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538 Cards in this Set

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Definition of CKD
irreversible loss of renal function that may or may not lead to ESRD

-duration >3 months
irreversible renal failure to point of needing RRT

-GFR creatinine clearance <10mL/min
Acute Renal Failure Definition
rapid deterioration in renal func, resulting in accum of nitrogenous waste

-days to weeks, <3 months for sure
Azotemia definition
the accumulation of abnormally large amounts of nitrogenous waste products in the blood, as in uremic poisoning.
2 medications affecting creatinine?
1) trimethoprim/bactrim
2) Cimetidine (tagame) H2 blocker to prevent gastric acidity

Serum creatinine could rise w/ normal renal function, but would lead you to check CPK levels in what 3 cases?
1) trauma
2) statins
3) seizures
Acute Renal Failure CHARAC:
***renal size >10cm***
normal echogenicity
absent osterodystrophy
***GRANULAR CASTS or BLAND SEDIMENT on urinalysis***
renal size <9cm
increased echogenicity (scar tissue)
renal osteodrystrophy
waxy casts
Factors NOT associated clearly with either ARF or CRF/CKD
If a lesion is pre-renal, it means that there's...
inadequate perfusion of the kidney
If a lesion is renal, it means that there's...
specific damage to the kidney- physical damage
If a lesion is post-renal, it means that there's...
obstruction to urinary flow with preserved perfusion and lack of direct nephrotoxic damage

-obstruction to flow, like a stone
4 causes of renal-based ARF (as opposed to pre- or post-renal):
1) Acute Tubular Necrosis
2) Interstitial nephritis
3) Glomerulonephritis
4) Vascular
What's the major cause of ARF in outpatient settings?
pre-renal azotemia
What's the major cause of ARF in hospital settings?
Acute Tubular Necrosis
Factors of vasconstriction
Factors of Vasodilation
PGE2 acts by...
dilating the Afferent arteriole
How do you restrict the Efferent arteriole?
with Angiotensin II
Prostaglandins act to do what 2 things?
1) vasodilation of the renal arterioles

2) activation of renin production, and eventually leading to AII production, which constricts the efferent arteriole to MAINTAIN INTRAGLOMERULAR PRESSURE AND PERMIT CONTINUED URINE FORMATION
Pre-renal azotemia is a state of...
underperfusion of the kidneys
-normal response: REABSORB sodium and water, expand the intravasc volume

80% of Na reabs occurs in prox tubule, 20% in thin ascending loop, <5% in distal convoluted tubule
4 CHARAC of Pre-Renal Azotemia:
1) absolute volume depletion
2) relative volume depletion
3) impaired CO
4) impaired renal autoreg
PRA: Absolute vol depletion mechanisms:



Relative Volume Depletion in PRA occurs via...
3rd spacing (interstitial space)
Nephrotic syndrome
Liver disease
Abnormal autoreg leading to PRA:
blockage of angiotensin activity via ARBs or ACE inhibitors

also: prostaglandin inhibitors
Disruption of renal autoreg by NSAIDS or ACEI shifts the curve...
NSAIDS mess with autoreg by...
blocking COX so you don't get prostaglandins and the vasodilation and renin prod associated with them
ACEI/ARB mess with...
efferent arteriole. It's dilated, so there's reduced intraglomerular pressure, since no AII is present.
Patients at highest risk of impaired renal autoreg:
renovascular disease- renal artery stenosis

NSAIDS COMPLETELY PROHIBITED in these patients, even COX-2
NSAIDS COMPLETELY PROHIBITED in what patients, even COX-2?
renovascular disease- renal artery stenosis
The JNC recommends using what for renal insufficiency?
AEI/ARBs, the benefits far outweighs the risks of ARF

-key is people need to be properly profused, volume sufficient
What are the 2 types of ATN?
60% are ischemic

40% are toxic
What part of the kidney is most vulnerable to ischemia?
outer medulla
ATN occurs in which part of the nephron?
primarily the Thin Ascending loop of henle!

proximal tubules- pars recta; can occur here too.
ATN can be the renal cause of...
ATN- Toxic Causes
Common clinical causes
Aminoglycosides – nephrotoxic antibiotics that result in damage to the proximal tubule after a cumulative dose exposure
Amphotericin – nephrotoxic antibiotic that results in damage to the distal tubule after cumulative dose exposure
IV Contrast – iodinated compound (radiology) that is directly toxic to the proximal tubule
Cis Platinum – antineoplastic drug toxic to the distal and proximal tubule

Heme pigments – Released from damaged muscle cells (Rhabdomyolysis) or damaged red cells (hemolysis) leading to toxicity of the proximal tubule
Light chains – Kappa >> Lambda light chains from overflow proteinuria as a result of a hematopoietic malignancy (myeloma) –proximal tubule damage
What defines orthostatic hypotension?
sys > 20mmHg drop
dias > 10mmHg drop
In PRA, what happens to Na and water?
the kidney will do everything it can to preserve them, i.e. reabsorption everywhere
Urine sodium in PRA looks like what?
it's low, < 20meq/L
due to intense Na avidity
Urine sodium in ATN looks like what?
-tubules damaged, Na can't be retained adequately, >40 meq/L, no attempt to retain the sodium
What happens to the FENA in PRA?
What FENA value do you expect for PRA?
< 1%!
What FENA value do you expect for ATN?
> 3%!
What's the only way to trick the FENA?
if you have a patient on diuretics
What does a low FENA when pt. on diuretics tell you?
INEFFECTIVE diuresis, super impt, and tells you there's serious problems
What kind of BUN/Cr do you expect in PRA?
> 20:1 with PRA
What kind of BUN/Cr do you expect in established renal failure?
est. renal failure = acute intrinsic, obstruction, or chronic

-tubules damaged to saem extent of glomeruli so that prevents creatinine secretion, and you'll get something like a BUN/CR of 10-15:1
For every 30 mosm/L increase in urine, the specific gravity increases by...
Lab Values for PRA:
Urine Sodium < 20
Urine Osmolality > 500
Specific gravity > 1.015
FENA < 1%
BUN/Cr > 20:1
Lab Values for ATN:
Urine Sodium > 40
Urine Osmolality 280
Specific gravity 1.010
FENA > 3%
BUN/Cr 10-15:1
ATN could show what kind of casts in urianalysis:
renal tubular cells
granulat casts
"Muddy brown" casts
renal tubular cell CASTS
Hyaline Casts are indicative of renal disease, true or false?
FALSE. They're normal.
If no casts in urianalysis, think what?
Granular casts are indicative of...
acute tubular damage.

not normal
also NOT present in PRA
Waxy casts, think...
RBC casts, think...
Acute Glomerulonephritis, blood's in there!
Urianalysis with Renal Tubular Cells, think...
WBC cast, think...
When is the only time you'll see dysmorphic RBCs in urinalysis?
What's the only thing you see in an ATN urinalysis, microscopically?
What do you see in glomerulonephritis urinalysis, microscopically?
dysmorphic RBCS, WBCS, RBC cast, even granular cast, all are possible.
What do you see in PRA, microscopically?
NOTHING, there's no casts present!
What's a urinalysis clue for CKD with an ARF exacerbation?
granular AND waxy casts are present.
All forms of ARF have the risk of...
hyperkalemia, all that cell death releases potassium, and the impair secretion from the distal tubule is also a possible problem.

-keep in mind use of ACEI/ARBs, Bactrim, and NSAIDs in this patient as well
What's the problem with Bacrtim and hyperkalemia?
trimethoprim is similar in structure to amiloride, which is a K-sparring diuretic, and it causes IMPAIRED distal tubule K+ secretion.
Any drug affecting RAAS can cause...
drug-induced hyperkalemia.
hyperkalemia can do what to the heart?
Cause it to stop because it can't re-polarize
How do you treat the hyperkalemia?
with Calcium! It raises the threshold potential of the cells, esp. in the heart
Hyperkalemia makes the resting membrane potential less negative and results in...
spontaneous depolarization but prevents repolarization.

calcium makes the threshold potential less negative, and that makes it harder for the cell to depolarize
What are the ways to treat hyperkalemia, outside of Ca++?
-insulin, beta-2 receptor stimulation

remove it from the body
-bicarb therapy if severe acidosis is present

-dialyze too, but that's not an immediate Tx
ARF dialysis indications?
-intractable fluid overload
-intractable metabo acidosis
No proven benefit of any treatment in enhancing recovery, just use supportive treatment until tubular cells can regenerate
What % of ATN patients die
50%, but no one dies of kidney failure, it's the complications associated with it that kill them, like pneumonia, gram-neg sepsis, cardiac, etc.
Define CKD:
<60 GFR >/= 3 months, with OR without kidney damage
3 major things leading to CKD:
1) Diabetes
2) HTN
3) Glomerular Disease

-goal is to avoid ESRD
Intraglomerular HTN leads to...
Glomerular growth/hypertrophy leads to...
inc. wall stress
Increased ammoniagenesis per nephron leads to...
complement activation and enhanced tubulointerstitial disease
Intact nephron hypothesis says that...
-each nephron upregulates or downregulates its function individually...nephrons act individually (declining or hypertrophy/overactivity)
How does the kidney respond, hemodynamically, to nephron loss?
compensatory hyperfiltration
What are the 2 major glomerular vasoconstrictors?
2) Endothelins
What are the 32 major glomerular vasodilators?
1) natriuretic peptides
2) prostaglandins
3) nitric oxide
How do the tubules adapt to nephron loss?
-inc FENA
-inc ANP to remove ECFV
-inc FE-potassium, also inc Na-K-ATPase pump on baseolateral surface of prinicpal cells
Sx's associated with water issues in CKD?
hyponatremia and nocturia, because there's impaired diluting and concentrating mechanisms
3 major criteria of Hepatorenal syndrome:
1) chronic/acute liver disease WITH hepatic failure
2) portal HTN
3) Low GFR- >1.5 mg/dL, or CrCl <40mL/min

