Coagulation Disorders

Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE) are often not optimally diagnosed by many physicians. These are serious but preventable medical conditions. Deep Vein Thrombosis (DVT) is a medical condition which occurs when a blood clot forms in deep vein. These clots usually could develop in the lower leg, thigh, or pelvis. These can also occur in arm. One should have knowledge about DVT, because it can happen to anybody and can cause serious illness, disability and morbidity. DVT is preventable and treatable if detected early.

Pulmonary Embolism (PE) is also referred to as complication of DVT. It happens when part of the clot breaks off and travels through the blood stream to the lungs, causing a blockage called Pulmonary Embolism (PE). If the clot is small; with appropriate treatment, people can recover from PE. However, there could be some damage to the lungs. If the clot is large, it could stop the blood reaching lungs and can be fatal.

Risk Factors that could cause DVT

Anybody can have a DVT. However, the factors listed below could increase the chance if having DVT. The chance increases for someone who has more than one of these factors at the same time.

·         Hospitalization and some major surgery.

·         Being bedridden for long time due to illness.

·         Travelling for extended time beyond four hours in continuity.

·         Older age.

·         Overweight or obese

·         Family history of Venous Thromboembolism (VTE.)

·         During and just after pregnancy.

·         Hormonal contraceptive medication (Estrogen based medication).

·         Hormonal Replacement Therapy (HRT).

·         Trauma due to injury.

Preventing tips for DVT

Following tips could help prevent DVT:

·         Move around as soon as possible after having confined to the bed, after illness, injury, or surgery.

·         If you are at risk of DVT talk to your Physician/Surgeon for appropriate medication.

·         When sitting for long periods of time such as travelling for more than 4 hours; get up and walk around after 1 to 2 hours.

·         Raising and lowering your heels while keeping your toes on floor.

·         Raising and lowering your toes while keeping your heels on the floor.

Symptoms of DVT

Most of the people with DVT have no symptoms at all. The following are the most common symptoms of DVT that could occur in affected part of the body:

·         Swelling

·         Pain

·         Redness of the skin

·         Tenderness

If you have any doubt of having DVT consult your doctor as soon as possible.

Pulmonary Embolism (PE)

One can have Pulmonary Embolism (PE) without any symptoms of a DVT. Signs and symptoms of PE could be:

·         Difficulty in breathing

·         Faster than normal or irregular heartbeat.

·         Uneasiness

Coagulation Mechanisms of our Body

Our blood is a very complex tissue of our body, in the form of a fluid. It plays a variety of roles for homoeostasis. Our blood has cellular and noncellular components uniformly suspended in liquid phase. Blood plays multiple roles in our body for sustain life and longevity. There are three types of cells in our blood:

·         Red Blood Cells (RBCs) or Erythrocytes

·         White Blood Cells (WBCs) or Leucocytes

·         Platelets

Red Blood Cells (RBCs) or Erythrocytes provide red color to our blood. RBCs carry oxygen from lungs to various organs and parts of our body. White Blood Cells (WBCs) provide us natural and acquired immunity. Platelets along with other soluble coagulation factors (CFs) take part in coagulation of blood to safeguard us from internal of external bleeding. There are ‘XIII’ coagulation factors (CFs) in our blood. We know the chemistry and role of all the coagulation factors. Coagulation of Blood occurs through two mechanisms:

·         Intrinsic Pathway and

·         Extrinsic Pathway

Both the coagulation mechanisms involve various coagulation factors and finally lead to activation of factor ‘X’. Factor ‘X’ along with certain factors leads to formation of Thrombin from Prothrombin. Thrombin is central in clotting process, and it converts Fibrinogen to Fibrin; activates factor ‘V’, ‘VIII’ and ‘XI’, leading to generation of more Thrombin and stimulation of Platelets. Further by activating factor ‘XIII’, thrombin favors the formation of cross-linked bonds among Fibrin molecules, thus stabilizing the clot.

This determines that direct inhibition of Thrombin is a highly desirable target for prophylaxis and therapy of various Coagulation Disorders (CDs). Thrombin  has 3-sites for target activation:

Sites 1 and 2 are called Exosites and site-3 is called an active site. Exosite-1 is the Fibrin binding site of Thrombin and Exosite-2 serves as the Heparin-Binding Domain. The clotting pathway has traditionally been inhibited by using Heparin and Warfarin for treatment and prophylaxis of Coagulation Disorders (CDs).

Heparin inhibits free Thrombin by binding simultaneously to Exosites on Thrombin and Antithrombin, forming a Heparin-Thrombin-Antithrombin Complex. But Heparin cannot inhibit Fibrin bound Thrombin. Heparin can bind independently to Fibrin and Thrombin to form Fibrin-Heparin-Thrombin bridge.

It has been documented that both unfractionated heparin (UFH) and low molecular weight heparin (LMWH) are associated with variable anticoagulant effect and heparin induced thrombocytopenia (HIT) in around 3% cases. Warfarin acts as a Vitamin-K antagonist to inhibit formation of clotting factors (II, VII, IX, X). Vitamin-K antagonists have a number of shortcomings, including a delayed onset of action and interindividual variability in anticoagulant effect. Other drugs and foods have also been reported to alter anticoagulant effect of Vitamin-K antagonists. Anticoagulant treatment requires regular and frequent monitoring.

