Human Anatomy & Physiology and Renal Disorders

How does kidney develop during gestation ?

2011-04-07T07:26:00.002-06:00

The students of renal pathology, medicine, nephrology and urology would always like to imbibe knowledge about the origin and development of kidney to understand the pathogenesis of developmental kidney diseases. The urogenital system is derived and developed from the intermediate mesoderm and the primitive urogenital sinus of the cloaca. The ureteral bud (UB) develops from the Wolffian duct (WD) at approximately 28 days of gestation. The ureteral bud (UB) initiates the epithelialization/tubulogenesis of the metanephric mesenchyme (MM) while itself undergoes branching to form and adult kidney. Much knowledge about the development of kidney could be gathered from the experimental studies using mouse embryo. In the mouse the ureteral bud (UB) invaginates from the caudal end of the Wolffian duct (WD) and grows out into the adjacent metanephric mesenchyme cells.

The metanephric mesenchyme cells comprise of tubule precursors, endothelial precursors and stromal cells. These loose metanephric mesenchyme cells aggregate to form "pre tubular aggregate" which undergoes structural change to form a 'tear-drop' like structure called renal vesicle (RV). The renal vesicle rapidly undergoes mesenchymal-epithelial transformation (MET) to form a comma-shaped structure. The comma-shaped structure formed by the mesenchymal-epithelial transformation of RV undergoes series of tightly controlled transformations and form a very complex S-shaped body. The lower part of the "S" (of S-shaped body) gives rise to podocytes and Bowman's capsule. The upper part of the "S" (of S-shaped body) forms the distal convoluted tubule of the nephron. The middle segment of the "S" (of S-shaped body) gives rise to the proximal convoluted tubule and the loop of Henle of the nephron. Each tip of the ureteral bud gives rise to a nephron. After 20-22 weeks of gestation in humans, the ureteral bud stops branching but the nephron induction continues for other 8 to10 weeks, leading to arcade formation wherein each tip of the ureteral bud has 9-11 nephrons attached to it. The arcade formation is considered as the last step of the nephron induction in humans. However, in mice the process of nephron induction continues for about two weeks after birth. The mouse kidney has single papilla and carries around 35,000 nephrons/kidney. Human kidneys roughly contain 6x10⁵ to 1.1x10⁶ nephrons/kidney.

The knowledge of developmental stages of kidney is important to understand the pathogenesis of developmental cystic kidney diseases like renal agenesis (no kidney developed), renal hypoplasia (under developed kidneys) and renal dysplasia (abnormally developed kidneys). Renal hypoplasia (reduction in total number of nephrons), renal dysplasia (abnormally developed kidney due to failure of UB to induce formation of nephrons) and segmental hypoplasia are the major developmental cystic kidney diseases. Simple hypoplasia leads to very small sized kidney called miniature kidney. Miniature kidney would represent reduction in renal calyces with glomerular disarray and reduction of tubules, medulla & cortex. Segmental hypoplasia presents during the late childhood with renal insufficiency associated with hypertension and recurrent urinary tract infection (UTI). Patients with segmental hypoplasia have small sized kidney (s) with a transverse groove on the capsular surface at the upper pole, overlying an area of marked parenchymal thinning. Areas of segmental hypoplasia represented by scarred zones with no glomeruli, atrophic tubules and thick walled blood vessels could be revealed under light microscopy of histological sections.

Podocytes and Podocytopathies

2010-07-27T09:16:00.004-06:00

Kidneys play a vital role in excretion and water/fluid volume regulation. Glomeruli are the filtration units of nephrons in the kidneys and these contain cellular and non cellular components in addition to capillary space and urinary space. Podocytes (cells with pedicles or feet) are post-mitotic epithelial cells resting in the urinary space of glomeruli. The number, size and morphology of podocytes are influenced by biochemical, immunological, therapeutic and genetic factors. According to the old classification of renal disorders, the patients having nephrotic syndrome can be grouped into two groups: (1) Non-immune complex mediated nephrotic syndrome, and (2) Immune complex mediated nephrotic syndrome. Now, patients with non-immune complex mediated nephrotic syndrome may have three possible diagnoses:

Minimal change disease: Wherein morphologic evaluation of the renal biopsy (kidney biopsy) by light microscopy does not exhibit any glomerular damage. However, extensive effacement of foot processes of podocytes can be revealed by electron microscopy.
Focal segmental glomerulosclerosis (FSGS): Wherein segmental sclerosis/solidification of the glomerular tuft, along with hyalinosis and adhesion of tuft to the Bowman's capsule is exhibited on the renal biopsy (kidney biopsy) evaluation by light microscopy. In these cases, variable degree of foot process effacement can be revealed by electron microscopy.
Collapsing glomerulopathy: FSGS associated with the rapid deterioration of renal function was described as "Malignant FSGS" in 1978. During HIV pandemic in 1980's the associated nephropathy showing collapse of glomerular capillary wall along with increased cellularity in the urinary space was termed as HIV associated nephropathy (HIV-AN). Collapsing glomerulopathy was first time described in non-HIV patients in 1986 by Weiss and associates.

Now we know that podocyte number and effacement of their foot processes due to genetic or biological factors are very much associated with the primary nephrotic syndrome or proteinuric renal disorders. The etiology and pathogenic mechanisms are known to influence the morphologic diagnosis of podocytopathies. Podocytopathies are proteinuric renal disorders caused due to intrinsic or extrinsic podocyte injury exhibited by variable degree of foot process effacement and altered genotypic and/or phenotypic expression. Podocytes may reorganize their foot processes (altered cell morphology without change in cell count/number). There may be decreased number of podocytes (podocytopenia) if the injured podocytes die. There may be podocyte developmental arrest as seen in congenital nephrotic syndrome of Finnish type (CNF). Podocytes may dedifferentiate and proliferate under genetic, immunological, viral or therapeutic insult and re-enter the cell cycle despite the fact that podocytes are post-mitotic cells. Two electron micrographs are exhibited below to illustrate the normal (Figure-1) and increased number(Figure-2) podocytes in the urinary space of glomeruli from different cases.

Figure-1: Electron micrograph through a portion of glomerulus from a case of minimal change disease showing normal number of podocytes. (GBM: glomerular basement membrane, CL: capillary lumen, EnC: Endothelial cell, US: urinary space and Pc: podocyte)

Figure-2: Electron micrograph through a portion of glomerulus from a case of podocytopathy showing increased number of podocytes. (GBM: glomerular basement membrane, CL: capillary lumen, US: urinary space and Pc: podocytes)

End Stage Renal Disease: Management Issues

2010-06-30T09:14:00.002-06:00

The patents with end stage renal disease (ESRD) need regular hemodialysis or renal replacement (kidney transplantation) for survival. Both the hemodialysis and kidney transplantation are very costly procedures for the patients and their families. The patients with chronic kidney disease (CKD) are at high risk of developing end stage renal disease (ESRD). Chronic kidney disease (CKD) is diagnosed on the basis of persistently high level of serum creatinine (more than 1.8 mg/dl). As a rough estimate one person in every 150 people may be suffering from CKD and around 3% of CKD cases are sure to develop ESRD. In a country with 500 million population there could be more than 100,000 patients with ESRD and around 3.5 million patients with CKD. Half of the projected figures could be annual incidence.

It has been worked out that the cost of annual dialysis is much more than the renal replacement therapy (RRT). Though the renal transplantation (kidney transplantation) is the more effective and sustainable therapy but the economic factors, availability of kidney and facilities retard its scope. The annual cost of dialysis may range from US$5000 to 10,000 depending on condition of the patient; whereas the one-time cost of renal transplantation at government funded hospitals in most of the developing countries ranges from US$1500 to US$2000 and annual cost of immunosuppressive therapy would be around US$3000 to 4000. As compared to patients on dialysis, the quality of life for the patients of renal transplantation is extremely better. A renal transplantation at an optimum time minimizes the graft maintenance costs and maximizes the graft survival. The patient can return to productive life within a year after renal transplantation. My friend AB, who got renal transplantation around 10 year ago, is living a normal life.

Kidney Diseases caused by Plasma Cell and B-Cell Disorders

2010-06-29T06:20:00.002-06:00

A wide spectrum of clinical manifestations may result from the renal involvement with disorders of B-cells (B lymphocytes) and plasma cells. B lymphocytes and plasma cells are responsible cells for providing acquired and active immunity to our body through production of antibodies (immunoglobulins) against infectious organisms. But the disorders related to the function and number of B-cells and plasma cells lead to excessive or incomplete production of immunoglobulin molecules leading to deposition of immunoglobulins or their components in the kidneys. Deposition of immunoglobulins or their light or heavy chains cause a variety of renal disorders affecting glomeruli, extraglomerular blood vessels, tubules and interstitium. Two major classes of such diseases are as under:

A) Glomerular and vascular diseases

Glomerular and vascular diseases caused by B-cell and plasma cell disorders include amyloidosis (AL, AH and AHL type), light chain deposition disease (LCDD), heavy chain deposition disease (HCDD), light & heavy chain deposition disease (LHCDD), cryoglobulinemic glomerulonephritis (type I & II), monoclonal immunotactoid glomerulopathy and proliferative glomerulonephritis with monoclonal IgG deposits.

B) Tubulointerstitial diseases

Cast nephropathy and light chain proximal tubulopathy are the tubulointerstitial diseases caused due to renal involvement in multiple myeloma (Plasma cell disorder).

Important Investigations

Routine urine examination along with microscopy, blood biochemistry to ascertain renal functions and kidney biopsy evaluation by light, fluorescence and electron microscopy is required to establish an accurate diagnosis of renal disorder in patients affected by B-cell and plasma cell disorders.

The Role of Lymphatic System in Cellular Nutrition and Immunity

2010-04-19T07:11:00.003-06:00

Every single cell in our body tissues and organs needs nutrition and clearing away of its waste products for survival and vital functioning. Lymphatic system plays a vital role in the circulation and regulation of interstitial fluid or tissue fluid. As the blood passes through blood capillaries in the tissues; plasma or tissue fluid oozes out through the porous walls of blood capillaries. The tissue fluid or the interstitial fluid fills the spaces or interstices between the cells of different tissues and organs. The blood circulates only through the blood vessels but the tissue fluid circulates through the actual tissue and carries food, oxygen and water from the blood stream to each individual cell and carries away its waste products like carbon dioxide, water and urea and pours out all these in the blood stream for final disposal. Lymphatic system is pump less system and runs parallel to the circulatory system and is comprised of following components.