4) NO IMPROVEMENT following volume expansion with 1.5L of 0.9% NS
Urine Na in HRS is...
<10mEq/L, aka FENA <1%
3 Poss. Complications of Cirrhosis/Portal HTN:
1) ascites- primary causes: portal HTN and low albumin
2) varices
3) splenomegaly


-may see 'capit medua'
Most common risk for developing Type I HRS?
spontaneous bacterial pertonitis
In HRS, your Cardiac Output is _____, and your systemic resistance is ______?
CO- Increased

Sys Vasc Resist- Decreased
2 Key substances in HRS:
1) Nitric Oxide
2) Glucagon
What's one of the most impt predictors of survival in patients with cirrhosis and ascites?
arterial blood pressure
When you have a cirrhosis patient, what meds are CONTRAindicated?
Patients with HRS have lower and higher what?
Lower baseline CO

Higher baseline renin/aldosterone/catecholamines
Can you use Serum Creatinine and BUN and HRS patients?
NO, marked muscle wasting secondary to protein and calorie malnutrition, lower than normal creatinine levels, same for BUN, so the BUN/Cr ratio sens is diminished.
Diff on lab data of PRA and HRS?
FENAs both <1%
Urine Spec Grav both >1.010
Urine sediments both normal


Urine Na in PRA: <20
Urine Na in HRS: <10!!!!!
Most common HRS Tx target?
glucagon antagonist, goal is to inc. MAP 10-15mm Hg,

Also give albumin 20g/day, and poss. increased to 40g/day

Midrodrine has 80% success, and it's an alpha1-AGONIST

Vasopressins, too.
What is Chinese herb nephropathy?
-disease with non-neprotic range proteinuria
-minimal HTN

-pathologyially, see chronic tubulointerstitial fibrosis and minimal infiltrate

IMPT FACT: INC risk of uroepithelial cancers
Chinese herbs lead to what pathology?
chronic interstital nephritis, where there is a bunch of space between the tubules, due to fibrosis
What's the culprit for disease in Chinese Herb neprhopathy?
aristolochic acid

-From fangCHI

causes nephrotoxicity, inhibits tubular protein reabsorption, and there is ***EXTENSIVE aa-DNA adduct formation, it's cancerous!***
-that's a non-repairable genomic lesion
-it causes cancer, at a dose-dependent rate, too!
-high-grade transitional cells are found in the bladder/renal pelvis
Summary of Chinese herb nephropathy:
causes hypocellular chronic interstitial fibrosis, and there is a life-long, dose-dependent risk of developing urothelial malignancy
Drug interactions of St. John's Wort:
1) induces the intestinal P-glycoprotein/MDR1
-inc export of drug from the blood into the intestinal lumen, less bioavailability ensues

2) induce hepatic cytochrome P450, which is involved in the oxidative metabo of >50% of pharm meds
If organ transplants patients are seen, what's some counsel they should be given?
if they're taking a calcineurin inhibitor, like cyclosporine or tacrolimus, they SHOULD NOT USE St. John's Wort
Grapefruit juice issues:
-inhibits the liver and sm. intest cytochrome P4503A4
-increases drug bioavailability
-240cc of juice dec. P450 levels for 24 hours

-ALSO ihibits P-glycoprotein and MRP2

Grapefruit juice acts to...
dec cytochrome P450 while INC drug levels in the blood
St. John's Wort acts to...
INC cytochrome P450 to DECREASE drug levels in the blood
Star Fruit CHARAC:
-lots of oxalate in it

Clinical presentation:
-acute oxalate neprhopathy
-CKD patients at HIGH RISK
Star fruit can put a patient at risk for...
oxalate-based renal failure
How does use of Ma Huang present?"
-aka ephedra, alpha-adrenergic stimulant

-Kidney Stones- radiolucent, compositions of ephedrine, pseudoephedrine, and epinephrine
Noni juice CHARAC:
-high K+ content
-risk for patients with ARF/CKD/ESRD

Licroice CHARAC:
glycyrrhizin, found int he rhizome, or underground stem

-supplements in U.S. have deglycyrrhizinated licorice, of DGL

-11Beta hydroxysteroid dehydrogenase immediately degrades cortisol when it enters the cell, to avoid it binding with the aldosterone receptor (found in the distal tubule), BUTTTTTT....
glycyrrhizic acid acts to BLOCK 11Beta hydroxysteroid and allows cortisol to continually activate the aldo receptor, causing renal Na+ retention, and K+ loss

Clinical syndrome associated with licorice?
Apparent Mineralocorticoid excess (AME)
-Metabo ALKalosis
-low renin
Clinical Px of Lead toxicity?
acute and chronic toxicity

-lead-based paints
-prod of ammunitions, batteries, cable, and wire
-lead leached into food during storage or processing
-home-brewed illegal alchy
-environmental exposure, like gasoline or industrial fumes
What happens to lead once absorbed?
99% of it is bound to RBCs
half-life is 30 days, and clearance is exclusively renal
-skeletal lead reps 95% of body burden, half-life is DECADES
Lead Toxicity Renal Issues
-Fanconi's syndrome
-proximal tubule damage
-intranuclear inclusions

NON-Renal manifestations:
-GI colic
-visual disturbances
What 3 things might yuo see in chronic lead toxicity?
1) HTN
2) renal failure
3) Gout

-also may see:
small, shrunken kidneys
chronic interstitial fibrosis
minimal cellular infiltrate
tubular proteinuria
proximal tubular cell damage
Acute lead toxicity leads to ATN and Fanconi's syndrome, while chronic leads to interstitial fibrosis, with BOTH leadignt o...
How do you Dx and Tx chronic lead toxicity?
use a fluorescence bone x-ray, and following iwth a chelation stimulation test, which mobilizes the lead for renal excretion

-renal func may improve based on degree of interstitial fibrosis
2 key exposures to cadmium?
fish and cigarettes!

-also see it in contaminated workplaces, especially worldwide
Cadmimum can lead to what disease?


What's the nephrotoxicity of cadmium?
1) tubular proteinuria
-inc excretion, irreversible EVEN AFTER CESSATION OF EXPOSURE

2) hypercalciuria, see Ca-oxalate stones
3) imapried Vit D prod in the proximal tubule
What all do you see clinically with lead exposure?
Fanconi's Syndrome

Tx- Chelation therapy
What all do you see clinically with cadmium exposure?

Kidney in pregnancy GFR considerations
-reaches peak of 40-50% ABOVE baseline levels by end of first trimester

-decreases by 20% during the LAST trimester

-returns to prepregnancy levels within 3 months post-delivery
Normal creatinine in pregnancy?
-Cr of 1.1 could mean CKD!!!
Expected pregnancy hematocrit?
Hyponatremia in pregnancy, normal or abnormal?
Normal, if mild.

-Plasma Na+ falls about 5mEq/L
-downward resetting of the osmostat, dec. ADH release point
-RELEASE OF RELAXIN!!!- relaxes the BVs
-spontaneously resolves 1-2 months post-delivery
4 effects of pregnancy on renal disease?
1) hyperfiltration
2) INC Urinary protein excretion
3) preeclampsia
4) poss. of permanent loss of func.
2 Renal disease effects on pregnancy?
1) increased incidence of preeclampsia
2) increased incidence of prematurity, and intrauterine growth retardation
What are the keys to mgmt of CKD during pregnancy?
***Maintain a BP of 120-140/80-90***

-watch for preeclampsia
-preconception counseling
-multdisc approach
-freq. monitoring of BP (1-2 weeks) and renal func (once/month)
BP in a pregnant women deeming it an extreme emergency?
>160 SysBP
>110 DiasBP
Gestational HTN CHARAC:
-detected for 1st time after midpregnancy
-no proteinuria
-only until more specific Dx can be assigned postpartum

-If preeclampsia does NOT develop AND
-BP returns to normal by 12 weeks postpartum, Dx is TRANSIENT HTN
-BP remains high postpartum, Dx is CHRONIC HTN

Criteria of gestational HTN:
Sys BP >140
Dias BP >90

No proteinuria

Developing AFTER 20th week of gestation in women known to be normotensive before pregnancy

-if before 20th week, most likely it's gonna be chronic HTN
HTN in pregnancy, prior to 20-week mark:
Chronic HTN
> 20 weeks into pregnancy, see HTN, what's the DDx:
1) preeclampsia
2) chronic HTN
3) chronic HTN w/ preeclampsia
4) transient HTN
Preeclampsia definition:
-pregnancy-induced HTN that affects 3-5% of FIRST pregnancies

-LEADING CAUSE of maternal and fetal mortality and morbidity

-if none in the first pregnancy, then it's very UNlikely to occur
Preeclampsia risk factors:
-1st pregnancy
-multiple gestations
-hydatidiform mole- gestational trophoblastic disease

-preexisting vascular disease
-metabo syndrome- obesity, insulin resistance, dyslipidemia
-thrombophilia- Factor V leiden, antiphospholipid, i.e. HEREDITARY coagulation abnormalities
Definition of Preeclampsia:
Sys BP >140
DiasBP >90

Proteinuria of 0.3g or greater in 24-hr urine specimen

-elevated BP should be documented on two occasions, at least 6 hours but no more than 7 days apart
What in a pregnant woman requires emergent attention?
severe BP-
>160 systolic
>110 diastolic
How do you manage preeclampsia?
-maintain diastolic BP <110 mmHg
-seizure prophylaxis- MgSO4
-timely delivery
What the central component of preeclampsia?
decreased uteroplacental blood flow and placental ischemia

-lowering BP doesn't prevent/cure preeclampsia and doesn't benefit the fetus unless delivery can be safely postponed

-lowering BP is appropriate measure for maternal safety, but keep it in the 130-150/85-100 range
What drugs do you use to treat/manage preeclampsia?
Imminent delivery uses:

