Breast cancer

Breast cancer

Incidence

Carcinoma of the breast is the most common cancer in women in the United States (32%) and is second only to lung cancer as a cause of cancer death in women (15%).
Estimated new cases and deaths from breast cancer (women only) in the United States in 2005:

• New cases: 211,240.
• Deaths: 40,410.

The lifetime risk for women of being diagnosed with breast cancer is currently about 1 in 8.

Gender

Breast cancer is relatively uncommon in men; the female-to-male ratio is approximately 100:1.

Age

The risk of developing breast cancer increases with age. Only about 0.8% of breast cancers occur in women < 30 years old and approximately 6.5% develop in women between 30 and 40 years old. Most cases occur in patients over 40 years of age.

Race and ethnicity

White women have a higher overall rate of breast cancer than African-American women; however, this difference is not apparent until after menopause. American Asian and Hispanic women have approximately half the incidence of American Caucasian women. Native-American women extremely low risk of developing breast cancer.

Geography

The incidence of breast cancer is significantly higher in the United States and European countries such as the United Kingdom, Denmark, the Netherlands, New Zealand and Switzerland than in India, Japan, Thailand, Nigeria. It has been suggested that these trends in breast cancer incidence may be related to dietary fat consumption.

Nephrotic syndrome and Treatment

Nephrotic syndrome and Treatment 


Nephrotic syndrome and Treatment 

Definition

Nephrotic syndrome Is a clinical syndrome associated with proteinuria in the nephrotic range (3.5mg/m2/24hrs), edema and hyperlipidemia.

Nephrotic syndrome is not due to inflammatory processes but due to direct action of the membrane attack unit of complement on the glomerulus.

Clinical suspicion

It should be suspected when a patient presents with generalized oedema, protein detected in urine, hypoalbuminemia.

Diagnosis

The diagnosis maybe established with proteinuria in the nephrotic range alone without the other criteria.

1.  Proteinuria > 3.5 g/m2/day:
On detection of protein in urine a 24 hour urinary protein test is in order. There are two cut off values for this test: 1. increased urinary protein <1.5g/day; this is refered to as isolated proteinuria. 2. >3.5g/day; this establishes nephrotic syndrome.

2.  Hypoalbuminaemia

3.  Hyperlipidaemia:
As albumen in serum is lost through the kidneys, the liver increases its production of albumen and concomitantly increases the production of cholesterol.

4.  Oedema: resulting from loss of intravascular fluid to the extravascular space due decreased intravascular oncotic pressure (decreased albumen).

However, the presence of proteinuria in the nephrotic range (3.5g/day) establishes the diagnosis.

Differential diagnosis: proteinuria

Causes

Once the diagnosis of nephrotic syndrome is established the cause of the syndrome is sought in order to treat accordingly.

Nephrotic syndrome with active sediment (mixed nephrotic/ nephritic)

This denotes the presence of RBC casts (active sediment). Causes include:

1ry glomerular diseases as MPGN (main cause), and 2ry glomerular diseases as SLE (most common presentation of SLE), vasculitis such as Henoch Schonlein purpura, mixed essential cryoglobulinemia.

Nephrotic syndrome with bland sediment (Pure nephrotic)

1ry glomerular diseases such as MCNS, Membranous glomerulonephritis, Focal glomerulosclerosis. As well as 2ry glomerular diseases that result from Diabetes (Klemelsteli-Wilson syndrome) and amyloidosis.

Treatment

Treatment of nephrotic syndrome depends primarily on the cause, however, it frequently involves the use the glucorticoids given over long periods of time. Especially in cases of minimal change disease. Here the role of steroids is to suppress the autoimmune basis for this disease. The use of cytotoxic agents maybe required in some cases (e.g. cyclophosphamide).
Dietary salt control, treatment of hypertension and hypercholestrolemia is also recommended. ACE inhibitors, in addition to controlling blood pressure have also been found to decrease the protein loss. Diuretics may help control the edema and the hypertension.

Acute Renal Failure

Definition-Causes-Diagnosis

Definition

Renal failure depicts a group of diseases that may be associated with decreased GFR and manifested by retention of BUN and creatinine. Acute renal failure is defined as a rapidly (over a period of days) increasing creatinine level or decreasing urine output.

Causes

Causes of acute renal failure is caused by failure of the kidneys to perform their normal functions due to:

• Prerenal - Problems affecting the flow of blood before it reaches the kidneys
• Postrenal - Problems affecting the movement of urine out of the kidneys
• Renal - Problems with the kidney itself that prevent proper filtration of blood or production of urine 

Prerenal failure

This is by far the most common type of acute renal failure. Your kidneys do not receive enough blood to filter. Prerenal failure can be caused by the following conditions:

• Dehydration - From vomiting, diarrhea, water pills, or blood loss
• Disruption of blood flow to the kidneys - From a variety of causes
  • Drastic drop in blood pressure - From major surgery, severe injury or burns, or infection in the bloodstream (sepsis)
  • Blockage or narrowing of a blood vessel leading to the kidneys
  • Heart failure or heart attacks
  • Liver failure

There is no actual damage to the kidneys with prerenal failure. With appropriate treatment, it usually can be reversed. 

