ALTERED RENAL FUNCTION

ALTERED RENAL FUNCTION

This is the typical appearance of the blood vessels (vasculature) and urine flow pattern in the kidney. The blood vessels are shown in red and the urine flow pattern in yellow.

Overview of Kidney Diseases• Organized by site or cause of disease

• Organization by site:

• Prerenal

– From inadequate blood flow to the kidney

– Examples:

• Decr’d intravascular volume

• Lesions in renal arteries

• Hypotension decr’d perfusion at the glomerulus

– Would these patients’ Pcr be higher or lower than normal? Blood creatinine?

• Intrarenal

– Result from direct damage to nephron

– “Tubulointerstitial” disorders

• Disorders of renal tubules or of interstitial cells that comprise rest of kidney and surround tubules

– Examples:

• Glomerular injury

• Diseases of the tubules

• Postrenal

– Commonly from urinary tract obstruction

– Examples:

• Kidney stones

• Tumors/lesions of the bladder/ureters/etc.

• Further divided into chronic, acute

Intrarenal Disorders

• Glomerular disorders

– Due to change or dysfunction of specialized glomerular capillary, or cells of Bowman’s capsule

– Often see decr’d GFR

– Chronic – in patients w/ recurrent obstructions

• Persistent, recurrent autoimmune dysfunction of kidney

• Onset insidious, often asymptomatic until renal damage

• Inflammation scarring gradual obstruction of tubules

• Can cause chronic renal failure

– Chronic glomerular disorders – cont’d

• Clinical

– Pain, fever

– Wbc’s in urine

– Possible bacteriuria

– Systemic hypertension

• Treatment

– Relieve obstructions

– Antibiotics

• Glomerulonephritis (GN)

– Defined: inflammation of the glomerulus

• KNOW THIS DEFINITION!

– Relatively common

– Causes vary; most common = abnormal immune response

Immune complexes

• Precipitate out of blood, fall on walls of glomerular capillary

Inflammatory response

– Body tries to get rid of these obstructions

– Wbc’s attack complexes BUT also cause destruction of glomerular capillary walls

Scar tissue formation

– Overall, glomerulus altered

• Filtration of blood constituents (out of the blood) decr’d

• Retention of blood constituents that would normally be excreted out

• What are the immune complexes composed of?

• What type of hypersensitivity is demonstrated?

• What type of wbc plays a role in this hypersensitivity reaction?

• Three types of glomerulonephritis (GN)

– Acute – commonly assoc’d w/ strep infection

• Abrupt onset – usually 7-10 days after strep infection of throat or skin

• Immune complexes deposit in glomerulus

Proliferation capillary endothelial cells

Thickening of the glomerular membrane

Decr’d GFR

• Treatment – antibiotics for strep

• Most patients recover without serious loss of renal function

• Commonly occurs in younger patients

• Types of GN – cont’d

– Chronic – chronic renal failure

• May be asymptomatic

• Caused by altered immune response, either by:

• Ag-Ab complexes deposit in the glomerulus

– Neutrophils attack, breaking down the capillary tissue; OR

• Ab’s attack glomerular capillary cells as non-self

– Followed by proliferation of cells among connective tissue that supports the glomerular capillaries

altered glomerular membrane permeability

– Chronic GN – cont’d

• At first, as glomerulus broken down

– Doesn’t act as a good filter

– Cells/molecules needed by body filtered out into tubule filtrate

– Urinalysis shows:

» Hematuria

» Proteinuria (high levels of protein in the urine)

» Tubular dilation, atrophy may also result

• Later, compensation “clogged filter”

• Treatment

– Treat primary disease if it triggered the immune response (so antibiotics, immunomodulators)

– Correct accompanying problems (volume disorders, changes in blood pressure)

• Types of GN – cont’d

– Rapidly progressive glomerulonephritis = Goodpasture’s syndrome

• Mostly seen in adults 50-60 years

• Crescent formation

– Proliferating cells mixed with fibrin accumulate in Bowman’s space

» What changes in fluid pressures in the glomerulus would you expect? Would GFR go up or down? Would blood pressure go up or down?

– Rapid decline in glomerular function, possibly renal failure w/in months, weeks.