***Delivery Postponed***
-CCBs, hydralazine also good
Leading causes of ESRD:
-polycystic kidney disease
Lab indications to start RRT:
-unmanageable hyperkalemai
-metabo acidosis
-GRF <10 is "in range" to begin
-PE findings like CNS issues, pericardial friction rub
-unmanageable volume overload
-subjective, such as nausea, vomiting, mental activity
What are 3 ABSOLUTE indications to begin dialysis?
1) pericarditis
2) intractable fluid overload
3) encephalopathy
Leading cause of death in ESRD?
contributed to by:
Ca/Phos deposition in the vessels
many pts. are ALSO DIABETICS
What's a complication seen in long-term hemodialysis patients?
acquired cystic diease
-potential for malignant degeneration

-also access failure, which is the #1 problem
Is the cardiovascular disease DEATH RISK reduced once you get a kidney transplant?
Is it better to dialyze then transplant, or just go straight to transplant?
Preemptive transplant is the absolute best choice!
What's the blood type issue with renal transplant?
there are a LOT of B-type blood people awaiting transplant, many AAs are B-type blood, and it's hard to get them transplant organs, so they're on the list for even longer
5 groups of immunosuppressive drugs given to transplant patients?
1) corticosteroids
2) calcineurin inhibitors
3) purine synthesis inhibitors
-mycophenolate mofetil
4) IL-2 signal inhibitor
5) Abs for induction therapy
6) Maintenance Ab therapy
Allograft dysfunc in the first week, what do you see?
-art thrombosis
-venous thrombosis
-bladder leak/obstruction
Hyperacute rejection
Delayed graft function- ischemic injury- possibly ATN, could take time to start functioning
Allograft rejection in the weeks-months realm:
Acute rejection
Mechanical, i.e. lymphocele
Allograft rejection in the months-years realm:
Chronic allograft nephropathy
-calcineurin inhibitor nephrotoxicity
-recurrent disease, like an old kidney disease showing back up
-de novo disease
Long-term issues of transplants, what's #1?
Cardiovascular disease is STILL the #1 issue!

liver disease
bone disease
health maintenance
What areas of the kidney are most susceptible to ischemia and WHY?
the TALH and pars recta BECAUSE they use the greatest % of Oxygen delivered to them.
What are the 4 phases of ATN Acute Renal Failure?
1) Initiation Phase
-time of exposure to hemodynamic or toxic insukt
2) Oliguric Phase
-period of lack of urination, urine volume <400mL/day
3) Diuretic phase
-increasing urine output, but NO CHANGE in renal function
4) Recovery phase
-may last 3-12 months before full functional recovery occurs; consider acid-base and water homeostasis during this time
pharmacokinetics is...
the study of dose and concentrations

"the quantitative analysis of the time course of drug absorption, distribution, metabolism, and excretion (ADME)"
pharmacodynamics is...
the study of how the concentration effects the body.
4 Components of pharmacokinetics:
1) Absorption
2) Distribution
3) Metabolism
4) Excretion
2 main ways to absorb drugs:
Bioavailability is...
the fraction of the administered dose reaching the systemic circulation.
What are the components of the first-pass system:
Intestinal Mucosa
-CYP enzymes- CytoP450 system

-Cyp enzymes
What's the MOST COMMON CAUSE of kidney failure in the U.S.?
Diabetes mellitus
-present in 40% of CKD patients
-increases time for oral drug to be present to go towards 2 hours, because of DIABETIC GASTROPARESIS
What drugs need an acid environment for absorption, which is messed up (more alkaline) in CKD patients?
iron supplements
Phosphate binders alter the binding of...

Fix the problem by spacing out admin by giving drugs an hour before or an hour AFTER the use of phosphate binders.
Is the P450 system enhanced or decline in CKD?
it's declined, therefore, DRUG ABSORPTION IS ENHANCED, so you need to account for that by giving LESS drug.
Is the P-Glycoprotein system enhanced or decline in CKD?
similar to P450, its activity may be decreased, so the drug accumulation will be GREATER.
CKD Leads to INCREASED activity of these drugs:
Enhance activity:
Anti-seizure medications
Phenytoin (Dilantin)
Carbamazapine (Tegretol)

Anti-TB medications
CKD Leads to DECREASED activity of these drugs:
Decrease Activity:
Calcium Channel Blockers

Anti-Fungal Agents

Vd of hydrophobic drugs?
Vd of hydrophilic drugs?
Vd of drugs with a high degree of receptor binding?
Drugs like diazepam or digoxin create problems in CKD patients because...
their Vd is above the cutoff of 40L/70kg, where they are distributed in every cell, so you're going to have to give a ton of them to get it to stay in the intravascular compartment
Is the [albumin] reduced/increased in CKD?
REDUCED, also abnormal binding kinetics due to messed up middle molecules- uremic toxins.
Pheytoin is a drug altered by CKD, how is it altered?
-in CKD the unbound fraction increases in relationship to the bound portion.

-target therapeutic range thus must be DECREASED in CKD
Phenytoin is a good example of a drug in CKD that...
must be altered in terms of dosage.

-the higher doses give toxicities, and when there is CKD, there is more FREE fraction of the drug, which is clinically active.

-normally 90% protein bound, but in kidney disease, only 75% bound, leaving 15% MORE FREE AND CLINICALLY ACTIVE

Vd increases from 0.64L/kg to 1.4L/kg!

-increased free drug is due to DISPLACED BINDING
A drug with a small Vd requires what change in dosage?
-need an INCREASE in dose to achieve adequate blood levels
3 ways kidney eliminates drugs from the body?
1) filtration
2) secretion (reabsorption)
3) metabolize
2 ways liver eliminates drugs from the body?
1) metabolism
2) secretion- Hepatic P450 is MOST IMPORTANT, and that's reduced in CKD
CKD leads to a what effect on drug metabolism?
-decreased GFR which results in less filtered drug, and thus less metabolism

True for ONLY drugs that are:
-low protein binding
-relatively small size- to fit through the glomerulus
CKD reduces filtration, which has 2 effects on drug removal:
1) reduced clearance of unmetabo but filtered drugs
2) reduced clearance of ACTIVE METABOLITES< like from codein, meperidene, morphine, and procainamide
Type II diabetic might experience what diabetes mgmt complication in CKD?
30% of insulin metabo is done in the kidney, and accumulation of endogenous insulin will overwhelm the insulin resistance, normalizing the diabetes, but creating MORE FREQUENT EPISODES OF HYPOGLYCEMIA

-so, these type II patients might not need exogenous insulin, but once you transplant them, "return of diabetes" ensues immediately!!!
Urinary pH can be very IMPT in ionizing drugs so they can't be reabsorbed. Aspirin is a good example, explain what happens and Tx?
-aspirin is a weak acid, and the first line therapy is urinary alkalinization, so you infuse IV bicarbonate, with a goal of increasing the urinary pH > 7.0

-same could happen with phenobarbital
Amphetamine overdose in a CKD patient would be treated with...
urinary acidification, which can be used to enhance renal clearance, goal is to get the urinary pH < 7.0
What's the key to drug removal via hemodialysis?
degree of protein binding

Also consider:
-water solubility
-Dialysis CHARAC:
-composition of dialysis membrane
-dialyzer surface area
-BFlow rate/Dialysis Flow rate
-length of Tx
Na balance dictates...
H2O balance dictates...
Edema is an issue with what?
Na balance
How do you determine ECFV?
it is ESTIMATED mainly by physical exam
How do you asses the water balance in a patient?
check the [Na]
What do you use 0.9% saline for?
ECF volume expansion

-could cause ECFV overload
-must be used carefully in pts. w/ cardiac or renal disease
-monitor DAILY WEIGHT and electrolytes
True/False: there is no blood test to measure TBNa?
TRUE. It is only estimated clinically by physical exam.
Increased TBNa, and thus ECFV overload, clues:
-pleural effusions
-distended neck veins
Decreased TBNa, ECFV depletion, clues:
-poor skin turgor
-orthostatic BP and pulse changes, via tilt test
-urine Na <20 mEq/L
-BUN/Cr >20:1
-high urine OSM (ASH), thirst (All)
TBNa determines the size of the...
When water overloaded, restrict...
When sodium overloaded, restrict
How is Na retention controlled?
it's stimulated by ECFV depletion

How is Na excretion controlled?
-stimulated by ECFV overload

-renal prostaglandins
What 2 things are needed for ECFV overload?
1) impaired renal sodium excretion
2) continued sodium intake

AKA: Kidney can't get rid of the sodium load it's facing
What kind of urine sodium do you expect when ECFV overloaded?
LOW, urine Na <20mEq/L, because you're having abnormal renal sodium retention
Disorders of volume overload
1) advanced CKD
Tx: Na restrict, loop diruetics
2) CHF
Tx: Na restrict, loop diruetics
3) Hepatic cirrhosis
4) glomerular disease- nephrotic syndrome and glomerulonephritis
Tx: Na restrict, loop diruetics
Tx of ECFV overload
-issue is Na overload, so:

Na restriction
-CHF: loop
-Cirrhosis: spironolactone
-Nephrotic syndrome and glomerulonephritis: loop
ECFV depletion CHARAC:
-poor skin turgor
-orthostatic BP and pulse changes
-INC in hematocrit over BRIEF TIME INTERVAL
-urine volume <500mL/24 hrs
-urine Na <20 mEq/L
-BUN/Cr >20
How do you treat ECFV depletion?
0.9% normal saline

-follow clinical signs of EFCV depletion/overload
-daily CAREFUL chest ascultation
-urine volume

Why do you use D5W?
to administer free water

-water dist. b/n ECFV (1/3) and ICFV (2/3)

-can cause hypOnatremia
-NEVER use in pts. already having hypOnatremia
-NOT SUITABLE: EFCV depletion pts.- they need SALINE
-can result in poor glucose control in pts. with DM
-monitor daily weight and electrolytes
Osmolality equation:
2[Na] + [gluc]/18 + [BUN]/2.8
How do you control Na balance?
By controlling WATER BALANCE!
Hyponatremia and hypernatremia would be issues of...
water balance!
Hyponatremia means..
abnormal water balance and is caused by impaired water excretion PLUS water intake.
Hypernatremia means...
abnormal water balance and is caused by WATER LOSS withOUT REPLACEMENT!
Serum [Na] tells you 3 things:
1) tells you about water balance- whether body is handlin' it properly
2) tells you about water balance- whether body is handlin' it properly
3) tells you about water balance- whether body is handlin' it properly
Hyponatremia is caused by what 2 things?
-impaired water excretion
-continued water intake

What is ALWAYS contraindicated in patients with hyponatremia?
How do you treat a bout of acute hyponatremia?
3% saline
-esp. with these Sx's:
-obtundation- being very poorly responsive

GOAL: acutely raise osmolality to pull H2O out of the brain
How do you treat chronic hyponatremia?
-gradual fall in [Na]
-brain swells slowly


-rapid correct could cause Osmotic Demyelination Syndrome
If pt. is awake, yes or no to 3% saline?
When using 3% saline, how do you deliver it?
correcting 1-2 mEq/L/Hr until 6-8 mEq/L TOTAL increase or Sx's improve...THEN STOP!

