Happy New Year - 2009

Let us pray for the Peace, Happiness and Prosperity throughout the World. Let God decorate every ray of the sun reaching you with the fragrance of success and prosperity for you. Keep smiling and rocking in 2K9. Wish you a “Very Happy New Year” Dr. Rayat

How Hypertension Is Related To Kidney

High blood pressure or hypertension is one of the most characteristic phenomenon of chronic glomerulonephritis. It is evident that renal lesions (pathological abnormality in kidney) of an ischemic kidney (kidney with poor blood supply) may cause hypertension. This has been seen in the secondary hypertension which develops in the course of glomerulonephritis. Mechanical as well as pathological compression of renal parenchyma has been found to cause hypertension in experimental animals. Chronic pyelonephritis may also cause hypertension.

A variety of renal disorders (kidney diseases) may give rise to hypertension. The kidney disease may be parenchymal or of vascular origin primarily. Morbid anatomical studies have revealed that partial occluding of even one of the renal arteries due to intimal thickening (thickening of internal lining of artery) could be a cause of hypertension due to renal involvement. The vascular or presser substance can be formed by an ischemic kidney. Healthy kidneys are capable of eliminating any presser substance formed in the system. The circulating presser substance is called hypertensin or angiotonin. The angiotonin is formed in the blood by the interaction of an enzyme, renin, secreted by ischemic kidney. The maintenance of normal blood pressure depends on a correct balance between the production of a presser material by the adrenal cortex and its removal by the kidneys. The hypertension may be the result of over-activity of the adrenal gland or some renal disorder.

The primary hypertension and the renal hypertension could be ruled out by the family physician of the patient. In the primary hypertension, the high blood pressure develops early without any renal insufficiency, but in glomerulonephritis, the hypertension develops gradually with renal insufficiency and anemia (fall in hemoglobin level in blood). However, if the patient is seen only after the development of uremia (high level of urea in blood) making distinction between the primary or secondary hypertension could be difficult.

What Could Be The Cause Of Swelling On Face

The swelling on face or facial edema should be taken seriously if there is no history of insect bite, wasp sting or honey bee sting and when it is after a throat infection. The swelling on face or facial edema could be due to renal disorder (kidney disease). If on routine examination of urine of the patient, excretion of albumin or protein is detected; there is a need to consult a nephrologist for proper investigations. Blood biochemistry for blood urea, serum creatinine, serum proteins, serum electrophoresis, urine electrophoresis and 24-hour urinary protein should be done. Excretion of protein in 24-hours through urine will help the physician to assess the loss of proteins and possible course of action. Urine electrophoresis would show the type of protein being excreted in the urine. In a patient with nephrotic syndrome, serum electrophoresis would show hypoalbuminemia (low level of albumin in blood), hypogammaglobulinemia (low level of globulins in blood) and raised alpha-2 (a-2) globulin, and urine electrophoresis may show albuminuria (excretion of albumin in urine) or non-selective proteinuria (excretion of almost all the fractions of serum proteins in urine). Total serum protein and its fractions like albumin and globulin would show the altered albumin-globulin ratio. The normal albumin-globulin ratio (^Albumin/_Globulin) is 3:1 and it may be reversed in patients with swelling on face due to kidney disease.

The swelling on face or facial edema is directly associated with albuminuria (excretion of albumin in urine) and salt retention. The loss of blood albumin through urine hinders the return of fluid from the tissues into the blood and may thus lead to development of edema. It is well known that 68 to 70% weight of our body is due to water content in the blood and tissues. Around 12 to 14% of the total water volume of our body is in the blood and the rest is present in the tissues of the body. There is direct correlation between albuminuria (excretion of albumin in urine) and edema. Retention of Chloride is also a common accompaniment of edema. However, there may not be any retention of Chloride in majority of the cases with edema. The edema is perhaps the greatest problem confronting the students of nephrology. Pathological lesions in the kidney need to be evaluated microscopically through renal biopsy examination. Blood urea and serum creatinine may be normal. There may be salt retention without edema and edema without salt retention. The Chloride may collect in watery subcutaneous tissue due to some external factors also without involvement of any renal lesion.

Two forms of swelling on face or facial edema could be recognized and these are called nephritic edema and nephrotic edema. In nephritic edema the protein content of the edema fluid is over 1 gram/dl whereas in nephrotic edema the protein content of the edema fluid is always less than 0.1 gram/dl. Nephritic edema occurs in acute glomerulonephritis. The capillaries in the subcutaneous tissue become more permeable leading to leakage of proteins in the extra cellular fluid. Nephrotic edema occurs in the wet nephritis or second stage of nephritis, in nephrosis and also in renal amyloidosis. The edema is caused due to the great fall in the osmotic pressure of the blood due to constant loss of protein in urine; so, the fluid from the blood vessels escapes into the tissues in an effort to correct the viscosity of blood plasma.

How Electrolyte Imbalance Causes Renal Disease Or Renal Disease Leads To Electrolyte Imbalance

Electrolytes or essential ions should always be in the state of homoeostasis. The Normal or standard range of electrolytes reflects the normal functional status of our kidneys. Our kidneys play a vital role in preserving the internal environment while excreting the waste products of metabolism, extra water and electrolytes. There is two way selectivity between the cause and effect between the electrolytes (essential ions) and renal disorder (kidney disease). Depletion of Sodium (Na⁺) or Potassium (K⁺) or Calcium (Ca⁺⁺) through excessive urinary excretion may cause renal failure or renal failure may lead to depletion of these ions or electrolytes in the blood plasma.

The renal tubules play a vital role in regulation and preservation of water and electrolytes. The function of tubular epithelium and tubular enzymes is under the control of hormones of some endocrine glands. Suboptimal response of tubular enzymes or over production of corresponding hormone may cause renal disorder (kidney disease). Anti-diuretic hormone of pituitary gland, aldosterone and parathyroid hormone affect the renal tubules to regulate and preserve the water and electrolytes. Potassium (K⁺) content of the cells plays a critical role in retention or excretion of potassium. The glomeruli of our kidneys excrete Potassium (K⁺) in glomerular filtrate and tubular epithelial cells also excrete Potassium (K⁺) by ion exchange in which Potassium (K⁺) of tubular cells is exchanged by Sodium (Na⁺) of glomerular filtrate. Re-absorption is controlled by proximal tubules whereas the excretion is controlled by distal tubules.

