Renal Failure Lecture Notes PDF

Renal failure Lecture 20 Unit 3 Table of contents 1. Classifications (covered in introduction) 2. Acute renal injury 3. Chronic kidney disease 2. Acute kidney injury Inulin: only gets filtered, best way to define GFR AKI: drop in...

Renal failure Lecture 20 Unit 3 Table of contents 1. Classifications (covered in introduction) 2. Acute renal injury 3. Chronic kidney disease 2. Acute kidney injury Inulin: only gets filtered, best way to define GFR AKI: drop in GFR within 3 months, associated with creatinine rise CKD: progressive drop in GFR 1. Prerenal injury longer than 3 months, drop in albumin albumin in urine - characterized as a marked dec. in renal blood flow ; etiologies include: 1) dec. vascular volume due to hypovolemia (hemorrhage or ECF volume loss), distributive shock (expansion of vascular comp.), or use of vasoactive medications. 2) impaired perfusion due to heart failure and cardiogenic shock. 3) impairment of renal compensation mechanisms due to medications. 3 2. Acute kidney injury 1. Prerenal injury - kidneys receive 20-25% of the cardiac output. - this is necessary to remove wastes and balance fluids and electrolytes and provide blood to the renal structures. - kidneys can tolerate large changes in perfusion: up to a 75% dec. in blood flow. - tubular epithelial cells are vulnerable to ischemia and toxins, during which they can aggravate interstitial inflammation and fibrosis. 1.2 million nephrons in each kidney kidney transplant: other compensates by hypertrophy 4 2. Acute kidney injury 1. Prerenal injury: vasoactive compounds - these compounds contribute to glomerular hypoperfusion via different mechanisms. - ACE inhibitors and angiotensin receptor blockers reduce the effect of renin to inc. renal perfusion. restrict blood flow : hypoperfusion of the kidneys - NSAIDs exacerbate hypoperfusion by preventing blood vessel dilation. - vasoactive drugs and mediators that cause vasoconstriction will also cause hypoperfusion. 5 2. Acute kidney injury 1. Prerenal injury: manifestations - a sharp dec. in urine output due to a dec. in GFR. - a disproportionate inc. in BUN compared to creatinine. Text - a normal BUN to creatinine ratio is 10:1 - prerenal failure BUN to creatinine ratio rises to 15:1 to 20:1. creatinine is excreted BUN is reabsorbed : urea is used to concentrate our urine body reabsorbs urea: less toxic than ammonia 6 2. Acute kidney injury prerenal:c an lead to ischemia: ischemia will cause intrinsic injuries 2. Intrinsic injury - this occurs with damage to the glomerulus, tubular structures, or interstitial cells. - damage results from acute tubular necrosis , and there a few etiologies: 1) prerenal injury resulting in ischemia, 2) nephrotoxic drugs, 3) tubular obstruction, and 4) injury from infection. - acute glomerulonephritis (inflammation of the glomerulus) and pyelonephritis (caused by sepsis) are examples of this type of AKI. 7 2. Acute kidney injury 2. Intrinsic injury drop in GFR - as with other forms of AKI, GFR is decreased. - nephrotoxicity -related glomerulonephritis results from ischemia, direct tubular damage, or intratubular obstruction. - toxicity is more common in the kidneys because of the its rich blood supply and ability to concentrate toxins. 8 2. Acute kidney injury 2. Intrinsic injury: nephrotoxic drugs - antimicrobials like aminoglycosides (gentamicin) damage the PCT. - chemotherapeutic drugs accumulate and also damage the PCT. - radiocontrast agents cause ALD: sodium retention at the expense of Na+/K+ pump direct tubular cell and endothelial cell toxicity via DNA damage. loop: water reabsorbtion 9 2. Acute kidney injury 2. Intrinsic injury: intratubular obstruction myloglobin: in muscle breakdown, RBC breakdown - presence of myoglobin , hemoglobin , excess uric acid, and myeloma light chains in the urine is indicative of an obstruction. WBC cancer - presence of myoglobin results from muscle trauma (as in rhabdomyolysis); it can precipitate in the urine causing an obstruction. - presence of hemoglobin can occur due to transfusion reactions. produced by cancerous cells: Mast destruction of cancer cells : because of chemo and radiation - presence of myeloma light chains can occur after massive tumor destruction during treatment or widespread malignancy. 10 2. Acute kidney injury Phases of acute tubular necrosis - injury marks the initiating phase , and next, maintenance phase , we see a marked dec. in GFR and retention of toxic metabolites. - retention of metabolites can cause fluid retention (edema, water toxicity, and pulmonary congestion) causing hypertension. - retention of potassium can cause hyperkalemia. - recovery phase begins as urine output inc. and serum urine output is improved creatinine, potassium, and BUN levels gradually fall (but may remain elevated for some time). 