-late overcorrection leads to ODS, especially after 6-8 hours

ORDERS: 3% saline at 100cc/hr for first hour or so
Pt. Px's with low serum [Na] and altered mental status, what do you do?
Acute hyponatremia, use 3% saline, at least for the first hour.
What's the max correction done with a saline delivery?
NEVER do more than 12 mEq/L in 24 hours!
If hyponatremia is <135 mEq/L of [Na], what is severe hyponatremia?
<120 mEq/L
Most common electrolyte issue in hospitalized pts.?
15% Na <134
5% Na <125
2 roles of hyponatremia for us:
1) predictor of death
2) CNA disease- causing by itself!
Osmolality of plasma =
osmolality of interstitial fluid = osmolality of intracellular fluid
Where is vasopressin secreted?
ADH stimuli, 2 of them, what are they?
1) volume
-supraoptic nucleus, sends signals north to say "Need more H2O"
2) tonicity
-paraventricular nucleus: responsible for the osmotic control
What happens to [Na+] when osmolality increases?
Which is more important for ADH production, osmolality or volume control?
In short term, as little as a 2% change in osmolality stimulates a linear-based response of ADH


when the body volume changes >10%, then there is an EXPONENTIAL change in ADH secretion, because at this point volume maintenance is more important because of the need to maintain organ perfusion at all costs
What's the key principle when talking about ADH production?
the body protects VOLUME over tonicity.

ADH retains electrolyte-free H2O!
Hyponatremia in the brain can be corrected by...
-can occur quickly
2) extrusion of organic solutes such as myoinositol
-takes time

Whole process: may take up to 48 hours!
Osmolality is defined as...
number of particles that exists in the fluid environment
Tonicity is defined as the...
number of particles that exist in the fluid environment that have the potential to exert transmembrane water movement, i.e. effective osmolality
Clinical complications ONLY OCCUR with what osmolality/tonicity state?
hypotonic hyponatremia
How do you treat a patient presenting with a glucose of 900 and a sodium of 139?
Short answer is that it's pseudohyponatremia due to other osmoles, and here give insulin and correction by the body will occur easily.
What are 2 poss. causes of pseudohyponatremia?
hyperlipidemia or hyperproteinemia
What's behind isovolemic hypotonic hyponatremia?
-underfilling of arterial circulation
-dimished H2O excretion
-INC Na reabsorption, giving low urine Na

water intoxication
K+ losses
reset osmostat
Impaired adrenal/thyroid func
Cockroft-Gault equation =
[(140-age)*ideal body weight *0.85 if female]/ 72*creatinine
HypERvolemic hypOtonic hypOnatremia basis:
proximal stimu;lation of H20 and Na uptake, high ADH levles

-proximal causes of hyponatremia
-total body is H20 overloaded

kidney failure
How does hyponatremia come about in cirrhosis, CHF, and nephrotic syndrome?
Underfilling arterial circulation-->
RAAS activation --> INC renal tubular Na reabsorption --> Low urine Na <20mEq/L

vasopresin --> INC urine osmolality --> DEC water extreion (due to ADH prod)
Mechanism behind SIADH:
ADH prod. --> INC Urine osmolality --> DEC Free H20 excretion --> Overfilled arterial circulation leading to BOTH:
DEC Renin and
-ESP IMPORTANT: Urine Na >100, Specific gravity is >1.015
-TRUE plasma hypoomolality and hypotonicity
-elevated urine Na
-overall volume is normal
-normal thyroid, adrenal, and renal function
Poss. temporary causes of SIADH?
Major cause of SIADH:
Small cell carcinoma

-paraneoplastic syndromes
3 lab tests for Hyponatremia:
1) plasma osmolality
2) urine osmolality
-deter whether or not free water clearance affected by
-Excess ASH- urine osm
>100-200 mosm/L
-Suppressed ADH
-polydipsia, malnutrition:
both show Uosm <100 mosm/L
3) urine sodium
-DEC: hypovolemic hyponatremia
What drug can cause hyponatremia that we should definitely remember?

-remember ecstasy too!
What happens in an ODS patient?
-improvement of neuro Sx's for 2-6 days, followed by rapid devo of:
-pseudobulbar palsy
-pseudo coma 'locked-in syndrome'
Central Pontine myelinolysis -->
extra pontine myelinolysis --> Osmotic demyelinating syndrome
How do you treat hyponatremia if it's severe?
Na <120 so you see CLINICAL Sx's that are of ACUTE ONSET, so you

-give hypertonic saline- 3%
-loop diuretics
-free water is restricted

-can also now give AQUARETICS
-inhibit vasopresin, V2 receptor antagonists
4 causes; HypERnatremia DDx, via Polyuria:
1) Central Diabetes Insipidus
-issue making ADH
2) Nephrogenic Diabetes Insipidus
-issue responding to ADH
3) Osmotic diuresis
4) Primary polydipsia
>3L urine per day, how to DDx this:
Osmotic diuresis if:
Urine Osmolality >300mosm/L, spot check

Urine Osmolality >900mosm/L, 24-hour period

Water Diuresis if:
Urine Osmolality <300mosm/L, means that ADH not working

Urine Osmolality 600-900mosm/L
Primary polydipsia is most prevalent in what pt. group?
psychiatric patients!
osmotic diuresis most likely caused by..
diabetic ketoacidosis (Type I), or severe hyperglycemia (Type II)

for this, just treat the hyperglycemia or alter the protein intake if it's due to a feeding tube
CAUSE of Nephrogenic Diabetes Insipidus:
damages kidney affecting ADH effectiveness

-hypercalcemia could be a problem too, also hypokalemia
How to DDx b/n Central DI and Nephrogenic DI?
Central will CONCENTRATE their urine, nephrogenic WILL NOT
Tx of Nephrogenic DI:
-water restriction
-if partial, may give exogenous ADH
-thiazide diuretics
cystitis = issues with...
the bladder
What peopele are at risk for UTIs?
-women, avg. is 24 y/p
In men:
-intercourse with ifx'ed fmeale
-lack of circumcision
Major cause of acute uncomplicated cystits:
E.Coli 80% of the time

5-15% are due to S. Saprophyticus
Risk factors for acute uncomplicated cystitis
-diaphragm and spermicide
-delayed post-coital micturation
-Hx of recent UTI
-host factors
What's the key to a bug's ability to cause a UTI?
-its ability to express adherence factors

-bacteria do not attach unless fimbriae or other surface adhesins are present to overcome repelling forces
80% of pyelonephritis, 60% of cystitis, and 30% ASB cases are caused by...
E. Coli

-women are non-secreters of P-blood group Ags and show INC in vitro binding of E. Coli to urothelial cells and more UTIs
Which fimbriae promote persistance of ifx and INC the inflamm response?
-Type I
How to Dx cystitis:
-suprapubic pain

6 days Sx's, 2 days restricted activity, 1 day missed class/work, 0.5 days bed

Occasionally: fever, nausea/vomiting, CVA tenderness

Differentiate from: urethritis or vaginitis
To Dx pyuria, need:
10wbc/mm^3 uncentrifuged


>5 wbc/HPF centrifuged
Urine collected by suprapubic aspiration should be...
sterile, no WBCs unless IFX IS PRESENT!
Symptomatic patients with any degree of ____ signifies Ifx!
In uncomplicated UTI, pyuria or no?
ALWAYS SEE it unless OBSTRUCTED kidney!

Sx's/signs usually resolve in 48-72 hours, Tx in outpatient setting preferred in mild cases
Subgroup of pts. with asympto bacteriuria:
-pregnant women
-renal transplant
-young children with veciourethral reflux
-pts. ifx'ed with struvite stones
-catheterized pts.
Bacteriuria in pregnancy:
-6-7% of pregnancies
-UTI occuring at slightly higher rate
-greater chance of pyelonephritis
-POOR pregnancy OUTCOME
-up to 40% incidence of pyelnephritis
-Tx markedly influences outcome
What do hematogenous renal ifx's affect, what part of the kidney?
the cortex
What's the most common way of seeing a complicated UTI?
-they are uncommon infections
-ascending IFXs 75% of the time

-acute pyelonephritis followed by liquefaction which walls off the center of the pyelonephritic area
-really virulent bus are the likely cause
How do you treat a complicated UTI?
drain the abscess that's present! get rid of that pus!
2/3 of the kidney stones formed are made of...
calcium oxalate
Radio-opaque kidney stones:
-calcium oxalate
-triple phosphate, aka struvite
-calcium phosphate

X-ray negative: RULE OUT, then, these stones!
Radio-lucent stones:
-uric acid
Most common radio-lucent stone?
uric acid
Acidic kidney stones:
-calcium oxalate
-uric acid

pH: 5-6 range
Basic kidney stones:
-triple phosphate/Ifx stone/struvite
-calcium phosphate

-alkaline urine, pH 6.5-8.0
Urinary crystals/stone pathology
-Calcium oxalate: envelopes/dumbbels

-uric acid: rhomboiads/stellate

-cystine: hexagon- benzene ring

-triple phosphate: rectangles/coffins
What shape do calcium oxalate stones have?
Uric acid stone shape and urine pH?
Cystine stone shape, pH, and radio-lucent/opaque?
heagon/benzene ring
acidic urine
Uric acid stone CHARAC:
-acidic pH
-smooth, tan, multi-layering
Triple phosphate stone CHARAC:
aka struvite, ifx stones

-coffin appearance, rectangles
-BASIC urine pH
-large, branched, staghorn
calcium oxalate stone CHARAC:
-brown with spikes
Most common metabolic cause of calcium oxalate stones?

