Albumin & Casts in Urine and Associated Renal Lesions

Urine analysis is the cheapest and routine investigation which could be of great help to the clinician to reach at a diagnosis of a complex renal disorder. Albuminuria (excretion of albumin in urine) detected on heat test of the urine and the casts detected on microscopic examination of first morning specimen of urine reveal a lot about the associated renal lesions (pathological changes in kidney). Albuminuria we know definitely to be glomerular origin, although the tubules may also play their part in its production. It seems probable that this is mainly due to the glomerular basement membrane (GBM) which separates the epithelium of the tuft from the endothelium lining the capillaries, with increase of its permeability.

Casts are the microscopic accumulations of cells or coagulated proteins or lipids. Casts if present could be detected on microscopic examination of deposit obtained after centrifugation of urine. The casts must also be traced to the glomerulus, at least the essential hyaline matrix of the cast composed of coagulated albumin. Again the tubules add their contribution in the shape of epithelial cells and fatty and granular detritus which give to the casts their characteristic appearance. Careful examination casts is as informative as blood biochemistry investigations in cases of kidney disease. The cast gives a picture of the degenerative changes in the tubules. A hyaline cast indicates slight glomerular leakage without active tubular degeneration. Cellular casts denote marked activity of the morbid process. Granular casts denote moderate activity. The admixture of red blood cells (RBCs) is a sign of glomerular hemorrhage. We find that the study of casts is of remarkable importance in assessing the prognosis of a renal disorder. As long as there is considerable activity there is a scope for improvement. For such a study to be of value, the urine should be fresh. If the urine is alkaline or has been allowed to stand for long time, the casts may largely disappear. The absence of casts in an alkaline urine has not the same significance as when the urine is acidic. The acidity of the urine assists in the formation of casts. Deposition of casts in the tubules may lead to oliguria (low output of urine) leading to edema.

Reversible Renal Failure

When we come across the term reversible renal failure, it indicates that there was a scope for the repair of renal lesions or complete recovery of renal function. Reversible renal failure is of great importance for the clinician/nephrologist attending to the patient, because he/she could be able to do something for the well being of the patient. Clinical end picture may be same in many renal disorders though the origins are so different. Acute stage is characterized by pain in back, fever and edema, a rise in blood pressure and such urinary changes as oliguria (low output of urine), high specific gravity of urine with high coloration. Presence of albumin, red blood cells (RBCs) and casts have also been observed in urine with low urea content. It has been observed that reversible renal failure is generally extra-glomerular in origin, but it may be nephritic type. Most of the cases with acute glomerulonephritis also make a complete recovery with therapy and dialysis.  Tubular damage may also be repaired, as has been in the cases of mercuric chloride poisoning. Accumulation of nitrogenous waste products in blood is observed in these patients without any renal lesion on blood biochemistry and kidney biopsy evaluation. The condition may also be termed as extra-renal uremia or azotemia without corresponding renal lesion.

Do Emotions Rule Our Health

Do emotions rule our health? It is a pertinent question with a variety of answers. It is well established now that emotions do rule our health and psychophysiology and behavior. Experts in the field of behavioral medicine have demonstrated that we can increase our chances of avoiding disease by nurturing our minds as well as our bodies. There is always a link between a person’s emotional state and disease. Many people have sensed this link intuitively but the physicians of behavioral medicine got the scientific answers. Medical investigations have demonstrated that emotional upset triggers a chain of events involving the brain and the endocrine system. This neuro-endocrine response, which affects all vital bodily processes, is natural and necessary. Severe over-stimulation, however, may lead to disease. Neurophysiologists have demonstrated that passive emotions as grief and despair with feelings of loss or failure, register in the hippocampus, the part of the brain that activates the body’s pituitary-adrenal-cortical network. Hormones like cortisol, needed for the regulation of metabolism, are secreted in excessive quantities from the cortex of adrenal glands. Excessive release of cortisol may down regulate the immune mechanism thereby decreasing the defence against infectious organisms and tumors. Under such circumstances auto-immune diseases such as rheumatoid arthritis and myasthenia gravis, in which body attacks itself, may be more likely to develop. More aggressive emotions like anger and impatience, or threat to one’s family, insecurity of job, kidnapping and threat to life affect a different section of the brain – the amygdala, which sets off the adrenal-medullary system. The medulla of the adrenal glands releases catecholamines and adrenalin. Catecholamines and adrenalin increase the heart beat rate, elevate blood pressure and raise the level of fatty acids in the blood. Prolonged and/or repeated activation may lead to migraine and hypertension. It has been observed that people with supportive home, work and social life remain far healthier than those expressing dissatisfaction with their private lives and work. Everyone has setbacks or threats in life, but we find that some people sail through such circumstances while others fall apart. Effective coping involves a capacity to maintain neuro-psychological equilibrium without experiencing undue neuro-endocrine arousal. Effective coping is entirely dependent on a person’s self-esteem and social ties that bind him to others.

