CHRONIC RENAL FAILURE online presentation

All about chronic renal failure

1. 1 THE KIDNEY

2. Reddish-brown, bean shaped 11-12cm long, 6cm wide, 4cm thick AT level of T 12 to L 3 Retroperitoneal & against the dorsal body wall Right kidney is slightly lower than left Attached to ureters, renal blood vessels and nerves at renal hilus On the top of each kidney there is an adrenal gland 2 ANATOMY OF KIDNEY

3. A frontal section through kidney reveals two distinct regions: R enal cortex : superficial, light red region R enal medulla : deep, darker reddish-brown and consists of several cone-shaped renal pyramids. B ase of each pyramid faces renal cortex, and its apex, called a renal papilla, points toward the renal hilum . 3 ANATOMY OF KIDNEY

4. R enal cortex is extending from renal capsule to bases of renal pyramids and into the spaces between them and divided into outer-cortical zone and inner-juxtamedullary zone. Renal columns of Bertini : P ortions of renal cortex that extend between renal pyramids are called RENAL PARENCHYMA : renal cortex and renal pyramids of renal medulla. Within the parenchyma, functional units of the kidney-microscopic structures called nephrons. 4 ANATOMY OF KIDNEY

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6. Filtrate by nephrons drains into large papillary ducts . P apillary ducts drain into cuplike structures called minor and major calyces. Each kidney has 8 to 18 minor calyces and 2 or 3 major calyces. A minor calyx receives filtrate from the papillary ducts of one renal papilla and delivers it to a major calyx. 6 ANATOMY OF KIDNEY

7. Once the filtrate enters the calyces it becomes urine because no further reabsorption can occur. From the major calyces, urine drains into a single large cavity called the renal pelvis and then out through the ureter to the urinary bladder. 7 ANATOMY OF KIDNEY

8. Structural and functional units of the kidneys Over 1 million Responsible for forming urine Consist of Renal corpuscle: Knot of capillaries called Glomerulus Renal tubule: PCT DLOH ALOH DCT CD 8 NEPHRONS

9. 9 FUNCTIONS OF NEPHRON

10. Consists of an anastomosing network of capillaries lined by fenestrated endothelium invested by two layers of epithelial cells. Visceral epithelial cells Parietal epithelium 10 STRUCTURE OF GLOMERULUS

11. Visceral epithelial cells (podocytes ) : incorporated into and become an intrinsic part of the capillary wall, separated from endothelial cells by a BM. Parietal epithelium : situated on the Bowman capsule, lines urinary space in which plasma filtrate first collects. STRUCTURE OF GLOMERULUS

12. The glomerular capillary wall is the filtering membrane and consists of Fenestrated endothelial cells : with each fenestra being about 70 to 100 nm in diameter . Glomerular basement membrane (GBM ) Podocytes 12 Glomerular filtration barrier

13. Glomerular basement membrane (GBM) : Consist of 3 layers Lamina rara interna : inner thin layer Lamina densa : thick layer Lamina rara externa: outer dense layer Podocytes processes embedded in BM Adjacent foot processes of podocytes are separated by 20- to 30-nm–wide filtration slits.

14. GBM consists of collagen (mostly type IV), laminin, polyanionic proteoglycans (mostly heparan sulfate) & several other glycoproteins. Type IV collagen forms a network to which other glycoproteins attach. 14 GLOMERULAR BASEMENT MEMBRANE

15. Monomer of this network is a triple-helical molecule composed of six types of α chains (α1 to α6 or COL4A1 to COL4A6). GLOMERULAR BASEMENT MEMBRANE

16. Each molecule consists of : 7S domain at the N terminus, Triple-helical domain in the middle& Noncollagenous (NC1) domain at the C terminus. The NC1 domain is important for helix formation and for assembly of collagen monomers into the BM. GLOMERULAR BASEMENT MEMBRANE

17. Entire glomerular tuft is supported by the MESANGIUM. Cells of mesenchymal origin are contractile , phagocytic capable of proliferation , laying down both matrix and collagen, and secreting several biologically active mediators. 17