Components of the Lymphatic System:

Lymphatic capillaries: These are hair like fine vessels in the spaces in the tissues and gather up excess fluid from the tissues. Lymphatic capillaries unite to form lymphatic vessels.
Lymphatic vessels: These are similar to veins in structure but carry lymph instead of blood. They are finer and more in number than the veins and are provided with unidirectional valves, to prevent the back flow of lymph or the tissue fluid. Lymphatic vessels are present in all tissues except the central nervous system. These run in the subcutaneous tissue and pass through one or more lymphatic nodes.
Lymph nodes or lymphatic nodes: Lymph nodes are numerous in number and vary in size from a pinhead to an almond. Lymphatic vessels which bring lymph to them are called afferent vessels. afferent vessels divide up within the node and discharge the lymph into the mesh of the lymph node. The lymph is collected again into a fresh vessel known as efferent vessel, which ultimately empties into a lymph duct. Lymph nodes consist of cells similar to white blood cells and are encapsulated by connective tissue. Lymph nodes filter out bacteria, provide fresh lymphocytes for the circulation and also produce some antibodies and antitoxins and boost up immunity.
Lymphatic ducts: These are major lymph channels. There are two lymphatic ducts, the thoracic duct and the right lymphatic duct. The thoracic duct is larger and all the lymphatic vessels from the lower limbs, and abdominal and pelvic organs empty into it. The thoracic duct empties into the left subclavian vein. The right lymphatic duct is comparatively small vessel formed by union of lymphatic vessels from the right side of the head, thorax and the right upper limb at the root of the neck. The right lymphatic duct is about one centimeter long and empties into the right subclavian vein.
Spleen, the master lymphatic organ: The spleen is the largest nodule of the lymphoid tissue. It is deep purplish red in color and lies high up at the back of the abdomen, on the left side behind the stomach and is enclosed in a capsule of connective tissue. It is composed of fibrous meshwork filled with pulp like material known as splenic pulp. It is a source of fresh lymphocytes for the blood stream, an area for the destruction of worn red blood cells (RBCs) and a legendary organ for fighting out circulatory infections.

Functions of Lymphatic System:

Restoration of constant stream of fresh interstitial fluid or lymph in the interstitial spaces as depicted in the diagram given below:

Regulation excess proteins in the tissue fluid and passing that back to the blood stream.
The lymph nodes filter out the bacterial infection and harmful substances from the lymph before pouring it back into the blood stream.
Lymphatic vessels in the abdominal organs assist in the absorption of digested fat.
Lymph nodes also produce fresh lymphocytes for the circulation.

Disseminated Intravascular Coagulation: Pathophysiology and Diagnosis

2010-04-13T07:40:00.002-06:00

Disseminated intravascular coagulation (DIC) should be recognized as consumptive coagulopathy since it is not a primary disease. It is always a complication of an underlying disease that not only triggers it but also fuels it. Disease or trauma associated tissue injury with a release of thromboplastic material into the circulation is the major cause of DIC. The clotting system as well as the fibrinolytic system (bleeding system) are involved in the pathophysiology of disseminated intravascular coagulation. Clinically, coagulopathy could be recognized as acute hemorrhagic DIC and subacute or chronic DIC. A third type of consumptive coagulopathy could be recognized with fibrinolysis. Disseminated intravascular coagulation is an acquired coagulation disorder in which formation of microthrombi, consumption of coagulation factors, activation of fibrinolysis and a bleeding tendency may occur consecutively or simultaneously. In brief, it is a systemic pathologic process characterized by a disseminated (generalized) activation of clotting and/or fibrinolytic systems in the circulatory system of the patient. The common pathway of all inciting causes (independent of etiologies) is the formation of thrombin and plasmin (fibrinolysin).

Thrombin plays a vital role in DIC. The alterations of coagulation system detected in the laboratory during DIC reflect the multiple actions of thrombin. Thrombin cleaves fibrinogen to release fibrinopeptide-A (FPA) and fibrinopeptide-B (FPB). Subsequently the remaining fibrin monomers may combine with fibrinogen and circulate as soluble fibrin monomer complexes (SFMC) or polymerize to form fibrin microthrombi. Thrombin also activates factor XIII (fibrin stabilizing factor) to form factor XIIIa, and the factor XIIIa creates bridges, linking any two adjacent monomers of fibrin. Thrombin activates procoagulant cofactors, factors VIII and V, to participate in the process of its own generation. Thrombin also plays a regulatory role by activating protein-C, which acts as an anticoagulant to inactivate factors VIIIa and Va. In brief, thrombin alone accounts for decreased levels of fibrinogen and factors II, V, VIII & XIII and decreased count of platelets in patients with DIC.

Screening tests for DIC are: Prothrombin time (PT), Partial thromboplastin time (PTT), Fibrinogen assay and Platelet count. Platelet count, PT, Fibrinogen assay and Determination of Antithrombin-III (AT-III) should always be done to diagnose consumptive DIC.

Confirmatory tests for DIC are: Fibrin monomer assay (it measures thrombin cleaved fibrinogen), Detection of fibrin split products (i.e. detection of plasmin-cleaved fibrinogen or fibrin) and Detection of D-dimer (i.e. detection of plasmin-cleaved cross-linked fibrin). Activation of coagulation could be assessed by the detection of soluble fibrin monomer complexes(SFMC). Detection of fibrinogen degradation products (FDPs) is indicative of reactive fibrinolysis.

Medical conditions which may lead to 'Acute Hemorrhagic DIC':

Infections: Typhoid fever, Gram-positive and Gram-negative septicemia, viremia, parasites etc.
Tissue injury: Renal allograft rejection, snake bite, heat stroke, brain injury, crush injury, necrotizing enterocolitis, hemolytic transfusion reaction etc.
Malignancy: Acute promyelocytic leukemia.
Obstetric: Amniotic fluid embolism, eclampsia, abruptio placentae, hypertonic saline abortion.
Other causes: Severe liver disease.

Medical conditions which may lead to 'Subacute Chronic DIC':

Vascular: Chronic renal disease, connective tissue disorders, venous thrombosis, arterial embolization, pulmonary embolus etc
Obstetric: Retained dead fetus.
Malignancy: Mucin-producing adenocarcinomas.

Nephritic Syndrome and Urine Examination

2010-02-28T23:18:00.002-07:00

Examination of fresh urine as part of routine physical examination may show the presence of protein, blood or pus cells in the patients affected by nephritic syndrome. In many cases the renal disease is occult and is often detected during the routine physical examination. It is important to understand that acute nephritis, nephrotic syndrome and renal failure may occur either as a result of intrinsic disease of the kidneys or in association with a systemic disease. Metabolic and functional disturbances such as hypertension, uremia (elevated level of urea in blood), or anemia may cause occult renal disease.

Hypertension along with mild edema (swelling), apparently as suborbital puffy eyes is characteristic clinical feature of nephritic syndrome. Hematuria (blood in urine) with or without proteinuria (protein in urine), oliguria (low urinary output) and impaired excretory function are other characteristic features. The urine may be red or brownish to smoky brown in color in patients affected by nephritic syndrome. Microscopic examination of fresh urinary sediment in these patients may reveal very high count of dysmorphic red blood cells (dysmorphic RBCs). The detection of RBCs in the urinary casts signifies that the hematuria comes from the kidneys (renal parenchyma). Proteinuria may vary from 0.3g to 3.0g daily. Urinary sodium level (Na⁺ level) tends to be low due to sodium retention as a result of impaired excretory function by the kidneys. Retention of sodium and water in these patients lead to increased circulatory blood volume and cause hypertension. The uncontrolled hypertension may lead to cardiomegaly along with mild renal pain. Patients affected by nephritic syndrome need renal biopsy examination and specialized treatment under the supervision of a nephrologist.

Diagnosis and Type of Kidney Disease – Investigations and interpretations

2010-02-24T05:37:00.002-07:00

Correlation of clinical and laboratory features is must for an accurate diagnosis and type of a kidney disease (renal disease) or glomerulonephritis. An experienced nephrologist can make a diagnosis of glomerulonephritis from thorough history, physical examination, urine examination and microscopy of urinary sediment. The assessment of presenting features of the patient, such as nephritic or nephrotic syndrome is important. However, the decision on the type of glomerulonephritis can not be based on the clinical and laboratory features; as the nephrotic syndrome may occur with any histological glomerulonephritis, and nephritic syndrome is the outcome of proliferative glomerulonephritis. So the ultimate diagnostic tool is renal biopsy and its light and fluorescent microscopy as well as ultrastructural study by electron microscope.

The interpretation of clinical features in the light of histological diagnosis of renal biopsy helps the clinician to detect any systemic disease associated with the renal disease (kidney disease). Majority of the patients with suspected glomerulonephritis need renal biopsy evaluation. However, in children with nephrotic syndrome; if there is no microscopic hematuria (blood in urine) and red cells' or granular casts, renal biopsy procedure may be avoided initially. In patients, who do not respond to steroid therapy; renal biopsy investigation is must. There are around one million glomeruli (1x10⁶ glomeruli) in each kidney and at least 5 glomeruli should be included in the renal biopsy evaluated histologically to achieve a diagnosis of glomerulonephritis.

Radiological and laboratory investigations in glomerulonephritis:

The clinical presentation, urine-analysis and microscopy findings, and presence of a normal upper & lower urinary tract on intravenous pyelography (IVP: a radiological investigation) or ultrasonography without any renal scarring could be indicative of glomerulonephritis, but there could be a need for renal biopsy.

Immune system associated investigations:

Our body is equipped with a multitasking immune system composed on lymphocytes, antibodies and complement system. The immune system always defends our body internally against a variety of infections and pathological conditions; and assessment of its components and abnormal products produced by it helps in diagnostic conclusions. Complement system of our body is composed of 9-components and boosts the body defense in association with cellular components. The blood level of complement components C3, C4 and C1q may be reduced or normal in some renal diseases. Low total serum complement, C3, C4 and C1q levels are observed in glomerulonephritis associated with circulatory immune complex disorders like systemic-lupus erythematosis (SLE), bacterial endocarditis and serum sickness. Normal levels of C4 and C1q but decreased level of C3 is generally observed in membranoproliferative glomerulonephritis (MPGN) and dense deposit disease of the kidney.

Following investigations are considered important to ascertain the diagnosis and type of glomerulonephritis:

Investigations for likely diagnosis of glomerulonephritis:

Clinical presentation
Urine analysis (proteinuria, hematuria and electrophoresis)
Microscopy of urinary sediment
Intravenous pyelography (IVP: Radiological investigation)
Abdominal ultrasonography.

Investigations for likely type of glomerulonephritis:

Estimation of serum complement components' level
Detection of circulating immune complexes
Detection of auto-antibodies such as anti-nuclear antibodies (ANA), anti-DNA antibodies and anti-glomerular basement membrane antibodies (anti-GBM antibodies)
Renal biopsy

Investigations for assessing the implications of glomerulonephritis and monitoring the effect of therapy:

Determination of 24 hour urinary protein
Determination of level of serum proteins
Determination of serum cholesterol and/or lipid profile
Determination of serum creatinine, blood urea and serum electrolytes.

Diabetic Renal Disease

2010-01-27T06:28:00.004-07:00

Diabetes is a multidisciplinary disease, as many systems may need medical care. Optimal control of blood glucose level is essential to prevent diabetic complications like neuropathy, diabetic renal disease (diabetic nephropathy) and diabetic disease of eyes (diabetic retinopathy). There may also vascular and cardiac complications associated with diabetes in some patients. Diabetes may be insulin dependent (type-I) or non-insulin dependent diabetes mellitus (NIDDM or type-II diabetes). Diabetic patients develop progressive thickening of glomerular basement membrane (GBM) of glomerular capillaries along with widening of mesangium in majority of glomeruli of their kidneys. The unusual thickening of GBM and widening of mesangial area of the bundles of glomerular capillaries lead to narrowing down of functional lumen of these capillaries, there by causing pathophysiological change in the glomerular function affecting the glomerular filtration rate (GFR). Ultrastructural features of glomerulus affected by diabetes have been illustrated in Figure-1b below in comparison to normal features depicted in Figure-1a at the same magnification.