Blood: The Vehicle of the Life Force

The blood is a vital fluid composed of cellular components and liquid substance called plasma. The cellular components or blood corpuscles float in the plasma. About 40 to 45% of the volume is made up of blood cells and about 55-60% volume is fluid. The volume of cellular components is determined by hematocrit technique. The total volume of blood is about ¹/₁₂th to ¹/₁₃th of our body weight. The vital energy of the body is generated by metabolic processes through oxidation and enzymatic actions. The blood carries oxygen from the lungs and distributes the same to all organs and tissues. Infact, blood is a vehicle of life force.

Composition of Plasma of Blood: The blood plasma contains the following substances:

• Water: 91 - 92%
• Protein: 7 - 8% (Albumin, globulin and coagulation factors)
• Salts: 0.9% (Sodium chloride, potassium chloride, sodium bicarbonate, salts of calcium, magnesium, phosphorus, iron and trace metals).

In addition to above there are small amounts of organic materials like glucose, cholesterol, urea, uric acid, creatinine and amino acids along with hormones, enzymes and antigens.

Cellular Components: There are three types of cells present on blood:

• Red blood cells (RBCs) or erythrocytes.
• White blood cells (WBCs) or leucocytes.
• Platelets or thrombocytes.

Erythrocytes are circular, bi-concave disc like cells and originate in bone marrow. They are pale buff colored when seen singly, but in masses appear red and give the red color to blood , hence called red blood cells. They contain the vital substance hemoglobin. The amount of hemoglobin present in normal blood is about 15 g/dl. The normal count of RBCs in blood is about 5,000,000 (5 x 10⁶) per microlitre of blood. The average life of red blood cell is about 115 days. Hemoglobin is a complex protein rich in iron. It has an affinity for oxygen and combines with it to form oxy-hemoglobin in RBCs. By means of this function oxygen is carried to the tissues from the lungs. A balanced diet rich in iron and proteins is necessary for the replacement of worn out RBCs. Women require more iron as some is lost in the menstrual flow; in pregnancy the requirements are greater to supply iron for the developing fetus.

Blood Groups: Erythrocytes or RBCs carry at their surface the blood group antigens and there are antibodies in the plasma against the antigen absent at the surface of erythrocytes. There are two antigens: A-antigen and B-antigen. Depending upon the presence and absence of these antigens at the surface of RBCs, there are 4 blood groups:

• Blood group A: Antigen A present at the surface of erythrocytes.
• Blood group B: Antigen B present at the surface of erythrocytes.
• Blood group AB: Antigen A and B present at the surface of erythrocytes.
• Blood group O: No antigen present at the surface of erythrocytes.

In addition to above blood groups, there are a number of sub-groups. Sub-groups and Rhesus factor (Rh factor) in blood is important to be determined by agglutination procedures during compatibility testing. Rhesus factor of fetus is also important in Rh-factor negative mothers.

The white blood cells (WBCs) or leucocytes are transparent and not colored cells. The normal count of WBCs is 4000 to 11000 per microlitre of blood. There are five groups of WBCs:

• Granulocytes or polymorphonuclear cells or neutrophils form about 70 - 75% of total leucocytes' count in blood and provide first line of defence against infectious organisms by phagocytic function.
• Lymphocytes form about 20 - 25% of total leucocytes' count in blood. These cells are called immuno-competent cells and provide active immunity and defence against infectious organisms and tumors. There are further types sub-types of these cells like T-lymphocytes and B-lymphocytes; T-helper and T-suppressor lymphocytes etc.
• Monocytes also provide defence against infectious organisms through phagocytic function. They constitute about 5% of total leucocytes' count in blood.
• Eosinophils are the leucocytes which have active affinity for acidic staining material called eosin and appear red in a blood film after staining. These cells are associated with defence against allergic disorders. Normally they count about 2 - 3% of total leucocytes' count in blood.
• Basophils are the cells which stain with basic dyes and look blue in a stained blood film with blue granules in their cytoplasm. These cells count less than 1% of total leucocytes' count in blood and are associated with allergic disorders.

Platelets or thrombocytes are very small cells, about one third of the size of an erythrocyte. Their normal count is 150,000 to 300,000 per microlitre of blood. They play a vital role in the control of bleeding from an injury and in the clotting of blood.

The blood act as a vehicle or transport system of our body carrying all the cellular components, chemical substance, oxygen and nutrients for the nourishment and defence of body in order to maintain its normal function and preservation of life. Red blood cells convey oxygen to the tissues and remove carbon dioxide. Plasma distributes proteins needed for tissue formation and repair. Blood also carries waste products of metabolism for elimination through excretion by kidneys. Internal secretions, hormones and enzymes are also conveyed by blood from organ to organ or target site by the blood. In nutshell the blood is a vehicle of the life force.