-usually a hereditary basis, due to mild Ca++ transport issue OR a GI issue where they absorb too much

-rare, but could be a dietary etiology
Where do you find calcium phosphate stones?
in people with hyperPTH, such as primary hyperparathyroidism
Vitamin C INC production of...
Hyperuicosuria increases risk of...
calcium oxalate stones due to increased purine intake via the diet.
3 major stone inhibitors:
1) citrate
-binds calcium competing with oxalate
-reduces risk of stone disease because calcium citrate is soluble
2) magnesium
-binds to the calcification growth plate of the crystal and stops stone formation
3) phosphorous
-competes with oxalate for calcium, and calcphos is soluble in acidic urine
Most effective kidney stone therapy?
DRINKING! Want 2L of urine or more per day if possible.
Tx of calcium oxalate stones:
-DEC Na intake (<150mEq/day)
-Do NOT dec dietary calcium, it helps DEC stone formation
Worst case stone situation, what do you give?
potassium citrate pill

-most common medical Tx for calcium oxalate stones

-provided as the potassium salt
Cystinuria CHARAC:
-auto recessive disorder of aa transport

-DIBASIC amino acids

COLA: Cystine, Ornithine, Lysine, Arginine

-hetero: 1/200
-homozygous: 1/20,000

-may cause renal failure
-30% coexistence with calcium oxalate stone formation
Tx of cystinuria:
-ALKALIZE the urine, pH of 6.5-7.0
-use citrate salts rather than bicarbonate

-potassium salt is necessary to prevent hypercalciuria from Na load
What 3 cations bind in triple phos stones?

-ifx stones, a prereq for UTIs, UREASE-PRODUCING ORGANISMS
Triple Phos Stone demographics:

UREASE enzyme is the key here!
Metabolic acidosis pushes...
Metabolic alkalosis pushes...
Anion gap equation:
Na - Cl - HCO3
3 steps to Dx and Naming of Acid-Base disorders:
1) Dx and name ONE disorder from the ABG
2) Use the forumla to see if the compensation is correct
3) Check the anion gap
3 ways metabo acidosis pushes HCO3 down:
addition of acid HA
decreased excretion of acid HA
loss of HCO3
If AG >30, there is...
an AG metabo acidosis even if pH, pCO2, HCO3 are all normal.
If AG >20, there is...
PROBABLY an anion gap metabo acidosis even if pH, pCO2, and HCO3 are all normal.
Question when facing a metabolic acidosis/alkalosis:
What should the pCO2 be?

Metabolic acidosis:
pCO2 = 1.5(HCO3) + 8

Metabolic alkalosis:
pCO2 = 40 + 0.7(HCO3-24)
Question when facing a respiratory acidosis/alkalosis:
What should the HCO3 be?

Resp Acidosis:
Acute: HCO3 INC 1 for every 10mmHg INC in pCO2
Chronic: HCO3 inc 3.5 for every 10mmHg INC in pCO2

Resp. alkalosis:
Acute: HCO3 DEC 2 for every 10mmHg DEC in pCO2
Chronic: HCO3 DEC 5 for every 10mmHg DEC in pCO2
Resp Acidosis HCO3 Changes:
Acute: HCO3 INC 1 for every 10mmHg INC in pCO2

Chronic: HCO3 inc 3.5 for every 10mmHg INC in pCO2
Resp. alkalosis changes:
Acute: HCO3 DEC 2 for every 10mmHg DEC in pCO2

Chronic: HCO3 DEC 5 for every 10mmHg DEC in pCO2
Metabolic acidosis changes of pCO2:
pCO2 = 1.5(HCO3) + 8
Metabolic alkalosis expected change of pCO2:
pCO2 = 40 + 0.7(HCO3-24)
major causes of a metabolic alkalosis?
1) diuretic


2) nasogastric tube/vomiting (losing H+ ions)
MUDPILES is for...
High AG Acidosis

Lactic acid
Normal AG acidosis is aka

-acute severe diarrhea
-early chronic renal failure
RTA Type I occurs in the
distal tubule
hydrogen ion secretion defect
RTA Type II is an issue with...
proximal loss of HCO3
Metabolic alkalosis 2 main causes:
1) diuretics
2) gastric
-volume contraction with INC proximal tubule reclamation
Normal protein in the urine, upper max, per 24 hours?

EXCEPTION: pregnant woman allowance is <300mg
What does the dipstick measure?
NOT protein, ONLY albumin!
Cutoff between micro- and macroalbuminuria:
Define microalbuminuria:
albumin increased while the other protein remained the same
Proteinuria evaluation has 3 confounding factors:
1) urinary concentration
->1.015 indicates extreme urinary concentration and may falsely elevate concentration of urine, leading to a 1+ reading
-Dipstick is 2+ or higher, ALWAYS PATHOLOGIC, concentration independent
2) Infection
-bladder inflamm will cause plasma exudation into the urine, adding protein
-ALWAYS check urinalysis for protein AFTER ifx resolves
3) Hematuria
-every red cell is accompanied by plasma protein, which had albumin in it
24-hour urine collection is hard to do, so what do you do instead to quantitate protein?
spot random, and look at the urine protein/creatinine ratio

-correlates with the 24-hour sample in all forms of renal disease

-independent of volume
Tubular proteinuria CHARAC:
B2 microglobulin, albumin
positive for renal failure

-in ATN, would only show a mild degree of protein, like this
Overflow proteinuria CHARAC:

light chains (lambda/kappa)

VERY positive for renal failure
Orthostatic proteinuria CHARAC:
Glomerular proteinuria CHARAC:
VERY positive Renal failure
Very positive hematuria
fatty casts/oval fat bodies indicate:
nephrotic syndrome
RBC casts indicate:

so do dysmorphic RBCs
dysmorphic RBCs indicate:

so do RBC casts
Leurkocytes- PMNS/WBCs casts indicate:
leukocytes-eosinophils indicate:
Components of nephrotic syndrome:
>3.5g of protein/day or protein/creatinine of >3.5

-don't need the rest if you have that
Nephrotic syndrome seen ina 40-50 patient, likely:
Focal Sclerosis (FSGS)
10% of adult nephrotic proteinuria patients have it due to...
paraneoplastic origin
membranous nephropathy would be caused by what kind of neoplasm?
minimal change would be caused by what kind of neoplasm?
Patient with diabetes shows up with nephrotic syndrome, that indicates...
advanced renal disease!
Orthostatic proteinuria is:
-benign self-limited condition of non-nephrotic range proteinuria often seen in young adults

-need one overnight supine, and one upright daytime urine specimen

-increased lumbar lordosis and renal venous pressure result in the increased intraglomerular pressure that gives this issue
Fever, CHF, and strenuous exercise may all cause what kind of proteinuria?
-assoc with co-existent acute illness and returns to normal after resolution
-doesn't require long-term F/U
Overflow proteinuria:
-normal glomeruli
-excessive overpoduction of small MW proteins that are freely filtered through the golmerulus
-overhwlehm/saturatre proximal tubule reabsorption process

Most common adult causes:
-multiple myeloma

SSA/TCA- used to look for proteins in the urine, like this
-discrepancy b/n SSA and dip-stick indicates a non-albumin protein, such as light chains...SSA can never be grater than the dip-stick!
Where do you use the SSA test?
to determine if there's protein in the urine, such as in overflow proteinuria
Key clue to overflow proteinuria:
-look for discrepancy b/n spot urine protein/creatinine ratio AND dip-stick measurement

-indicative of NON-albumin protein
-if positive, NEED TO HAVE UPEP for subsequent clarification
(possible light-chain disorder, multiple myeloma, etc.)
2 poss. complications of nephrotic syndrome:
1) hyperlipidemia
2) hypercoaguability
What's the pathophys of hyperlipidemia as a complication of nephrotic syndrome?
-hepatic OVERPRODUCTION of apoproteins due to DEC oncotic pressure

-dec catabolism, so reduced receptor-mediated clearance, and dec lipoprotein lipase
Hypercoag in a nephrotic syndrome pt.:
-INC fibrinogen, facto V, VIII, von willebrand

-DEC Factor IX, XI, XII, anti-thrombin III, plasminogen, alpha-1 antitrypsin

-INC platelet agg

-renal vein thrombosis in 35% of cases
What are possible outcomes of nephrotic syndrome-induced hypercoaguability:
-renal vein thrombosis- 35%
-most common in membranous nephropathy
-rarely leads to renal dysfunction

thromboembolic complications- 20%
-50% are clinically silent
-venous >> arterial thrombi

-small thrombi, start wiping out diffusing capacity over time, by the time you find it, there are often already major issues present
Microalbuminuria is clinically important because...
it's indicative of incipient diabetic nephropathy in >85% of patients with DM

-MUST be measured in all Type I diabetics, post 5 yrs onset, and in all type II DM pts. upon initial presentation
Why is microalbuminuria in a DM pt. important?
Correlation with
-periph vasc occlusive disease

INDEPENDENT risk factor!
What does the dipstick measure in terms of hematuria?
free Hb

-free RBCs in urine lyse when hitting the dipstick analysis pad

90% sensitive test

-myoglobin- consider rhabdo

Way to tell:
-strong positive dipstick, but no RBCs on the microscopic analysis, THINK RHABDO!!!
3 tube test for hematuria:
1st third: urethral blood origin

Last third: trigone/base bladder

-hematuria through all 3: UPPER TRACT ORIGIN
When you see a patient with persistent ISOLATED hematuria, what should you consider?
-a urogenital mass lesion

-absence of a physical lesion should lead to a workup for intrinsic renal disease
Which Abs tend to be low affinity?

Which high?