18. Glomerular filtration Pressure differences result in a gradient and movement of solutes across the semipermeable glomerular basement membrane. 18

19. Glomerulus is highly permeable to water & small solutes because of the fenestrated nature of the endothelium. The permeability characteristics of the glomerular filtration barrier varies: depending on their size (the larger, the less permeable ) charge (the more cationic, the more permeable) 19 GLOMERULAR FILTRATION

20. The visceral epithelial cell is important for the maintenance of glomerular barrier function; slit diaphragm presents a size-selective distal diffusion barrier to the filtration of proteins. 20 GLOMERULAR FILTRATION

21. Within cytoplasm of the foot processes, nephrin forms connections with podocin, CD2-associated protein &ultimately actin cytoskeleton of visceral epithelial cells. mutations in genes encoding them give rise to defects in permeability and the nephrotic syndrome. 21

22. Edema Renal hypertension Flank pain& renal colic Lower urinary tract symptoms Uremia - Azotemia 22 CLINICAL MANIFESTATION OF RENAL DISEASES

23. Acute kidney injury Nephrotic syndrome Nephritic syndrome Isolated haematuria or proteinuria Chronic kidney diseases End stage renal diseases 23 SYNDROMES OF RENAL DISEASES

24. CHRONIC RENAL FAILURE

25. Progressive and irreversible loss of renal function over time, based on a gradual decline in the GFR and creatinine clearance ,frequently leading to end stage renal disease ( ESRD). I n which the body’s ability to maintain metabolic and fluid and electrolyte balance fails resulting in uremia or azotemia. DEFINITION

26. Multiple terms have been applied to chronic renal failure all of these terms are replaced with CKD It encompasses the continuum of kidney dysfunction from mild kidney damage to kidney failure, and includes end-stage renal disease (ESRD). CRF=CRI=CRD= CKD

27. ESTABLISHED CHRONIC KIDNEY DISEASE

28. A clinical state or condition in which there has been an irreversible loss of renal function, and these patients usually need to accept renal replacement therapy in order to avoid life-threatening uremia END STAGE RENAL DISEASE

29. The diseases leading to CRF can generally be classified into two major groups : those causing glomerular pathology those causing tubulointerstitial pathology ETIOLOGY

30. Primary glomerular pathology Systemic glomerular pathology Diseases causing glomerular pathology

31. Primary glomerular pathology : The major cause of CRF is chronic glomerulonephritis. various types of glomerulonephritis such as membranous glomerulonephritis, membranoproliferative glomerulonephritis , lipoid nephrosis (minimal change disease) anti-glomerular basement membrane nephritis. Diseases causing glomerular pathology

32. ii) Systemic glomerular pathology : Certain conditions originate outside the renal system but induce changes in the nephrons secondarily. Major examples of this type are systemic lupus erythematosus and diabetic nephropathy Diseases causing glomerular pathology

33. categorised according to initiating etiology into 4 groups : vascular - essential hypertension produces characteristic changes in renal arteries and arterioles referred to as nephrosclerosis Infectious - chronic pyelonephritis Toxic - analgesics Obstructive - stones , blood clots, tumours , strictures and enlarged prostate Diseases causing tubulointerstitial pathology

34. MOST COMMON CAUSES

35. PATHOPHYSIOLOGY OF CHRONIC RENAL FAILURE

36. PATHOPHYSIOLOGY Due to etiological factors renal function declines. N eph r on dama g e i s p r o g ess i v e dama g e ne p h r on can not function and to not recover. Decreased glomerular filtration rate. R emai n i n g neph r o n s unde r g o chan g e.

37. To compensate for those damaged nephrons. C ompensa t o r y e x c r et io n c on t inu e GFR di m in i shed. Filtration of more concentrated blood by the remaining nephrons. Damage of nephron results in hypertrophy and hyper phosphatenia of remaining nephron. Urine may contain abnormal amount of protein RBCs, white bloo d c ells or cast s .

38. