Renal insufficiency

Renal insufficiency is a pathological process in which the functions of kidney are severely damaged, leading to the accumulation of metabolic products, drugs and poisons, and disorders of water, electrolyte, acid-base balance, and renal endocrine function.

Renal failure: the terminal stage of renal insufficiency

Renal insufficiency

Dysfunction of glomerular filtration

Dysfunction of renal tubule

Renal endocrine dysfunction

Decreased GFR

a decrease in renal blood flow

a decrease in glomerular effective filtration pressure

a decrease in glomerular capillary surface area

a decrease in glomerular filtration coefficient

Increased permeability of glomerular filtration membrane

Dysfunction of glomerular filtration

Dysfunction of renal tubules

Dysfunction of proximal convoluted tubules

reabsorbing water, glucose, protein, amino acids, phosphate, bicarbonate, sodium, potassium

Dysfunction of Henles’ loop

reabsorbing chloride, sodium

Dysfunction of distal convoluted tubules and collecting ducts

secreting hydrogen, potassium and ammonia

Renal endocrine dysfunction

Renin-angiotensin-aldosterone system

A decrease in erythropoietin (EPO)

1,25-dihydroxyvitamin D3

Kallikrein-kinin-prostaglandin system

Decreased deactivation of parathyroid hormone (PTH) and gastrin

Renal failure

Acute renal failure

Chronic renal failure

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 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

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)

Pathogenesis

Decreased renal blood volume

Renal tubular injury

renal tubular obstruction increased intraluminal P

back leak of the glomerular filtrate

decreased urine; interstitial edema

impressing renal tubules and peri-tubular capillaries

Renal cell lesion

renal tubular cells, endothelial cells and mesangial cells

necrotic (tubulorrhexic and nephrotoxic) and apoptotic

ATP↓oxygen free radical↑reduced glutathione(GSH) ↓phospholipase ↑

cytoskeletal structural change activation of cell apoptosis

Alterations of metabolism and function

The oliguric stage

The diuretic stage

The recovery stage

Oliguric type and nonoliguric type

Oliguric type

The oliguric stage

Urinous alterations

Water intoxication

Hyperkalemia

Metabolic acidosis

Azotemia

Urinous alterations

oliguria, anuria

hyposthenuria, isosthenuria

an increase in urine sodium

hematuria, albuminuria, cyclindruria

Water intoxication

excretion ↓ (due to decreased GFR)

ADH ↑ (due to activation of RAS or decreased ECV)

endogenous water from catabolism ↑

water uptake ↑

Hyperkalemia

excretion ↓

tissue injury and increased catabolism,

acidosis

hyponatremia

transfusion of storage blood or excessive intake from food or drugs

Metabolic acidosis

decreased excretion of acidic metabolites

decreased secretion of hydrogen and ammonia

increased production of fixed acids

The diuretic stage

Restoration of renal perfusion and glomerular filtration

Reduced reabsorption function of neonatal renal tubules

Release of renal obstrction

Osmotic diuretics

The recovery stage

Treatment of acute renal failure

•Identifying and correcting the causes

•Maintaining water and electrolyte balance

•Supplying adequate calories

•Dialysis

Chronic renal failure

Chronic renal failure represents progressive and irreversible destruction of kidney structures, leading to the accumulation of metabolic products, drugs and poisons, and disorders of water, electrolyte, acid-base balance, and renal endocrine function.

•Diabetes

•Hypertension

•Glomerulonephritis

Stages of progression

Chronic renal failure is characterized by a reduction in the number of functional nephrons. The rate of nephron destruction ranges from several months to many years.

•Diminished renal conserve

•Renal insufficiency

•Renal failure

•Uremia

Pathogenesis

Several hypothesis on chronic failure

Intact nephron hypothesis

Trade-off hypothesis

Glomerular hyperfiltration hypothesis

Mechanism of nephron dysfunction

Actions of primary disease

Secondary and progressive glomerular sclerosis

protein flux

local inflammation

glomerular DIC

Tubulointerstitial injury

Alterations of function and metabolism

Alterations of urine

Azotemia

Disorders of water, electrolyte and acid-base balance

Renal hypertension

Renal anemia

Tendency to hemorrhage

Renal osteodystrophy

Alterations of urine

Early stage polyuria, nocturia, isosthenuria,

protein, RBC, WBC in urine

Late stage oliguria

Azotemia

Urea and creatinine

Disorders of water, electrolyte and acid-base balance

Edema or dehydration

Salt-wasting

Hypokalemia (early) or Hyperkalemia (late)

Hyperphosphatemia

Hypocalcemia

Metabolic acidosis

Hyperphosphatemia

Reduced absorption through intestinal tract caused by decreased 1,25-(OH)2 D3, inrestinal injury led by toxins, and calcium consumption through combining with phosphate to form calcium phosphate.

Osteodystrophy

Increased phosphate levels

Decreased calcium levels

Increased parathyroid hormone

Impaired renal activation of Vitamin D

Metabolic acidosis

Renal rickets, osteomalacia, osteitis fibrosa, osteoporosis, osteosclerosis

Hematologic disorders

Anemia

decreased EPO production

suppression of red cell production by uremic toxins

decreased life-span of red blood cell

iron deficiency

Coagulopothy---bleeding disorder

platelet function is impaired,

although platelet production is normal.

Hypertension

Increased blood volume led by water and sodium retention

Decreased levels of renal vasodilator prostaglandins

Increased activity of renin-angiotensin system

Treatment

Medical management

Dialysis and transplantation

hemodialysis

peritoneal dialysis

transplantation

Dietary management

protein restriction

adequate calorie intake (carbohydrate and fat)

potassium, sodium and fluid restriction