Nephrology

     Nephrology for Fifth Year Medical Students

Final Exam June 2012

1.    Kidney transport of Sodium, Chloride, and Potassium. Aldosterone Regulation of Ion Transport

2.    Disorders of Body Fluid Volume and Composition. Disorders of Water Balance. Hyponatremia

3.    Disorders of Acid-Base Balance. Interpretation of Electrolyte and Acid-Base Parameters in Blood and Urine. Metabolic acidosis and metabolic alkalosis.

4.    Clinical Approach to the Patient with Kidney Disease.Laboratory Assessment of Kidney Disease: Glomerular Filtration Rate, Urinalysis, and Proteinuria.

5.    Nephrotic syndrome. Minimal change disease.

6.    IgA Nephropathy.

7.    Post-infectious glomerulonephritis.

8.    Membranous glomerulonephritis.

9.    Focal segmental glomerular sclerosis and hyalinosis (FSGS)

10.   Acute Kidney Injury

11.   Chronic Kidney Disease (CKD)

12.   Urinary Tract Infections in Adults

13.   Interstitial cystitis and chronic prostatitis. Chronic pelvic pain syndrome.

14.   Polycystic Diseases of the Kidney

15.   Dialysis and Extracorporeal Therapies. Hemodialysis

16.   Kidney Transplantation. Donor and Recipient Issues

NEPHROLOGY POWERPOINT TEMPLATE

 

This is a Nephrology PowerPoint Template. Perfect for Renal Powerpoints. This Medical PowerPoint Background has a blended Picture of a kidney on the top left corner. See the template preview in the picture below:

 

If you want to download this Powerpoint template, (yes, no B.S, totally free!) click on the link below: 



or download the power point from mirror 2: 

 

DIDACTIC LECTURES:

ARCHIVED LECTURES

For reference: [NephronMap] A very useful, printable schema of the nephron, courtesy of Daniel K. Moon, P&S 2010.

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These notes were written by Dr Donald Landry and edited by him and Q. Al-Awqati. They are not meant to replace your syllabus.

• Acute Renal Failure
• Hypertension
• Volume
• Tonicity
• Glomerular Diseases
• Potassium
• Acid Base

Acute Tubular Necrosis

Case 2, question d.

Indications      CysticFibrosis with                         GI bleed with 
for dialysis      nonoliguric ATN                              hypotension 
                       ?2o to gentamicin                         and acute renal failure

1. Volume          non oliguric                                    oliguric - 
                         easier to manage fluids                  volume overload more likely

2. Acidosis         moderate acidosis due                  same mechanism but in 
                            to low GFR                                addition perhaps also lactic 
                            with "little opportunity                  acidosis due to hypotension 
                            for H+ to be added to 
                             urine" - p.80

3. K+               less of a problem because of           often hyperkalemic 
                        maintained urine volume                    because of oliguria

4. Uremia          BUN/Creatinine ratio normal        high BUN/Creatinine ratio

Causes of High BUN/Creatinine ratio 
Creatinine reflects the GFR while BUN  while reflecting GFR also reflects protein metabolism. Thus the causes of high BUN/Cr ratio include; high protein diet; blood in the GI tract; and high catabolic state (i.e. fever, sepsis)

Uremia is the syndrome produced by renal failure and is associated with anemia, platelet dysfunction and bleeding diathesis, pericarditis, encephalopathy, neuropathy. The syndrome is not due to high BUN per se; rather it reflects a composite of all things that the kidney doe; including its regulation of fluid and electrolytes, its hormonal function as well as the excretion of poorly characterized "toxins" that are the product of protein metabolism

Hypertension

 Evaluation for HTN: 
1. Evaluate for chronic damage 
Eyes                        Examine for hypertensive retinopathy 
Cardiovascular       Left Ventricular Hypertrophy by Chest X ray, EKG or Echocardiogram 
Kidneys                    increased Creatinine 
Peripheral Vasculature   decreased pulses, loss of cutaneous adnexal structures

2. Evaluate for acute hypertensive crisis - malignant Hypertension 
brain: encephalopathy (? in mental status, asterixis, etc.) 
eyes: papilledema 
cardiothoracic: acute CHF pulmonary edema, ischemic changes on EKG 
kidney: hematuria, acutely increasing creatinine.

