nikki & mon CHRONIC RENAL FAILURE CRF: irreversible destruction of nephron mass : alteration of function of virtually every

organ of the body : UREMIA- signs and symptoms brought about by profound loss of renal function ( w/ laboratory evidence) PATHOPHYSIOLOGY - initiating mechanism specific to the underlying etiology - Compensatory mechanism o Common consequence ff. long term reduction of renal mass o Hypertrophy- vasoactive molecules, expression of cytokines & Growth Factors, induced by HYPERFILTRATION (increased capillary pressure & flow) Later lead to MALADAPTATION CHRONIC KIDNEY DISEASE Kidney damage >= 3 mos., structural/functional, with or w/o Decrease in GFR, manifested by: - Pathologic abnormalities - Markers of Kidney damage o Abnormality of composition of blood or urine or abnormality in imaging studies GFR < 60 cc/min/1.73 cm2 for >= 3 mos., with or w/o kidney damage CHRONIC RENAL FAILURE 1. Kidney Damage (KD) Normal or GFR 2. KD w/ mild GFR 3. Moderate GFR Sxs evident 4. Severe GFR 5. Kidney Failure

AZOTEMIA- retention of nitrogenous waste due to renal insufficiency (Serum Crea/ BUN) UREMIC toxins - Urea (anorexia, malaise, vomiting, headache) - Guanidinosuccinic acid (platelet dysfunction) - PTH UREMIA: impairment of metabolic and endocrine functions subserved by the kidney PATHOPHYSIOLOGY - Conseq. to the accumulation of products of protein metabolites - Conseq. to loss of other renal functions i.e. Fluid and Electrolytes, hormonal d/o UREMIC SYNDROMES Metabolic Hypothermia- decrease in active transport of Na+ across cell membrane Azotemic pseudodiabetes- peripheral resistance to Insulin despite relative insulin o no need for Treatment of diabetes sx! Protein Intolerance- ability to eliminate products of protein catabolism Hypertriglyceridemia & HDL: accelerated atherosclerosis Fluid and Electrolytes, Acid-Base

total Na+ and water contributes to Hypertension leading to further decline in GFR (Interglomerular pressure ) Hyponatremia, Hypernatremia (extrarenal loss of water) K+ derangement: < 10 GFR, or endogenous or exogenous source

GFR>=90 GFR 60-89 GFR 30-59 GFR 15-29 GFR <15 or dialysis

Adaptation by colon and renal distal tubule via Aldosterone effect - HyperKalemia > HypoKalemia (usu.hereditary) (GI) METABOLIC ACIDOSIS- in total daily excretion of acid and buffer (NH3) production

CRF

- Normal annual decline in GFR- 1 cc/min/1.73cm

CKD can normally acidify their urine in the majority of cases

(start at 20-30 years of age up to GFR 70 of 70 yrs of age) - Use of MDRD (Levey) or the Cockroft Gault formulae

- Persistent albuminuria also as marker of nephron

injury (>17mg/mg Crea M; >25 mg/gm Crea F) - Decreased Renal reserve: 35-50 GFR - At 25-30 GFR, azotemia ensues and intercurrent events can cause overt uremia - Less < 20 GFR, frank uremia can occur w/o added stress - End stage renal failure- need for KRT (Stage V)

pH rarely < 7.35 (rule out ARF!) - Usually 20-30 mg/day of sodium bicarbonate (buffer nonvolatile acids) for stable renal insufficiency - Phosphate and calcium o Renal Osteodystrophy- skeletal abnormality brought about by CRF High bone turnover and high PTH levels - hyperPT bone disease osteitis fibrosa cystica (osteoclastic bone resorption, abnormal osteoid, fibrosis and cyst formation); predialysis Low bone t/o with low or normal PTH; aluminumrelated disease in ARBD, adynamic bone disease, osteomalacia

