triad for pheochromocytoma?
|
1. Sweating attacks
2. Tachycardia 3. Headaches |
|
|
(T/F) Absence of family hx confirms essential HTN.
|
False -- reason to believe there is a secondary cause of HTN.
|
|
|
If the onset of HTN is before puberty or after the age of 55....
|
Think about SECONDARY HTN.
|
|
|
(T/F) HTN is the 2nd most common cause of ESRD.
|
True.
|
|
|
VMA
|
Urine measurement for pheochromocytoma
|
|
|
Clonidine supression test
|
Confirmatory dx for pheochromocytoma [expect a drop to less than 500, if it doesn't occur - pheo exists]
|
|
|
If surgery for pheochromocytoma is not possible - what can you give?
|
Metyrosine [alpha-methyl-tyrosine]
|
|
|
(T/F) Primary hyperaldosteronism is more common in men.
|
False - women.
|
|
|
What is the classic triad for hyperaldosteronism?
|
1. HTN
2. Hypokalemia 3. Metabolic alkalosis |
|
|
What three diagnostic clues support an adenoma over bilateral hyperplasia for primary hyperaldosteronism?
|
1. Postural drop in aldosterone levels
2. Hypokalemia < 3 mEq/L 3. Overnight recumbent pre-aldosterone (18-hydroxycorticosterone) levels > 50 mg/dL |
|
|
What is the difference in rx between bilateral hyperplasia and adenoma?
|
1. Surgery = adenoma
2. eplerenone/spironolactone + thiazide for bilateral hyperplasia |
|
|
What two types of patients [demographics] would you highly suspect renovascular hypertension?
|
1. 30 y/o white woman [fibromuscular dysplasia]
2. >50 y/o w/vascular disease |
|
|
Why does renal dysfunction occur in those patients who are treated with ACEi who have renovascular hypertension?
|
ACEi causes dilation of efferent arteriole - thus further reducing GFR/RBF to the kidneys leading to ischemia.
|
|
|
(T/F) Renovascular hypertension has inappropriate elevated renin levels.
|
True.
|
|
|
Why do carbenicillin and penicillin cause hypokalemia?
|
increase negative charges in the tubular lumen which lead to increased K+ excretion.
|
|
|
EKG signs in hypokalemia
|
Flat T waves
U waves |
|
|
(T/F) Clincial symptoms typically don't start until [K+] < 3.0
|
True.
|
|
|
What is the order of correction in a hypokalemia?
|
Mg+ loss then K+ then acidosis
|
|
|
If Urine chloride is > 30 mEq/L - what can you see about the etiology?
|
Most likely due to RTA -- renal K+ wasting.
|
|
|
(T/F) 1 mEq/L decrease in serum K is equivalent to a 200-400 mEq deficit.
|
True.
|
|
|
What are some causes of false hyperkalemias?
|
1. Thrombocytosis
2. Finger stick 3. Hemolysis in test tube 4. Leukocytosis |
|
|
EKG sign at < 5.5 mEq/L of [K+]
|
Normal
|
|
|
EKG sign at 5.5-6.5 mEq/L of [K+]
|
Peaked T wave
|
|
|
EKG sign at 6.5-8 mEq/L of [K+]
|
prolonged PR
decreased P amplitude Widened QRS complex |
|
|
EKG SIGNS FOR > 8.0 [K+] mEq/L
|
sine wave pattern, VF, asystole
|
|
|
What is the use of Ca+ in hyperkalemia treatment?
|
Prevents unwanted depolarizations
|
|
|
See BIG K Drop
Rx for Hyperkalemia |
Calcium
Bicarb Insulin Glucose Kayexelate Diuretics Dialysis |