3. Evaluation for Secondary causes of Hypertension 
renal failure   check serum Cr 
Coarctation   check BP in upper and lower extremities, look for 
                      rib notching on Chest XRay 
Primary Hyperaldosteronism  caused by an adrenal tumor check for low serum K+ & high HCO3 and low plasma renin in the fact of low salt intake 
Reninoma    check for tumor (very rare) 
Renal Artery Stenosis High renin; listen for renal artery bruit (not a very specific finding especially in the elderly); renal scan or renal arteriogram & selective renal vein renins 
Cushing's Syndrome: physical exam, should show signs and symptoms of  glucorticoid excess labs as in Primary Hyperladosteronism.  If suggestive 
then check cortisol levels 
Pheochromocytoma   history of paroxysms of HTN, tremor, pallor 
24 hr urine for catecholamine metabolites(VMA, metanephrine) and check 
serum for catecholamines 
Note: The above is simplified but I wanted you to have a feel for relating the pathophysiology to the care of a patient.

Regulation of the Volume of the Body Fluids

Most Important Idea to remember is that the volume of the body fluids is a reflection of the Sodium Content not the Sodium Concentration. 
Therefore start your analysis always by finding out if the Sodium Intake matches the Sodium Output. 
Remember   Na Intake   diet; I.V. 
                 Na Output   urine; gi (stools or fistula), sweat

Volume status is determined by physical examination. 
ECF volume depletion: dry mouth, decreased axillary sweat, decreased skin turgor 
Intravascular volume depletion: 
        mild         tachycardia on standing 
        moderate orthostatic hypotension 
        severe      actual hypotension 
Laboratory correlates: hemoconcentration, increased serum albumin,    increased uric acid, increased BUN (and if severe increase Cr 2o to decrease    GFR), decreased urine sodium concentration

ECF volume Expansion: We can retain up to 3 liters of  saline without any signs or symptoms. Retention of greater amounts leads to peripheral edema and ascites

Intravascular volume expansion: hypertension and/or the overload patterns below 
"left-sided overload" SOB, dyspnea on exertion, orthopnea, PND, pulmonary edema with rales on physical examination 
" right-sided overload" pedal edema, increased liver size (and increased    LFT's), hepatojugular reflux, ascites, increased jugular venous distention

Laboratory correlates: hemodilution, decreased serum albumin,    hypoxia on arterial blood gas, and peripheral vascular congestion on chest x-ray

 Tonicity   Regulation of the Tonicity of the Body Fluids

Most Important Idea to remember is that the Tonicity of the body fluids is a reflection of its Water Content. This is measured most explicitly by the Osmolality. However, an excellent surrogate marker is the Serum Sodium Concentration.  Hyponatremiareflects high water content (more dilute solutes like Na) and Hypernatremia reflects low water content (more concentrated solutes like Na). 
Therefore start your analysis always by finding out if the Water Intake matches the Water Output. 
Remember  Water Intake   diet; I.V. 
                 Water Output   urine; gi (vomiting, diarrhea or fistula), sweat

The daily fluid in-take is hypoosmolar 
In order to cope with this water load a large volume of dilute urine must be generated 
1. A "large" volume requires the there not be increased proximal tabular reabsorption of salte and H2O(as there is in volume depletion, CHF etc.). 
2. Dilute urine requires that ADH not act on the distal nephron. [Also diuretics  which ? UNa preent a dilute urine.] 
3. Increased oral intake worsens the problem. [AII increases thirst & AII is increased in the situations lsited in 1.] 
 

