1. ACUTE AND CHRONIC RENAL FAILURE DR: Gehan Mohamed

2. Learning objectives
1- understand the sequences of abnormal kidney function.
2-define renal failure and mention its types.
3- discuss causes and pathogenesis of each prerenal ,renal,postrenal factors of ARF.
Understand clinical picture and stages of ARF.
Identify causes of CRF.
Discuss stages of CRF.
List methods of treatment of CRF.

3. Functions of abnormal kidney
Functions of normal kidney
Fluid overload
Sodium and water removal
Elevated wastes such as :
Potassium(K), urea ,creatinine
Wastes removal
Changes in hormone level controlling:
A- blood pressure (renin hormone)
B- red blood cell production (erythropoietin hormone).
C- calcium reabsorption (calcitrol hormone = active vitamin D)
Hormone production

4. Renal failure (RF) = uremia
Definition :is a decrease in renal function causing increase in urea ,creatinine in blood ,associated with any clinical manifestation such as edema,nausea ,vomiting due to gastroenteritis, uremic pericarditis.
But azotemia is accumlation of nitrogenous products as urea ,creatinine in the blood without any clinical manifestation so it indicate renal insufficiency but not failure .

5. Renal failure is divided into two types according to rate of onset into :
a- acute RF : if it occured rapidly over days to weeks
b- Chronic RF : if it occured slowly over months to years.

6. Acute Renal Failure (ARF)

7. Causes of ARF

9. Pathophysiology of ARF caused by hypoperfuison of the kidney
When there is hypovolemia, the blood perfusion to kidney would be less, and the GFR would decline.
at the same time, intrarenal vasoconstriction may be induced by the elevation of sympathetic stimulation and the increase of vasopressin, which may furthermore exaggerate the decline of GFR.

10. Pathophysiology of ARF caused by hypoperfuison of the kidney (cont.)
If rapid correction to hypovolemia occurred by fluid or blood transfuison so kidney function can return to normal.
But If decrease in blood supply to kidney persist it can lead to irreversible damage and necrosis to kidney tubules.

11. Post renal causes(obstructive renal failure)
it is often caused by something blocking elimination of urine produced by the kidneys..
At the ureter level, this condition can be caused by the following:
- stone , Cancer
At the bladder level, the following conditions can cause obstruction:
- migrating Kidney stone , Enlarged prostate (the most common cause), Bladder cancer causing obstruction to bladder neck.
- Neurologic disorders of the bladder as spinal cord injury causing bladder paralysis.
Treatment consists of relieving the obstruction. Once the blockage is removed, the kidneys usually recover in 1-2 weeks if there is no infection or other problem.

12. Pathophysiology of ARF with obstructive causes
During the early stages of obstruction, continued glomerular filtration leads to gradual distension of the proximal ureters, renal pelvis and calyces and increased intra-luminal pressure proximal to the site of obstruction leading to reabsorption of nitrogenous wastes by the blood.
As a result, there is decrease in glomerular filtration which will be evident by renal ultrasound showing hydroureter,hydronephrosis if the obstruction not relieved.

13. There is no actual damage to the kidneys with prerenal causes or post renal causes of kidney failure if there were appropriate and rapid treatment. 
But if there were no immediate interference there will be irreversible kidney damage (renal causes of renal failure)

14. ARF (renal causes)
1- Glomeruli : Rapidly progressive Glomerulonephritis (RPGN)
So Damage the filtering mechanisms
2- Renal Tubules: Acute tubular necrosis (ATN) caused by either:
a- Ischemia: decrease blood supply to kidney(↓oxygen &nutrients)
b- Toxins (Endogenous Toxins as precipitation of myoglobin, Myeloma light chains) or( Exogenous Toxins as Antibiotics e.g.aminoglycosides, amphotericin B, Radiocontrast agents.
3- interstitial tissue of the kidney: Acute interstitial Necrosis (AIN) secondary to allergic inflammation caused by analgesic.
4- renal blood vessels: occlusion of renovascular vesseles by thrombus.