Low dietary intake, fever, trauma, or hemolysis leads to tissue catabolism in patients with anuria (no urine output) leading to release of more Potassium (K⁺) from the cells. In these patients Potassium (K⁺) concentration in blood may reach lethal level (more than 100 mEq/litre). Normal level of Potassium (K⁺) in serum is 5.5 mEq/litre. The clinical features of hyperkalemia (high level of Potassium in blood) could be mainly cardiac (bradycardia or arrhythmia) with significant changes in electrocardiogram (ECG). Potassium (K⁺) depletion may be renal or non-renal in origin and may be suspected when pronounced muscular weakness and lethargy is associated with electrolyte imbalance. Commonest cause of Potassium (K⁺) deficiency could be the uncontrolled use of diuretics for the treatment of congestive heart failure. Potassium (K⁺) deficiency leads to vacuolation of tubular epithelium in proximal tubules (known as clear cell nephropathy). The associated renal changes are reversible with correction in Potassium (K⁺) level in blood/serum. Aldosterone is Sodium (Na⁺) retaining adrenal corticoid secreted by adrenal cortex. Excessive secretion of this corticoid as in cases of adenoma of adrenal cortex may lead to increase in the level of Sodium (Na⁺) and extracellular fluid volume and altered function of Sodium pump. In usual Potassium (K⁺) losing nephropathies there is failure of hydrogen ion excretion in association with the failure of retention or conservation of Potassium (K⁺).

Hypercalcemia (high level of Calcium in blood) as seen in primary hyperparathyroidism, sarcoidosis, excessive vitamin D intake or idiopathic hypercalcemia of infants, may also result in renal damage. Hypercalcemia is also a feature of acute osteoporosis of multiple myeloma and matastatic carcinomatosis of bone. Hypercalcemia could be a lethal complication associated with sarcoidosis but may successfully be reversed with timely steroid therapy. The serum level of Calcium (Ca⁺⁺) may return to normal in a few weeks but the reversal of renal insufficiency may take a year or longer. Calcium (Ca⁺⁺) is retained in our body in the form of Calcium phosphate. The hormone like action of vitamin D during excessive intake, causes increased excretion of phosphorus in urine, unsaturation of serum Calcium phosphate, demineralization of bone leading to increased level of Calcium in blood and increased loss of Calcium in urine. Hypercalcemia could cause nephrocalcinosis leading to renal insufficiency.

Renal Biopsy Procedure: Complications

Pathological lesions in affected kidneys of patients with renal disorder (kidney disease) could only be evaluated through histological, immunofluorescence and ultrastructural examination of renal biopsy. The renal biopsy (kidney biopsy) procedure as percutaneous needle biopsy was established long back in 1949 and has undergone a great refinement. At present, a large number of medical centers have been performing ultrasound guided percutaneous renal biopsy procedure for the diagnostic and prognostic evaluation of renal tissue. However, majority of the centers lack the facility of electron microscopy for ultrastructural examination of renal biopsies. Cases with microscopic hematuria (blood in urine) and hereditary nephropathies need ultrastructural examination of renal biopsy (kidney biopsy) for an accurate diagnosis. In expert hands the procedure is as safe as incision biopsy or percutaneous biopsy of liver, but post biopsy complications in rare cases could not be avoided. Hematuria (blood in urine) is a common complication and could rarely necessitate blood transfusion. There are 0.01 percent (1 in 10,000) chances of severe hemorrhage secondary to puncture leading to compulsive nephrectomy (surgical removal of kidney). Uncommon complications could be sepsis and hypertension due to perirenal hematoma. Renal biopsy (kidney biopsy) procedure is not advisable for patients with only one functional kidney.

CT Scanning And Its Side Effects

Computed Tomography (CT) scanning is used for assessing the health status of internal organs in a variety of conditions. X-ray computed tomography (CT) involves x-rays for the tomographic imaging. CT scanning promises a greater diagnostic accuracy in brain hemorrhage, tumors, arterial blockages, non-invasive angiography and status of internal organs in accidental cases. Though the harm associated with the medically necessary CT scan is below the unacceptable limits of radiation. A patient is exposed to 10 mSv radiation during a typical CT scan of chest whereas it gets only 0.02 mSv on a chest x-ray. The mSv is the symbol of milli-Seivert unit of radiation energy absorbed in tissues and 10 mSv stands for 1 Rem (Rad equivalent of man). Once or twice in life time, CT scan if required for medical diagnosis is not harmful but repeated CT scanning for the health assessment of asymptomatic individuals would jeopardize the safety limits. Age of an individual and frequency of exposure to radiation may affect the physical health and may lead to genetic mutations and cancer. Asymptomatic individuals approaching the commercial CT Scan Centers should be highlighted the side effects of CT scan. Such individuals should be referred back to their physicians for other medical examinations. In developed countries there are Radiation Safety Authorities to regulate the practice of such techniques. There are many conditions which could be diagnosed without CT scan. There is no evidence of any benefit of CT scanning for a lung disease or lesions of colon. If an asymptomatic or normal person with 40 years plus age receives a radiation dose of 10 mSv every year for five to 10 years, he/she will have 5 to 10 percent more chances of developing fatal cancer than without any exposure to radiation. CT scanning is very harmful for the pregnant females as the fetus should not be exposed to more than 5 mSv (0.5 Rem)radiation energy. As per ICRP guidelines, the maximum permissible exposure for the whole body in an adult is 20 mSv or 2 Rem/year. Avoid unwanted CT scanning to save your health and prolong your longevity.

Pulse As An Indicator Of Health And Disease

Radial pulse has been the technique of monitoring health status in humans from the time immemorial. The pioneer philosopher Heraclitus (540-475 BC) talked about two opposite forces; the fire or the heat and the water as essential components of life. These forces are always under rhythmic change under the influence of cosmic oscillations and influence our cardiovascular system. Medical practitioners generally assess the radial pulse on the wrist without any distinction of left or right wrist, but the Chinese concept makes distinction between the right and the left wrist and pulse palpation at the radial artery. There are fourteen radial pulses according to the Chinese system of medicine. There are three positions on the radial artery on each wrist. Position one is near the base of the thumb. On the left wrist there are six pulses; on each position one superficial and one deep pulse could be felt. On right wrist there are eight pulses; two pulses could be felt at position one and pulses at three levels (superficial, middle and deep) could be felt at the position number two and three. In addition to radial pulses, peripheral pulses could be felt at nine other points on human body. An experienced physician may fulfill the diagnostic needs of a patient through assessment of radial pulses only. Three levels of physical status; normal (standard), low activity or hypoactivity and high activity or hyperactivity could be assessed through analysis of the count and quality (length, sharpness and dullness) of the pulse.

The way to assess radial pulses as per the Chinese concept: Place the middle finger of your hand at the apophysis of radius (i.e. position-2) of the patient's wrist, the index and the ring fingers will automatically be placed on other two positions. Remember the position one is at the base of the thumb. Ideally the pulse on the right wrist of the patient should be assessed with the fingers of your right hand and on the left wrist with the fingers of your left hand. Develop an arbitrary scoring criterion of 1 to 7 for the quality of the pulse. Let score 4 represent the normal or standard, 3 to 1 represent hypoactivity or weakness and 5 to 7 represent the hyperactivity or over activity of some organs. Pulse count is taken as beats per minute whereas the qualitative parameters of pulse could be assessed in 3 to 5 minutes. It needs a lot of practice and experience to learn the Chinese concept of pulse evaluation. Please refer to the article "Pulse and pulse pressure" published on this blog in the month of July 2008 for additional information.