Postrenal failure

Postrenal renal failure is sometimes referred to as obstructive renal failure, since it is often caused by something blocking elimination of urine produced by the kidneys. This problem also can be reversed.
At the ureter level, this condition can be caused by the following:

• Kidney stone
• Cancer
• Medications

At the bladder level, the following conditions can cause obstruction:

• Kidney stone
• Enlarged prostate (the most common cause)
• Blood clot
• Bladder cancer
• Neurologic disorders of the bladder

Treatment consists of relieving the obstruction. Once the blockage is removed, the kidneys usually recover in 1-2 weeks if there is no infection or other problem.

Renal damage

Primary renal damage is the most complicated cause of renal failure. Renal causes of acute kidney failure can be subdivided into those affecting the filtering system of the kidney, those affecting the blood supply in the kidney, and those affecting kidney tissue.
Some of the kidney problems that can cause kidney failure include the following:

• Blood vessel diseases
• Blood clot in a vessel in the kidneys 
• Injury to kidney tissue and cells
• Glomerulonephritis
• Acute interstitial nephritis
• Acute tubular necrosis

Clinical manifestations

ARF passes through two phases 1. Destructive phase: oliguric and non-oliguric 2. Reconstructive phase: could be polyuric.

ARF due to pre-renal or renal causes (esp. ATN) usually presents as oliguric renal failure passing through the 3 phases of pathology:

1. Intitiation phase: due to the initiating insult on the kidney.
2. Maintenance phase: maintenance of oliguria (1-2 weeks).
3. Recovery phase: due to recovery of renal function (polyuria).

ARF due to other causes as partial obstruction may present as polyuria.
ARF due to postrenal obstruction may present as anuria.

Diagnosis

Renal failure is manifested by the rise of serum creatinine. The next step is to identify if chronic or acute renal failure. Then exclude if postrenal then identify if pre-renal or renal. If renal identify what type of intrisic renal disease ? if no diagnosis is reached then by exclusion the diagnosis is ATN.

1. Prerenal azotemia

• Urine/plasma creatinine ratio > 40
• Urinary Na decreased < 20
• Fractional excretion of Na is <1%
• Urine osmolarity is > 500

2. Renal azotemia

• Urine/plasma creatinine ratio < 20
• Urinary Na decreased > 40
• Fractional excretion of Na is >1%
• Urine osmolarity is > 350

?        These findings can be altered by diuretic use and urine sample should be taken before institution of diuretic use.

3. Postrenal azotemia

Post-renal azotemia develops only if the obstruction is bilateral or affects a solitary functioning kidney. During the early stages of obstruction, continued glomerular filtration leads to increased intra-luminal pressure proximal to the site of obstruction. As a result, there is gradual distension of the proximal ureters, renal pelvis and calyces and fall in glomerular filtration which will be evident by renal ultrasound.
N.B.: the level of creatinine in serum has nothing to do with whether the ARF is oliguric, anuric or non-oliguric: it is an indication that tubular function is lost as creatinine is not filtered- it is secreted. K+ and H+ are retained even in nonoliguric renal failure due to the same principal (they are both secreted and not filtered).

Treatment  

Treatment of acute renal failure usually should be conservative and largely supportive. It requires careful and precise management. All patients will require close monitoring, many of them within intensive care settings.
Supportive care includes stabilizing the patient, monitoring input and output strictly, weighing daily, determining electrolyte values frequently, preventing sepsis via reducing the number of intravenous lines and removing an indwelling urinary.

Therapy for prerenal failure

Rapid volume replacement and treatment of the underlying condition that resulted in prerenal failure are the cornerstones of therapy. Initial fluid administration of isotonic saline (0.9%) or 5% albumin (10 to 20 mL/kg per dose) should be used to restore intravascular volume. This can be both a diagnostic and a therapeutic trial. Fluid administration also can convert oliguric to nonoliguric renal failure in its early stage.

Therapy for postrenal failure

Therapy for postrenal failure includes removal of obstruction by decompression or diversion of the urinary tract, stabilization of electrolyte abnormalities, management of postobstructive diuresis, and therapy for voiding dysfunction and for urinary tract infection. Surgical intervention will require urologic consultation. The site of the obstruction will determine the approach: placement of a Foley catheter, vesicostomy, ureteral catheters (stents), or nephrostomy tubes.

Therapy for established renal failure

Maintaining Balance of Fluid and Electrolytes

In a euvolemic state, fluid intake, including water generated from endogenous metabolism (insensible fluid gain), is balanced by fluid output.

Treating Hypertension

Kidney failure in any form can present as hypertension and hypertensive encephalopathy. It is essential to lower the blood pressure quickly and safely. The blood pressure should be reduced by at least 25% within 1 hour with an antihypertensive medicine whose onset of action is rapid. It is advisable to start with one antihypertensive medicine and increase the dose to its maximum recommended level. Therapy is individualized and needs titration. In most cases, hypertension is the result of sodium and fluid retention, but other factors, such as activation of the renin-aldosterone-angiotensin II and/or the alpha-adrenergic system, may have roles in kidney failure.