Kidney Biopsy and Its Diagnostic Relevance

The entire focus of the modern medicine is to find a rational treatment for various ailments. The accurate diagnosis is the key to specific therapy for a disease. Kidney biopsy evaluation is of paramount importance to assess the pathological lesions associated with the disordered renal function and for deciding the course of a particular treatment regimen. Percutaneous needle biopsy of kidney was introduced by Iversen in 1949. Kidney biopsy, need not to be performed in every case with symptoms of renal disease. For kidney biopsy procedure, the patients must be selected carefully, excluding cases with only one functional kidney. Patient is briefly hospitalized for taking kidney biopsy. The blood coagulation parameters of the patient must be within normal limits. Needle biopsy of kidney is performed by the Nephrologist under ultrasound guidance, preserved in the suitable fixatives and immediately rushed to the Pathology Laboratory for histological, immunofluorescence and ultrastructural examination. Composite study of the kidney biopsy by the three methods mentioned above is essential to establish an accurate diagnosis of renal disorder or kidney disease and evolution of a particular renal disorder. A renal biopsy (kidney biopsy) must contain glomeruli to be considered adequate for achieving a diagnosis. Generally, the specimen is considered adequate when atleast 5 glomeruli with corresponding tubules are present. Many pathologists believe that interpretation of renal biopsies is extremely difficult. Obviously it has become more complex over the years because of changing approaches to the classification of glomerular diseases. A thorough knowledge of normal histology and ultrastructure of renal components is essential to recognize any alteration in various components of the kidney. An accurate diagnosis could only be achieved through clinicopathological correlation and consideration of family history of patient in cases of congenital and hereditary glomerular diseases.

Urine Analysis: Physical and Chemical Characteristics of Normal Urine

Urine analysis infers valuable information in a variety of ailments. Physical characteristics of urine have been used as diagnostic and prognostic tool from the time immemorial by the health physicians. We know that the major functions of kidneys are:

1. Removal of water not needed by the body fluids, the amount depending on the balance between glomerular filtrate and he degree of tubular reabsorption;
2. The excretion of certain substances normally present in the plasma when their concentration rises above a certain level;
3. The selective reabsorption of substances such as glucose which are of value to the body;
4. The excretion of useless substances; and
5. Regulation of acid base balance.

Disordered renal function may lead to a change in the volume of the urine excreted per day along with remarkable changes in its physical and chemical properties and microscopic contents. Urine analysis is the very first investigation of diagnostic importance not only in renal disorders but also in other diseases like diabetes, liver disease, jaundice etc. In diagnostic pathology the extent of abnormalities could only be understood in comparison with the reference values obtained from similar investigations in normal individuals. Hence, it is important to have an understanding of normal parameters of physical and chemical characteristics of urine.

Characteristics of normal urine:

1. Quantity: The quantity averages 1500 to 2000 ml in an adult man daily. It may vary with the amount of fluid taken. In fact it is linked with the protein metabolism; higher is the protein intake higher will be the urinary output since the urea produced from the protein needs to be flushed out from the body. Higher is the urea production in the body, the higher is the volume of urine to excrete it.
2. Color: The color should be clear pale amber without any deposits. However, a light flocculent cloud of mucus may sometimes be seen floating in the normal urine.
3. Specific gravity: It varies from 1.010 to 1.025. Specific gravity is determined with urinometer.
4. Odor: The odor is aromatic.
5. Reaction: The reaction of normal urine is slightly acidic with an average pH of 6.0.

Composition of normal urine: Urine is mainly composed of water, urea and sodium chloride. I an adult taking about 100 g protein in 24 hours, the composition of urine is likely to be as follows:

1. Water: Near about 96%
2. Solids: About 4% (urea 2% and other metabolic products 2%. Other metabolic products include: uric acid, creatinine, electrolytes or salts such as sodium chloride, potassium chloride and bicarbonate).

• Urea is one of the end products of protein metabolism. It is prepared from the deaminated amino-acid in the liver and reach the kidneys through blood circulation (The normal blood urea level is 20-40 mg/dl). About 30 gram urea is excreted by the kidneys daily.
• Uric Acid: The normal level of uric acid in blood is 2 to 6 mg/dl and about 1.5 to 2 gram is excreted daily in urine.
• Creatinine: Creatinine is the metabolic waste of creatin in muscle. Purine bodies, oxalates, phosphates, sulphates and urates are the other metabolic products.
• Electrolytes or salts such as sodium chloride and potassium chloride are also excreted in the urine to maintain the normal level in blood. These are the salts which are the part of our daily diet and are always taken in excess and need to be excreted to maintain normal physiological balance.