Essential Ions Of Our Body For Sustaining Life

Our life is sustained by complex interaction of inorganic and organic substances; and the water serves as the supportive medium and vehicle for the elements of life. There are nine types of most essential ions of our body which play a dynamic role in supporting and sustaining health and life. Out of nine, five are positively charged ions and four are negatively charged ions. The positively charged ions are called cations as these collect at the negative electrode or cathode during electrolysis; these are Na⁺ (Sodium ion), K⁺ (Potassium ion), Ca⁺⁺ (Calcium ion), Mg⁺⁺ (Magnesium ion) and H⁺ (Hydrogen ion). The negatively charged ions are called anions as these collect at positive electrode or anode during electrolysis; these are Cl^- (Chloride ion), HCO₃^- (Bicarbonate ion), PO₄^3- (Phosphate ion) and OH^- (Hydroxyl ion). The genius, Sir Humphrey Davy discovered in the second decade of the 19th Century that the passage of current through the aqueous solution of inorganic compounds dissociated them into positively charged and negatively charged parts. That was the beginning of a field which today has the great utility in the life sciences and industry. The Sodium (Na⁺), Chloride (Cl^-), Potassium (K⁺) and Bicarbonate (HCO₃^-) are called principle electrolytes and are present in the blood and various body fluids. Potassium (K⁺) is essential for heart function. The concentration of electrolytes is expressed in milli-Equivalents (mEq) per litre. In the plasma of our blood the normal concentration of Sodium is around 145 mEq/litre; Potassium ranges from 3 to 5 mEq/litre; Chloride is around 100 mEq/litre and Bicarbonate is around 30 mEq/litre. Hydrogen ions (H⁺) hydroxyl ions (OH^-), Bicarbonate ions (HCO₃^-) and Phosphate ions (PO₄^3-) govern the acid-base balance. Our kidneys play a vital role in maintaining the electrolyte balance and acid-base balance. The total sum of electrolytes also determines the osmotic pressure of intracellular and extracellular or interstitial body fluids. The osmotic pressure is a physical force and expressed in osmols (Osm) or milliosmols (mOsm). One mEq of monovalent ions would exert one mOsm and one mEq of divalent ions would exert two mOsm of osmotic pressure. Osmotic pressure regulates the movement of water from a compartment of lower concentration of electrolytes or ions to a compartment of higher concentration of electrolytes or ions.

Daily requirement of salts and minerals of and adult person is 3 to 5 grams. Common salt (Sodium Chloride) is a source of Sodium and Chloride ions. Rock salt also provides Potassium ions as it contains some Potassium Chloride in addition Sodium Chloride. Fruits, vegetables and animal products are rich in salts and minerals. Excess of salts taken as food additives are excreted in urine by kidneys. One may loose electrolytes and water due to excessive sweating, continued vomiting or profuse diarrhea resulting in dehydration. To offset the ill effects of dehydration and to correct the lost electrolytes we should drink the solution of oral rehydration salts that contains Sodium Chloride, Potassium Chloride, Sodium Citrate and Glucose in optimal proportions.

Oliguria Or Anuria: Cause May Be Renal Or Non-Renal

The term oliguria means low urine output and anuria stands for no urine output. The oliguria or anuria could be due to renal disease (kidney disease) or non-renal (non kidney) problem. The four possible causes which probably lead to oliguria or anuria are listed below:

1. Obstruction in a kidney: Obstruction in a kidney or lower urinary track may cause oliguria or anuria. Debris of epithelial cell may block the renal tubules. Hemoglobin or myoglobin pigments or crystals of some drugs have also been documented as the possible cause of casts blocking the renal tubules. Interstitial edema (swelling of interstitial tissue in kidney) could also compress tubules thereby leading to impairment of tubular function. Net result of any sort of obstruction in a kidney is the oliguria which could lead to a grave situation i.e. anuria.
2. Dehydration: Continued vomiting, severe diarrhea or profuse sweating may lead to dehydration resulting in oliguria or complete cessation of urine i.e. anuria.
3. Peripheral circulatory collapse: Peripheral circulatory collapse may occur due to post-operative surgical shock leading to reduced renal blood flow and glomerular filtration rate (GFR) resulting in anuria as the tubules reabsorb whatsoever the glomerular filtrate is produced by glomeruli.
4. Degeneration of tubular epithelium: Degeneration of tubular epithelium causes detachment of epithelium from tubular basement membrane (TBM) resulting in massive loss of tubular epithelial cells. The loss of tubular epithelium leads to loss of physiological barrier between glomerular filtrate in tubules and very strong osmotic pull of plasma in the peri-tubular capillaries (PTC), hence any glomerular filtrate present in tubules is sucked out by PTC, leading to anuria. Mercuric chloride poisoning may cause this type of anuria, however, it could be reversible and epithelial lining of tubules be restored within about two weeks. Avoid tasting unknown and unspecified chemicals to save your kidneys and life.

Control Diabetes To Save Your Vision And Kidneys

The global diabetic community is always at risk of diabetes associated complications. The disease may be hereditary or lifestyle associated. The growing number of cases per year among children and adolescents is a cause of concern. World Diabetes Day is celebrated on November every year in the memory of Sir Frederick Banting who discovered insulin, with an aim of awareness among masses about the alarming rise of diabetes through out the world. Knowledge about the 'warning signs of diabetes' and its control could definitely help us to control diabetes and diabetes associated complications. Abnormal carbohydrate metabolism leads to diabetes. The carbohydrates in the form of starch and sugars are acted upon by the enzymes of the saliva in our mouth and pancreatic and intestinal juices in the small intestine. The action of various digestive enzymes converts the complex sugars into simple sugar such as glucose. The glucose is absorbed by villi of the small intestine, passes into the blood capillaries, and is carried by the portal vein to the liver, where excess sugar is converted into glycogen and stored in the liver cells until required for use. The amount of starch and complex sugars and other chemicals we eat, influence our metabolism. Insulin is called anti-diabetic hormone and plays an important role in the carbohydrate metabolism. Insulin is secreted by pancreas and governs the ability of the cells of the body to absorb and use glucose and fats. Diabetes may be non-insulin dependent or insulin dependant depending on the involvement of insulin. Preservatives in food stuffs, coloring agents and taste maker chemicals could be the main cause of diabetes in children and adolescents.