15. Ischemic tubular necrosis
It is characterized by :
1- The distribution of tubular necrosis areas is segmental

16. Toxic tubular necrosis
It is characterized by :
1- diffuse necrosis of proximal tubules.

17. ischemic acute tubular necrosis (ATN) PAS stain: show detached necrotic epithelial lining of the tubules in their lumen (arrow) .
Another example

18. Clinical Stages of ACUTE RENAL FAILURE
1- INITIATION stage : normal urine output.
2 – OLIGURIA stage :(less than 400ml urine daily) : not present in all causes of ARF but usually present with prerenal causes of ARF with decrease in GFR.
3 – POLYURIA stage : ( >2.5L/24 hours) : specially if there is damage to the renal tubules so lost their power for concentrating urine.
4 – RECOVERY stage: specially in the prerenal or postrenal causes of ARF.
Patients with recovery are less then 30-10%

19. ARF Signs and Symptoms
Hypertension due to renal ischemia and increase production of renin.
Fluid retention leading to Pulmonary edema ,Peripheral edema ,Ascites (accumlation of fluid in peritoneal cavity in the abdomen).
Weight gain
Pale swollen kidney
Increase level of urea in blood Can affect :
A- Brain leading to Encephalopathy manifested by convulsions ,coma.
B- pericardium leading to pericarditis
C- GIT (Nausea/Vomiting) due to uremic gastroenteritis.
Later – s/s uraemia
Anorexia, nausea, vomiting, myocolonic jerks, confusion, flap, itch, chest pain, pericardial rub, hyperreflexia
May also have red urine – blood,myoglobin

21. Lab findings Investigating Blood chemistry reveal : Rising of :
- creatinine , urea
- potassium(hyperkalemia )
- hydrogen( metabolic Acidosis).
Decreasing of :
- Hb (anemia)
- Na (Hyponatraemia)
- Ca (Hypocalcaemia)
Other laboratory findings are progressive acidosis, hyperkalemia, hyponatremia, and anemia. Acidosis is ordinarily moderate, with a plasma HCO3 content of 15 to 20 mmol/L. Serum K concentration increases slowly, but when catabolism is markedly accelerated, it may rise by 1 to 2 mmol/L/day. Hyponatremia usually is moderate (serum Na, 125 to 135 mmol/L) and correlates with a surplus of water. Normochromic-normocytic anemia with an Hct of 25 to 30 % is typical.
Hypocalcemia is common and may be profound in patients with myoglobinuric ARF, apparently due to the combined effects of Ca deposition in necrotic muscle, reduced calcitriol production, and resistance of bone to parathyroid hormone (PTH). During recovery from ARF, hypercalcemia may supervene as renal calcitriol production increases, the bone becomes responsive to PTH, and Ca deposits are mobilized from damaged tissue.

22. factors which may help differentiate acute kidney injury from chronic kidney disease include:
Anemia
the kidney size on ultrasound.
Chronic kidney disease generally leads to anemia and small kidney size (contracted).

23. CHRONIC RENAL FAILURE

24. Causes of CHRONIC RENAL FAILURE
1- failure of treatment of ARF will change to CRF
2- or CRF is the final outcome of a variety of renal diseases which cause gradual damage to the kidney tissue.
Examples of renal diseases ending with CRF are :
a- Atherosclerosis of large renal arteries
b- Arterial hypertension with lesion of small renal arteries and arterioles
c- diabetes mellitus
d - Glomerulonephritis, pyelonephritis
e - cystic renal diseases
f- amyloidosis .

25. Polycystic kidney disease

26. Three stages of CHRONIC RENAL FAILURE
1- Diminished renal reserve which is charachterized by :
a- Glomerular filteration rate (GFR) is 50% of normal so Both blood urea nitrogen (BUN) and Creatinin is still normal.
(N.B normal GFR is 120 ml \ minute).
2- Renal insufficiency which is charachterized by :
a- The GFR is 20% - 50% of normal so patient presented with Azotemia.
3- Renal failure known as uremia which is charachterized by :
a-The GFR is less than 20% of normal so there are clinical manifestations as Edema, metabolic acidosis, hypocalcaemia

27. Comparison between normal kidney and kidney with chronic diseases ending with failure

28. treatment of chronic renal failure
1- permanent loss of kidney function require either permanent dialysis which is a mechanical filtration process used to remove toxins and waste from your body .
2- kidney transplant to survive but its side effect is need for immunosuppresion to prevent renal rejection by the body.

29. Hemodialysis