Part Three: Etiology & Pathophysiology of Chronic Kidney Disease Hi my name is Tes Parent, I am the nurse educator for the Community Hemodialysis units in providence Health. I don’t usually apologize before I start a presentation but I would have loved to do this presentation live for you as scheduled so that I would have been able to address any concerns or questions that you had regarding this topic. Currently, I am out of town and will be returning by March 23, 2015. In which time if you need to contact me feel free either by phone or email. My contact info is attached to this presentation at the end. So in your kidney pathophysiology presentation you had reviewed the function and structure of the kidney. That presentation talked about what is normal what I have been assigned to discuss is what is abnormal. What conditions can cause permanent damage to the kidneys or effect it's function I want you to keep in mind that Structure relates to function. And when you alter the structure you are altering the function. By T. Parent Nurse Educator, PHC Community Hemodialysis Units 2015

Interstitial Diseases overproduce monoclonal Ig Bence Jones proteins Myeloma obstructive disorders nephrotoxic drugs Acute tubular necrosis (ATN) Myeloma obstructive disorders: Patients with multiple myeloma overproduce monoclonal Ig light chains (Bence Jones proteins); these light chains are filtered by glomeruli, are nephrotoxic, and can damage virtually all areas of the kidney parenchyma. Acute tubular necrosis (ATN) is kidney injury characterized by acute tubular cell injury and dysfunction. Common causes are hypotension or sepsis that causes renal hypoperfusion and nephrotoxic drugs. The condition is asymptomatic unless it causes renal failure. The diagnosis is suspected when azotemia develops after a hypotensive event, severe sepsis, or drug exposure and is distinguished from prerenal azotemia by laboratory testing and response to volume expansion. Treatment is supportive. hypotension sepsis

Congenital, developmental and genetic disorders inherited disorder sensory loss Alport syndrome Genetic mutation inherited disorder So thou your presentation on pediatric disorders covers these topics I am going to briefly describe a few of them. Alport syndrome is an inherited progressive form of glomerular disease that is often associated with sensorineural hearing loss and ocular abnormalities. Genetic mutation of genes that are normally located in various basement membranes of the kidney, cochlea, and eye The primary indicator of Alport syndrome is a family history of chronic glomerular disease, although it may also involve hearing or vision impairment. This syndrome affects both men and women, but men are more likely to experience chronic kidney disease and sensory loss. Men with Alport syndrome usually first show evidence of renal insufficiency while in their twenties and reach total kidney failure by age 40. Women rarely have significant renal impairment, and hearing loss may be so slight that it can be detected only through testing with special equipment. Usually men can pass the disease only to their daughters. Women can transmit the disease to either their sons or their daughters. Treatment focuses on controlling blood pressure to maintain kidney function. Fabry disease is an inherited disorder that results from the buildup of a particular type of fat, called globotriaosylceramide, in the body's cells. Beginning in childhood, this buildup causes signs and symptoms that affect many parts of the body. Characteristic features of Fabry disease include episodes of pain, particularly in the hands and feet (acroparesthesias); clusters of small, dark red spots on the skin called angiokeratomas; a decreased ability to sweat (hypohidrosis); cloudiness of the front part of the eye (corneal opacity); problems with the gastrointestinal system; ringing in the ears (tinnitus); and hearing loss. Fabry disease also involves potentially life-threatening complications such as progressive kidney damage, heart attack, and stroke. Some affected individuals have milder forms of the disorder that appear later in life and affect only the heart or kidneys. Leads to insufficient breakdown of lipids causing a harmful build up of lipids. Genetic Fabry disease buildup of a particular type of fat, called globotriaosylceramide

Cystic Diseases Autosomal Dominant Polycystic Kidney Disease Polycystic Kidney Disease (PKD): Polycystic means “many fluid-foiled sacs” or “many cysts. It is a genetic disorder but on rare occasion it can be a genetic mutation ADPKD Usually referred to as adult PKD as it normally becomes apparent in adult life between ages of 30 and 40 years old. However it is know that children can now develop the disease. Only one parent needs this disease to pass it on. If one parent has it the kids have 50% chance of getting it. It some cases there can be no family history present. However, there could have be actually family members affected with the disease but didn’t show any signs or symptoms before dying of other causes. ARPKD less common S&S different because they usually appear shortly after birth but sometimes it can appear later in childhood or during adolescence. Both parents need to carry a gene and every child has 25% chance of getting the disease. This disease has the ability to form cyst also in other organs such as the liver. Cyst that form clusters and are non cancerous A normal kidney weights less than one- third of a pound while a kidney containing cyst can weigh as much as 20 to 30 pounds How does Polycystic kidney disease affect the kidneys? Pressure from expanding cysts, compressing normal kidney tissue Scarring in the normal support tissue in the kidney Autosomal Dominant Polycystic Kidney Disease Autosomal Recessive Polycystic Kidney Disease