Diabetes associated complications are related to duration of diabetes. The longer is the duration of diabetes, the greater is the risk of diabetic complications. It has been documented that 80 per cent of the patients who suffer from diabetes for more than 15 years would have damage to retina. The diabetic retinopathy is a serious diabetic complication. Diabetic retinopathy damages the blood vessels of the retina and could lead to blindness. Early detection of diabetes and its control through regular exercise, medication and change in lifestyle and food habits is the key to avoiding diabetic complications. To reduce the incidence of various diabetic complications, it is important to keep the blood sugar levels under control and have regular checkup. Diabetic retinopathy may be non-proliferative diabetic retinopathy (NPDR) or if unchecked that may lead to proliferative diabetic retinopathy (PDR). Lack of blood supply to retina in proliferative diabetic retinopathy may lead to complete vision loss.

Diabetic nephropathy, a kidney disease is another serious complication associated with diabetes. Kidneys play a vital role in our body to excrete toxic waste products of metabolism and to maintain balance of electrolytes and water as well. Uncontrolled diabetes causes irreversible damage to renal glomeruli, the filtration units of our kidneys. There is a great need for the diabetic friends to control diabetes through conventional and non conventional methods to lead a healthy and cheerful life without much complication. All diabetic patients must have a medical and eye examination at regular intervals to avoid diabetes associated complications.

Physiology of Sweating or Hidrosis

Sweating or hidrosis is a normal phenomenon. Considerable quantities of water, chloride, sodium and potassium may be lost in the sweat. There are two type of sweat: a) insensible sweat and b) sensible sweat. Insensible sweat continuously evaporates from our body under all conditions and about 500-600 ml of water is lost daily in an adult. Sensible sweat is secreted when body temperature rises due to exercise, hard labour or due to environmental factors. Sensible sweat may contain 25 to 90 milli-Equivalent (mEq) of chloride per litre. The average amount of chloride lost is about 45 mEq per litre. We compensate the loss of water through drinking water. However, if electrolytes are not taken with water the chloride level in blood/plasma may fall. This condition may be found in industrial workers, miners, labourers and athletes. One may suffer from muscular cramps due to deficiency of sodium and potassium a condition known as miners' cramps as it occurs frequently in miners as they loose electrolytes due to hyper-hidrosis or excessive sweating.

Work and exercise related hyper-hidrosis or excessive sweating is normal but unconditional hyper-hidrosis may cause emotional problems. Sweat is excreted through the sweat glands present all over the body. The cause of excessive sweating is unknown but it results due to over activity of sweat glands. There is individual variation in the intensity of sweating. Some people may also complain of sweat with bad odour or bromhidrosis. Bromhidrosis is caused by the decomposition of biological substances present in the sweat by the bacteria. Hyper-hidrosis may be generalized or continuous phenomenon or may be localized. Imbalance in the body temperature due to life style, fever, diabetes, obesity or intake of certain drugs may cause generalized hyper-hidrosis or excessive sweating. Localized hyper-hidrosis on palms and/or soles may be caused by emotional disturbances or stress or after eating certain food stuffs. Protein rich foods may help control hyper-hidrosis. Use deodorants for bromhidrosis or consult your physician. Some people my also have colored sweat or chromhidrosis. In cases of chromhidrosis saliva and urine may also be colored. Chromhidrosis may be occupation associated or food or drug associated. Change in eating habits and occupation may help overcome the problem of chromhidrosis. Use of deodorant soaps may help reduce the problem of bromhidrosis. Our kidneys play a vital role in the management of cation-anion balance and acid-base balance in our body.

Tissues of Human Body: Types and Subtypes

Human body consists of countless cells as an essential component of different tissues. The entire lot of cells originates from typical cell, the ovum or the egg cell. Ovum or the egg cell is composed of protoplasm and contains a nucleus. After fertilization this cell multiplies to form a ball shaped structure called embryo, which by the way of differentiation develops into various tissues required to form organs and various parts of the body. The embryo or the ball of cells developed from the fertilized ovum could be divided into three layers at the very early stage:

1. Outer Layer or Ectoderm: The outer part of the skin, nails, hair follicle and sweat glands mucus membrane lining of the mouth and nasal cavities develop from the ectoderm. The nervous system also develops from the ectoderm.
2. Middle Layer or Mesoderm: Muscles, bones, fat and some parts of the cardiovascular system develop from the mesoderm.
3. Inner Layer or Endoderm: The lining of the alimentary canal and respiratory tract develop from the endoderm.

Tissue: A tissue is an aggregation of cells of a unique shape and size destined to perform a particular task. The special function of a tissue may be governed by biological substances and/or nervous system. Elementary tissues of our body are of four types:

1. Epithelial Tissue
2. Connective Tissue
3. Muscular Tissue
4. Nervous Tissue

Subtypes of Epithelial Tissue:

A). Covering and Lining Epithelial Tissue: [1. Simple Epithelial Tissue (Pavement Epithelium: Figure-1, Cuboidal Epithelium: Figure-2, Columnar Epithelium: Figure-3); 2. Stratified Epithelial Tissue; 3. Transitional Epithelial Tissue]

Fig-1: Pavement Epithelium

Fig-2: Columnar Epithelium

Fig-3: Ciliated Columnar Epithelium

B). Glands: [Exocrine Glands (Simple Exocrine Glands, Compound Exocrine Glands); Endocrine Glands]

Subtypes of Connective Tissue:

A). Loose Connective Tissue or Areolar Tissue

B). Fatty Connective Tissue or Adipose Tissue

C). Dense Connective Tissue or Fibrous Tissue. Ultrastructural view of collagenous fibres has been depicted in figure-4.

Fig-4: Ultrastructural view of Collagenous Fibres, 27000x

D). Cartilage

E). Bone

F: Blood (Blood is also a form of connective tissue suspended in liquid matrix called plasma).

Subtypes of Muscular Tissue:

A). Voluntary Muscle (Striated or striped muscle). Ultrastructural view of striated muscle has been depicted in figure-5.

Fig-4: Ultrastructural view of Striated Muscle, 6000x

B). Involuntary Muscle (Smooth or plain muscle)

C). Cardiac Muscle (Striated involuntary muscle)

Tissues of Human Body: Distribution of Various Tissues

Distribution of Various Tissues:

Epithelial Tissue:

Covering and lining epithelia has been classified according to shape and arrangement of their cells. Simple epithelium composed of flat cells as single layer attached to a basement membrane is called pavement epithelium. These are found lining the blood vessels and peritoneum. Cuboidal epithelium is characterized by cube shaped cells and is found covering the ovaries. Columnar epithelium is composed of taller cells supported by a basement membrane. This type of epithelium is found where wear and tear is little more. It is found lining the stomach and intestine. Ciliated columnar epithelium show hair like projections at the free surface of cells under microscopes and is found in the respiratory tract. A brush border is found in the cells specialized for absorption. These cells have minute fingerlike projections called microvilli. Such cells are found lining the small intestine.