What's the immunology basis of Goodpasture's?
-autoantibody binding to collage type IV
Order of potentcy of complement components:
C5 > C3 >C4
C5 stimulates what?
migration of neutrophils, eosinophils, basophils, and monocytes
C3 stimulates what?
it has chemotactic activity for neutrophils
Where are Abs reacting in Goodpasture's?
with the alpha3 chain of collagen type IV
Which immunoglobulins usually implicated in mixed cryoglobulinemia?
Therapeutic approaches to Immune Complex Diseases:
-eradication of source of persistent Ag production
-diminish inflammatory rxn w/ corticosteroids
-suppression of Ab production with immunosuppresive drugs
If you see RBC casts, it must mean...
they only come from the tubules, so there must be a glomerular cause of bleeding!!!
What kind of RBCs do you see in urine of a UTI patient?
isomorphic, they're not deformed, they're NORMAL!
Sx's of nephritic syndrome:
WBC casts can be seen in:
-acute pyelonephritis
-tubulo-interstitial nephritis
In most glomerulonephritides, there is edema because...
there is enhanced proximal tubule sodium reabsorption, which in conjunction with an impaired renal function leads to edema and HTN
Nephrotic syndrome Sx's:
-proteinuria >3.5g
What's in waxy casts?
various proteins

Key figure of a waxy cast: maltese cross
Why do you see edema in nephrOtic syndrome?
consequence of low oncotic pressure due to the severe protein loss.

-also in many pts. due to increased sodium reabsorption
Define rapidly progressive glomerulonephritis:
creatinine doubles in <3 months
-relentless loss of renal function within weeks or months
Minimal change disease always shows...
NEPHROTIC syndrome


-normal on light microscopy
Focal segmental glomerulosclerosis usually has...
nephrotic syndrome or nephrotic range proteinuria


-localized, glomerulus-specific scarring
Membranous nephropathy has...
nephrOtic syndrome, few RBC or WBC may be present in urine

*****"More common in Caucasians over 40"*****

-MOST COMMON diagnosis in the age group 40 and above

-in young caucasians, the others are equally common!

-basement membrane thickening
IgA nephropathy classically shows..
intermittent gross hematuria or asympto hematuria


-a LOT of IgA deposition in the glomerulus, seen by IMMUNOFLUORESCENCE
How do you Dx minimal change disease?
with ELECTRON microscopy...looks normal on light, but on EM:

-see fusion of the foot processes, and that's often the only finding
-podocyte injury is thought to be the pathogenesis here
What's a term used when looking at the microscopy of a membranous glomerulopathy case?

-immune-complex mediated, they're the spikes seen on the silver stain; domes are from the membrane growing around the ICs
Is membranous glomerlopathy IF positive or negative?

-see a granular staining pattern

remember that with Goodpasture's you would see a linear staining pattern
How do you treat the primary glomerulonephritides?
-corticosteroids to reduce inflamm
-immunosuppressants to reduce cellular response and Ab production

-SAME Tx for Renal involvement in small vessel vasculitides
-ACEIs- to change glomerular hemodynamics, reducing proteinuria
Postinfectious glomerulonephritis CHARAC:
-classic description: poststrep glomerulonephritis

-specific strains of group-Am beta-hemolytic streptococci, determined by the M protein

-prevention poss by prompt ABx Tx

-Streptococcus is the major cause, but by NO MEANS the sole cause
Clinical presentation of Postinfectious glomerulonephritis:
-recent URI (10 days) or skin ifx (21d)
-nephritic syndrome
-poss. gross hematuria

-resolves w/in 6 wks, but hematuria may last 6 months

vs. Iga nephropathy
-URI only 5 days ago
-GROSS hematuria but WITHOUT the nephritic syndrome
-persistent or recurrent hematuria for YEARS
Iga nephropathy clinical Px:
-URI only 5 days ago
-GROSS hematuria but WITHOUT the nephritic syndrome
-persistent or recurrent hematuria for YEARS
Poststrep GN lab findings:
-nephritic syndrome
-acute renal failure
***-low complements in the acute phase!!!***

-intracapillary proliferation
-large glomeruli, many cells
-capillary loops are closed
-immune complex depos and C3 complement components in GRANULAR PATTERN

-large sub-EPIthelial immune complex deposits, or HUMPS
What are the secondary GNs that could give low complements:
1) post-infectious GN
2) membranoproliferative GN
3) cyroglobulinemia
4) lupus nephritis
Prognosis of post-ifx GN:
85% full recovery
15% partial

rarely any death
MPGN, think...
hepatitis C!
MPGN clinical Px:
-vasculitis with PALPABLE purpura
-poss. arthralgias and weakness

-may Px with nephrOtic syndrome
-BUT could Px with nephritic, or even asymptomatic proteinuria and hematuria
Microscopic appearance of MPGN?
-thick basement memb, may appear SPLIT

-too many cells, some loops closed, that's the proliferative part
Where do you see the ICs of MPGN?

-may see cryoglobulinemia in the histology of kidney slides, not just in blood labs
Mixed cryoglobulinemia Px:
vasculitis with PALPABLE PURPURA
-mixture of asympto proteinuria and hematuria
Px of cyroglobulinemia AND MPGN:
-cryoprecipitates may be seen in glomerular capillary loops

-persistently LOW SERUM COMPLEMENT concentrations

-if you test for complement, see it low for 8 weeks, and then back to normal, that's NOT MPGN
Systemic vasculitis renal involvement, what do you see?
-small vessels
What ar ethe crescentic, pauci-immune GNs?
-Microscopic polyangitis
-Isolated pauci-immune GN

-all are secondary GNs bcuz it's the vasculitis first that affects the WHOLE BODY
(exception being that isolated pauci-immun GN is FOCAL)
Key finding in Wegener's?
NON-caseating granuloma
DDx b/n Wegener's and Microscopic polyangitis?
-NO GRANULOMA in microscopic
Isolated pauci-immune GN Px:
-same as Wegener's, BUT disease LIMITED TO THE KIDNEY

nephritic syndrome
Key finding in Churg-Strauss?
necrosis on the elbows, but also:

(ASTHMA too!)
-otherwise disease has same basic tenants of small vessel vasculitides, i.e.:
-pauci-immun GN
-formation of cellular crests w/ focal necrosis
-evidence of vasculitis
Summary of
Microscopic polyangitis
Churg-Strauss Syndrome
-granuloma, sinusitis, dicharge

Microscopic polyangitis:

Churg-Strauss Syndrome:
-asthma, wheezing, eosinophilia
Tx of Small Vessel Vasculitides?
-corticosteroids to reduce inflamm
-immunosuppressants to reduce cellular response and Ab production

-ACEIs- to change glomerular hemodynamics, reducing proteinuria

How does goodpasture's often present?

What's the renal involvement:
-nephritic syndrome
-rapidly-progressive (Cr doubles in 3 months or les)
-crescentic, necrotizing GN
Where do you see Garland-type staining?
posstrep GN, it's IF positive, and aka HUMPS...keep in mind it's focal
Granulat staining is for...
membranous glomerulonephropathy, a primary, most often seen in Caucasian adults
Where else might you see linear IF staining?
-in Alport's syndrome, when the patient gets the new kidney, that missing collagen is treated as a foreign molecule, so you might see Abs to it, BUT THIS IS NOT AN anti-GBM disease and usually you won't need aggressive Tx
Lupus nephritis:
-COMMON AND SERIOUS complication of SLE, which primarily affects young women
-LN can present as ANY glomerular clinicopathologic syndrome, and mimic and glomerular disease on light microscopy, BUT on IF stainds for Igs and complement components are positive, too...aka "FULL HOUSE"
Positive ANA stain, what is likely disease?
SLE, possibly here it's Lupus Nephritis you're talking about

-note a DIFFUSE pattern, or possibly a RIM pattern, which is more specific for SLE

-test by ImmunFluorescence
Most common cause of ESRD in U.S.?
diabetic nephropathy
How many Type I and Type II diabetics will develop diabetic nephropathy?
80% of Type I's
-duration of diabetes
-high BP
-poorly-controlled diabetes
-if not w/in 1st 20 years of DM, UNLIKELY to get it

20% of Type II's
-high BP
-poorly-controlled diabetes
What % of pts. with Diabetic nephropathy will develop ESRD?
Screening tests for diabetic nephropathy:
1) estimate GFR
If Cockroft-Gault, then:
= 140-age * weight / Serum creatinine, and remember if woman *0.85

2)measure for microalbuminuria
Where do you see Kimmelstein-Wilson nodules?
diabetic nephropathy
-nodular glomerulosclerosis appearance on light micro
-TONS of scarring, not many cells really there
Very IMPT drug for prevention of diabetic nephropathy:
ACEIs, or ARBS...prevent/delay onset of the disease!!!

-there is no cure
-screening is also REALLY important
Primary Amyloidosis:
AL amyloidosis
-composed of light chains
-most commonly in the context of MULTIPLE MYELOMA
-AL = amyloidosis with Light chains!
Secondary amyloidosis:
AA amyloid
-composed of an abnormal protein, such as serum amyloid
-AS = amyloidosis with amyloid
-many other proteins can also form amyloid deposits
-several hereditary forms possible
Amyloid deposits in the kidney cause...
nephrotic syndrome
asympto proteinuria
amyloidosis, microscopically, can be confused with:-
-there's deposition of large amorphous material that may be confused with diabetic neuropathy
Congo red, goes green, what does that mean?
amyloid protein is present!!!!

