Chapter 11 Pathophysiology of Renal disorders. By Dr. Uche Amaefuna-Obasi (MD)

THERE ARE MORE TO LECTURES THAN JUST SLIDES

Renal Diseases

Introduction: 150gm: each kidney 1700 liters of blood filtered  180 L of G. filtrate  1.5 L of urine / day. Kidney is a retro-peritoneal organ Blood supply: Renal Artery & Vein One half of kidney is sufficient – reserve kidney function: Filtration, Excretion, Secretion, Hormone synthesis.

Kidney Location:

Kidney Anatomy:

Renal Pathology Outline Glomerular diseases: Glomerulonephritis Tubular diseases: Acute tubular necrosis interstitial diseases: Pyelonephritis Diseases involving blood vessels: Nephrosclerosis Cystic diseases Tumors

Clinical Syndromes: Nephritic syndrome. Oliguria, Haematuria, Proteinuria, Oedema. Nephrotic syndrome. Gross proteinuria, hyperlipidemia, Acute renal failure Oliguria, loss of Kidney function - within weeks Chronic renal failure. Over months and years - Uremia

Introduction Functions of the kidney: excretion of waste products regulation of water/salt maintenance of acid/base balance secretion of hormones Diseases of the kidney glomeruli tubules interstitium vessels

Kidneys Nephron Working unit of the kidney Consists of Glomerulus: works like a sieve Tubules: fluid reabsorbed or sent to bladder

Kidney Functions Regulates extracellular fluid & osmolarity, electrolyte concentrations, & acid-base balance Excretes wastes Secretes renin Produces erythropoietin Converts vitamin D to active form

Azotemia:  BUN ( A blood urea nitrogen (BUN) test measures the amount of nitrogen in your blood that comes from the waste product urea. Urea is made when protein is broken down in your body. Urea is made in the liver and passed out of your body in the urine. A BUN test is done to see how well your kidneys are working), creatinine Uremia: azotemia + more problems Acute renal failure: oliguria Chronic renal failure: prolonged uremia Abnormal findings

Hematuria Oliguria Azotemia Hypertension Nephritic syndrome Massive proteinuria Hypoalbuminemia Edema Hyperlipidemia/-uria Nephrotic syndrome

Glomerular diseases Nephrotic syndrome Minimal change disease Focal segmental glomerulosclerosis Membranous nephropathy Nephritic syndrome Post-infectious GN IgA (immune) nephropathy

Nephrotic Syndrome Massive proteinuria Hypoalbuminemia Edema Hyperlipidemia

Adults: systemic disease (diabetes) Children: minimal change disease Characterized by loss of foot processes Good prognosis Causes

Nephrotic Syndrome Any kidney disorder that results in proteinuria exceeding 3.5 g/day Cause Any damage to glomeruli increasing their permeability to plasma proteins

Nephrotic Syndrome Possible causes Infections Chemical damage Immunological & hereditary disorders Diabetes mellitus Clinical findings Proteinuria Low serum albumin Edema Elevated blood lipids Blood coagulation disorders

Consequences Disturbances in protein metabolism Edema Loss of albumin Sodium retention Risk of CVD Elevated LDL, VLDL & lipoprotein(a) Loss of blood clotting proteins Loss of antibodies Decreased vitamin D-binding protein Lower D & calcium levels Protein energy malnutrition (PEM)

© 2007 Thomson - Wadsworth Consequences of Protein Loss

Treatment Medications Anti-inflammatory drugs, ACE inhibitors, antihypertensives, immunosuppressants, lipid-lowering drugs, diuretics Protein & energy grams/day 35 kcalories/kg Fat Low saturated fat, cholesterol, & refined sugars Sodium 2-3 g/day Vitamin D & calcium Multivitamin

Nephritic Syndrome Hematuria Oliguria, azotemia Hypertension

Post-infectious GN, IgA nephropathy Immunologically-mediated Characterized by proliferative changes and inflammation Causes

Post-Infectious Glomerulonephritis Child after streptococcal throat infection Immune complexes Hypercellular glomeruli Subepithelial humps

IgA Nephropathy Common! Child with hematuria after (URI) Upper Respiratory Infection IgA in mesangium Variable prognosis