Stratified epithelium is made up of many layers of cells. The deepest layer of columnar cells rests on the basement membrane and is called germinal layer. Cells of the germinal layer keep on dividing frequently and as they divide the parent cells are pushed nearer the surface and become flattened. The cells on the surface are rubbed off frequently and are replaced by new cell from below. Skin is the dry stratified epithelium and the cells of surface layer have keratin that made our skin water proof. In moist surfaces of cavities like mouth, the cells of surface layer survive until they are rubbed off and keratin is not developed in these cells.

Transitional epithelium is also like stratified epithelium. The only difference in transitional epithelium and stratified epithelium is that the surface cells are round in shape and are capable of spreading out when the organ expands. Transitional epithelium is found lining the urinary bladder.

Glands: Glands are a special type of epithelial tissue. Glands have ability to manufacture essential substances from the basic material supplied by blood. The substances produced by glands are called as secretions of glands. Gastric glands can produce hydrochloric acid from sodium chloride provided by the blood. Exocrine glands pour their secretions through a duct. Secretions of majority of exocrine glands are enzymes. Endocrine glands are ductless glands and pour their secretions into the blood stream. Secretions of endocrine glands are hormones and reach the target sites through the blood stream. Pituitary gland in the skull and thyroid gland in the neck are two important examples of endocrine glands.

Connective Tissue:

Connective tissue supports and binds other tissues. There are three main components of connective tissue: Cells, intercellular substances called matrix and fibres. Matrix and fibres form the supporting material of our body. Fibres may be collagenous fibres or elastic fibres. Collagenous fibres originate from fibroblast cells. These coarse fibres occur in bundles. Elastic fibres are fine branching fibres with elastic like property. These are found layers surrounding the organs and in fibrous tendons joining the muscles.

Areolar tissue is loose connective tissue and is composed of loose network of collagenous fibres and elastic fibres with scattered groups of fat cells and fibroblasts. Areolar tissue forms a very thin, transparent and tough layer and is found between and around the organs of our body.

Adipose tissue is a fatty tissue. It is similar to areolar tissue but the spaces of the network of fibres are filled with fat cells. It is known for its food reserve in the form of fat globules in fat cells. It retains body heat and protects our delicate organs like kidneys and eyes being the poor conductor of heat.

Dense connective tissue or fibrous tissue is composed mainly of bundles of collagenous fibres embedded with fibroblasts. It is found in the ligaments and fascia.

Cartilage consists of cells known as chondrocytes, separated by fibres. There are no blood vessels in cartilage tissue. Cartilage is tough and flexible tissue and found in the trachea, covering heads of bones, joints, between body of vertebrae, and auricles of the ear and the epiglottis.

Bone is known as a specialized type of cartilage. In bone, the collagen is impregnated with calcium. It is tough and rigid due to collagen and calcium respectively and gives support to soft tissues of our body. The cells between the fibres are called osteocytes. Bone has very rich blood supply through blood vessels.

Muscular Tissue:

Muscular tissue provides movement to our body through its specialized function of contraction. Where there is movement in the body there must be muscular tissue. Voluntary or striped muscular tissue forms the flesh of our body and supports movement of our body. It consist long cells varying in size from a few millimeters to 30 centimeters depending on the length of muscle. Each muscle cell contains numerous threads like fibres called myofibrils. The diameter of myofibrils varies from 10 micrometers to 100 micrometers. Myofibrils are symmetrically striped in alternate dark and light bands throughout their length. Each fibril is enclosed in connective tissue sheath called sarcolemma. This muscle is under the control will and need energy for contraction. Energy for contraction is supplied by conversion of adenosine triphosphate (ATP) to adenosine diphosphate (ADP). Adenosine diphosphate (ADP) is again converted into ATP by utilization of energy provided by oxygenation of glycogen. Oxygen for energy generation is supplied by the blood supply to the muscle. Blood capillaries run through voluntary muscle cells to ensure adequate blood supply. Contraction of muscle is controlled through nerves. Ultrastructural view of voluntary muscle has been depicted in Fig-1.

Fig-1: Ultrastructural view of voluntary muscle, 6000x

Cardiac muscle is involuntary but irregularly striped also. It is found in the heart wall only and is different from any other skeletal muscle. Cardiac muscle is composed of short cylindrical fibres with centrally placed nuclei. Muscle fibres of cardiac muscle have no sheath but are bound together by connective tissue. It is not under the control of will but contracts automatically in rhythmic fashion throughout life. Rhythmic contractions are controlled by nerves.

Nervous Tissue:

Nervous tissue receives information from inside as well as outside of our body through network of nerves. It is specially designed tissue to carry impulses. Nervous tissue is composed of nerve cells called neurons and supporting network called neuroglia. Each neuron has a large cell body and short processes called dendrites. Dendrites bring impulses from other cells and tissues. There is a long process called axon, which carries impulses away from the cell body.

Who Could Be Labeled Hypertensive

High blood pressure and heart conditions are our top fear and health concerns. Not only high blood pressure (hypertension) but the low blood pressure (hypotension) could also harm our body. Who could be labeled hypertensive is a million dollar question? Anybody showing high blood pressure at a given moment could not be labeled as hypertensive. There is a procedure to be followed before labeling a person hypertensive and starting treatment. The variability of blood pressure increases with age and is more marked with systolic (upper limit) than with diastolic (lower limit) blood pressure. Even in normal individuals, the blood pressure varies throughout the day. Blood pressure may be highest in early morning hours and lowest at night. The measurement of blood pressure needs precision (there should be less than 3% variation in the measurements at regular intervals of time) and consideration of a number of factors before labeling a person as hypertensive. At the first stage the blood pressure should be measured in both arms, and all the subsequent measurements should be performed on the arm with high blood pressure. There is a scope for postural variations in blood pressure.

Blood pressure should always be measured in lying down or sitting position as well as in standing position. The experience of the physician measuring your blood pressure matters a lot. Postural hypertension is common in elderly patients and diabetics. There are many patho-physiological conditions associated with hypertension. Only an expert physician could make accurate diagnosis of hypertension. A number of readings on regular intervals for some days are required to label a person as hypertensive. All hypertensive do not need drugs as the life style modifications may help to control the blood pressure. There is a need to maintain normal body weight. Body Mass Index (BMI) is an important indicator to check the health disorders and health fitness. You can calculate BMI by the following formula:

BMI = [^{Weight (in Kg)}/_{Height (M}²₎]

If your BMI is between 18 to 25, you have normal body weight as per your height. BMI >25 indicates, you are over weight and BMI >30 indicates, you are fatty or obese. Salt restriction and diet modifications as per the advice of your physician may help you to stay fit.