Figure-1a: Electron micrograph of a portion of the tuft of a normal glomerulus depicting normal GBM: glomerular basement membrane, Mes: mesangial area, EpC: epithelial cells or podocytes, CL: capillary lumen and US: urinary space.

Figure-1b: Electron micrograph of a portion of the tuft of a glomerulus affected by diabetes, depicting thickened GBM: glomerular basement membrane, Mes: mesangial area (widened), EpC: epithelial cell or podocyte, CL: capillary lumen (narrowed down) and US: urinary space. Note: Just compare the feature with the electron micrograph shown in figure-1a.

Uncontrolled diabetes may lead to global sclerosis of glomeruli resulting in 'end stage renal disease' (ESRD) or renal failure. Retinopathy, neuropathy and vascular and/or cardiac disease accompanying ESRD may complicate the management of prospective patients. So, diabetic patients are advised to comply sincerely with the advice of general physician or diabetologist to avoid diabetes associated complications, otherwise they may require the consultation of a nephrologist, ophthalmologist and cardiologist to manage the complications. The treatment of diabetes associated renal disease should ideally be introduced when 'traces of albumin in urine' (microalbuminuria) and polyuria (increased urine output) are detected in diabetic patients. Optimal control of diabetes by insulin and/or diet and exercise is must to avoid complications. Once massive proteinuria (excretion of >3.5 g protein per 24 hours) is developed in diabetic patients, the cost of reversal of complications may be many times higher. Just be health conscious and stay healthy & live-long.

Various Causes of Acute Renal Failure

2009-11-27T05:21:00.002-07:00

The cause and/or precipitating factor of acute renal failure (ARF) is always responsible for the effectiveness of therapy and supportive care techniques including hemodialysis. A rapid loss of renal function is exhibited through elevated levels of serum creatinine and blood urea due to fall in the clearance of these nitrogenous wastes by the kidneys in all cases of ARF. It has been observed that a loss of 50% of glomerular filtration rate (GFR) leads to significant elevation of the level of creatinine in the blood with a decrease in the urine output (oliguria). There could be three types of causes and implicating factors of acute renal failure: 1) Pre-renal, 2) Renal and 3) Post-renal. In pre-renal type ARF causes are the physiological factors or conditions which lead to poor renal perfusion and severe impairment of renal function. Hemorrhage in gastrointestinal tract (stomach and intestines) and other internal spaces, sepsis, hepatic failure (liver failure), over compliance of antihypertensive drugs or non-steroidal anti-inflammatory drugs (NSAID), arterial or venous thrombosis and intra-vascular hemolysis due to transfusion reactions, are the major pre-renal causes of ARF.

Acute tubular necrosis (ATN), rapidly progressive glomerulonephritis (RPGN), post infection glomerulonephritis and interstitial nephritis are some major renal causes of ARF. Pre-renal factors and use of nephrotoxic drugs may also be associated cause of ATN. Some viral infections, drugs, multiple myeloma, lymphoma and granuloma may cause interstitial nephritis leading to renal type ARF.

Post-renal type ARF is caused by intra-tubular obstruction due to fibrosis, stones or tumors. Every case of acute renal failure needs urgent investigations to establish the cause and efficient mode of supportive care and line of treatment. A comprehensive physical examination is required to look for possible causes of ARF and planning the investigations to classify the type of ARF. By timely diagnosis and treatment, renal function could be restored in majority of cases of pre-renal type acute renal failure.

Nephrotic Syndrome and its Serious Effects

2009-10-30T06:20:00.003-06:00

Urine examination shows critical abnormalities in nephrotic syndrome. The urine may froth if passed in a container or if shaken in a test tube. The dipstick test always shows extensive excretion of protein in urine. Total excretion of protein per day should be measured in 24-hour's collection of urine. The nephrotic syndrome is the consequence of prolonged massive proteinuria (excretion of protein in urine). The proteinuria exceeds 3.5 g/24-hours in adults or 50 mg/kg body-weight in children. Nephrotic syndrome is characterized by proteinuria, hematuria (blood in urine), hypertension (high blood pressure), oliguria (low output of urine per day), edema (swelling: apparently suborbital puffy eyes) and diminished renal function. Urine may be brown or red. Sodium (Na⁺) retention, increased circulating blood volume and hypertension (high blood pressure) may lead to cardiomegaly (enlargement of heart). Nephrotic syndrome is usually characterized by insidious onset of massive edema, proteinuria, hypoalbuminemia (low level of albumin in blood) and hyperlipidemia (high level of cholesterol in blood). There could be massive retention of sodium (Na⁺) and a tendency to excessive potassium (K⁺) loss. Serious ill effect of the nephrotic syndrome could be a tendency towards hypercoagulability (blood clotting disorder) which may lead to venous or arterial thrombosis and embolism. Susceptibility to chest (lung) infections may increase due to decreased immunoglobulins' level in blood. Serum calcium (Ca⁺⁺) level could be low as this is related to the level of albumin in blood. Dysfunction of proximal tubules of kidneys may cause glycosuria (excretion of glucose/sugar in urine) or aminoaciduria.

Amyloidosis: Causes and Detection

2009-10-03T10:20:00.011-06:00

Amyloidosis or deposition of amyloid in vital organs could be labeled as chronic pathological state. Amyloid is an abnormal protein derivative and amyloidosis is characterized by extracellular accumulation of this abnormal protein, which could be detected with Congo-Red staining during histological examination of biopsies/tissues. Genesis of amyloid is associated with B-cell (B Lymphocytes) and Plasma-cell disorders or chronic infections like tuberculosis. Renal (kidney) involvement in amyloidosis may affect all compartments of kidneys. Renal glomeruli, extraglomerular blood vessels, uriniferous tubules and even interstitium could be severely affected leading to impairment of renal function and can cause renal failure. Amyloid could be composed of one or more proteins out of around two dozen different monotypic polypeptides, including immunoglobulin light chains (AL type amyloid), immunoglobulin heavy chains (AH type amyloid), amyloid-A-protein (AA type amyloid), prealbumin, b-2 microglobulin, b-amyloid protein, islet amyloid polypeptide, procalcitonin, cystatin-C, apolipoprotein A-1 or A-2, gelsolin, lysozymes etc. Immunoglobulin light chains type (AL type) and amyloid-A-protein (AA type) amyloid mostly affect the kidneys. Almost all the patients with amyloidosis of kidneys have proteinuria (excretion of proteins in urine; >3g/day) and around 70% also have diminished renal function. On electron microscopy amyloid could be resolved as approximately 10 nm thick non branching and randomly arranged fibrils as illustrated in Figure-1.

Figure-1: Electron micrograph showing randomly arranged non-branching fibrils of amyloid in the mesangial area of a renal glomerulus. Original magnification 36000x.

Amyloid-A-protein type (AA type) amyloidosis is most often associated with chronic inflammatory diseases like tuberculosis, osteoarthritis, or rheumatoid arthritis. Some viral infections can also boost amyloidosis. Production of amyloidogenic light chains is associated with B-cell lymphoma, multiple myeloma or plasma-cell dyscrasia. AL and AA type amyloid have identical physicochemical properties. On renal biopsy evaluation we find acidophilic deposits which stain weakly with Periodic acid Schiff's stain or Silver stain. Amyloid stains bright red with Congo-Red stain and shows apple green birefringence by polarized light microscopy. Amyloid deposits could be revealed in the mesangium and peripheral capillary wall of renal glomerulus depending on the chronicity of the disease process. In advanced stages of amyloidosis, the amyloid deposits could be detected in arteries and interstitial tissue of kidneys in addition to glomeruli, by conventional methods and electron microscopy.

IgA Nephropathy as a cause of End Stage Renal Disease

2009-09-28T11:32:00.005-06:00

There are a variety of causes of end stage renal disease (ESRD) in teenagers and adults. Immunoglobulin-A (IgA) nephropathy could be a cause of end stage renal disease (ESRD) in around 25% of cases. There are five types of immunoglobulins in our body for protection against microorganisms and IgA provides defence at mucous membranes. Colostrum and breast milk are rich sources of IgA and protect us during infancy through breast-feeding. However, later in life, chronic mucosal inflammation (inflammation of respiratory, oral, or gastrointestinal mucous membranes) may lead to IgA-nephropathy (IgAN). Viral (including HIV), bacterial, yeast and parasitic infections have been found to be associated with IgAN. Environmental and food antigens have also been implicated in IgAN as these may mimic molecular structure of microbial antigens and lead to excessive IgA production, aggregation and breakdown of mucosal barrier. Patients affected by IgAN may present with hematuria (blood in urine) and/or proteinuria (protein in urine) with or without rise in serum creatinine. The most common initial symptom in children is microscopic hematuria. Some adults may present with acute or chronic renal failure.

IgA nephropathy is a common nephropathy, which could be detected on renal (kidney) biopsy evaluation through light and fluorescence microscopy. However, electron microscopic study of renal biopsy acts as a diagnostic adjunct as the location of immune complexes in the renal glomerulus could be pronounced on electron micrographs. Figures 1 and 2 are the electron micrographs from a proven case of IgAN, illustrating mesangial deposits of IgA.

Figure-1: Electron micrograph of an area of glomerulus of a case of IgAN showing electron dense deposits (D) in the mesangial (Mes) area. Glomerular basement membrane (GBM), capillary lumen (CL), podocyte or epithelial cell (EpC) and urinary space (US) are also exhibited; Original Magnification 4600x.

Figure-2: Electron micrograph of an area of glomerulus of a case of IgAN showing electron dense deposits (D) in the mesangial (Mes) area. Glomerular basement membrane (GBM), capillary lumen (CL), podocyte or epithelial cell (EpC) and urinary space (US) are also exhibited; Original Magnification 6000x.

The pathology of IgAN may be variable depending on underlying cause. Mesangioproliferative glomerulonephritis is the most common pattern in many renal biopsies; however, glomeruli may appear normal on light microscopy in some of the cases. Renal biopsies in a few cases may also show crescent formation in occasional glomeruli. Diagnosis of IgA nephropathy is established by direct immunofluorescence technique on renal biopsies and the pattern may be dominant or co-dominant for IgA staining. The incidence of ESRD has been found to be high in patients presenting with >1g/day proteinuria with increased level of serum creatinine as compared to those having proteinuria <1g/day with increased level of serum creatinine. Pathogenesis of IgAN is very complex. A variety of underlying diseases including hepato-biliary disease can be associated with IgA nephropathy. Defective detection and clearance by liver of polymeric immune complexes of IgA (IgA1) due to abnormal galactosylation of O-linked glycans is probably the major cause of IgAN in addition to loss of mucosal barrier and chronic mucosal inflammation. Recurrent tonsillitis may also lead to IgA nephropathy and tonsillectomy may be helpful in these cases to remove the mucosal foci of infection. Optimal treatment of tonsillitis and other oromucosal infections with antibiotics along with conventional treatment of IgAN would be helpful to put brakes on the progression of IgA nephropathy. Patients with acute or chronic renal failure due to advanced stage of IgAN may need hemodialysis or renal transplantation. Use of anti-oxidants and fish oil as food supplements in some cases of IgA nephropathy have been found beneficial.