11 2. Acute kidney injury 3. Postrenal injury - results from obstruction of urine flow from the kidneys; obstruction can occur in the ureters, bladder, or urethra. - obstruction causes reflux of urine into the renal pelvis, impairing kidney function. - prostatic hyperplasia and prostate cancer is a common underlying problem in males. - calculi (stones), trauma, and extrarenal tumors are other common causes. - treatable if identified before permanent kidney injury. 12 2. Acute kidney injury Diagnosis and treatment - due to high morbidity and mortality, early detection is key. - AKI is defined as an abrupt drop (in less than 3 months) in GFR and rise in serum creatinine. - monitoring urine output and urine osmolarity and sodium levels; fractional excretion of sodium helps differentiate prerenal azotemia (low GFR without impaired reabsorption) from tubular necrosis (low GFR with impaired reabsorption). - blood tests will monitor BUN, creatinine, metabolic acidosis, and hyperkalemia. 13 2. Acute kidney injury kidneys are damaged they cant reabsorb sodium Diagnosis and treatment - important to identify and correct the cause ; is it improving renal perfusion or stopping nephrotoxic drugs? - adequate caloric intake is necessary to prevent the use of proteins for energy (inc. nitrogenous wastes). - infections must be prevented or treated quickly as sepsis can cause tubular necrosis to progress further (if an underlying cause). - dialysis may be necessary if maintaining fluid volume and electrolyte levels is impossible by other means. 14 3. Chronic kidney disease Physiological changes in CKD - damage to and loss of nephrons contributes to dec. GFR, dec. tubular reabsorption, and dec. endocrine function. - largely asymptomatic until ~half of nephrons remain (i.e. stage 4 or 5). 3-4 - remaining nephrons hypertrophy to compensate. - damaged areas develop fibrotic scar tissue and can no longer support nephrons, permanently reducing the kidney’s functional capacity. 15 3. Chronic kidney disease Progressive loss of renal function - categorized across three stages: 1) decreased renal reserve, 2) renal insufficiency, and 3) uremia. development of azotemia: - decreased renal reserve occurs as 10-20% of nephrons are lost (i.e. stage 1 or 2). - we see : a dec. in GFR, serum creatinine is normal or high, serum urea levels are normal. - largely asymptomatic because remaining nephrons compensate. 16 3. Chronic kidney disease in DKA: glucose pulls water by osmosis : in CKD: sodium Progressive loss of function during kidney failure - renal insufficiency occurs as 30-80% of nephrons are lost (i.e. stage 3 or 4). - GFR progresses to 20-50% normal - capacity. hyponatremia and azotemia (↑ BUN and Cr) occur as reabsorption and secretion are impaired. plasma high levels of sodium early on: hyponatremia and azotemia urine is isotonic to blood: loss of water and sodium uremia: end level of - salt wasting causes osmotic diuresis ; the elimination of large volumes of conc. urine. Kidneys release: EPO (anemia), renin (BP) (hypotension because of water retention, calcitiriol - anemia occurs and the heart compensates by inc. CO and inc. patient’s BP. 17 3. Chronic kidney disease Progressive loss of function during kidney failure - uremia describes end-stage kidney failure where 90% of nephrons are lost (i.e. stage 5). thickening of the filtration barrier: fewer things are going through - GFR is now less than 15 ml/min/1.73m2. - water, electrolytes, and wastes are retained , and all body systems are affected. - oliguria or anuria develops. - renal replacement therapy (dialysis or transplant) is now necessary. 18 3. Chronic kidney disease Signs and symptoms - symptoms of CKD are associated with uremia (“urine in the blood”). - azotemia progresses to uremia as BUN levels rise beyond 7.1 mmol/L. 19 3. Chronic kidney disease Signs and symptoms - early sign of CKD is urine isotonic with plasma (isosthenuria) leading to hyponatremia (salt wasting). - chronically , as nephrons die and GFR dec. further, fluid and ions retained; this inc. vascular volume. - this can exacerbate heart conditions and lead to heart failure ; edema is also common. 20 3. Chronic kidney disease Signs and symptoms - chronically, renin-synthesis capacities are impaired, hyperkalemia occurs. - H + secretion and HCO 3- reabsorption is altered; this may cause metabolic acidosis if fixed acids are not secreted or if HCO3- is lost via diarrhea. osteodystrophies: bones exchange calcium with ions - acidosis may not be present as bones buffer the blood by exchanging H+ and Ca2+. 