Kidney Biopsy Evaluation and Clinicopathological Understanding

Kidney biopsy evaluation is must to understand the renal lesions in association with clinical picture. An adequate kidney biopsy should contain five to ten glomeruli and corresponding tubules and cortical tissue. The adequacy of needle biopsy of kidney depends on the expertise of nephrologist, performing the biopsy technique. Pathologist performs a methodic approach in the microscopic evaluation of kidney biopsy (renal biopsy). Patient may find microscopic description of glomeruli, tubules, blood vessels and interstitial tissue in the surgical pathology (histopathology) report of kidney biopsy. There are several categories of kidney diseases in which histomorphologic features obtained from renal biopsy may prove clinically helpful. Some such conditions are:

1. Nephritic syndrome and acute renal failure (Sudden impairment of renal function).
2. Nephrotic syndrome (Clinical picture characterized by marked edema, massive albuminuria, hypoproteinemia together with high blood cholesterol, normal blood pressure and absence of signs of renal failure)
3. Systemic diseases with associated renal disorders.
4. Evaluation of asymptomatic patients in whom routine laboratory examination has disclosed proteinuria (protein in urine) and/or microscopic hematuria (blood in urine).
5. Evaluation of prospective kidney donors, to be sure that they did not have any occult renal disease.
6. Assessment of renal microstructure of patients with renal transplant.
7. Evaluation of siblings of patients with hereditary renal disorders like Alport's syndrome.

The biopsies are classified by combining the clinical presentation, the histopathology, the immunopathology and ultrastructural pathology. There are several defined patterns of renal lesions and syndromes and these would be discussed separately.

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.

Adverse Drug Reaction and Kidney

Adverse Drug Reaction (ADR) is defined as any unintended and undesired effect of a duly prescribed drug which occurs at a dose used in humans for prophylactic, therapeutic or diagnostic purposes. All drugs taken externally or internally produce some undesirable effects along with their beneficial effects. Adverse events that occur as a result of drug use may range from local reaction, respiratory distress, renal lesions/damage or liver function impairment to serious life threatening condition. The liver and kidney are the organs which bear the brunt of majority of adverse drug reactions (ADRs) as these are associated with the drug metabolism and clearing from the body. The nature of the beneficial effects of a drug is predictable, but the nature of adverse reaction could be predictable to some extent otherwise unpredictable. The term drug here means any substance or product used to modify or explore physiological system and pathological states for the benefit of the patient/recipient. The health products considered to be drugs include vaccines, food supplements, blood and blood products, herbals, traditional or complementary medicines, pace maker devices and implants. Mismatched blood would cause transfusion reaction with life threatening implications. Blood products like platelet rich plasma (PRP) which is normally infused in patients suffering from Dengue virus infection may lead to the development of antibodies against human leukocyte antigens (HLAs) as platelets carry Major Histocompatibilty Complex, class-I (MHC class-I) antigens i.e. HLA-A, HLA-B, & HLA-C antigens at their surface and these antibodies may lead to lyses of platelets and thrombocytopenia (decreased platelet count) at a later stage.

Regulatory approval to market drug is usually based on the results of controlled clinical trials, as such, these short term studies in a specific population may not be sufficient to explore the ill effects of a particular drug. The ADR monitoring begins with the earliest administration of a drug to man and continues throughout, as long as a drug is on prescription list of clinicians.

Long term surveillance studies are also being undertaken to evaluate effectiveness and safety of a drug in various subpopulations such as, children, elderly patients and patients with associated ailments like impaired liver function, kidney disease and diabetes. In order to highlight the ADR events, the pharmacovigilance is important. The ADR events include the events due to non-compliance, drug interactions with co-administered drugs and drug over dosages and adverse effect of the drug per se. As per the data available to-date, about 6% of Emergency visits are related to ADRs and about 0.1% of these could be life threatening.

Can We Prevent Adverse Drug Reactions: Yes, a lot of these ADRs are preventable, most probably those resulting from mere ignorance of route of administration or non-compliance. There are ADR cases wherein patients have swallowed the tablets prescribed for intra vaginal infection.

How and Whom to Report ADR: Independent reporting can be undertaken by any one who is prescribing a drug, administering a drug or consuming a duly prescribed drug. This type of reporting is called Voluntary Reporting or Spontaneous Reporting. One should be ready with the following information while reporting ADR: Patient"s short name, age, sex, height, weight, trade name of drug, manufacturer, date of manufacture, date of expiry, mode of administration, type of reaction, duration of administration, route of use, date of reaction, date of recovery and associated medication etc. Adverse Drug Reaction should be reported to the Pharmacovigilance Center. There are National, Zonal, Regional and Peripheral Pharmacovigilance Centers in all the countries. The matter can also be reported to the Drug Controller General of the Country or reported directly to the United States FDA. For reporting the ADR or adverse events to International Regulatory Authority like US FDA one can use online reporting facility at the  website http://www.fda.gov/medwatch/ .  Go to the FDA-Medwatch website and visit the link-Medical Product Reporting for reporting adverse drug reaction or adverse events.

Pulse and Pulse Pressure

Pulse and pulse pressure are two wonderful parameters of circulatory system in association with cardiac cycle. Anybody and everybody can feel pulse, but there are very few who could recognize pulse and diagnose ailments in the light of pulse characteristics. Arterial pulse is a wave of increased pressure which is felt in the arteries when blood is pumped out by the heart. It may conveniently be felt at a point where an artery lies superficially over a bone. The most common is the radial artery at the front of the wrist. Pulse may also be felt at the temporal artery over the temporal bone or the dorsalis pedis artery at the bend of ankle. Pulse is the pressure transmitted from the aorta which travels faster than the blood. The pulse rate is directly associated with the cardiac cycle. The pumping rate of the heart varies in a normal person with reference to age and emotional state. Pulse rate may also vary in a person in relation to activity of the body like walking, running, sleeping or after taking food. If the pulse count is 72 per minute, the cardiac cycle would have occurred 72 times per minute.

The Cardiac Cycle: The pumping events which take place in the heart during handling of blood for the circulation to various organs and tissues of the body, are called cardiac cycle. As we know, the action of heart is controlled by sino-atrial-node (S.A.) and is described in two parts, systole or contraction and diastole or relaxation. Contraction of atria (upper chambers of heart) is called atrial systole and their relaxation is called atrial diastole. It is worth mentioning here that the left and right atria contract or relax simultaneously. The contraction and relaxation of ventricles (lower chambers of heart) is called ventricular systole and ventricular diastole respectively. It is pertinent to add that the ventricular contraction lasts 0.3 seconds and the relaxation phase is about 0.5 seconds. The only time, the cardiac muscle gets rest is during the periods of ventricular diastole. The heart keeps on beating continuously the day and night during the life.