nikki & mon

o Osteomalacia- unmineralized
- Dialysis-related amyloidosis or DRA(microglobulin) SPONTANEOUS FRACTURES o Osteitis fibrosa cystica- ribs o ARBD & DRA- femoral head o ABD> Osteitis fibrosa cyst *Calciphylaxis- arteriolapathy CV & PULMONARY o CHF & pulmonary edema common due to fluid overload o Low pressure pulmonary edema- permeability of pulmonary capillary (butterfly-wing destruction) o Hpn- most common complication, ESRD o Ischemic Heart Disease o Uremic Pericarditis- usually hemorrhagic o Accelerated atherosclerosis HEMATOLOGIC o Normochromic normocytic anemia (may be due to anorexia): usu. starts at Stage 3 CKD o erythropoiesis due to depressed marrow, erythropoietin produced by kidney, erythropoietin inhibition Other Causes of Anemia o extracorpuscular hemolysis o GI loss (from GI lesions/ptlet dysfcn), hypersplenism o Abnormal hemostasis, prolonged BT, ptlet Fx 3, impaired ptlet aggregation, & Prothrombin aggregation NEUROMUSCULAR o Inability to concentrate, drowsiness or insomnia, loss of memory, neuromuscular irritability (singeltis cramps, twitching of muscles) o Asterixis, myoclonus, chorea, seizure, comaterminal uremia o Peripheral neuropathy (Stage 4 CKD): Sensory>Motor nerves; lower ext > UE Distal > proximal o Restless leg Syndrome, Loss of DTRs, foot drops (Peroneal nerve palsy), flaccid quadriplegia GI o o Anorexia, hiccups, nausea and vomiting Uremic fetor- urineferous odor of breath from urea breakdown in saliva to ammonia PUD- altered gastric acidity, H. pylori colonization, gastrin secretion

o ABD- BV and mineralization

matrix. osteoid bone volume

oligospermia, Dec. testosterone levels DERMATOLOGIC o Pallor, defective hemostasis (ecchymoses and hematoma), pruritus (Ca+ deposition and hyperparathyroidism) o Sallow yellow skin- pallor and urochrome (pigmented metabolites) retention o Uremic frost- urea in sweat dry-up TREATMENT of CKD o Slowing progression of CKD o Protein restriction 0.6gm/kg/d, 35kcal/kg/day o Reduce Intraglomural Hpn & proteinuria ACEI and ARB RENAL REPLACEMENT THERAPY Hemodialysis Principle: solute difference across a semipermeable membrane- metabolites down a concentration gradient DIFFUSION CLEARANCE: larger solutes have a slow rate of clearance CONVECTIVE CLEARANCE: solvent drug with solutes swept across the membrane FACTORS FOR RATE OF DIFFUSION o Magnitude of gradient o Membrane surface area o Size of solute molecules o Condition of flow on 2 sides of the membrane (direction & rate of flow) 3 ESSENTIAL COMPONENTS: 1. Dialyzer 2. Composition/delivery of dialysate (bicarbonate buffer) 3. Blood delivery system Hemodialysis Absolute CI: No vascular access possible Relative CI: difficulty in vascular access Needle phobia Cardiac failure Coagulapathy Complication: most common- Hpn Other common Complications: cramps, anaphylaxis Major causes of death: CV disease Peritoneal dialysis (3-4x a day?) Complication: peritonitis Absolute CI: loss of function producing inadequate Clearance Adhesive blocking dialysate flow Surgically uncorrectable abd. Hernia Abdominal wall stoma Diaphragmatic fluid leak Inability to perform exchanges in Absence of assistant

o Amenorrhea, low estrogen, fetal loss,

ENDOCRINE Pit, thyroid & adrenal gland fxning normally

nikki & mon Relative CI: Recent abdominal aortic graft Ventriculoperitoneal shunt Large muscle mass Morbid obesity Severe malnutrition Skin Infxn Bowel disease Kidney Transplantation o Most efficient tx of advanced CRF o Pxs receiveing KT have better life expectancy than risk-matched Pxs on dialysis Selection of Recipient and Donor -Issue of compatibility -Diseases which is affected by the transplant operation and eventual immunosuppresion (hepatitis, diabetes) -Diseases which may be conferred to the recipient Basic Immunosuppresive Agents Induction agents Maintenance agents Calcineurin inhibitors Azethioprine Mycophenolate mofetil Corticosteroid Antirejection agents ACUTE REJECTION: immunologic process resulting in a serum creatinine increase of >0.4mg/dL over the baseline, & histological confirmation standardized to the Banff criteria CHRONIC REJECTION: a gradual detoriation in kidney fcn that occurs in the absence of other causes of allograft dysfcn -Glomerulosclerosis, interstitial fibrosis, & fibrointimal proliferation

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