Urea Synthesis and Clearing: Role of Liver and Kidneys

2009-08-22T10:34:00.002-06:00

The proteins we eat contain about 20% nitrogen. A person consuming around 100g proteins daily will excrete about 17g of nitrogen daily in the form of urea. In man and other vertebrate animals the major excretory product of protein metabolism is urea, and they are classified as ureotelic animals. Birds and reptiles excrete the waste nitrogen in the form of relatively insoluble uric acid as the end product of nitrogen metabolism and are called uricotelic animals. Urea is synthesized in liver and is released into the blood and cleared by kidneys in the urine.

Urea synthesis in the liver involves five enzymes: (1) Carbamoyl phosphate synthetase 2) Ornithine carbamoyl transferase (3) Argininosuccinate synthetase (4) Argininosuccinate lyase and (5) Arginase. Deficiency in any of these enzymes may lead to metabolic disorder. The sole function of urea cycle is to convert the ammonia to non-toxic compound urea. All metabolic disorders of urea synthesis cause ammonia intoxication. Catabolism of amino acids in the most of cells produces ammonia. Considerable quantity of ammonia is produced by intestinal bacteria from the dietary proteins and from the urea present in cellular fluids secreted into the gastrointestinal tract. The ammonia produced in the intestine is absorbed into the portal venous blood and is promptly removed by the liver, where urea is synthesized from the ammonia. At first step, carbamoyl phosphate is produced by condensation of one molecule each of ammonia, carbon dioxide and phosphate, under the action of intramitochondrial carbamoyl phosphate synthetase-1 (CPS-1) in the presence of Mg⁺⁺ and N-acetyl glutamate. Now citrulline is formed from the carbamoyl phosphate by union of carbamoyl phosphate and ornithine under the action of another intramitochondrial enzyme called ornithine carbamoyl transferase. The rest of the steps in the urea synthesis take place in cytosol. Citrulline diffuses out from the mitochondrial membrane into the cytosol, where it is linked with aspartate to form argininosuccinate under the action of enzyme argininosuccinate synthetase in the presence of Mg⁺⁺ ions and ATP. There after the cleavage of argininosuccinate to arginine and fumarate is catalyzed by argininosuccinate lyase. The final step in the urea synthesis is the hydrolysis of arginine to urea and ornithine. Ornithine from the cytosol enters the mitochondria and is recycled in urea synthesis. Though other body tissues also exhibit the presence of urea synthesis enzymes but the physiologic contribution of extrahepatic urea synthesis is very low. Urea produced by the hepatic cells enters the blood and is excreted in the urine by the kidneys. Low level of blood/plasma urea and respiratory alkalosis are indicative of urea cycle disorders.

Renal Transplantation and Immune Profiling

2009-08-03T08:46:00.003-06:00

Organ transplantation is analogous to blood transfusion and we need to detect and match the tissue antigens of the donor and the recipient before transplantation of an organ, say kidney. Tissue antigens are known as human leucocyte antigens (HLA). There are four loci called A, B, C and D on the 6th chromosome, which govern these tissue antigens or HLA. We inherit one gene (each gene has sub-genes) each on each locus from our mother and father. There is antigenic polymorphism at each locus (A, B, C, and D). Unless the kidney donor and the recipient (patient) are identical twins, a 100% match of these HLA is not possible. There is 50% match of HLA amongst parents and children, and the siblings. Unrelated donor and recipient may also have 50% matching of tissue antigens or HLA. The participation of immune mechanisms in allogenic kidney transplant begins with the identification and appropriate reaction to the donor organ, by the recipient, depending on the degree of HLA mismatch. Immunosuppressive therapeutic protocols are prescribed for the adoption and survival of grafted/transplanted kidney. There is very complex immune pathway in our body involving antigen presenting cells and T & B cells (Lymphocytes), which get activated and lead to injury of the target cells. The intragraft cell trafficking and their effector mechanisms may have serious implications. Post transplant immune profiling is a way of monitoring the allograft function and to elucidate pathogenic mechanisms and molecular pathways causing tissue injury and disease.

Transplant tolerance could only be achieved through sincere compliance of immunosuppressive therapy. The immune system of the recipient following renal transplantation, though challenged by the exposure to donor antigens to initiate an early sub-clinical or acute rejection process, attempts to regulate the inflammatory processes or maintain homoeostasis in the body. The acute rejection may be cell or antibody mediated. The transplant tolerance is defined as maintenance of stable allograft function without clinical evidence of immunosuppression. There are many therapeutic approaches to achieve the transplant tolerance, however, the best one is donor specific transfusion or hematopoietic cell infusion. Almost all the transplant recipients have to depend on a variety of immunosuppressive protocols to ward of any chance of allograft rejection.

End Stage Renal Disease and Renal Transplantation

2009-07-30T21:12:00.001-06:00

Chronic glomerulonephritis, diabetic nephropathy, chronic tubulointerstitial disease, benign nephrosclerosis and polycystic kidney disease are the major causes of end stage renal disease (ESRD) and renal failure. Patients with ESRD exhibit a variety of abnormalities in their autonomic functions. Precise mechanisms of evaluating autonomic functions have revealed abnormalities in efferent parasympathetic pathway and baroreceptor sensitivity in patients with end stage renal disease. An increase in expiration-inspiration, lying standing and valsalva ratios, and baroreceptor sensitivity slope have been well documented in ESRD. Uremic patients with ESRD respond poorly to antihypertensive drugs as compared to otherwise healthy controls. Renal involvement in multiple myeloma is an other cause of ESRD and renal failure. Dialysis is an adoptive procedure in patients having end stage renal disease and ultimate surgical measure is renal (kidney) transplantation. Adequate dialysis in patients with ESRD reverses the elevated levels of urea, creatinine and electrolytes in blood.

Though renal transplantation is must in patients with ESRD, but it needs a lot of medication and post transplantation care for the successful adoption and survival of renal allograft. Systemic fungal infections (cryptococcosis, mucuromycosis, candidiasis, aspergillosis and mixed infections) have been documented after renal transplantation. Though these infections are treatable but may complicate the post operative care as additional medication will be required in addition to immunosuppressive therapy. High incidence of tuberculosis has also been observed in recipients of renal transplant along with viral infections like BK virus and cytomegalovirus (CMV). Adverse impact of pre-transplant polyoma virus (BK virus) infection on the graft survival has also been documented. Molecular technology has been developed for the early detection and identification of these viruses from the time of renal transplantation onwards by using protocol biopsies from the grafted kidney.

Acute Renal Failure: Medical and Other Causes

2009-07-30T21:05:00.003-06:00

If we look at the spectrum of acute renal failure (ARF), we find that in more than 65% of cases medical causes or ailments are associated. Around 20% of cases generally have obstetrical causes and 15% of cases of acute renal failure may have surgical or other causes. Diarrhoea, mismatched blood transfusion, intravenous hemolysis in glucose-6-phosphate dehydrogenate (G-6-PD) deficient patients, hemolytic uremic syndrome (HUS), severe glomerulonephritis, falciparum malaria, snake bite, insect stings, septicemia and copper sulphate, mercuric chloride and zinc phosphide poisoning are some medical conditions in which if effective treatment is delayed may lead to acute renal failure. Intake of nephrotoxic drugs can also cause acute renal failure. Obstetrical causes include toxemia of pregnancy, postpartum hemorrhage, puerperal sepsis and post abortal sepsis. Major surgery may cause ARF in some cases. Nephrotoxic drugs and sepsis could be compounding factors in cases ARF with surgical cause.

Acute gastroenteritis, septicemia and HUS may singly or in combination be the major cause of ARF in tropical countries. Rhabdomyolysis has been observed to play a significant role in causing ARF in a variety of conditions including toxemia of pregnancy, status asthmaticus, status epilepticus, hypothermia, burns, dermatomycosis, wasp and hornet strings, and copper sulphate, mercuric chloride and zinc phosphide poisoning. The main causative factors for intravenous hemolysis in G-6-PD deficient patients include the commonly used drugs like aspirin, chloramphenicol, chloroquine, quinine and phenylbutazone. Bilateral mucuromycosis has also been documented to cause ARF even in non-immunocompromized subjects. Sometimes nephrectomy may be required in cases of ARF due to mucuromycosis. The spectrum of community acquired acute renal failure and hospital acquired acute renal failure is almost similar throughout the world. Decreased renal perfusion in cases of hypothermia and hypotension (low blood pressure) may cause ARF if not treated well in time. Timely treatment and hemo-dialysis or peritoneal dialysis can definitely benefit the patient in restoration of renal function and reversal of acute renal failure.

The Space Within and Outside Our Body

2009-06-30T08:13:00.007-06:00

The space has a great role in our life. Our body is composed of five basic components: the earth, water, air, fire (heat or temperature) and the sky or space. The space within and outside our body is must for the existence of life. The outer space is composed of air (mixture of gases), vapours, finer particles, microorganisms, radiation, light, cold and heat. The composition of environment influences our breathing, metabolism and physiology. Our body reacts in a variety of ways to the external space and the environment possessed by it. In fact the particles floating in the air or transmitted through it may cause allergic reactions, infections, hot or cold skin burns or even skin cancer. All activities of human beings or animals are space oriented.

Just think of the life without space and you would understand its importance. Our body is like a tube open from both ends. You may appreciate space in your mouth (oral cavity), throat, nostrils, ears and lungs. In addition to these gross pockets of space there are hollow organs like heart (four chambers are there for blood flow regulation), gall bladder, urinary bladder and uterus (in females). Other examples of space within our body are cranial cavity, visceral cavity and cavities around all vital organs. There are micro-spaces in glandular tissues, alveoli of lungs, blood vessels and nephrons (glomeruli have capillary lumen and urinary space) in kidneys. In some of the renal disorders there are ultrastructural alterations in the areas/volumes of these micro-spaces within the kidneys leading to altered renal physiology and renal function. The figure-1 below illustrates normal urinary space (US) and capillary lumen (CL) or capillary space in a normal kidney; and figure-2 illustrates congestion of capillary lumen (CL) due to deposition of subendothelial deposits (SeD) in a kidney affected by lupus nephritis.

Figure-1: Ultramicrograph of a capillary loop from a normal human kidney illustrating normal urinary space (US) and capillary lumen (CL) with normal thickening of glomerular basement membrane (GBM); Uranyl acetate and Lead citrate stain.

Figure-2: Ultramicrograph of a capillary loop from human kidney affected by lupus nephritis, illustrating congestion of capillary lumen (CL) due to deposition of subendothelial deposits (SeD) with normal urinary space (US) but irregular thickening of glomerular basement membrane GBM); Uranyl acetate and Lead citrate stain.

In the illustration cited above you have seen the alteration in the space within the renal glomerulus. Abdominal tumors, brain tumors, polyps in the uterus, enlargement of spleen and liver, all these lead to functional as well as physiological changes in the body of a patient due to impact on space within the body.