Normal Pulse Rate in Relation to Age or Stage of Life

Stage of Life	Pulse: Beats/minute
New Born	135-140
During the first year of life	115-120
During the second year of life	105-110
At the age of 5 to 10 years	95-100
At the age of 11 to 18 years	80-90
Adults	60-80

Blood Pressure and Pulse Pressure: Arterial Blood Pressure is the force of pressure, which the blood exerts against the walls of blood vessels during circulation. The blood pressure varies during thecardiac cycle. The cardiac cycle has been discussed above. The blood pressure recorded as upper or systolic blood pressure and lower or diastolic blood pressure. During the ventricular systole, when the left ventricle forces the blood into the aorta, the pressure rises to a peak and is called systolic blood pressure. During the diastole the pressure falls and the lowest value it reaches is called diastolic blood pressure. The range of systolic blood pressure in an adult is 105 to 130 mm Hg (millimeters of Mercury) and the range of diastolic blood pressure is 60 to 80 mm Hg. As the age advances the range of systolic blood pressure increases as 130 to 150 mm Hg and diastolic blood pressure ranging from 80 to 90 mm Hg is considered normal. In women the blood pressure is 5 to 10 mm Hg less than in men. The difference in systolic anddiastolic blood pressure is called the pulse pressure and normally it should be around 30 to 50 mm Hg.

Renal Function in Infants

We know that the main function of kidneys is their ability to produce the glomerular filtrate and thereby concentrating the urine by way of absorption of water from the glomerular filtrate. The ability to concentrate urine is not well developed in infants. Indeed the ability to concentrate urine is partially developed after three months of life and fully developed renal function is acquired by the end of first year of life. The lack of concentrating urine is because the kidneys are not adapted to the action of antidiuretic hormone (ADH) of pituitary gland. The kidneys gradually start responding to the ADH and acquire full ability within one year. If the infants are not given sufficient fluids during the first five days of life they are sure to loose 10% of their body weight. Adults with well developed renal function are capable of conserving fluid by reabsorption. The lack of concentrating power in the kidneys of infants is probably due to imperfect development of loop of Henle. In infants the tubular function is lower than the glomerular filtration rate (GFR). The reabsorption of water in infants is 70% to 80% less than the adults. An infant, therefore, has a narrow margin of defense against the factors which decrease body fluids. The renalfunction in infants is helpless to regulate water balance when water is lost by any reason like fever, vomiting or diarrhea and leads to clinical implications. Infants need special care during fever, vomiting or diarrhea to offset any dehydration.

Renal Transplantation & BK Virus Nephropathy in Allograft Recipients

Renal transplantation is the ultimate surgical treatment to save the life of a patient with irreversible renal failure. As we do blood grouping and cross matching before blood transfusion likewise we have to do tissue typing and cross matching to check the histocompatibility between the kidney donor and kidney recipient (the patient). Like the blood group antigens the other genetic system is 'human leukocyte antigens' (HLA) system controlling the histocompatibility. The success of the organ transplantation is related mainly to these two genetic systems as the immune response of an individual is controlled by the genes linked to the major histocompatibility complex (MHC). Renal transplantation is generally carried out after testing the histocompatibility even then there are chances of rejection of transplanted kidney as the immune system of the recipient recognizes it as foreign material. To avoid the transplant rejection the allograft recipient is put on immunosuppressive therapy. The survival and adaptation of transplanted kidney could only be achieved through non-nephrotoxic immunosuppression. The adverse effect of immunosuppression is that it promotes viral infections. BK virus nephritis (BKN) in recipients of renal allograft has been on the rise. Despite increased incidence, therapeutic options remain limited and progression of disease often leads to allograft failure (transplanted kidney failure). BK virus (BKV) replication in kidney transplant recipients may progress from asymptomatic viruria (viruses in urine) to progressive allograft dysfunction leading to allograft failure. BK virus infection may also lead to systemic infection and bladder cancer. The diagnosis of BKN could be achieved on the histology examination of the allograft biopsy by specific immunohistochemical (IHC) staining for BKV. The clinical and functional parameters often correlate with the duration and histological progression (stage) of nephropathy. Over or intense immunosuppression leads to complications. In the absence of specificantiviral therapy, the treatment of choice is to reduce the dose of maintenance immunosuppressive therapy. Non-nephrotoxic immunosuppressive drugs are the need of the hour for effective immunosuppression and renal allograft survival.

Tags: allograft failure, allograft recipient, antiviral therapy, histocompatibility, immunosuppressive therapy, kidney donor, kidney recipient, non-nephrotoxic immunosuppression, transplant rejection