Evaluation of hyponatremia 
First, exclude pseudohyponatremia due to hyperlipemia or hyperproteinemia 
Check serum osmolality just to be sure that this is not a hyperosmolar state that has depressed serum sodium - for example hyperglycemia - then evaluate 
Hyponatremia from whatever cause has only one physiological cause: Water Intake must have been greater than Water Excretion. Low Na concentration reflects dilution and not necessarily a Na deficit. 
Check Volume status. Hyponatremia can exist in states of Volume Depletion, Normal Volume State or in Volume Expansion

Hyponatremia in ECF Volume Depletion 
body weight likely to be lower than previously 
pulse and blood pressure might show orthostatic changes 
No edema 
True Intravascular volume actually low 
Causes include; vomiting or diarrhea or excessive use of laxatives, excess use of diuretics; osmotic diuresis (due to hyperglycemia in untreated diabetes mellitus) 
"3rd Space" 
The Urine Na is often Low (i.e. below 20 mEq/L) except, of course when the patient is taking a diuretic. 
Pathophysiology    Whatever the state of volume, hyponatremia can only develop if the patient's water intake is greater than excretion. 
Decreased Volume increases ADH release 
Low volume increases renin, and angiotensin II levels. That causes increases in filtration fraction and increased proximal reabsorption. Therefore amount delivered to distal diluting segment is reduced. Hence total amount of dilute urine that can be generated is low. 
Treatment    Isotonic Saline

Hyponatremia when theECF Volume is Normal 
body weight likely to be same, no orthostatic changes 
One rare cause is Psychogenic Polydipsia where water intake is greater than the kidney's ability to excrete dilute urine (about 20 Liters /day) 
Common Cause include decreased "Effective" Plasma Volume where there is arterial underfilling. This is seen in Heart Failure, Cirrhosis and Nephrotic Syndrome. Such patientsoften have Edema. Other causes include hypothyroidism, hypopituitarism and reduced glucocorticoid activity as in Addison's disease. 
Urine Na is often low 
Pathophysiology    Decreased Effective Volume also increases ADH release by non-osmotic stimuli. 
Low Effective volume and decreased arterial filling increases renin, and angiotensin II levels. That causes increases in filtration fraction and increased proximal reabsorption. Therefore amount delivered to distal diluting segment is reduced. Hence total amount of dilute urine that can be generated is low. 
Treatment  Water Restriction

Hyponatremia when theECF Volume is High 
Syndrome of inappropriate ADH (same as infused ADH): 
seen in many conditions; see Table in your syllabus. 
Urine Na is often high (if patient's salt intake in maintained. 
No edema because you can retain up to 3 L of saline without getting edema. 
Pathphysiology 
1) free H2O is retained due to ADH induced increased H2O permeability at the collecting duct. 
2) The retained H2O dilutes the total body water - a portion of this is the intravascular volume, hence serum Na is decreased (diluted) and the volume increases. 
3) The increased intravascular volume suppresses sympathetic outflow, suppresses renin/AII and activates ANF 
4) The increased intravascular volume and suppressed AII  decreases aldosterone secretion. Therefore less Na is reabsorbed distally. 
5) As a result of 3 & 4 urine Na is high 
 

Etiology of Hypernatremia 
H2O intake has not kept up with output.  Remember that thirst should have prevented this.  Identify why it has not. 
1. decreased H2O input, e.g. inability to reach H2O (ex: coma) or 2o to vomiting 
2. increased H2O output 
Non renal -  1. sweat (especially with fever) 
Renal  2. osmotic diuresis (eg: hyperglycemia); See notes for details - the glucose particles cannot be reabsorbed; H2O > Na is lost with the excretion of the particle 
3. diabetes insipidus 
- central - no ADH;   Tumor, head trauma, etc 
- nephrogenic - insensitivity to ADH 2o to: low K+   high prostaglandins effect on cAmp, decreased Na reaborption in thick ascending limb 
    high CA++  decreases effect of adenylate cyclase 
    ETOH inhibitor of ADH release 
    Lithium inhibits adenylate cyclase 
    amyloidosis direct effect on collecting duct 
drug induced - demeclocycline 
or congenital 
Hypernatremia  decreased  H2O content relative to Na+ not necessarily Na excess.  Serum sodium level reflects H2O handling. 
 