Obstructive Disorders Kidney Stones Birth Defects narrowing of the upper or lower ureter Enlarged prostate Obstruction caused in the ureter or outlet of the bladder Kidney stones are made up of calcium and other minerals normally found in urine. Small masses of these elements are formed into kidney stones. Some people are more prone to stone formation and developed frequent kidney stones that cause damage to the kidneys. Kidney stones sometimes cause obstructions and infection and when they pass through the urinary tract, they cause extreme pain. Drinking lots of water, taking medication prescribed by your physician, and certain treatments can help kidney pass out of the body, usually in the urine. We will talk about tumours in the next couple of slides. Enlarged prostate you can see visually that it is blocking the flow of urine by compressing onto the urethra. Birth defects narrowing of the upper or lower ureters. Tumors

Kidney function during pregnancy Anatomical positioning mechanical obstruction high levels of progesterone dilation of the upper urinary tract increase in the glomerular filtration rate increase in the creatinine clearance decrease in the serum creatinine and BUN Like the heart, the kidneys work harder throughout pregnancy. The kidney undergoes tremendous anatomic and physiologic changes during pregnancy. After the 12th week of gestation, There is a significant dilation of the upper urinary tract (the renal calyses and ureters), primarily due to the mechanical obstruction of the ureters at the pelvic brim by the enlarged uterus. These changes may contribute to the frequency of urinary tract infections during pregnancy. The dilatation is also facilitated by the high levels of progesterone (which is a smooth muscle relaxant). Of particular importance is the fact that these anatomic changes may persist for up to 6 weeks postpartum and may be mistaken for other causes of obstructive uropathy. As early as the 8th or 10th week of gestation there is an increase in blood volume and cardiac output. The volume of blood filtered by the kidneys reaches a maximum between 16 and 24 weeks and remains at the maximum until just before the baby is due. Then, pressure from the enlarging uterus may slightly decrease the blood supply to the kidneys. Increase glomerular filtration rate of 40 to 50% of normal. This is the only condition know to medicine that can increase the glomerular filtration rate that much. evidenced by a decrease in the serum creatinine and BUN as well as an increase in the creatinine clearance The decrease in serum creatinine and BUN is very important from a clinical standpoint. Pregnant patients who have a serum creatinine or BUN at the upper limit of normal as defined by the laboratory for non-pregnant individuals should be viewed with marked suspicion of renal impairment. The serum creatinine should normally be below 0.8 mg% and the BUN below 13 mg% in the pregnant patient. [ 1 ] Plasma concentrations of electrolytes, glucose and urea, fall if more water than sodium, for example, is retained. Over the whole period of gestation there is retention of 7.5L of water and 900 mmol of sodium. Activity of the kidneys normally increases when a person lies down and decreases when a person stands. This difference is amplified during pregnancy—one reason a pregnant woman needs to urinate frequently while trying to sleep. Late in pregnancy, lying on the side, particularly the left side, increases kidney activity more than lying on the back. Lying on the left side relieves the pressure that the enlarged uterus puts on the main vein that carries blood from the legs. As a result, blood flow improves and kidney activity increases. The uterus presses on the bladder, reducing its size so that it fills with urine more quickly than usual. This pressure also makes a pregnant woman need to urinate more often and more urgently. electrolytes increasing blood volume and cardiac output glucose Fluid retention urea