Therapy and Management of Glomerulonephritis

2009-06-18T07:37:00.004-06:00

In my other articles you must have got ample information regarding classes or types of glomerulonephritis (GN). Primary glomerulonephritis accounts for about 30% patients requiring dialysis (a medical procedure of purifying blood with by passing through artificial kidney) and hospitalization. The yearly prevalence of primary GN is 0.002% that means 2 new patients per 100,000 population in a year. There are a variety of causes of primary GN with identical histopathological features. It is worth to mention here that there may be many immunopathological reasons in membranous glomerulonephritis (MGN). The character and severity of GN varies with the status of altered immune status of an individual. The understanding of pathogenesis of GN is must before initiating any therapy.

Regular follow-up in a clinic/renal clinic is must for the patient diagnosed of having a renal disease or glomerulonephritis. The follow-up provides an opportunity to the patient to learn about the complications of persistent GN and/or chronic renal failure. It has been observed that hypertension often develops coincidental with progression of renal disease. The hypertension needs to be kept under control in patients affected by persistent GN. The renal function deterioration causes edema in patients with glomerulonephritis. Though restriction in salt and water intake may cure the edema to some extent but diuretic drugs are preferred to treat the edema. Dietary management of progression of renal disease demands moderate reduction in protein intake (recommended: 0.8-1.0 g/kg body weight/day, during edema) to reduce the nephrotic overload and correction of proteinuria. Effective measures to reduce proteinuria are must to speed-up healing of renal lesions.

Corticosteroids, cyclophosphamide, chlorambucil and cyclosporin are the drugs of choice for the treatment of GN. About 95% of children generally respond to the first course of steroids within 8 weeks of commencement of treatment, whereas in adults it may take up-to 16 weeks and the percentage responding to the therapy could be around 80%. Oral prednisolone in single daily dose of 1mg/kg body weight is generally administered in adults. In children somewhat higher dose is required with reference to their body weights. Treatment of glomerulonephritis should never be tried as self help protocol as it needs regular follow-up. Parameters like body weight, blood pressure, 24 hour urinary protein, blood cells' count, blood urea and creatinine need to be worked out periodically to taper down the dose of steroids. Remission can also be achieved with cyclophosphamide, chlorambucil, cyclosporin and azathioprine. About 20-25% of patients are permanently cured with single course of treatment and around 50% may have relapse and need a repeat course of steroid treatment in combination with other immunosuppressive drugs. The dietary advice of nephrologist, controlled blood pressure and a treatment regimen for a sufficient time period may help a patient to keep a check on the complications of glomerulonephritis.

Nephrotic Syndrome and Associated Renal Lesions

2009-05-30T11:56:00.001-06:00

Nephrotic syndrome may occur in any type of primary or secondary glomerulonephritis. Around two dozen histopathological categories or subcategories of glomerulonephritis are now recognized and etiological factors are largely determined. However, prevention and treatment of glomerulonephritis needs momentum to curb the development of irreversible renal failure. The main diagnostic feature of nephrotic syndrome is massive proteinuria (excretion of protein in urine) exceeding 3 g/24 hour. The other features of nephrotic syndrome, such as, hypoproteinemia (decreased level of proteins in blood), edema (swelling) and hyperlipidemia (elevated levels of lipids in blood) are consequential due to excretion of proteins in urine. Clinically the patient does not bother to consult a nephrologist or general physician until edema becomes evident. With the fall in the plasma osmotic pressure due to loss of the plasma proteins in urine the fluid from blood would leak into the interstitial space resulting in a reduction in circulating blood volume, but the kidneys try to maintain blood volume by retaining salts and water.

In children around 80% cases of nephrotic syndrome are due to minimal change disease(MCD) and in adults the dominance of MCD is lost. In adults the cause of nephrotic syndrome may be minimal change disease, membranous glomerulonephritis (MGN), focal glomerulosclerosis, mesangial proliferative glomerulonephritis or membranoproliferative glomerulonephritis (MPGN). Metabolic disorders like diabetes mellitus could also be a cause of nephrotic syndrome. Secondary amyloidosis is also known to cause renal lesions associated with nephrotic syndrome. Immunological disorders like systemic lupus erythematosis and vasculitis may also be a cause of glomerulonephritis. Renal biopsy evaluation by light microscopy (LM), immunofluorescence microscopy (IFM) and electron microscopy (EM) is must for an accurate diagnosis of type of glomerulonephritis in a patient of nephrotic syndrome. Minimal change disease, membranous glomerulonephritis (MGN), focal glomerulosclerosis, mesangial proliferative glomerulonephritis, membranoproliferative glomerulonephritis (MPGN) and diffuse endocapillary glomerulonephritis are the common and primary causes of nephrotic syndrome. Focal segmental proliferative glomerulonephritis and diffuse proliferative glomerulonephritis with crescents are considered as uncommon-primary causes of nephrotic syndrome. Glomerulonephritis due to metabolic disorders, immunological disorders, toxemia of pregnancy or malignant conditions of kidney are labeled as secondary causes of nephrotic syndrome.

Bacterial Endocarditis and Associated Kidney Disease

2009-05-29T08:39:00.003-06:00

There is very strong association between bacterial endocarditis or heart valve infection and kidney disease. Prior to the discovery, development and active use of antibiotics, the majority of the patients developed renal disease (kidney disease) as a consequence of subacute valvular infection. The incidence of clinical renal involvement has dropped significantly with the introduction of effective treatment of bacterial endocarditis with antibiotics. The assessment of renal involvement in bacterial endocarditis is quite difficult as transient changes in urine sediment are generally observed. There may be focal and segmental lesions with normal creatinine clearance. Intravenous drug users are at greater risk of developing bacterial endocarditis.

Staphylococcus aureus infection as the cause of bacterial endocarditis has been reported in majority of the cases that lead to a higher frequency of diffuse glomerular disease. The renal lesions associated with endocarditis involved embolization and infection. The renal lesions could also have immunological basis as immune complex deposits within glomeruli have been detected in majority of the cases. The involvement of complement (an immune response modulator protein in our blood) system during active disease (bacterial endocarditis) in association with immune complexes complicates the severity of intra-glomerular lesions. The two major categories of renal lesions found in patients affected by bacterial endocarditis are: (1) Focal segmental abnormality due to subacute infection and (2) Diffuse glomerular lesions in the patients with acute bacterial endocarditis mimicking the pattern of post-streptococcal glomerulonephritis. The electron micrograph (Fig-1) from the kidney biopsy of a patient with acute glomerulonephritis and acute bacterial endocarditis illustrates the subepithelial immune complex deposits.

Fig-1: Electron micrograph illustrating the hump shaped subepithelial immune complex deposits (D) alongside the glomerular basement membrane (GBM) and urinary space (US), during acute glomerulonephritis. Uranyl acetate and Lead citrate stain.

The assessment of renal involvement in endocarditis may be difficult diagnostic entity as only minor and transient changes are observed in urinary deposit with variable changes in blood biochemistry. The clinician must recognize the status of impaired cardiac output in the first stage and later workout the potential risk of treatment associated antibiotic nephrotoxicity. The assessment of renal function at the time of presentation of case could be helpful to rule out endocarditis associate renal disease or treatment associated antibiotic nephrotoxicity.

Kidney Diseases and Elevated Levels of Blood Urea, Uric Acid and Creatinine

2009-04-09T23:00:00.002-06:00

There could be minimal to gross impairment of renal function during the onset and progression of a kidney disease or renal disorder. This impairment of renal function may range from subclinical to complete renal failure. Urine analysis and blood biochemistry have been of great help in the assessment of renal function. Simultaneous increase in the levels of blood urea and uric acid has been observed during a variety of renal disorders. Uric acid is an end product of purine (a component of nucleic acids and nucleoproteins) metabolism. The level of uric acid in the blood depends on its endogenous production through purine metabolism as well as from the exogenously taken purines in the food items. Normal range of uric acid in blood is 2 - 6mg/dl. Elevated level of uric acid is also observed in gout. Urea is an end product of protein metabolism and its normal range in blood is 20 - 40mg/dl.

Formation of Urea: The amino acids derived by the digestion of proteins of the food we eat are absorbed by the villi of the small intestine and brought to the liver through the portal vein. The essential amino acids required for the growth and repair of body tissues are passed on to the blood circulation by the liver and others are used to produce the blood proteins and useful proteins for the body. Useless proteins are broken down in the liver to form bioenergy composed of carbon, hydrogen and oxygen and a waste product urea. Urea is a water soluble substance and carried away buy the blood stream.

The uric acid level may increase earlier than the blood urea level during the course of renal disease. The serum uric acid could be found markedly increased from the normal level of 2 -6mg/dl to 10 - 30mg/dl with minimal impairment of renal function. The creatinine level in blood starts rising after 2 to 4 fold rise in the blood urea level. The level of urea may rise in a variety of conditions, but increased level of creatinine is considered more severe than the increased level of blood urea. The creatinine is derived from the creatine and is a waste product; on the other hand the creatine is necessary for the muscle contraction and is related to the phosphocreatine breakdown. The normal level of creatinine in the blood plasma or serum is 1 - 2mg/dl and its normal daily excretion ranges from 1 to 2 grams. The serum creatinine values of up to and even exceeding occasionally 20mg/dl have been seen in the later stages of renal failure. The major cause of increased levels of serum creatinine and blood urea is the poor clearance of these substances by the kidneys rather than excessive production. In acute glomerulonephritis values from normal to over 300mg/dl are generally observed. In conditions such as malignant hypertension, chronic pyelonephritis and heavy metal poisoning 10 to 15 fold increase in blood urea level may be detected. However, in cases of hypoadrenalism (Addison's disease) blood urea level of about 100mg/dl could be detected. Fifteen to 20 fold increase in the level of blood urea (i.e. a level of 600 - 800mg/dl) may lead to uremic coma in more than 80% cases of cases affected by severe renal disease or renal failure.

Role of Adrenal Glands in Renal Physiology

2009-04-07T08:20:00.002-06:00

The role of adrenal glands in the control of functioning of kidneys is very well established in terms of renal physiology. Every organ of our body has an embryonal origin and relationship with other organs. This relationship helps us to establish the physiology of systems associated with each other. There exists a pair of adrenal glands in our body and their position is suprarenal. Each adrenal gland has a cortex and medulla. There exists three layers of specialized cells in the adrenal cortex and these are: (1) Zona glomerulosa, (2) Zona fasciculata and (3) Zona reticularis. The medullae of adrenal glands belong to chromaffin system. The pituitary adrenocorticotrophic hormone (ACTH) controls the activity of adrenal glands in the production of cortisol (hydrocortisone). The inner medullary portion of the adrenal glands produces adrenaline (epinephrine) and noradrenaline (norepinephrine). The adrenal glands function under the control of sympathetic nervous system. The production of adrenal hormones increases in the conditions of emotions like anger or fear and states of asphyxia (lack of oxygen) and starvation and in turn raises the blood pressure in order to overcome the shock. The adrenaline epinephrine) influences the flow of urine and helps in the water balance by kidneys. Noradrenaline norepinephrine) is known to stimulate the muscle fibres in the walls of blood vessels, causing them to contract and thus raising the blood pressure. Adrenaline (epinephrine) also accelerates the carbohydrate metabolism by increasing the output of glucose from the liver.