Internal Environment & Renal Physiology

Internal Environment: The body is made up of organs and tissues each composed of cells and fibers that constitute their histology. Water with its solvents needed for the health of the cells is termed as body fluid and this fluid is partly inside and partly outside the cells. Water constitutes about 70 per cent of fat free body weight. Water is the fabric of everything that lives. The body of a baby contains mostly water, whilst the old man or woman shrivels up like a wilted plant. We are completely immersed in water during the first nine months of life in the mother's womb. Water is involved in the health, disease and death. Loss of water leads to dehydration and may cause death if not corrected. Retention of water leads to edema and may cause death if remedial action is not taken. For each cell in the body the same conditions prevail as for the single-celled creatures fixed on the bed of a flowing stream which brings their food and oxygen and carries away their waste material. In our body water or the body fluid is controlled in the two major compartments: (1) intracellular compartment for intracellular fluid (2) extracellular compartment for extracellular fluid. The extracellular fluid is of two subtype (1) interstitial fluid (2) blood plasma. Intracellular fluid makes up about 40 to 50 per cent of the body weight and bulk of it being contained in muscles. Extracellular fluid represents about 20 per cent of the body weight, of which 15 per cent is interstitial fluid including lymph and 5 per cent constitute the blood plasma. The interstitial fluid constitutes the real internal environment. It is the adjustable segment in the total water content of the body. Its volume and solutes are regulated by the kidneys, lungs, endocrine glands, and are influenced by sweat glands and gastrointestinal tract. The blood plasma is in equilibrium with the interstitial fluid. Both the vascular and intracellular compartments contain a lot of protein. The normal intake of water in an adult is about 2500 ml. About 2100-2200 ml of this is taken by mouth as food and pure water and rest is the endogenous water from cellular oxidation. Renal Physiology: The word renal pertains to kidney in medical terminology. Water regulation in our body is achieved by water loss through four routes: (1) intestine (2) lungs (3) skin and (4) kidneys. Kidneys play a major role in water regulation as these excrete 50 to 70 per cent of excess water. Major functions of kidneys are: (a) excretion/elimination of excess water from body (b) excretion/elimination of waste products of metabolism e.g. urea and creatinine (c) excretion/elimination of foreign substances such as drugs (d) retention of substances necessary for normal body functions (major substances are proteins, amino acids and glucose) (e) regulation of electrolyte balance and osmotic pressure of the body fluids. Sodium ions, potassium ions, bicarbonate ions and chloride ions are major electrolytes. Urea is the main product of protein metabolism in the body. Removal of amino groups from amino-acids, from which urea is formed, takes place in the liver. Urine urea estimations are most commonly carried out as part of renal efficiency tests. A high concentration of urea in the urine shows that the kidneys possess a good concentrating power. However, in cases where there is increased blood urea due to non-renal or pre-renal factors, urine urea may be quite high. On an average concentration of urea in urine should be 2.0 per cent over the day. The total urea excretion in an adult is about 30 grams daily. At least 1500 ml of water must be excreted by kidneys daily to carry the solids which have to be eliminated. There is a pair of kidneys in our body to accomplish the above task. The kidney is the organ concerned with the regulation of the volume and composition of body fluids. Each kidney contains over 1000,000 functional units called nephrons. Each nephron consists of (a) glomerulus with its afferent and efferent arteriole (b) proximal convoluted tubule (c) loop of Henle (d) distal convoluted tubule and (e) collecting tubule. The structure of the glomerulus is that of a filtration mechanism. The afferent arteriole divides into 3 or 4 branches, which gives the lobulated appearance to the glomerular tuft. Each branch gives rise to 40 to 50 capillary loops, which probably do not anastomose with one another. The diameter of efferent arteriole is only half of that of afferent arteriole and the efferent arteriole splits up into a huge network of capillaries containing blood that is highly viscous by reason of the preceding loss of water. The viscous blood moves slowly, so raises the pressure in the glomerular tuft and thus facilitate filtration. The glomerular tuft consists of four main components: (i) the endothelium lining the capillaries (ii) the basement membrane which separates the endothelium from (iii) the epithelium and (iv) the mesangium. Mechanism of Renal Function: Every minute about 1000 ml of blood containing about 500 ml of plasma flows through the glomeruli of kidneys and about 100 ml of it is filtered out as raw-urine called glomerular filtrate. The plasma containing all the salts, glucose and other small substances is filtered in the glomerular filtrate. The cells and plasma proteins are too big to pass through the pores of the filter and stay behind in the blood stream. The glomerular filtrate then passes through the real tubules and 85% of it is absorbed automatically by the proximal tubules, where essential substances are reabsorbed. The fate of remaining 15% depends upon the degree of further reabsorption of water in the distal tubules. The reabsorption is controlled by antidiuretic hormone (ADH) released from the posterior pituitary gland (an endocrine gland). Loss of ADH results in defective reabsorption of water in the distal tubules and causes diabetes insipidus. An increase in the electrolyte osmotic pressure (osmolality) of the extracellular fluids results in an increased release of ADH with an increased water reabsorption in distal tubules. Conversely any decrease in the osmolality will lead to opposite effect. This complex controlling mechanism is termed as neurohypophysial-renal axis. Just as the electrolytic osmotic pressure of the extracellular fluid is controlled by the ADH, the volume of that fluid is controlled by aldosterone from the adrenal gland. The ADH regulates the retention or excretion of water and the aldosterone regulates the reabsorption of sodium and thus the retention of water. Thus the secretion of urine is accomplished in three steps: (a) glomerular filtration. (b) tubular reabsorption and (c) tubular secretion. By comparing the amount filtered by the glomeruli per day with the amount usually excreted in the urine we can see how selective is renal function? Daily about 150 liters of water is filtered and about 1500 ml is excreted; about 750 grams of salts are filtered and 15 grams are excreted; about 150 grams of glucose are filtered and no amount is excreted and about 50 grams of urea are filtered and about 30 grams excreted.

Human Anatomy & Physiology: Introduction

Anatomy: The study of the structure of the human body and the relationship of its constituent parts to each other or one or the other is called general anatomy. In regional anatomy, a geographical study is made and each region e.g. arms, legs, head, ears, eyes. nose, trunk, genitalia etc., is being studied in terms of its components. Different regions of human body do have some common structures such as bones muscles, nerves and blood vessels. An anatomical region performing a particular function is called a system. There are a variety of systems in human body. The systematic study of these systems is called the systematic anatomy. The functional relationship of different parts or organs of the body is called the functional anatomy. The anatomical features of our body which could be appreciated by naked eye are covered under the macroscopic anatomy and the finer structures which could be revealed with the help of a microscope are termed as microscopic anatomy. Closely allied to the anatomy are histology and cytology, the study of tissues and cells respectively. Human body is studied from the erect position with the arms by the sides and the palms of the hands facing forwards, the head erect and eyes looking straight in front. This is the universal description of anatomical position. Various parts of the body are described in relation to certain imaginary lines or planes. The median plane runs through the center of the body. Any structure which lies nearer to the median plane of the body is said to be medial to the other. For example the inner side of the thigh is described as the medial aspect and the outer as the lateral aspect. The terms internal and external are used to describe the relative distance of an organ or structure from the center of a cavity. The ribs for example have an internal and external surface. The terms superficial and deep are used to denote relative distance from the surface of the body. The terms superior and inferior are used to denote the positions relatively high or low in relation to trunk and the terms proximal and distal are employed to describe nearness to or distance from a given point particularly in relation to limbs. For example the proximal phalanges are nearer to the wrist and the distal ones are the farthest away. When three structures are running from the medial plane of the body outwards, they are described as being placed in medial, intermediate and lateral position. The terms anterior and posterior are synonymous with ventral and dorsal. These terms are only adapted to man in the erect attitude or anatomical position. For example the anterior and posterior tibial arteries lie in front and back in the leg. In describing hand the terms palmar and dorsal are used instead of anterior and posterior and in describing foot the terms plantar and dorsal are employed. Many parts of the body are symmetrically arranged. For example left and right limbs are similar. The eyes, ears lungs and kidneys too are left and right and symmetrically arranged. There is also a good deal of asymmetry in the arrangement of the body. The spleen lies entirely on the left side; the pancreas lies partly on each side and the larger part of the liver lies on the right side. Physiology: It is the study of the internal functions of the normal human body and closely linked to the study of internal functions of all the living creatures in the subject of biology. The body is made up of many tissues and organs each having its own particular function to perform. The cell is the smallest unit of the body of which all the body parts are comprised. The cells and/or organs are adapted to perform the special functions in a system. The cells of the nervous system and muscle are very specialized. Other cells such as those in the connective tissue are not so highly developed as compared to muscle and nerve cells. Bioenergetic pathways, cellular interactions and their biochemical products such as enzymes and hormones are at the core of the physiology.