Bacterial endocarditis Infectious Diseases Pyelonephritis HIV Acute post-streptococcal glomerulonephritis (PSGN) Pyelonephritis –caused by bacterial infections that have spread up the urinary tract or travelled through the blood stream to the kidneys Kidney infection typically occurs when bacteria enter your urinary tract through the tube that carries urine from your body (urethra) and begin to multiply. Bacteria from an infection elsewhere in your body also can spread through your bloodstream to your kidneys. Kidney infection is unusual through this route, but it can happen — for instance, if you have an artificial joint or heart valve that becomes infected. Rarely, kidney infection results after kidney surgery. Glomerular disease sometimes develops rapidly after an infection in other parts of the body. Acute post-streptococcal glomerulonephritis (PSGN) can occur after an episode of strep throat or, in rare cases, impetigo (a skin infection). The Streptococcus bacteria do not attack the kidney directly, but an infection may stimulate the immune system to overproduce antibodies, which are circulated in the blood and finally deposited in the glomeruli, causing damage. PSGN can bring on sudden symptoms of swelling (edema), reduced urine output (oliguria), and blood in the urine (hematuria). Tests will show large amounts of protein in the urine and elevated levels of creatinine and urea nitrogen in the blood, thus indicating reduced kidney function. High blood pressure frequently accompanies reduced kidney function in this disease. PSGN is most common in children between the ages of 3 and 7, although it can strike at any age, and it most often affects boys. It lasts only a brief time and usually allows the kidneys to recover. In a few cases, however, kidney damage may be permanent, requiring dialysis or transplantation to replace renal function. Bacterial endocarditis, infection of the tissues inside the heart, is also associated with subsequent glomerular disease. Researchers are not sure whether the renal lesions that form after a heart infection are caused entirely by the immune response or whether some other disease mechanism contributes to kidney damage. Treating the heart infection is the most effective way of minimizing kidney damage. Endocarditis sometimes produces chronic kidney disease (CKD). HIV, the virus that leads to AIDS, can also cause glomerular disease. Between 5 and 10 percent of people with HIV experience kidney failure, even before developing full-blown AIDS. HIV-associated nephropathy usually begins with heavy proteinuria and progresses rapidly (within a year of detection) to total kidney failure. Researchers are looking for therapies that can slow down or reverse this rapid deterioration of renal function, but some possible solutions involving immunosuppression are risky because of the patients' already compromised immune system. Hemolytic Uremic Syndrome (HUS), commonly referred to as “Hamburger Disease”, is a disease that affects the kidneys and other organs. It poses a substantial threat to Canadian children as on of the leading causes of both acute and chronic kidney failure. It follows a gastrointestinal illness caused primarily by a particular strain of bacteria known as E. Coli 0157: H7. This strain is know to produce toxins Bacterial endocarditis Hemolytic uremic syndrome

Drugs and medications Reflux nephropathy Toxic nephropathies Drugs and medications Reflux nephropathy Reflux nephropathy – kidneys scarred because of abnormal flow of the urine from the bladder into the kidney usually affects children. Normally, as the bladder empties, the ureter closes automatically to prevent urine being forced backwards up the ureter towards the kidneys. In both of these diagrams, the kidney on the right is shown 'cut open'. In  reflux, the valves don't close, and urine is forced back towards the kidney - REFLUX. This may also be called vesico-ureteric reflux, because the urine goes from the bladder (vesico-) to the ureter. In this illustration the kidneys are both scarred, the right more than the left. Drug and medications induced kidney problems: There is always a cause and affect to everything we consume. Illegal drugs have many negative effects on the body, including damage to the kidneys. Heroin users are more likely to develop kidney disease compared to users of other illegal drugs. Over-the-counter (OTC) medicines such as pain relievers like ibuprofen and acetaminophen can negatively affect the kidneys. Talk to your doctor before you take any type of over-the-counter medicine. Herbal products may contain ingredients that are harmful to your kidneys. Although the marketing of these products may entice you to try them, be aware there have been numerous cases of kidney damage related to herbal supplements.

Autoimmune disorders Good Pasteur's syndrome Scleroderma autoantibody that specifically targets the kidneys and the lungs Scleroderma hardening connective tissue Systemic Lupus Nephritis Lupus nephritis is kidney inflammation caused by systemic lupus erythematosus (SLE or lupus). SLE is an autoimmune disease a disorder in which the body’s immune system attacks the body’s own cells and organs. Up to 60 percent of people with SLE are diagnosed with lupus nephritis, which can lead to significant illness and even death.1 When the body's immune system functions properly, it creates protein-like substances called antibodies and immunoglobulins to protect the body against invading organisms. In an autoimmune disease, the immune system creates autoantibodies, which are antibodies or immunoglobulins that attack the body itself. Autoimmune diseases may be systemic and affect many parts of the body, or they may affect only specific organs or regions. Systemic lupus erythematosus (SLE) affects many parts of the body: primarily the skin and joints, but also the kidneys. Because women are more likely to develop SLE than men, some researchers believe that a sex-linked genetic factor may play a part in making a person susceptible, although viral infection has also been implicated as a triggering factor. Lupus nephritis is the name given to the kidney disease caused by SLE, and it occurs when autoantibodies form or are deposited in the glomeruli, causing inflammation. Ultimately, the inflammation may create scars that keep the kidneys from functioning properly. Goodpasture's Syndrome involves an autoantibody that specifically targets the kidneys and the lungs. Often, the first indication that patients have the autoantibody is when they cough up blood. But lung damage in Goodpasture's Syndrome is usually superficial compared with progressive and permanent damage to the kidneys. Goodpasture's Syndrome is a rare condition that affects mostly young men but also occurs in women, children, and older adults. Scleroderma: Scleroderma is an autoimmune, rheumatic, and chronic disease that affects the body by hardening connective tissue. Amyloidosis is the general term used to refer to the extracellular tissue deposition of fibrils autoantibodies form or are deposited in the glomeruli, causing inflammation Amyloidosis extracellular tissue deposition of fibrils