Glomerular Disease

- Nephritic Syndrome 
RBC casts and/or dysmorphic RBC's 
Proteinuria may or may not be nephrotic range 
Pathophysiology: "primary" salt retention with edema and hypertension

- Nephrotic Syndrome 
24 hr urine protein > 3.5 g  [but first Rule Out multiple myeloma] 
Pathophysiology of edema either 2o to decreased arterial falling or to primary salt retention 
Urinary protein content is a sufficient criterion for diagnosis but true syndrome includes low Serum albumin, edema, high serum cholesterol.  Also a hypercoaguable state or Fanconi's syndrome may be present.

- Isolated urinary abnormalities 
proteinuria < nephrotic range; or hematuria or both 
If pure nephrotic syndrome (benign urinary sediment) is present, then attempt to differentiate secondary NS - due to drugs, tumor etc - from idiopathic NS; bx usually required; serum creatinine may or may not be ?; if ?'ing then usually very slowly unless a special insult such as HIV nephropathy is present. 
If a nephritic (or active) urinary sediment is present serum creatinine may increase over course of weeks. 
? serum complement  ? anti GBM Ab  ? anti neutrophil                      cytoplasmic antibody 
re immune complex  re Goodpasture or  re Wegners 
or isolated renal   or Microscopic PAN 
variant

If complement is low   ? post infectious  check ASLO titer 
check for SLE    check ANA 
For mixed cryogobulinemia  check cryoglobulins 
renal biopsy required for the diagnosis of idiopathic membranoproliferative 
  
  
               
Potassium
In K balance, you should remember that most of the total body K is intracellular, hence serum K is only a gross measure of K content. Therefore, you have to think about K intake, K excretion and re-distribution of K between intracellular and extracellular spaces.

·         Hypokalemia

A)  Low Input   Dietary insufficiency (uncommon) 
B)  High output (renal) 
 i) Primary Hyperaldosteronism (or Cushings with glucocorticoids binding to aldosterone receptor) 
ii) Alkalosis (K+ enters cell) causing increased cellular K+ in distal tubular cells leading to K+ secretion) 
iii) high urine flow in distal (salt & H2O not just H2O as in D.I.) 
Osmotic diuretics - glucose, mannitol; 
loop diuretics-lasix; also HCTZ (non-loop); 
NaHCO3 wasting in distal or proximal RTA. 
Note: volume depletion causes increased aldo but urine volume and distal delivery of Na re decreased; therefore K+ losses are not excessive.  However in (1) primary hyperaldosteronism, urine Na+ and volume are in steady state and likely not low i.e. increased distal Na reabsorption increased urine volume due to low AII and low FF causing decreased prox reab and increased  distal delivery which eventually overcomes even the aldo stimulated distal Na+ reabsorption and in (2) volume depletion with diuretics.  Aldo is increased but urine output and distal delivery of Na is maintained by diuretics.  And in each of these cases, perhaps more important then flow per se, is the delivery of Na to the distal nephron - Na reabsorption generates a negative membrane potential that drives K+ secretion.

C)  Increased Non Renal Output 
i) Sweat 
ii) diarrhea, villus adenoma, laxative abuse, etc.

D)   cellular shifts  - alkalosis 
(K+ moves  into cells) - Rx with glucose & insulin or with glucose alone in a non-diabetic 
- Rx with ? agonist 
Note: often several mechanisms operate simultaneously for example: Type II diabetic   with high glucose, nausea & vomiting: 
1) vomiting  with volume depletion and high aldo 
2) vomiting with increased H+ loss  causing  alkalosis 
3) high glucose causing osmotic diuresis with high urine flow & increased distal delivery of Na 
 