21 3. Chronic kidney disease hydroxyapetite (mineral from teeth) Signs and symptoms - chronically, hypocalcemia occurs as calcitriol production drops: 1) Ca2+ is not absorbed from food and 2) Ca2+ is lost in the urine. - hyperparathyroidism occurs as PTH secretion inc. and osteodystrophies occur as calcium is leached from bone. parathyroidism: parathyroid exhaustion: Low PTH - along with calcium released from bone is phosphate, hyperphosphatemia occurs. 22 3. Chronic kidney disease Signs and symptoms - osteodystrophies describe impaired bone remodeling and decreased bone density. - decreased bone density may lead to muscle weakness. 23 3. Chronic kidney disease Signs and symptoms - hematological disorders also occur for a few reasons: - erythropoietin production is impaired, blood loss (coagulopathies), bone marrow suppression (uremia), and Fe deficiencies (uremia-related anorexia). - anemia must be monitored and treated, as hypoxemia may occur. 24 3. Chronic kidney disease Signs and symptoms - hypertension in CKD is multifactorial: - hypervolemia occurs due to fluid retention. - treating hypertension slows the progression of CKD , and may prevent heart failure (ventricular hypertrophy due to inc. vascular volume). 25 3. Chronic kidney disease Signs and symptoms - uremic encephalopathy : a reduction in awareness and alertness. - uremia suppresses the immune system. - pruritus results from crystallization of phosphate salts on the skin; scratching breaks the skin and predisposes patient to infections. - drug and drug metabolite excretion is impaired; these may be nephrotoxic, while some drugs contain other electrolytes. 26 3. Chronic kidney disease Diagnosis - CKD is diagnosed if GFR progressively dec. over 3 or more months and presents with albuminuria. - in early stages (2 or 3), we see osmotic diuresis; large volumes of conc. urine are produced and patient may be hyponatremic and azotemic. - in later stages (4 or 5), azotemia progresses to uremia and renal insufficiency is so great that water, electrolyte, and wastes are retained: - hypervolemia, hyperkalemia, hyperphosphatemia occur. - endocrine disregulation leads to anemia (↓ EPO) and hypocalcemia (↓ calcitriol). 27 3. Chronic kidney disease Treatment - there are three treatment strategies to consider: 1) Slowing the progression of kidney disease 2) Dialysis and transplantation 3) Dietary management 28 3. Chronic kidney disease Treatment: 1) Slowing its progression - this is largely related to controlling blood pressure with anti-hypertensive medications. - high BP causes proteinuria (due to inc. glomerular filtration); ACE inhibitors help dilate efferent arterioles. - reducing or quitting smoking ; effects of smoking incl. inc. BP, intraglomerular pressure, albumin excretion, and endothelial cell dysfunction. high blood pressure damages the glomerulus and thickens the filtration barrier faster 29 3. Chronic kidney disease Treatment: 1) Dialysis and transplantation - dialysate solution ensures solutes move in or out or remain in the blood. - potassium and wastes are hypotonic, ensuring these move out of the blood. - other solutes may be adjusted according to need ; bicarbonate may be hypertonic to treat acidosis. - success of transplantation depends on level of histocompatibility, organ quality, and immunological management. 30 3. Chronic kidney disease maintain essential amino acids in nutrition: produce a lot of ammonia tho Treatment: 3) Dietary management - this management depends on kidney function: - for example, in early stages when osmotic diuresis occurs, salt and water wasting may require fluid resuscitation and maintaining sodium levels. - in later stages , when patients is uremia, hypervolemic, and hypertonic, water intake must be restricted (to prevent volume overload ) and electrolytes must be managed. - protein-restricted diets , considered against protein malnutrition, will dec. BUN levels and manage hyperphosphatemia and acidosis. 31 3. Review Questions - How is urine made and how is it concentrated? - Other than filtrating the blood, what are some of the other important roles of the kidneys? - What is GFR? What can affect GFR? Is serum creatinine a good way of measuring GFR? - What are the 3 categories of acute renal failure? - What are the phases of acute tubular necrosis? What are some key events that occur in each phase? Are the treatments the same for all phases? - What are the stages of chronic kidney disease? What are the signs and symptoms of renal insufficiency and uremia? - What are the treatments for chronic kidney failure? 32