-remember it's with polarizing light
EM of amyloidosis shows:
randomly oriented thin fibrils with a diameter of 10-12nm
Characteristic kidney biopsy findings for amyloidosis:
-NODULAR deposits that are positive for CONGO RED

whereas, diabetic nephropathy would be congo red NEGATIVE
Henoch-Schonlein purpura may get confused with...
IgA nephropathy
FSGS may get confused with...
HIV-associated nephropathy
Px if Henoch-Schonlein purpura:
-systemic small vessel vasculitis
-may manifest, like IgA nephropathy, after a URI
-may have kidney involvement just like IgA nephropathy, but it's a secondary GN
-typical skin finding is PALPABLE PURPURA, the biopsy shows IgA deposits, BUT


Part of classic tetrad of H-S purpura:
-abdominal pain
-renal involvement
KEY TO H-S purpura:
if it looks like IgA nephropathy, but there are signs of systemic vasculitis, then think H-S purpura, ESPECIALLY IN CHILDREN AND YOUNG ADULTS
-AAs at higher risk

Light micro: most commonly looks like FSGS, with following typical features:
-collapsing type
-reticular aggregates in glomerular endothelial cells
If HIV+ and nephrotic, think:
HIVAN, and may look like FSGS, but it's a secondary GN

other keys:

collapsing type
reticular inclusion bodies
Most common HIV nephropathy pattern?
collapsing FSGS
What cells form crescents?
parietal cells of the glomerulus, the podocytes
Where do you see microcystic dilation?

-flattening and atrophy of the tubular epitheliam cells, which collapses the capillary by shear weight and number

-variable lymphocytic infiltrate occurs, too
Who gets HIVAN?
black males 20-64 get almost 90% of the cases

-3rd-leading cause of ESRF in this age group, AFTER diabetes and HTN
Keys to HIVAN clinical Px:
-tubular defect, and HIV-related cytokine disease- which causes the BP to be normal

-rapid course of progression to ESRD in ONLY 3-6 months.

-normal to large size echogenic kidneys, jusy like a diabetic kidney

-size is due to microcystic disease

-primarily a disease of advanced infection
What receptor may predispose blacks to HIV ifx?
-mutations with CXCR4/CCR5
What 3 cell-types are infected by HIV in the nephron:
1) visceral epithelial cells
2) tubular epithelial cells
3) mesangial cells

-direct viral ifx
-viral gene products delivered by infiltrating cells

-podocytes LOSE their foot process adherence
Pathogenesis of HIVAN
Capillary loop collapse because of podocyte dysregulation, along with loss of differentiation markers


tubular degeneration and regeneration, along with microcyst formation
Key to Tx'ing HIVAN?

-doing so reduced the continued infection of renal cells
3 drug classes of HAART
protease inhibitors
nucleoside reverse transcriptase inhibitors

non-nucleoside reverse transcriptase inhibitors
Potential benefits of early use of HAART in HIVAN:
-reverse podocyte dysregulation
-re-establish integrity of the foot processes
-decrease the interstitial infiltrate

-persistent HIV ifx of podocytes is consistent with subclinical viral activity, i.e. there's a reservoir all the time
-HIV+ pts. get other renal diseases than HIVAN (30-50%) BUT HIVAN is TREATABLE DISEASE THAT MAY REVERSE WITH HAART Tx!
What makes Hep C unique among the viruses?
it causes an autoimmune disease!

-cryoglubulinemic glomerulonephritis (MPGN)

-INC # of cells, thickened membranes
-a membranoproliferative disease
Histology of the major disease of renal Hep C ifx:
which is MPGN

-intraglomerular deposits, IgM kappa cryoglobulin


-significant renal failure ensues!
What kind of cryoglobulinemia are you seeing with Hep C ifx?
-Type II, mixed, where IgM is reacting to IgGs, which are acting on the Hep C RNA and E2 proteins

While there's a 50% incidence of HCV-related cryoglobulinemia, only...
2-3% is asymptomatic.
What's the infectivity of HCV?
it infects BOTH:
liver cells
B cells (lymphotrophic)

HCV does NOT directly infect the kidney, there's secondary lodging of exogenous immune complexes
How long does it take to see HCV with Type II MC?
14.2 years

-advanced stages of B cell production are the key to the outcomes
Clinical clues to HIVAN or HCV renal disease:
-low C1, C2, C4 due to activity of the system
-active sediment in the urine
-cutaneous vasculitis, occasionally
-RAPID rate of renal function DECLINE
Classical complement pathway activation shows decreased levels of...
C4 and C3
Alternate/Lectin complement pathway activation shows decreased levels of...
C4 and C3, and becoming more recognized as the problem in many forms of GN
How do you DDx b/n HRS and HCV ifx?
normal protein
bland urinalysis
low BP
normal C4, C3
no extra-renal signs

-neprhotic or non-nephrotic range
-microhematuria, RBC casts on urinalysis
-high BP
-low C4, C3
-Extra-renal: purpura/ulcers, arthralgias, polyneuropathy
Hep B Ifx...
-stable in 95% of children, but 25% of adults get ESRD

-due to circulating immune complexes, like HCV
Top 2 causes of ESRD:
1) Diabetes
2) HTN
Interstitium is composed of...
-peritubular space
-periarterial space
-mixture of cells and ground substance
-significant difference in the extent of the interstitium b/n cortex and medulla (MUCH MORE in the medulla)

-most interstitial disease is found in the cortex of the kidney
Func CHARAC of interstitium:
-structural support
-1-OH hydroxylation of Vitamin D
What cell types are in the interstitium NORMALLY?
-fibroblasts, mononuclear cells

-if we see immune system cells, THAT"S BADDDDDDDD
KEY to long-term prediction of ANY renal disease?
Stability of the interstitium!

-defree of fibrosis predicts how quickly kidney will fail
2 types of acute interstitial nephritis:
1) drug exposure- allergic
2) infection, i.e. pyelonephritis
What type of cells are found in acute allergic interstitial nephritis?
T lymphocytes!!!

-also see eosinophils, it's an allergic rxn
What cells WON'T you see in acute allergic interstitial nephritis?

-edema in AIN will separate the tubules from one another
Pathogenesis of acute allergic interstitial nephritis:
-activated T cells are the key
-Helper >> cytotoxic subsets
-cytotoxic are the ones responsible for tubulitis--> T cells attack Ags on the kidney too and thus start attacking the tubules
Constellation of findings in acute allergic interstitial nephritis?
fever- 85%
rash- 50%
eosinophilia- 80%

EOSINOPHILURIA!!! finding them in the urine
Px of acute allergic interstitial nephritis:
ever- 85%
rash- 50%
eosinophilia- 80%

EOSINOPHILURIA!!! finding them in the urine

-acute rise in Cr
-occasional back pain 2ndary to distention of renal capsule from cell infiltrates and swelling
When do you see acute allergic interstitial nephritis:
2-3 weeks after primary exposure, EXCEPT with NSAIDS: then it's 2-3 months post-primary exposure

-3-5 days OR LESS after a repeat exposure
What's the major drug causing problems in acute allergic interstitial nephritis?

NSAID profile in acute allergic interstitial nephritis:
3-6 months for onset

NEVER fever

not much rash or eosinophilia, BUT THERE IS NEPHROTIC-range PROTEINURIA

-recovery takes 3-12 months
Px of AIN:
-Normal/Large Kidney
-hyperchloremic, non-anion gap
-SEVERE hyperkalemia or hypokalemia
-BP normal or mildly elevated
-SEVERE anemia
-minimal edema
<2g proteinuria
What's the only disease with eosinophiluria?

need to see >5% for it to be AIN

atheroembolic disease
Acute pyelonephritis
-all forms of bacterial, viral, and funal disease

-predominant PMN infiltration
-reflux of infected urine from the bladder up into the kidney
Pyelonpehritis differs from allergic AIN in that...
-there are PMNs
-often see sepsis syndrome
-common fever and flank pain
-NO eosinophiluria
True/False: Chronic Interstitial Nephritis can be treated?
-it's not amenable to Tx, that's why you need to find AINs when you can, and treat them before they become CINs
What's the outcome of CIN?
SCAR tissue, lots of fibroblasts there, get tubular atrophy, dilation

-diffuse or patchy distribution, but not many infiltrates AT ALL

-may get hyalinized casts, THYROIDIZATION!
What's a key clinical finding of CIN?
WAXY casts!
-small kidney!
-pt. may be anemic due to loss of prod. of EPO
What's a possible etiology of CIN, something important to ask the pt.?
Herbal USE!

-chinese herbs, anything containing aristolochic acid, where there's a high incidence of cellular atypia of the urogential tract (90%), and carcinoma in situ is found 40% of the time!
What are the most common drugs worldwide responsible for CIN?
-analgeis nephropathy
-key drugs:

-Phenacetin +/- acetaminophen
-ASA or caffeine

-NSAIDs may be able to induce same syndrome INDEPENDENTLY
How does analgesic nephropathy develop?
-years of chronic use
-daily ingestion of 1g/day over 3 years
-pathogenesis: intra-renal conversion to REACTIVE metabolites
-enhanced concentration in the medulla/papillae
NSAIDs are an important cause of...
acute AND chronic interstitial nephritis
If a patient is dip-stick negative, but you suspect protein issues, what do you do next?
SSA test
-detects albumin, light chains, and polypeptides

then do SPEP/UPEP!
Criteria for multiple myeloma:
-B-cell prolif disorder
***-bone marrow with cloncal plasma cells (10% of the BM)***
-monocloncal protein in serum or urine
-end organ damage (CRAB)

75-80% have serum monoclonal Ig
-need the M-spike for Dx!!!
10-20% make light chains ALONE
-do urine electrophoresis
Hypercalcemia Clinical Px:
-CNA: lethargy, headache, irritable, confusion, coma

-polyuria- defect in vassopressin-induced H20 reabsorption

-renal insufficiency- from volume contraction and nephrocalcinosis in the tubules
Cast Nephropathy CHARAC:
-filtered light chains co-aggregate with Tamm-Horsfall glycoprotein secreted from TAL

-casts obstruct and rupture causing interstitial nephritis and tubular atrophy
-really key: they exert a LOT of pressure on the tubules
Tx of Cast Nephropathy:
-correct reversible factors causing lower GFR and cast precipitation
-reduce level of light chains by inducing remission
-plasmaphoresis felt to be no benefit
-support with dialysis
-transplant not viable

Fanconi syndrome CHARAC:
-some light chaings resistant to proteases, and tend to accum in tubule epithelial cells and FORM CRYSTALS

Damage due to:
1) light chaint oxic effects
2) indirectly from the release of intracellular lysosomal enzymes
How do you treat Fanconi?
-Txs underlying plasma cell dyscrasia
Microscopically: amorphous, eosinophilic appearance compressing the capillary loops