The cortical layers of adrenal glands produce three types of steroids: (1) Mineralocorticoids are produced by the zona glomerulosa layer of the adrenal cortex and are associated with renal control of water and electrolytes. The mineralocorticoid naturally produced by the adrenal glands is aldosterone which controls the reabsorption of salts by the renal tubules. When there is deficiency of this hormone, too much water and sodium are lost from the body in the urine and too little potassium is excreted and this may lead to toxic levels of potassium in the blood. This results in polyuria, the passage of an excessive quantity of urine. The first of the adrenal steroids isolated or synthesized was the mineralocorticoid called desoxycorticosterone (DOC), which is used in the treatment of shock and polyuria, (2) Glucocorticoids are produced by the middle layer or zona fasciculata of the adrenal cortex and are associated with the metabolism of carbohydrates, fats and proteins. Glucocorticoids promote the conversion of proteins into glucose and storage of glucose as glycogen in the liver. Mineralocorticoids and glucocorticoids complement the action of each other and (3) Androsterone or androgens (sex hormones) are produced by the innermost layer or zona reticularis of the adrenal cortex. Androgens possess 19 carbon atoms in their chemical structure, with one oxygen atom attached to the 17^th carbon atom and are also known as 17-ketosteroids and could normally be detected in the urine. Corticoids are chemically similar to cholesterol, sex hormones or corticosteroids. Our kidneys regulate the volume and composition of our body fluids in terms of water and electrolytes' balance through filtration, secretion, reabsorption and excretion. It is well established that kidneys function under the intelligent control of hormones, without which it would not be possible for the kidneys to maintain a state of homoeostasis in the body.

Kidney Diseases: Diagnostic Terms and Features

2009-03-30T06:23:00.009-06:00

The genetic, environmental, chemical and biological factors are known to influence the bio-physiology and microanatomy of kidneys. A possible clinical diagnosis of kidney diseases or renal disorders could be achieved through ultrasonography, biochemical investigations of blood and urine analysis. The pathological diagnosis of non-neoplastic and neoplastic kidney diseases needs light microscopy (LM), immunofluorescence microscopy (IFM) and electron microscopy (EM) study of the kidney biopsy. Narrowing down at the appropriate and accurate diagnosis of a kidney disease needs expertise in the evaluation of LM, IFM and EM features. The light microcopy has its limitations in the exploration of microanatomy of renal lesions due to its low resolution power. The initial task in the pathological diagnosis of a kidney disease is to decide the renal compartments associated with the primary lesion or initial site of injury. The glomeruli, tubules, interstitium, extraglomerular vessels or podocytes may be affected primarily in various combinations in various renal diseases. The history of hypertension or diabetes in addition to chronic inflammatory disease like rheumatoid arthritis, osteomyelitis, tonsillitis and tuberculosis has its own implications in renal disorders. In some kidney diseases multiple components may be affected simultaneously by the pathogenic process. The glomeruli and blood vessels are found affected in certain forms of vasculitis. Immunological findings are mandatory to achieve an accurate diagnosis of vasculitis associated kidney diseases. Tubules and interstitium are found affected in tubulointerstitial nephritis. The role of EM and ultrastructural morphometry is implicit in achieving a diagnosis of thin basement membrane disease (TBMD), Alport's syndrome (hereditary nephropathy), minimal change disease (MCD), amyloidosis and evaluation of podocyte injury. The thickness and texture of glomerular basement membrane (GBM), reorganization of foot processes of podocytes and podocyte injury are directly associated with the biophysiology of proteinuria (excretion of protein in urine) and hematuria in some kidney diseases. The histopathologic lesions in the affected kidneys could only be explained with a thorough knowledge of universally accepted appropriate terms which could be understood by a clinician. The term focal is used when <50% of glomeruli are involved and the term diffuse refers to the involvement of 50% or more glomeruli. The term segmental is used when a part of a glomerular tuft is affected and the term global is used when entire glomerular tuft is affected. The term mesangial hypercellularity means >4 nuclei in the matrix of a peripheral mesangial segment. The term sclerosis refers to increased collagenous extracellular matrix causing mesangial expansion, obliterating capillary lumen or forming contact to Bowman's capsule. Some of the important diagnostic features of kidney biopsy evaluation have been cited below in a tabulated form: (For a full view of the Table - Just click on the image below)

The neoplastic kidney disease are renal cell carcinoma, juxta glomerular cell tumor, renal adenoma, oncocytoma and metastatic tumors which need immunohistochemical (IHC) and EM study for an accurate diagnosis.

Urinary Deposits in Health and Disease

2009-03-28T11:54:00.004-06:00

The water and salt balance of our body is taken care by our kidneys through excretion of water and salts under the strict regulatory control of various hormones. The chemical and microscopic examination of urine for the evaluation of health status is a routine procedure at health centers. The abnormal excretion of biochemical substances on physical and chemical analysis of urine and presence of chemical crystals, various cell types and casts in the urine is the first alarming point about many diseases. The microscopic examination of urinary deposits would yield a valuable information about a positive or negative character. The components of the urinary deposit can be classified into three groups: 1) Chemicals as crystals or amorphous deposits, 2) Cells from the blood or urinary tract, and 3) Casts

Chemical substances as crystals or amorphous deposits: Some of the inorganic and organic chemical substances could be appreciated in the urine of normal people of all age groups, but some other chemicals are always associated with pathological conditions. The presence of crystals of chemical substances in the urinary deposits is influenced by acidic or alkaline reaction of the urine. Phosphates (ammonium magnesium phosphate, Calcium hydrogen phosphate and magnesium phosphate), Calcium oxalate, uric acid and urates (of Ammonium, Sodium, Potassium, Calcium and Magnesium) are most commonly detected in the urinary deposits. Other chemical substances viewed in the urinary deposits may be Calcium carbonate, Calcium sulphate, amino acids (cystine, tyrosine and leucine), hippuric acid, cholesterol, xanthine, Sulphonamide drugs and pigments like bilirubin. Phosphates are deposited in alkaline urine and get dissolved in dilute acetic acid. Calcium oxalate crystals are soluble in hydrochloric acid but uric acid crystals are not soluble in acetic acid or hydrochloric acid. Presence of red blood cells(RBCs) in the urine may give color to the deposits. The crystals of chemical substance have very typical shapes. Microscopic examination of urinary deposits by an experienced medical technologist or pathologist is needed for an accurate assessment of chemicals, cells or casts excreted in the urine. Calcium oxalate is present in some fruits and vegetables and notable among them are strawberries, rhubarb and spinach. The crystals of Tyrosine appear like tufts of needles and those of Leucine are in spherical shape. Crystals of tyrosine and leucine are seen very rarely in the cases of severe liver disease and cirrhosis. Crystals of cholesterol appear as rectangular or rhomboid plates with notched corners and occur the urine form the patients affected by some kidney disease. Sulphonamide crystals could be found in urinary deposits during treatment with such drugs. These are formed from acetyl derivatives in the urinary tract.
Cells: Red blood cells (RBCs) could be detected in the urinary deposits during macrohematuria (>1000 RBCs/ml of urine) as well as microhematuria (<1000 RBCs/ml of urine). Pus cells: Less than 10 leucocytes or pus cells per microlitre (µl) of urine may occur in normal urine. An increase in the number of pus cells is called pyuria and is indicative of some inflammatory disease in the urinary tract. Urine culture may help to establish the causative agent of urinary tract infection. The cells present during the acute inflammation are mainly polymorphonuclear cells. Microscopic examination of the urinary deposit is the only satisfactory test to establish the presence of pus cells. Epithelial Cells: Epithelial cells may be detected normally in urine from female patients but an increased number could be due to pathological reasons. Epithelial cells in the urine of males are normally very few in number. Epithelial cells could be from the squamous epithelium, transitional epithelium (from the bladder, prostate, ureters and pelvis of kidneys), and basal or parabasal cells. Abnormal cells such as tumor cells may also be detected in the urinary deposits. Sometimes spermatozoa may also be present in the normal urine of males.
Casts: Casts are formed in renal tubules whose shape these take. Subsequently the casts are pushed by the fluid along the tubules and appear in the urine. These are seen on microscopic examination of urinary deposits. The casts could be classified on the basis of their appearance under the microscope as: 1) Hyaline casts: are simplest, pale transparent and homogenous structures with cylindrical shape and do not contain cells or granules. 2) Epithelial casts: When there is tubular damage, cells from the tubular epithelium could be trapped into casts and give rise to epithelial casts. 3) Granular casts: Casts containing closely packed granules of various size and shape are generally formed due to degeneration of tubular epithelial cells and are indicative of renal disease. 4) Fatty casts: are derived from epithelial cells when fat granules are present along with granular material. Such casts are found in tubulopathy and are indicative of degeneration of tubular epithelium.

Important Points:

Collection of urine from each kidney by ureteric catheterization and from urinary bladder may be used to locate the site of pus formation.
Cytological examination of the first morning urine for three consecutive days should be performed to rule out any malignancy in doubtful case.
If large number of pus cells are detected in the urine, a urine culture is advisable to rule out the infectious organism.

Types and Causes of Proteinuria

2009-03-24T08:01:00.002-06:00

Proteinuria means the excretion of protein in the urine. A healthy person does not excrete proteins in the urine or the excretion of proteins is less than 150 mg per day. The proteins most commonly found in the urine are those derived from the plasma of blood and consist of a mixture of albumin and globulin. Predominantly albuminuria (excretion of albumin in urine) is detectable on routine urine analysis during a medical examination. Albuminuria could be organic (due to involvement of kidneys or other organs) or functional (due to physiological or biological stress on kidneys). The functional albuminuria is usually intermittent and not accompanied by any symptoms or evidence of kidney disease. Renal function tests and urinary deposits are found to be normal during the functional albuminuria. It may be connected with posture; being absent when the person is lying down and present when standing. The functional albuminuria usually clears up in early adult life and seems to be associated with the growth and development of kidneys. Any severe stress may also lead to transient albuminuria. Exposure to severe cold and excessive exercise or physical activity may cause functional or transient proteinuria. However, there is nothing to worry about as the functional albuminuria is self limiting with respect to the cause. Mild to moderate functional albuminuria may also be detected during last two months of pregnancy due to pressure on kidneys.

Organic albuminuria is of three types: 1) Renal Albuminuria - When the cause is the kidney disease. 2) Pre-renal Albuminuria - When the kidneys are affected secondarily to some other disease. Post-renal Albuminuria - When the protein is added to the urine after it has left the renal tubules.