Tubular and interstitial diseases Inflammatory lesions pyelonephritis

Pyelonephritis Invasive kidney infection Usually ascends from UTI Fever, flank pain Organisms: E. coli, Proteus

Women, elderly Patients with catheters or mal-formations Dysuria, frequency Organisms: E. coli, Proteus Urinary Tract Infection

Acute pyelonephritis with abscesses

Chronic pyelonephritis

Drug-Induced Interstitial Nephritis Antibiotics, NSAIDS IgE and T-cell-mediated immune reaction Fever, eosinophilia, hematuria Patient usually recovers Analgesic nephritis is different (bad)

Acute Tubular Necrosis The most common cause of ARF! Reversible tubular injury Many causes: ischemic (shock), toxic (drugs) Most patients recover

Benign Nephrosclerosis Found in patients with benign hypertension Hyaline thickening of arterial walls Leads to mild functional impairment Rarely fatal

Malignant nephrosclerosis Arises in malignant hypertension Hyperplastic vessels Ischemia of kidney Medical emergency

5% of cases of hypertension Super-high blood pressure, encephalopathy, heart abnormalities First sign often headache, scotomas Decreased blood flow to kidney leads to increased renin, which leads to increased BP! 5y survival: 50% Malignant Hypertension

Adult Polycystic Kidney Disease Autosomal dominant Huge kidneys full of cysts Usually no symptoms until 30 years Associated with brain aneurysms.

Adult polycystic kidney disease

Childhood Polycystic Kidney Disease Autosomal recessive Numerous small cortical cysts Associated with liver cysts Patients often die in infancy

Childhood polycystic kidney disease

Medullary Cystic Kidney Disease Chronic renal failure in children Complex inheritance Kidneys contracted, with many cysts Progresses to end-stage renal disease

Tumors Renal cell carcinoma Bladder carcinoma

Renal Cell Carcinoma Derived from tubular epithelium Smoking, hypertension, cadmium exposure Hematuria, abdominal mass, flank pain If metastatic, 5y survival = 5%

Renal cell carcinoma

Bladder Carcinoma Derived from transitional epithelium Present with painless hematuria Prognosis depends on grade and depth of invasion Overall 5y survival = 50%

Acute renal failure Acute renal failure represents a rapid decline in renal function leading to increased blood levels of nitrogenous wastes and impaired water and electrolyte balance, and manifesting water intoxication, azotemia, hyperkalemia, and metabolic acidosis.

Acute Renal Failure Function rapidly deteriorates Reduced urine output Build up of nitrogenous wastes Mortality rates are high

Acute renal failure is reversible if the cause can be identified and corrected before permanent kidney damage has occurred. The most common indicator is azotemia, which is an accumulation of nitrogenous wastes (urea nitrogen, uric acid and creatinine)

Etiology and classification Prerenal failure Intrarenal failure Postrenal failure

Causes Prerenal Heart failure Shock Blood loss Intrarenal Infections Toxins Drugs Direct trauma Postrenal Factors preventing excretion of urine Urinary tract obstructions

Prerenal failure- functional failure Prerenal failure is the most common form of acute renal failure. It is caused by a marked decrease in renal blood flow. Causes Hypovolemia Heart failure Intrarenal vasoconstriction Increased blood vessel bed

Intrarenal failure- parenchymal renal failure Intrarenal failure results from conditions that can cause damage to structures within the kidney, glomerular, tubular and interstitial.

Causes Acute tubular necrosis (ATN) Prolonged renal ischemia (ischemic ATN) or ischemia-reperfusion injury Toxic insult of tubules by drugs, heavy metals (nephrotoxic ATN) Intratubular obstruction hemoglobin and myoglobin severe hypokalemia, hypercalcemia Acute glomerulonephritis and acute pyelonephritis

Postrenal failure – obstructive renal failure Obstruction of urine outflow from the kidneys. (ureter, bladder and urethra) Prostatic hypertrophy (most common)

Consequences Oliguria < than 400 mL urine/day Sodium retention Elevated potassium, phosphate, & magnesium Edema Uremia BUN, creatinine & uric acid accumulate in blood Fatigue, lethargy, confusion, headache, anorexia, metallic taste, N & V, diarrhea