– Rapidly progressive GN – cont’d

• Clinical

– Hematuria

– Proteinuria

– Edema

– Hypertension

• Treatment ‑ prednisone, immunosuppressants, anticoagulants, dialysis, eventual transplant

– GN, regardless of cause, common systemic effects:

• Nephrotic syndrome

– Excretion >3.5g protein/day in urine

» So glomerulus too permeable

– Pathophysiology related to loss of plasma proteins

» Hypoalbuminemia (or loss of albumins)

» What might loss of these proteins do to fluid pressures throughout the body? (Hint: think COP)

– Susceptibility to infection

» Due to loss of immunoglobulins

– Nephrotic syndrome pathophys – cont’d

– Edema

» COP reduced GFR changed plasma volume decr’d

Hormonal compensation response Na+ and water retention

» Over time, see incr’d fluid volume, which spills into interstitium

– Increased plasma lipid levels

» Body’s feedback response to decr’d protein concentrations by increasing lipoprotein synthesis

– Vitamin D deficiency

» Due to loss of proteins needed for proper Ca+2 absorption

» In turn affects Vitamin D metabolism

– Nephrotic syndrome pathophys – cont’d

– Treatment

» Diet – patient must be monitored for sufficient nutrition (loss of proteins, other important molecules through urine)

» Diuretics, Na restriction

» Protein supplements

– Nephritic syndrome

• Alteration of filtration rbc’s excreted out of the body (so hematuria)

– Also decr’d GFR

– Decr’d urinary output and

– Incr’d water retention

• Azotemia (increased nitrogenous wastes in blood)

– What would BUN and Pcr results be?

• As GFR is chronically decreased, renal tubules undergo disuse atrophy scarring of tubules

• Tubulointerstitial Disorders

– Tubulo = of the renal tubule; interstitial = cells surrounding the nephrons

– Pyelonephritis – infection of interstitium and renal pelvis

• May be by bacteria in blood, or bacteria ascending from genitourinary tract

• Acute ‑ caused by bacteria ascending from ureters

– Second most common infectious disease

– Common risk factors:

» Female

» Urinary obstruction

» Disorders that lead to reflux urine from the bladder

• Acute Pyelonephritis – cont’d

– Inflamm’n wbc’s in kidney medulla edema, purulent urine

– If severe form local abcesses

» May affect renal tubules

» Glomerulus seldom affected

– With healing, may get scar tissue formation; tubule atrophy poss

– Rarely causes renal failure, BUT may progress chronic form, so renal failure

– Clinical – fever, chills, groin pain, increased pain/frequency of urination

– Treatment – antibiotics

Pus in tubules appears as yellow streaks in the cortex and medulla.

Renal Obstructions• Kidney stones = urinary calculi

– Affect about 1% of the U.S. population

– Composition of crystals

• Ca+2 or Mg+2 OR

• Uric acid (gout) OR

• Ammonium or phosphate

– Get incr’d concentrations in urine, with

• Incr’d renal excretion of these (so higher concent’s in normal volume of filtrate) OR

• Decr’d urine volume (so decr’d amount of filtrate incr’d concent’s) OR

• Change in urine pH (may precipitation of salts out of urine)

–Usually grow in renal tubules, calyces, ureter, bladder

•Back pressures may renal damage and/or secondary infection

–Symptoms

•Pain (=renal colic) if in tubules, ureter

•Nausea/vomiting

•Chills, fever

•Hematuria

–Treatment

•Removal by surgery, instrumentation

•Drugs to dissolve stones

•Treatment to prevent further stone formation

Urinary Tract Infection

• Caused by bacteria

• Retrograde movement from outside environment

– Urethra bladder ureter kidney

– Affect 10-20% of all females in the U.S.

– Risk factors as for pyelonephritis

• Cystitis ‑ bladder inflammation

– Generally uncomplicated

– Resolves spontaneously

– BUT, if advanced form develops, can hemorrhage, pus formation in the tubules

– Clinical

• Urination painful, may increase in frequency/urgency

• Low back pain

• Hematuria possible

• Nonbacterial cystitis

– Symptoms same as cystitis, but patient demonstrates negative urine culture

– Due to dysfunction or infection of tissues/organs surrounding bladder

• May be autoimmune dysfunction

– Treatment

• Relieve inflammation

Consequences of Renal Disorders

• Acute Renal Failure (ARF)

– Abrupt decrease in renal function decr’d urinary output

– See incr’d BUN, Pcr

– Reversible with early diagnosis and treatment

• Many causes (including drugs/toxins, disease, trauma, etc.)