Renal Albuminuria: It is found in all forms of kidney disease. The cause of renal disorder or kidney disease may be inflammatory (infectious), degenerative (immunological) or destructive (toxic or malignant). The plasma globulin and red blood cells (RBCs) may also be excreted along with albumin during some renal disorders. The urine would be smoky in color if macroscopic hematuria (blood in urine) is also associated with proteinuria. The cases of acute glomerulonephritis may excrete 0.5 to 2.0 percent (0.5 g to 2.0 g/dl) protein in the urine, whereas the cases affected by chronic glomerulonephritis generally excrete less than 0.5 percent (0.5 g/dl) protein in the urine. The amount of protein excreted daily would vary depending on the volume of urine voided daily. The ratio of albumin to globulin excreted in the urine may vary from 10:1 to 5:1. A routine and quantitative urine analysis is required to evaluate the extent of excretion of proteins in the urine.
Pre-renal Albuminuria: It is found in a variety of conditions exerting stress on the kidneys. The pre-renal albuminuria usually disappears when the primary disease is cured. Impairment of renal circulation due to dehydration, diarrhea or vomiting, blood loss due to accidental injuries or anemia are the most common conditions, which could lead to pre-renal albuminuria.
Post-renal Albuminuria: The proteinuria or albuminuria is termed as post-renal albuminuria if protein is possibly added to the urine as it passes along the urinary tract after leaving the urinary tubules of the kidneys. The major causes of the post-renal albuminuria are the lesions of the renal pelvis or urinary bladder. Lesions of the prostate (in male patients) and urethra also lead to post-renal albuminuria. Admixture of discharges from the vagina (in female patients) and semen (in male patients) may also give positive tests for protein.

Micturition Disorders and Neurogenic Bladder

2009-02-11T23:34:00.003-07:00

Micturition:

The process of voiding urine is called micturition. The urine is formed in the kidneys and collected into the urinary bladder. The urinary bladder is connected to kidneys through a pair of ureters. When a pressure of accumulated urine develops in the urinary bladder, we have a desire to urinate. An accumulation of 150 ml to 200 ml of urine activates the nerve endings in the muscular wall of the urinary bladder. The micturition is a reflex act controlled and inhibited by the higher centers in our brain. The act leads to the contraction of the muscular coat of the urinary bladder and relaxation of sphincter muscles. The urinary bladder is controlled by the pelvic nerves and the synaptic fibers from the hypogastric plexus. It may be voluntarily assisted by the contraction of abdominal muscles by increasing pressure in the abdominal cavity. The voluntary contraction of abdominal muscles exerts pressure on the visceral organs and in turn on the urinary bladder and helps in emptying of the bladder.

Neurogenic Bladder:

As stated above, the urinary bladder activity is controlled by the pelvic nerves and the sympathetic nerve fibers from the hypogastric plexus. A condition may arise due to a variety of causes leading to an interruption of the nerve messages between the brain and the urinary bladder. Due to lack of dynamic control over the muscles of the urinary bladder, the bladder fails to store or release the urine properly. Spinal cord injury due to some fatal accident, brain tumor, stroke, diseases such as multiple sclerosis or diabetes mellitus and congenital disorders could be the cause of neurogenic bladder.

There may be varied symptoms of neurogenic bladder depending on the lesion and the site of the injury and severity of injury. The patient may express inability to store the urine, excessive frequency of micturition and incontinence. All this is caused by overactive urinary bladder or a weak sphincter (outlet controlling muscles). On the other hand a weak urinary bladder or an over tight sphincter may lead to retention of urine and difficulty in urinating. Though the problem is associated with the urinary system but the cause is neurological and only a neurologist could help the patient in the right perspective. Renal function tests and ultrasound examination is must to evaluate the status of kidneys. A thorough evaluation is needed to ascertain the cause of neurogenic bladder disorder. Urodynamic testing with video x-rays and uroflometry should be carried out to evaluate the extent of emptying of the urinary bladder.

Altered Physiology and Diseases of the Muscles

2009-02-09T08:11:00.003-07:00

The skeletal muscles or flesh are essential for the motor functions as well as the shape and features of our body. The muscular atrophy (shrinkage of muscle mass) may lead to a variety of diseases of the muscles. These diseases are distinguished with respect o the site of origin of a disorder as mentioned below:

1. Origin in motor neurons: Polymyelitis, progressive muscular atrophy

2. Origin in the nerve fibers: Polyneuritis

3. Origin in the myoneural junction: Myasthenia gravis, myotonia congenital, and

4. Origin in the muscle only: Primary muscular dystrophy.

All voluntary muscle have innervation by motor neurons. The muscle fibers are composed of myofibrils and these fibrils appear to be the ultimate functional units of the muscle and have alternate light and dark bands. The contractile protein of the muscle is called actomycin (AM) and is composed of actin and myosin. The actomycin is considered to be the structural protein of the resting myofibrils and contain many enzymes necessary the muscle metabolism. The organic phosphate compound called adenosine triphosphate (ATP) is an energy rich compound and is attached to actomycin of myofibrils. The neuronal spark of the motor neurons fires the adenosine triphosphate-actomycin linkage and breaks it. The adenosine triphosphate (ATP) is liberated and its breakdown provides energy for the muscle contraction. During contraction of the muscle, the actin threads could be shortened to 40% of its original relaxed phase size. The physiology of muscle contraction involves a series of molecular interactions and rearrangements within the complex structure of actin, myosin, and adenosine triphosphate.

The change in the functions of any part of the above cited metabolic pathway may lead muscle weakness. The microscopic examination of muscle biopsy may help to achieve a proper diagnosis. There muscle biopsy could reveal an involvement of a whole bundle of muscle fibers in the cases with neurogenic origin. I cases affected by primary muscular dystrophy only some the fibrils may be involved. The ultrastructural study of the muscle biopsy by a transmission electron microscope is always helpful in achieving an accurate diagnosis of the diseases of the muscles.

Physiology of Muscle Contraction

2009-02-09T08:06:00.002-07:00

The essential function of the skeletal muscle is contraction and relaxation in response to a command from a motor neuron. The muscle is very unique organ and is capable converting stored chemical energy into mechanical energy through metabolic processes. The skeletal muscles constitute from 40 to 45 percent of the body weight in an adult. There are 434 voluntary muscles in our body and about 250 million muscle fibers constitute these muscles. The muscle cells or sarcomeres are very complex in structure, metabolism and functions.

All voluntary muscle have innervation by motor neurons. The muscle fibers are composed of myofibrils within the sarcoplasm. The myofibrils appear to be the ultimate functional units of the muscle and have alternate light and dark bands. The contractile protein of the muscle is called actomycin (AM) and is composed of two components: (1) actin and (2) myosin. The actomycin is considered to be the structural protein of the resting myofibrils and contain many enzymes necessary the muscle metabolism. The organic phosphate compound called adenosine triphosphate (ATP) is an energy rich compound and is attached to actomycin of myofibrils. The neuronal spark of the motor neurons fires the ATP-AM linkage and breaks it. The ATP is liberated and its breakdown provides energy for the muscle contraction. During contraction of the muscle, the actin threads could be shortened to 40% of its original relaxed phase size. Physiology of muscle contraction involves a series of molecular interactions and rearrangements within the system composed of actin, myosin, and adenosine triphosphate.

Role of Grey Matter and White Matter in Our Nervous System

2009-02-06T07:14:00.003-07:00

Our nervous system could be studied under two main headings for quick understanding: (1) The Central Nervous System (CNS) or Cerebrospinal Nervous System and (2) The Autonomic Nervous System. The autonomic nervous system includes the sympathetic nervous system and parasympathetic nervous system.

The central nervous system includes the brain and the spinal cord, and the nerves arising out from these. The nerves arising from the brain and the spinal cord are called peripheral nerves. The nervous tissue is one of the four elementary tissues of our body and commands the sensory and motor functions of our body in addition to intellect, emotions and memory functions. The nervous tissue is composed of nerve cells, dendrites, nerve fibres and nerve endings. The composite mass of nerve cells is called grey matter. The grey matter is found in the cortex of the brain, inner part of the spinal cord and cerebral ganglia. The role of the grey matter is the processing of the sensory and motor information, control of emotions, memory and intellect. The control of emotions, memory and intellect is associated with the growth and development of the brain. The nerve fibres and or axons constitute the white matter. The white color of the sheath of fatty matter called the myelin sheath covering the axons or nerve fibres is the reason behind the nomenclature as white matter. The white matter is the major component of the central portion of cerebral part of brain. The myelin sheath serves to protect, nourish and insulate the nerve fibres from each other. A nerve cell along with its dendrites, nerve fibre or axon and nerve endings is called a neuron as depicted in the figure-1 below:

Figure-1: Components of a Neuron

There are two types of neurons in our body. The neurons which carry impulses out from the brain to the tissues are called efferent neurons and the neurons which carry impulses to the brain from the tissues are called afferent neurons. Efferent neurons which supply impulses to the muscles and produce movement are called motor neurons and which supply impulses to the glands and produce secretion are called secretory neurons. Afferent neurons are also known as sensory neurons since these help us to assess a feeling of touch, pain and heat or cold.

Quick Tips on the Surface Anatomy of Our Body

2009-02-03T07:16:00.002-07:00

Our own body is a live specimen for understanding the surface anatomy of human body. Knowledge of surface anatomy may help us to understand the diagnostic terms used by a physician or surgeon. The physical examination parameters of a patient are recorded with reference to certain landmark points which are universally understood. By inspection, palpitation, percussion and auscultations a physician or surgeon studies condition of his/her patient to arrive at a diagnosis. The position of many internal structures and organs is described in relation to various bony points termed as landmark points.

There are some land mark points of surface anatomy of the head; like longitudinal fissure, superior longitudinal sinus, central sucus or fissure of Ronaldo, mastoid processes ete. There are anterior and posterior triangles of neck formed by sternomastoid muscle. In the trunk many of the organs are being described in relation to their surface anatomy. The apex beat of the heart can be heard in the fifth intercostal space, 3¹/₂ inches from the midline. The abdomen is divided into 9 parts by four imaginary lines (two vertical and two horizontal). These 9 parts have been depicted in the figure-1 below:

Figure-1: Abdominal Regions (1: Right Hypochondriac Region, 2: Epigastric Region, 3: Left Hypochondriac Region, 4: Right Lumbar Region, 5: Umbilical Region, 6: Left Lumbar Region, 7: Right Iliac Region, 8: Hypogastric, 9: Left Iliac Region.

The liver occupies parts of the right hypochondriac and epigastric areas, and extends transversely into the left hypochondriac region and also occupies a part of the right lumbar region. The lungs and the heart occupy the thoracic cavity and are well secured there in the protective bony cage. The spleen lies on the left side beneath the ninth, tenth and eleventh ribs. The left kidney lies between the eleventh thoracic to the third lumbar vertebra. The right kidney is slightly lower as its upper pole touches the lower part of the liver.

The rectus abdominus could be felt along each side of the middle line of the abdomen. The umbilicus lies on level with the disc between the third and fourth lumbar vertebrae. The stomach lies in the upper and left aspect of the abdomen, partly behind the lower ribs and cartilages. The fundus of the stomach reaches as high as the fifth left intercostal space. The gall bladder projects slightly from the costal margins at the level of the ninth right costal cartilage. The pancreas lies at the back of the abdominal cavity across the first lumbar vertebra. The aorta passes through the common iliac arteries in front of the fourth lumbar vertebra. The caecum is present on the right side and the commencement of the sigmoid fissure of the colon lie respectively in the right and left iliac fossae.

Why Respiration is Necessary for Propagation of Life ?