-various amyloid precursor proteins misfold and autoaggregate in highly-ordered fibrils with Beta-sheet structure
Key to an amyloid Dx:
binds congo red
Clinical Px of Amyloidosis
-median age of 64 year
-80% Px w/ proteinuria
-50% w/ renal insufficiency
-urine/serum monoclonal protein- 90%
-free light chains- 70%- most often LAMBDA
-myeloma present i
Tx of amyloidosis:
-reduce supply of precursors
-support or replace function of AFFECTED organs
i.e. dialysis
Monoclonal Ig Deposition Disease:
-Ig chains deposited in mult organs
-renal involvement is CONSTANT feature

-see nodularglomerulosclerosis
-looks almost identical to diabetic glomerulosclerosis
BUT see IF positive for Kappa or Lambda
Px of MIDD:
55 y/o typically
>90% nephrotic proteinuria
->60% renal insufficiency
-80% have urine/serum monoclonal
-80% have kappa
-40-70% have myeloma

renal disease often earliest manifestation
Glomerular injury is most often caused by...
immunologically-based issues
Tubular or interstitial injury is most often...
toxic or infectious injury
Acute nephritic syndrome:
1) hematuria w/ RBC casts and Hb casts in urine
2) some degree of oliguria and azotemia
3) HTN

-usually not enough proteinuria to cause nephrotic syndrome
Histologic picture of RPGN shows
crescentic GN in MOST of the glomeruli
Causes of RPGN:
-post-infectious RPGN
-assoc w/ systemic disease: SLE, polyarteritis, Goodpasture's syndrome
-idiopathic: pauci-immun (ANCA)
What's one way to Dx Goodpasture's?
-test the seurm, 95% of patients have circulating antibodies

-hypercellular glomeruli, segmental necrosis, crescents

What do you see microscopically with acute pyelo?
neutrophilic aggregates!
Clinical Px of Acute Pyelo:
-sudden onset
-pain at CVAs
-Leukocyte casts in the urine
-Sx's disappear after ABx Tx

KEYS: pain at CVAs AND leukocyte casts in the urine
Where is the damage in the kidney for chronic pyelonephritis?
interstitial inflammation and fibrosis
ATN overall outcome:
reduced GFR, leading to oliguria
Drugs/Toxins can cause what two categories of damage:
1) nephrotoxic- gentamicin, contrast, heavy metals, organic solvents
-proximal convoluted tubule vulnerability
2) drug-induced interstitial nephritis
-acute drug-induced interstitial nephritis
-analgesic nephropathy possible too, but usually more chronic
What kind of cells are involved in acute drug-induced interstitial nephritis?
eosinophils and lymphocytes
Analgesic nephropathy shows what pattern:
chronic interstitial nephritis with renal papillary necrosis

-combo of acetaminophen, aspirin, caffeine, or codeine
BP Classification:
Normal: <120/<80

PreHTN: 120-129/80-89

Stage 1 HTN: 140-159/90-99

Stage 2 HTN: >160/>100
Stage 1 HTN:
Stage 2 HTN:
ISH is...
isolated systolic HTN
Systolic BP rises with...
INC resistance
INC stiffness
Diastolic BP falls/rises with...
RISES with INC resistance


FALLS with INC stiffness
At what point on the HTN staging can you do something to reverse the damage?
When at pre-HTN.
HTN does what to the risk of CVD?
Elevated systolic pressures are HIGHLY ASSOCIATED WITH...
athersclerotic disease, EVEN IN the presence of normal diastolic pressure.
Top 2 Dx that lead to dialysis:
1) Diabetes
2) HTN
How to work on HTN pts.:
-physical inactivity
-serum cholesterol
Causes of 2ndary HTN:
-excess renin
-mineralocorticoid exceess, like primary alodsteronism, mimics, and genetic diseases of tubular transport
-aortic coarctation
-renal disease

primary aldosteronism
-renal disease
Primary aldosteronism definition:
-syndrome from autonomous hypersecretion of aldosterone from the adrenal cortex gland

-30-60% of cases are a solitary adenoma, benign proliferation of aldosterone-producing cells
Clinical Px of Primary Aldosteronism:
-metabo alkalosis

-LACK of edema

REMEMBER: aldos INC H+ excretion
1st-screening test for primary aldosteronism:
plasma aldos/renin ratio

-IF POSITIVE, would see HIGH plasma aldos (PAC) and LOW Renina (PRA)

-but that alone doesn't give a Dx.

CONFIRM with demonstrating inappropriate aldosterone secretion
-orally administer NaCL- 5 gm salt diet for 3 days
-STILL see >14mcg/24 hours of aldosterone confirms that diagnosis
IDEA: giving huge amount of salt in the diet, so there should be no need to retain any, i.e. aldosterone secretion should fall off, but it continues to stay HIGH
How do you Tx primary aldosteronism?
-normalize plasma potassium
-normalize blood pressure
-reversal of effects of hyperaldosteronism on heart and kidney
What to do if it's a unilateral aldosterone hypersecretion?
surgical removal
What to do if it's a bilateral aldosterone hypersecretion?
-mineralocorticoid receptor antagonists
-spironolactone OR eplerenone
Pheochromocytoma CHARAC:

-2 possible causes
-now, talking about the MEDULLA of the adrenal gland
-catecholamine-secreting tumors that arise from chromaffin cells in the adrenal medulla

extra-adrenal catecholamine-secreting paragangliomas
-arise from the symathetic ganglia, prevalence is 10-15%
Classic triad of pheochromocytoma:
-episodic headache

see it in SPELLS
What gives a high indication of likely pheochromocytoma?
-resistant HTN
-hyperadrenergic spells
-family Hx of pheo
-genetic syndrome predispoing to pheo
-past Hx of resected pheo and current history of recurrent HTN or spells
-imaging study positive for mass resembling a pheo
What do you do to screen for pheo lab-wise?
look for plasma metanephrines and normetanephrines
Possible false positives of catecholamine and metanephrine screen:
-drugs with catecholamines
-clonidine withdrawal
renovasc HTN CHARC:
-1% of hypertensives
-10-45% of severe/refractory/malignant HTN THOUGH!

-renal ischemia from renal artery stenosis in >75% of cases, gives off excressive renin and INC AII
-Px: men >50 w./ diffuse atherosclerosis and young women with fibromuscular dysplasia
Dx of renovascular HTN:
-MRA or CT angiography
-confirm with renal arteriography
Tx of renovascular HTN:
-medical Tx: anti-HTNs
-percutaneous angiplasty w/ or w/o stent
Where do you usually find renal artery stenosis?
-proximal-most 2cm
-branch disease rare

-progression occurs in 50% of cases, often to TOTAL occlusion
Rarer Px of renovascular HTN is due to:
fibromuscular dysplasia
-10-20% incidence
-25-50y/o patients
-distal main renal artery and its branches- classic STRING OD BEADS appearance
Clinical clues of renovascular HTN:
-severe refractory HTN
-acute rise in BP over previously stable value
-moderate to severe HTN in pt. with diffuse athersclerosis or incidientally discovered renal size asymmetry
-acute elevation in plasma creatinine that's unexplained or occurs after ACEI/ARB tx (here, think of bilateral renal artery stenosis)
-systolic-disatolic abdo bruit unilaterall
-negative family Hx for HTn, esp if youn
-proven age of onset before puberty or above 50
-moderate to severe HTN in pt. with recurrent episodes of acugte/flash pulmonary edema or unexplained heart failure
How do you Tx pts with both HTN and CKD?
ACEI/ARB are preferred
Glucocorticoid-remediable aldosteronism (GRA) CHARAC:
Familial hyperaldosteronism type I
-auto dom
-usually associated with bilat adrenal hyperplasia

Rare form of primary aldosteronism
-suspected from positive family Hx, and typical pre-age 21 onset

-hypersecretion of aldosterone can be reversed with GLUCOCORTICOID THERAPY!!!
Patients with GRA, what's their problem?
they have an ACTH-sensitive aldosterone production occurring in the ZONA FASCICULATA

-messed up genetic issue!

so, AII stims aldosterone synthase in ZG, AND ACTH stims 11-beta-hydroxylase to produce cortisol in the ZF

pts. getting ACTH-stim aldosterone synthase prod in ZG AND ZF!!!
What kind of HTN do GRA pts have?

-high aldo state, but varies throughout the day because ACTH is circadian-controlled
How to Dx GRA:
plasma aldos is high, but plasma renin is low, and ratio not high enough to be primary hyperaldosteronism

-Dx by dexamethasone suppression, which suppresses ACTH
-when given the adlosterone level will shut off!
How to Tx GRA:
-glucocorticoids will correct overprod of aldosterone by dimishing ACTH released, and that should normalized the BP
Basis of apparent mineralocorticoid excess syndromes:
-deficiency in the 11-beta-hydroxysteroid dehydrogenase enzyme type 2 isoform- which is the kidney isoform

Px's as low birh weight, childhood severe HTN, hypercalciuria, nephrocalcinosis, and renal failure
What's the issue in apparent mineralocorticoid excess syndrome:
-cortisol ninds as avidly as aldosterone to the mineralcorticoid receptor

-w/o 11-beta-HSD2, the cortisol can overwhelm the receptor, and you see what looks like hyperaldosteronism, but the aldo level is actually low
Px of Apparent mineralocorticoid excess syndrome:
-metabolic alkalosis
-low PRA
-urinary free cortisol to cortisone levels are VERY HIGH
Tx of Apparent mineralocorticoid excess syndrome:
=blockade of mineralocorticoid effects

-dec Na channel with amiloride or traimterene
-direct mineralocorticoid receptor blockade with spironolactone or eplerenone

-dexamethasone to suppress ACTH and reduce endogenous cortisol rpoduction w/o activating mineralocorticoid receptor
Px of Liddle's Syndrome:-
GOF mutation in Na channel:
-INC Na reabsorption

Tx; diuretics blocking Na channel, i.e. triamterene and amiloride