– Most common: acute tubular necrosis

– May be due to problems within kidney or anatomically pre- or post-kidney

– Prerenal ARF – due to impaired blood flow

• Examples:

– Vasoconstriction

– Hypotension

– Hemorrhage, burns

• All may renal ischemia

• See decr’d GFR due to decr’d pressures of filtration

– Intrarenal ARF – due to diseases, dysfunctions within kidney itself, most commonly within nephron

• Possible causes:

– Acute glomerulonephritis

– Acute tubular necrosis, occurring

» After surgery

» With sepsis

» With severe burns

» With obstetrical complications

– Regardless of cause decreased GFR

– Postrenal ARF – usually with urinary obstruction

• Affects both kidneys

• Characteristic ‑ several hours anuria, then flank pain, then polyuria

– Anuria = no urine output

– Polyuria = increased urine output

• Clinical symptoms of ARF divided into 3 stages:

– First stage -- Oliguria

• Decr’d urine volume to anuria

– About 25% of normal = about 400 mL/day

• Lasts 1-3 weeks, depending on severity

• BUN, Pcr increased (with decr'd GFR)

• Clinical

– Increased K+ in body (hyperkalemia)

– How might this be a problem?

– Other electrolyte imbalances

– Fluid retention edema

– Congestive heart failure

• May require maintenance dialysis

– Second stage of ARF Symptoms – Diuresis

• Body beginning to recover, now attempts to compensate

• 3-4 L/day urine excretion possible

• Tubules still damaged early in phase, but gradually recovering

• Na+, K+ lost in incr’d urine volume

– Electrolyte imbalances occur (now in opposite direction)

– May see ECF volume depletion

• Closely follow electrolytes

– Third stage -- Recovery

• May be 3-12 months for normal Pcr

• About 30% of all ARF patients never regain normal kidney function

• Treatment

– Prevention if possible (ex: planned surgeries, monitoring obstetrical patients)

– Maintain fluid volume

– Mannitol

Incr’d renal vasodilation, so incr’d GFR

• Also decr’d Na+/water reabsorption

– Other diuretics

• ARF Treatment – cont’d

– Maintain life functions until kidneys can take over

• Correct fluid imbalances

• Treat any infections

• Maintain nutrition, cardiac function

– Dialysis if necessary

Chronic Renal Failure

• A progressive condition with slow development (may be years)

• Common causes:

– Chronic glomerulonephritis

– Chronic pyelonephritis

• Diagnosed with loss of 50-70% of functional nephrons, then:

– Renal insufficiency = GFR < 25% of normal

• Clinical: BUN, Pcr steeply increase

• Then:

– End‑stage renal failure = GFR < 10% of normal

• So GFR = approx 5-10 mL/min

• BUT still excess water loss because tubules lose ability to reabsorb water

• Now may lead to uremic syndrome

• At first, remaining (healthy) nephrons hypertrophy

Incr’d GFR, tubular reabsorption and secretion in these nephrons

– BUT compensation breaks down at GFR = 25% of normal

– Now, diet and fluid intake are crucial

• Note: Removal of one kidney causes hypertrophy of other kidney, allowing the body to maintain function (can maintain >25% GFR)

• Uremic syndrome = GFR=5-10% of normal, regardless of cause

• Accumulation of toxins in plasma

– Most common toxins: urea, creatinine

Cecline in renal function, so

Varied dysfunctions and symptoms

• Metabolic acidosis

– Impaired ability to excrete H+ and/or reabsorb HCO3-

– So blood pH decr’d and blood buffer concentrations deviate from 20:1 ratio

– How will the ratio now differ?

– Deep respirations to blow off excess CO2

– What will this do to blood acid? How will that change the 20:1 ratio?

– Dysfunctions, symptoms of uremic syndrome – cont’d

• Sodium imbalance

– Some compensation from hypertrophied tubules, BUT:

– At terminal stages, compensation fails, so

» Na+ retention problems

» Hypertension

» Edema

• Cardiovascular difficulties related to electrolyte imbalances

– K+ retained

– Ca+2 lost (with tubule failure to reabsorb)

– Na+/water retained

– Leads to

» Hypertension

» Congestive heart failure

– Dysfunctions, symptoms of uremic syndrome – cont’d

• Hematologic problems

– Kidneys produce erythropoietin

– Anemia possible

– Blood coagulation problems possible

» Probably due to K+, Ca+2 imbalances

• CNS dysfunctions

– Decreased nerve conduction with electrolyte imbalances

– Weakness

– Confusion

– Convulsions coma