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 productsregulation of water/saltmaintenance of acid/base balancesecretion of hormones

• Diseases of the kidneyglomerulitubules interstitiumvessels

Kidneys• Nephron

Working unit of the kidneyConsists 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 diseasesNephrotic 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

InfectionsChemical damage Immunological &

hereditary disorders

Diabetes mellitus

• Clinical findingsProteinuria Low serum albuminEdemaElevated blood

lipidsBlood coagulation

disorders

Consequences• Disturbances in

protein metabolism• Edema

Loss of albuminSodium retention

• Risk of CVDElevated LDL, VLDL

& lipoprotein(a)Loss of blood clotting

proteins

• Loss of antibodies• Decreased

vitamin D-binding proteinLower 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 & energy0.8-1.0 grams/day35 kcalories/kg

• FatLow saturated fat,

cholesterol, & refined sugars

• Sodium2-3 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

• TumorsRenal cell carcinomaBladder 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 failureAcute 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 deterioratesReduced urine outputBuild 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 failureShockBlood loss

• Intrarenal InfectionsToxinsDrugsDirect trauma

• PostrenalFactors preventing

excretion of urineUrinary 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.

CausesAcute 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

• UremiaBUN, creatinine & uric

acid accumulate in blood

Fatigue, lethargy, confusion, headache, anorexia, metallic taste, N & V, diarrhea

Treatment• Drug therapy

DiureticsPotassium exchange

resins Insulin, glucose Bicarbonate

• ProteinDepends on kidney

function, degree of catabolism, use of dialysis

• FluidsMeasure output and

add 500 mLCan 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

• CausesDiabetes 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

• DrugsAntihypertensivesErythropoietinPhosphate bindersSodium bicarbonateCholesterol-lowering

medicationsActive 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 dietCan increase when

on dialysis• Lipids

Restrict saturated fat & cholesterol

• FluidsNot 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 restrictionsRestrict proteinRestrict milk &

milk products

• Dietary supplementsGenerous folate and B6Recommended

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 tractSevere painCan obstruct tract

• Formation is promoted by:Reduced urine

volumeBlocked urine flow Increased

concentrations of stone-forming substances

Types of Stones• Calcium oxalate

stonesMost commonReduce intake of

oxalateAvoid vitamin C

supplements

• Uric acid stonesAbnormally acidic urineAssociated with goutLow-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 complicationsUrgencyFrequency Inability to urinateObstruction Infection

Prevention & Treatment• Drink 12-16

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 hours3 times/weekComplications

• Infections• Blood clotting• Hypotension• Muscle cramping• Headaches, weakness• Nausea & vomiting• Agitation

• Peritoneal dialysisVascular access not

requiredFewer dietary

restrictions Can be scheduled

when convenient• Acute failure

Continuous renal replacement therapy (CRRT)