2009-01-30T05:41:00.007-07:00

One can survive without food and water for many hours but survival without the air or oxygen is not possible beyond a few minutes. Every cell in our body is programmed to perform a definite metabolic function necessary for our life. By means of breathing we assimilate oxygen from the air for intracellular metabolism. Through metabolic processes, cells of our body release carbon dioxide (CO₂) and water (H₂O), which are transported away by the circulating blood. Respiration is a two fold process: (1) The interchange of gases in the lungs is called external respiration and (2) The interchange of gases in the tissues is called internal respiration. In the external respiration, oxygen is taken in through the nose and mouth and flows down to the alveoli in the lungs, where it comes in contact with the alveolar capillary membrane and is taken up by the hemoglobin of the red blood cells (RBCs). The oxygenated blood goes to the heart and is further pumped to the various parts of our body. In the lungs, carbon dioxide (CO₂), a waste product of the metabolism is released out through the alveolar capillary membranes and breathed out through the nose and mouth.

The air we breathe in, contains 79% of nitrogen, 20% of oxygen and 0.04 carbon dioxide (CO₂) along with atmospheric water vapors; where as the air we breathe out, contains 79% of nitrogen, 16% of oxygen and 4.04 carbon dioxide (CO₂) along with water vapors released from the alveoli. The total air capacity of our lungs is about 4.5 to 5.0 liters of air and only ¹/₁₀th (500 ml) is generally inspired or expired. The volume of the air under exchange is also termed as tidal air. Our breathing is controlled by two factors: (1) The chemical control of respiration and (2) The nervous control of respiration through the medulla oblongata of our brain. The normal rate of respiration in different age groups is as under:

Status of Age	Respiration Rate per minute
Newborn	38 - 42
Up to 12 months	28 - 32
2 years to 5 years	24 - 26
6 years to 16 years	20 - 24
Adults	10 - 20

The oxygen need of our body varies with the type of activity we perform. Rate of respiration goes up during exercise or running and is considered a vital health parameter for medical fitness evaluation of an individual. As stated above the oxygen (O₂) is the essence of the life force and lack of it may lead to a state of hypoxia or anoxia and brain damage.

What causes Pyelonephritis and How Serious is It?

2009-01-29T05:11:00.002-07:00

The pyelonephritis is said to be very serious renal disease. The well documented cause of pyelonephritis is an infection of interstitial (intertubular) tissue with pyogenic bacteria, most frequently E. coli and Staphylococci, and sometimes Proteus vulgaris and Pseudomonas pyocyaneus. In almost 66% of cases the infection could be secondary to the urinary tract infection and in 33% of cases the infection could be primary through infection of blood. The ascending infection of kidney or kidneys from the urinary tract is quite common in infants. There could be ascending infection of kidneys in pregnant women and also in women with the cancer of the cervix. In the elderly male patients, the ascending infection of kidneys is possible if their prostate is enlarged and the urethra is obstructed causing partial or full retention of urine. Irrespective of the sex of the patient, the obstruction plays a vital role in causing the infection of kidneys. It has been proved through experimental study on rabbits that the obstruction of urinary system was the main cause of renal infection and pyelonephritis. In man infection of blood may cause unilateral or bilateral pyelonephritis depending on the obstruction. The obstruction may be functional or organic. The ultrasonography or the serial radiographical study is required to rule out the obstruction.

The pyelonephritis in its chronic form is very dangerous disease. The kidney may become a bag of pus due to infection with pyogenic bacteria cited above. The condition is also called pyonephrosis. A pure hydronephrosis (nephrosis caused due to back pressure of accumulated urine) in an advanced stage may become infected. The kidneys get much enlarged due to hydronephrosis or pyelonephritis. There is possibility of complete erosion of functional architecture in side the kidney due to pyogenic infection. Pyelonephritis may also develop in a gradual manner with little frank suppuration. The early detection of disease could be better for the patient as it could be treated effectively.

Acute Glomerulonephritis

2009-01-22T05:48:00.004-07:00

The term acute glomerulonephritis is used by clinicians as well as pathologists to describe the sudden onset of kidney disease. Irrespective of the cause, there would be enlargement of a kidney or kidneys and the capsule around the kidney is strained and stretched. Ultrasonography is always helpful to ascertain the size of kidneys. Histological examination of kidney biopsy would present densely cellular glomerular tuft with polymorphonuclear cells (a type of white blood cells) in the glomerular capillaries. Accumulation of leukocytes (white blood cells) in the glomerular capillaries with swelling and proliferation of the vascular endothelium (inner lining of capillaries) is rapidly followed by edema (swelling) and mesangial proliferation (enlargement of inner stalk of a cluster of glomerular capillaries)leading to capillary ischemia (poor blood supply).

The glomerular basement membrane (GBM) is the other important component affected by acute glomerulonephritis. By electron microscopic study of kidney biopsy, electron dense deposits of antigen-antibody complexes could be revealed in and around the glomerular basement membrane. The ultrastructural features of normal GBM have been depicted in the figure-1 and the figure-2 is from a case affected by acute glomerulonephritis.

Figure-1: Electron micrograph of a capillary loop of glomerular tuft showing normal features; CL: capillary lumen, US; urinary space, En: endothelium, GBM: glomerular basement membrane, EpC: epithelial cell or podocyte.

Figure-2: Electron micrograph of a capillary loop of glomerular tuft from a case affected by acute glomerulonephritis is showing sub-epithelial deposits; CL: capillary lumen, US; urinary space, GBM: glomerular basement membrane, dep: deposits on sub-epithelial site of GBM.

The tubules in the kidney may show slight degenerative changes. The degree of degenerative changes in the tubules depends on the extent of the glomerular obstruction. The interstitial tissue and the blood vessels are observed to be normal on the histological study of kidney biopsy.

The Mind and Brain: Functions and Physiology

2009-01-10T03:28:00.003-07:00

The most important fact is that the brain is the organ of the mind and the mind is like the software of a computer. The mental functions are related to the cerebral cortex of the brain. In humans the cerebral cortex is better developed than the inferior animals. Our sense organs are like input devices of a computer. Our brain processes and stores the data in encapsulated form with respect to attributes. Our ears transmit sound signals to our brain, which are analyzed by our mind and classified as noise, vocal audio and music. Music files are further categorized as per specific attributes and stored in our brain. Whenever we listen to the same sound again we could easily name a person as per tonal quality of voice, instrument as per the pitch and rhythm of the music and the birds and animals as per their specific vocal attributes. Human mind is capable of distinguishing a variety of fragrances and odors, human faces and pictures, fonts and shapes, smooth and rough surfaces, bitter, sweet or sour tastes etc. Expressions of thoughts and emotions are special functions of our mind.

The brain, like other organs is powered by chemicals. Whenever the chemistry of brain is disturbed, mental symptoms are an early result. The glucose and oxygen have a vital role in the physiology and bio-energy generation of our body. The anoxia (low oxygen supply) of airmen and in the early stages of anesthesia may lead to chock. The hypoglycemia in diabetics on insulin therapy has been known to cause insulin shock or hypoglycemic shock. Certain groups of chemicals or drugs can cause mental disturbance and there are other chemicals or drugs which are capable of improving the mental function. For example hallucinogens like LSD disturb the mental functioning of normal people whereas tranquilizers and psychic energizers are known to improve the mental functioning of abnormal people. Except the numerical ability, the human mind and brain are faster than any computer in answering a variety of questions related to memory and experiences. Till date no computer could store the attributes of taste, smell, feelings and emotions. The super programming and coding of our mind is updated every moment through our observation and experience.

Azotemic or Hydropic Glomerulonephritis

2009-01-08T05:04:00.001-07:00

The high concentration of non protein nitrogen (NPN) in the blood of a patient, mainly due to elevated level of urea is termed as azotemia. Elevated level of urea in blood is termed as uremia and it may be due to renal abnormality or due to other health problems like dehydration and excessive burns on the body. The glomerulonephritis (inflammation of glomeruli of kidneys) may be azotemic or hydropic type depending on the nature of glomerular lesions. There may be marked narrowing of the glomerular capillaries leading to azotemia with renal insufficiency and hypertension. On the other hand the status of glomerular capillaries may remain normal but there could be an increase in the permeability of glomerular basement membrane (GBM), the filtration barrier of kidneys. The clinical picture would be hydropic (accumulation of water in the tissues of the body) in character. The hydropic glomerulonephritis is clinically represented with edema associated with hypoproteinemia (low level of protein in blood) and hyperlipemia (high concentration of lipids or cholesterol in blood).

A child or an adult affected with fever or some other acute disease finds the increase in the daily output of urine. There may be tinge of blood in the urine of the patient affected by glomerulonephritis. Sudden appearance of features like puffiness or swelling on face (facial edema), ankles and hands after any acute disease needs expert medical attention and medication. The urine of such patients would show notable excretion of albumin. The patient may be less perspiring with dry skin. The pulse could be full and hard. The loin pain and a feeling of heaviness in the lower abdominal region are the associated symptoms. The polyuria (excessive output of urine) is probably compensatory action of affected kidneys to flush out solid wastes of metabolism form the body. An effective therapy would definitely reverse the associated symptoms and lesions.

Happy New Year - 2009

2008-12-30T09:31:00.003-07:00

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

2008-12-29T05:11:00.000-07:00

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

2008-12-23T07:12:00.002-07:00

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

2008-12-15T07:09:00.002-07:00

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

2008-12-11T09:40:00.002-07:00

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

2008-12-08T10:22:00.002-07:00

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

2008-12-08T10:12:00.003-07:00

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

2008-11-21T05:39:00.006-07:00

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

2008-11-21T05:22:00.001-07:00

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:

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.
Dehydration: Continued vomiting, severe diarrhea or profuse sweating may lead to dehydration resulting in oliguria or complete cessation of urine i.e. anuria.
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.
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

2008-11-14T08:50:00.002-07:00

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

2008-11-07T08:11:00.002-07:00

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

2008-10-31T10:20:00.007-06:00

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:

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.
Middle Layer or Mesoderm: Muscles, bones, fat and some parts of the cardiovascular system develop from the mesoderm.
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:

Epithelial Tissue
Connective Tissue
Muscular Tissue
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

2008-10-31T09:20:00.006-06:00

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

2008-09-30T03:08:00.001-06:00

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

2008-09-17T07:44:00.003-06:00

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:

Nephritic syndrome and acute renal failure (Sudden impairment of renal function).
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)
Systemic diseases with associated renal disorders.
Evaluation of asymptomatic patients in whom routine laboratory examination has disclosed proteinuria (protein in urine) and/or microscopic hematuria (blood in urine).
Evaluation of prospective kidney donors, to be sure that they did not have any occult renal disease.
Assessment of renal microstructure of patients with renal transplant.
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

2008-08-31T02:16:00.001-06:00

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

2008-08-31T02:13:00.001-06:00

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

2008-08-28T08:48:00.008-06:00

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

2008-08-15T08:06:00.000-06:00

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

2008-08-08T07:36:00.000-06:00

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

2008-08-02T10:44:00.000-06:00

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:

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

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.
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.
Specific gravity: It varies from 1.010 to 1.025. Specific gravity is determined with urinometer.
Odor: The odor is aromatic.
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:

Water: Near about 96%
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

2008-07-21T08:52:00.000-06:00

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

2008-07-18T10:48:00.001-06:00

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

2008-07-16T02:14:00.000-06:00

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

2008-07-10T02:19:00.000-06:00

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

2008-07-08T00:56:00.000-06:00

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

2008-07-01T08:20:00.000-06:00

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.