Nephrotic syndrom

What are the diagnostic criteria for nephrotic syndrome?
Nephrotic syndrome is a syndrome that results from severe proteinuria. Heavy glomerular
protein losses (3.5 g in an adult or .40 mg/m2/hour in a child) lead to the other three
criteria for nephrotic syndrome: hypoalbuminemia, hyperlipidemia, and usually edema.
From a practical standpoint, measuring a urine total protein/creatinine ratio is preferable
to collecting a 24-hour urine for protein. A ratio of 3.5 correlates with nephrotic-range
proteinuria.
2. What is minimal change disease (minimal change nephrotic syndrome)?
Minimal change disease (MCD) is a disorder of glomeruli that leads to heavy proteinuria.
Renal biopsy shows normal glomeruli by light microscopy but will show effacement of the
podocyte foot processes by electron microscopy. Immunofluorescent microscopy typically
is negative, although some patients may show staining for immunoglobulin M (IgM) in the
mesangial regions of the glomeruli. Technically, a patient cannot be said to have MCD with
certainty without having had a kidney biopsy. However, so many young children with
nephrotic syndrome have MCD that kidney biopsies are only performed in those children
with atypical findings or in those who are resistant to immunosuppressive therapy. Older
adolescents and adults are diagnosed with MCD after a kidney biopsy is performed.
3. How likely is MCD to be the cause of nephrotic syndrome in any individual?
MCD is the cause of nephrotic syndrome in about 90% of children younger than age 6, in
about 65% of older children, and in about 20% to 30% of adolescents. In adults only about
10% to 25% of nephrotic syndrome results from MCD, but it represents the third most
common cause of nephrotic syndrome in adults after membranous nephropathy and focal,
segmental glomerulosclerosis.
4. What causes MCD?
MCD is an immune-mediated disease, felt to be mediated by a circulating factor capable of
inducing proteinuria. Presumably the circulating factor is secreted by lymphoid cells, and it
functions as a vascular permeability factor that directly affects the function of the podocytes.
Although the majority of cases of MCD are idiopathic, MCD, particularly in adults, may be
associated with neoplastic disease such as lymphoma, toxic or allergic reactions to drugs,
certain infections, allergies, or other autoimmune disorders.
5. How common is MCD?
The prevalence of MCD in children is about 16 per 100,000 children, but it is much less
prevalent in adults.
6. What is the typical clinical presentation of MCD?
Patients with MCD typically present with mild to severe edema. Because the onset with
periorbital edema commonly follows an upper respiratory infection in young children,
nephrotic syndrome may sometimes be confused with an allergic reaction until a more
thorough evaluation is performed. I

Acid Base Disorder

Question 1

Describe the acid-base diagnosis in the following case (for example, metabolic acidosis with compensatoryrespiratory alkalosis):

A 41 year old male presents to the ER with the following lab results (hint: look for multiple simultaneous problems).

Na 140 mmol/L
K 4.0 mmol/L
Cl 110 mmol/L
pH 7.0
pCO2 35 mmHg
pO2 75 mmHg
HCO3 8 mmol/L

Answer:
The primary disturbance in this patient is an acidosis, as indicated by the acidemic pH in the blood (pH 7.0). The normal bicarbonate concentration is 24 mmol/L but this patient’s bicarbonate concentration is 8 mmol/L. This indicates a fall in bicarbonate of 16 mmol/L.
Thus, there is a primary metabolic acidosis.
The anion gap is 22.
Recall, anion gap is calculated by the formula:
AG = Na – HCO3 – Cl
AG = 140 – 8 – 110
AG = 22
The normal anion gap is about 12, so the anion gap is increased.
Thus, there is an anion gap metabolic acidosis.
The anion gap is increased by 10 but the bicarbonate has fallen by 16mmol/L. Therefore, there is also a fall in bicarbonate that is not accounted for by the H+ ions that accompanied the unmeasured anions in this case – this means there is also a non-anion gap metabolic acidosis.
The bicarbonate has decreased by 16.
We would expect that in a metabolic acidosis, there would be a 1 mmHg fall in pCO2 for every 1 mmol/L of bicarbonate.

Therefore, we would expect that the pCO2 would be 24 mmHg. Since it is 35mmHg, it is too high and this represents a respiratory acidosis.