The effectiveness of heparin and warfarin in prophylaxis and treatment of various thromboembolitic disorders has been well established.  Effective use of these drugs comes with a steep cost of various side effects and problems like bleeding tendencies and immune thrombocytopenia. Parenteral administration needs hospitalization and constant monitoring during therapy.

Happy New Year - 2018

Dr. CS Rayat wishes his Followers & Friends “A Very Happy & Prosperous New Year-2018”.

“May every ray of the Sun fill your life with Success and Ultimate Happiness in 2018”

CS Rayat

Tuberculosis of Kidneys and Genital Glands

The tuberculosis of kidneys, testicles or ovaries (genital glands) is always secondary to primary lesion in the lungs, lymph glands or bones. The tuberculosis of kidneys may occur in early adult life. In the beginning it is commonly confined to one kidney but can spread to second kidney if chemotherapy is delayed. If the disease is not detected and treated well in time, it may spread to urinary bladder. In addition to low grade fever in the evening, feeling of general weakness and loss of appetite, it has three additional symptoms: increased frequency of urination, painless hematuria or passage of red blood cells or blood in the urine and a feeling of dull pain in the lower back or region of loin. The 'tubercular toxemia' is there. The treatment with anti-tubercular drugs is must to avoid surgical nephrectomy.

The tuberculosis of testicles or ovaries (genital glands) is also a serious manifestation of pulmonary tuberculosis. Initially there is swelling of one testicle in the male patient which can be easily felt. Later on it may transform into 'cold abscess' and a sinus is produced. Such patients show highly reactive 'tuberculin test'. The diagnosis is not difficult in a case of 'tuberculosis of ovary'. The swelling of the ovary can be palpated by experienced gynaecologist or can be detected by abdominal ultrasonography. The diagnosis can be confirmed easily by 'fine needle aspiration cytology' (FNAC). The signs and symptoms of 'tubercular toxemia' are there as stated in the case of tuberculosis of kidneys. The treatment with anti-tubercular drugs is must to avoid surgical removal of testicle or ovary.

The treatment begins with active anti-tubercular therapy by the use of at least three drugs and a longer course of treatment may be required in these cases. Surgical treatment will be required if the medical treatment alone is not capable of controlling the disease. If the disease is unilateral in one kidney or one testicle and there is no arrest of the disease with medical treatment, these organs would have to be removed surgically with informed consent of the patient.

To read more about ‘tuberculosis of lymph glands’ just click the following link: http://ntips4u.blogspot.in/2014/03/tuberculosis-of-lymph-glands-common.html

Dialysis Technology: Application of dialysis in acute renal failure !

Our kidneys are destined to perform excretory as well as regulatory function to maintain a state of homoeostasis in our body. Acute renal failure (ARF) is a syndrome defined as sudden or rapid loss of renal function (kidney function) leading to accumulation of urea and creatinine (nitrogenous waste compounds). If hyperbolic relationship between plasma creatinine or urea and glomerular filtration rate (GFR) is observed after investigations, the diagnosis is established as ARF. The early clinical signs of ARF/uremia are anorexia, nausea, vomiting, and sometimes pericarditis also. The ARF is an implication of loss of more than 50% of renal function. Dialysis should be instituted whenever early signs of uremia (elevated levels of urea in the blood) are present. Cases of metabolic acidosis as well as electrolyte and fluid imbalance also need dialysis for the reversal of hemodyanmics to normal.

Dialysis is a procedure for artificially purifying the blood of a patient through meticulous surgical intervention and electromechanical equipment. No specific elevated value of plasma creatinine or urea could be regarded as critical. The fluid intake and nutritional requirements are taken into consideration for deciding the timing and mode of dialysis. Cases of ARF should be put on dialysis without much delay for the successful recovery of their renal function. However, cases of chronic renal failure (CRF) may be kept in waiting. The dialysis procedure is of two types: i)  Hemodialysis (where patient's blood is passed through artificial kidney in conjunction with dialysis solution) and ii)  Peritoneal dialysis (where dialysis fluid is passed through the abdominal peritoneal cavity of the patient). The technique of dialysis was established long back in USA by Dr. Alan P Kendal, who also patented a 'suitcase kidney' in 1978.

Conventional hemodialysis remains the preferred and the best mode of dialysis. The hemodialysis is ideal for non-hypotensive and hemodynamically stable patients. Peritoneal dialysis is probably less effective in patients with hypercatabolic disorder and/or with undiagnosed abdominal disease. Peritoneal dialysis should be avoided in patients with recent abdominal surgery. The surgical intervention for hemodialysis can be in the following ways: i)  Continuous arteriovenous hemofiltration (CAVH), ii)  Continuous arteriovenous hemofiltration with/without concomitant dialysis (CAVHD), iii)  Continuous veno-venous filtration (CVVHD). These hemodialysis techniques are simpler, safe and very effective. The biochemical recovery is monitored during the dialysis for needful correction of fluid and electrolytes. After successive dialysis sessions the patient would return to normal health.

How does kidney develop during gestation ?

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.