Treatment Drug therapy Diuretics Potassium exchange resins Insulin, glucose Bicarbonate Protein Depends on kidney function, degree of catabolism, use of dialysis Fluids Measure output and add 500 mL Can increase if on dialysis Electrolytes Restrict potassium, phosphorus, sodium

Chronic Renal Failure Is a gradual & irreversible deterioration Usually not diagnosed until 75% of function is lost Causes Diabetes mellitus 43% Hypertension 26% Inflammatory, immunological, or hereditary diseases May follow acute failure

Consequences Nephrons enlarge to compensate Overburdened nephrons degenerate End-stage renal disease occurs Evaluation Glomerular filtration rate (GFR) Rate at which kidneys form filtrate

Consequences Electrolyte imbalances occur when GFR becomes extremely low Hormonal adaptations are inadequate Intake of water & electrolytes are very restrictive or excessive Renal osteodystrophy Increased parathyroid hormone contributes to bone loss Acidosis may develop Uremic syndrome Mental dysfunctions Neuromuscular changes Muscle cramping, twitching, restless leg syndrome Protein energy malnutrition

Complications of Uremic Syndrome Impaired hormone synthesis Impaired hormone degradation Bleeding abnormalities Increased cardiovascular disease risk Reduced immunity

Treatment Goal Slow disease progression Prevent or alleviate symptoms Drugs Antihypertensives Erythropoietin Phosphate binders Sodium bicarbonate Cholesterol-lowering medications Active vitamin D supplements

Dialysis Removes excess fluid & wastes from blood Blood is circulated though a dialyzer Blood is bathed by dialysate Hemodialysis & peritoneal dialysis

Medical Nutrition Therapy Energy Enough to maintain healthy weight & prevent wasting Low-protein diet Can increase when on dialysis Lipids Restrict saturated fat & cholesterol Fluids Not restricted until output decreases Sodium Mild restriction Potassium May need to restrict high- potassium foods

Medical Nutrition Therapy Calcium & vitamin D needs increase May need phosphorus restrictions Restrict protein Restrict milk & milk products Dietary supplements Generous folate and B 6 Recommended amounts of water- soluble vitamins except vitamin C IV iron administration Intradialytic parenteral nutrition

Kidney Transplants Restores function Allows a more liberal diet Frees patient from dialysis Immunosuppressive drug therapy Many side effects affecting nutrition Protein & energy requirements increase Control CHO & lipids Sodium, potassium, & phosphorus intakes liberalized Calcium supplementation Be alert for potential food borne infection

Kidney Stones Affects 12% of men & 5% of women Crystalline mass in urinary tract Severe pain Can obstruct tract Formation is promoted by: Reduced urine volume Blocked urine flow Increased concentrations of stone-forming substances

Types of Stones Calcium oxalate stones Most common Reduce intake of oxalate Avoid vitamin C supplements Uric acid stones Abnormally acidic urine Associated with gout Low-purine diet Cystine stones Inherited disorder cystinuria Struvite stones Form in alkaline urine

Calcium Oxalate Stone

Consequences Renal colic Severe, continuous pain Begins in the back & travels toward bladder Nausea & vomiting Urinary tract complications Urgency Frequency Inability to urinate Obstruction Infection

Prevention & Treatment Drink cups of fluids/day Tea, coffee, wine, beer No apple or grapefruit juices

Other Dietary Measures Consume enough calcium to control oxalate absorption Restrict dietary oxalate & purine Moderate protein intake Sodium restriction

Dialysis

How Does Dialysis Work? Employs diffusion, osmosis, & ultrafiltration If a substance is lower in dialysate, substance will diffuse out of the blood If substance is higher in the dialysate, substance will diffuse into the blood Ultrafiltration removes fluid from the blood

Dialysis Hemodialysis Lasts 3-4 hours 3 times/week Complications Infections Blood clotting Hypotension Muscle cramping Headaches, weakness Nausea & vomiting Agitation Peritoneal dialysis Vascular access not required Fewer dietary restrictions Can be scheduled when convenient Acute failure Continuous renal replacement therapy (CRRT)