Therefore, this is a case of a

1. Anion gap metabolic acidosis
2. Non-anion gap metabolic acidosis
3. Respiratory acidosis

HYPERKALEMIA

What ECG changes occur in patients with hyperkalemia?
The characteristic ECG changes seen in hyperkalemia progress from peaked T waves initially,
followed by lengthening of the PR interval and QRS prolongation, leading to the QRS
progressively widening to a “sine wave,” which eventually results in cardiac standstill.
As in hypokalemia, the actual potassium concentration associated with the progression
of ECG changes varies widely from patient to patient, and continual monitoring of the ECG is
essential when managing patients with hyperkalemia.
9. What are some of the signs and symptoms of hypokalemia?
In addition to arrhythmias, hypokalemia can induce systemic symptoms. In mild hypokalemia
(serum potassium 3.0–3.5 mEq/L), patients are often asymptomatic. As hypokalemia
progresses, nonspecific symptoms develop, such as weakness and malaise. When serum
potassium drops below 2.0 mEq/L, it can precipitate muscle necrosis and paralysis, causing
respiratory failure.
10. What are some of the signs and symptoms of hyperkalemia?
Similar to hypokalemia, hyperkalemia can cause systemic symptoms in addition to cardiac
arrhythmias. Symptoms usually do not become clinically apparent until serum potassium
levels are very high (more than 7.0 mEq/L) and include ascending muscle paralysis
progressing to a flaccid paralysis.
11. What is pseudohyperkalemia and what are some of its causes?
Pseudohyperkalemia is the elevation of the serum potassium level in the absence of either cell
shifts or an increase in total body potassium. It can be present in the setting of thrombocytosis,
leukocytosis, and hemolysis. It results from the movement of potassium out of cells during or
after the blood sample has been drawn.
12. How can one determine if an elevated serum potassium is “real”?
Obtaining a plasma potassium, rather than a serum potassium, will differentiate
pseudohyperkalemia from true hyperkalemia.
13. What factors determine renal potassium excretion?
Renal potassium excretion is dependent on distal nephron sodium delivery, aldosterone, and
urine flow.
14. How does distal delivery of volume and sodium increase potassium
excretion?
Sodium is reabsorbed in the collecting duct via epithelial sodium channels, which stimulates
the basolateral Na-K-ATPase, which in turn facilitates the movement of potassium into the
collecting duct (i.e., into the urine) via potassium channels. With poor urine flow or distal
sodium delivery, the gradient for potassium to be secreted into the collecting duct is too steep
and there is insufficient sodium for uptake by sodium channels.
15. How does aldosterone effect renal potassium excretion?
Aldosterone increases renal potassium excretion by acting on principal cells in the collecting
duct. Aldosterone stimulates renal uptake of sodium and renal secretion of potassium.
16. What conditions stimulate release of aldosterone in a normal person?
Aldosterone is released in response to hypotension and hyperkalemia.





 

Relation of Sodium to body tonicity

1. Is the serum sodium a reflection of total body sodium?
No.
2. Then what is it a reflection of?
It is a reflection of the relative concentration of sodium in water in a liter of plasma. Disorders
of total body sodium reflect disturbances in extracellular fluid (ECF) volume because sodium
is the predominant cation in ECF, as was discussed in Chapter 74. Increases (hypernatremia)
and decreases (hyponatremia) in serum sodium concentration can therefore occur in settings
of low, normal, and high total body sodium. The term dehydration, which strictly speaking
reflects loss of total body water resulting in hypernatremia, is often misused to describe
hypovolemic states. The assessment of total body sodium is an important component of the
approach to the diagnosis and treatment of dysnatremic disorders. Dysnatremias are reflected
in alterations in plasma osmolality.
3. How is plasma osmolality determined?
Plasma osmolality can be either measured by an osmometer or calculated using the following
formula:
Plasma osmolality (mOsm/kg) 5 2[Na](mEq/L) 1
urea (mg/dL)/2.8 1 glucose (mg/dL)/18
Please note the central role of the sodium concentration as the primary determinate of
plasma osmolality based on this equation. Normally, the measured plasma osmolality is no
more than 10 mOsm/kg higher than the calculated plasma osmolality. If the measured osmolality
greatly exceeds 10 mOsm, an osmolar gap reflecting the presence of an osmotically active
substance is not routinely measured in the ECF.
4. Is there a difference between tonicity and osmolality?
Yes. Tonicity is determined by the presence of impermeable solutes such as sodium and
chloride in the ECF. Such solutes set up osmotic gradients that cause water movement across
cell membranes. In contrast, solutes that are permeable to cell membranes (alcohols, urea)
contribute to the measured osmolality of body fluids but do not cause water movement and
therefore are not effective solutes and do not contribute to tonicity.
5. Does hypernatremia always reflect hyperosmolality?
Yes. Not only are patients with hypernatremia hyperosmolar, but they are also hypertonic. In
contrast, not every patient with hyperosmolality is hypertonic. Such is the case with alcohol
ingestion and azotemia.
6. Does hyponatremia always reflect hypo-osmolality?
No. Hyponatremia can also occur with normal or even hyperosmolality.

FSGS: Key points

1. Focal segmental glomerulosclerosis (FSGS) represents a spectrum of idiopathic and
secondary diseases affecting the glomerulus and the kidney in a similar way.
2. In adults, FSGS is the fourth most common cause of end-stage renal disease.
3. FSGS may present as either subnephrotic- or nephrotic-range proteinuria, with or without
hypertension.
4. Mutations in multiple genes that direct the structure and function of the glomerular basement
membrane have been implicated in familial and sporadic FSGS.
5. Angiotensin-converting enzyme inhibitor/angiotensin receptor blocker therapy and treatment
of hyperlipidemia associated with FSGS are presumed to be beneficial therapies for most
patients with FSGS based on studies of proteinuric kidney diseases, although there are little
data from randomized trials specifically addressing these therapies in FSGS.
6. Primary FSGS has a high incidence of recurrence in allografts, and recurrence may lead to loss of allograft.