 Hyperkalemia 
A)   Increased Input alone is rarely a cause

B) Decreased Output 
i) low urine volume such as in acute tubular necrosis with oligiuria 
[Simple volume depletion has  low urine volume but high aldosterone; hence we usually see normal K+.  This is true for "effective" vol depletion such as CHF however if Rx with aldosterone inhibitor such as spironolactone ? see marked hyperkalemia]

ii) acidosis (decreased cellular K+ decreased distal tubular cell K+ causing decreased K+ secretion)

iii) hypoaldosteronism

- hyporenin hypoaldo (remember type IV RTA) in diabetes mellitus 
- adrenal insufficiency

C) Cellular Shifts 
i) acidosis   (K+ out of cells) 
ii) B blocker 
iii) digoxin intoxication

D) Ultimate Cellular Shift 
i) hemolysis 
ii) rhabdomyolysis

E)  Pseudohyperkalemia 
hemolysis of sample 
high plts (> 800,000) 
high WBC (>50,000) 
  
  
 

Acid Base Abnormalities

Metabolic Alkalosis

A) Generation of alkali 
I Non renal 
i.    vomiting or gastric aspiration (H+ loss) 
ii.    infusion of sodium salt of carboxylic acid (ex Na lactate) that is 
         metabolized to NaHCO3 
II Renal 
i. Diuretics and volume depletion 
ii Primary hyperaldosteronism 
iii Primary hyper glucocorticoidism (Cushing's) (also binds to aldo receptor) 
iv  other (there is renal generation of HCO3  but not alkalosis until respiratory function improves; therefore requires a maintenance mechanism) 
v  Sudden Correction of chronic respiratory acidosis that exposes the renal retention of HCO3-.

B) Maintenance of Alkalosis 
    Alkalosis is largely maintained by the Kidney where most of the causes are associated with an increased H secretion; i.e. increased HCO3 formation which serves to maintain the alkalosis. 
i volume depletion increases proximal & distal HCO3-reabsorption  
ii decreased GFR (less HCO3- is filtered - perhaps important in some cases of volume depletion) 
iii low K+ - increased prox reabsorption of HCO3. 
There are some non renal causes of maintenance

Metabolic Acidosis

Two basic conditions: 
a) HCO3  has been lost directly, or inadequately generated by the kidney 
b) an increase in the acid load has titrated body fluid HCO3 
A-H + HCO3-----> A + H2CO3 -----> H2O + CO2)

The situation in (a) gives rise to a normal anion gap (but see renal failure #1 & #3 below),whereas (b) results in an increased anion gap - unless the increased acid is HCl or its equivalent such as arginine HCl.

NORMAL ANION GAP 
Renal: 
i  renal HCO3 loss: distal RTA, proximal RTA, carbonic anhydrase inhibitors ii inadequate HCO3 generation:  Type 4 RTA (hyporenin hypoaldo) results in high K+ which decreases NH3 synthesis and reduces titrable acid excretion leading to low HCO3 generation by the tubule. Also, see renal failure #2

Non renal: 
i. GI HCO3 loss: diarrhea, bile drainage etc. 
ii Administration of HCl, arginine HCl, etc.

INCREASED ANION GAP

1. lactic acidosis - metabolic poisoning, hypoxia/hypoperfusion 
2.  ketoacidosis - DKA, alcoholic ketoacidosis 
3.  poisoning with ethylene glycol, methanol, paraldehyde 
4.  renal failure 
renal failure deserves special mention 
i.  acute renal failure results in decreased titrable acid excretion, retention of anions and a high anion gap

ii moderate chronic renal failure - with a CrCl < 20-25 cc/min - the ability of the remaining nephrons to increase NH3 is exceeded and acidosis results.  Anions are not noticeably retained and the Anion Gap is nl.  Compare to Type 4 RTA.

iii. Severe chronic renal failure - CrCl < 15 cc/min - at this point the ability of the kidney to excrete anions is exceeded and the acidosis becomes one of high AG. 
  
Approach to the patient when Arterial Blood Gases demonstrates metabolic acidosis 
Determine anion gap