These notes were written by Dr Donald Landry and edited by him and Q. Al-Awqati. They are not meant to replace your syllabus.
Case 2, question d.
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
| Evaluation for HTN: |
| 1. Evaluate for chronic damage |
| Eyes |
Examine for hypertensive retinopathy |
| Cardiovascular |
Left Ventricular Hypertrophy by Chest X ray, EKG or Echocardiogram |
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Kidneys |
increased Creatinine |
| Peripheral Vasculature |
decreased pulses, loss of cutaneous adnexal structures |
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| 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. |
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| 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 |
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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 |
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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 |
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| 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 |
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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 |
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| Laboratory correlates: |
hemodilution, decreased serum albumin, hypoxia on arterial blood gas, and peripheral vascular congestion on chest x-ray |
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| Tonicity |
Regulation of the Tonicity of the Body Fluids |
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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. Hyponatremia reflects 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. |
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| Remember |
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| Water Intake |
diet; I.V. |
| Water Output |
urine; gi (vomiting, diarrhea or fistula), sweat |
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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.]
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| 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 |
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| 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. |
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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 |
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| 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 |
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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 |
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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 |
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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 |
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Non renal - 1 |
sweat (especially with fever) |
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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 |
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| 3. diabetes insipidus |
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central - no ADH; |
Tumor, head trauma, etc |
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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 |
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drug induced |
demeclocycline
or congenital |
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| Hypernatremia decreased H2O content relative to Na+ not necessarily Na excess. Serum sodium level reflects H2O handling. |
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| 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 |
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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. |
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Hypokalemia |
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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 |
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Hyperkalemia |
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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) |
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| Acid Base Abnormalities |
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Metabolic Alkalosis |
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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 |
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Metabolic Acidosis |
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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 |
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| Normal |
High |
| R/O renal failure |
R/O renal failure |
R/O HCl gain (history)
-identify renal or non-renal |
Identify "hidden" anion i.e. measure lactate "acetone" increased in source of HCO3 loss
Measure serum osm which is high in ethylene glycol methanol or paraldehyde intoxication |
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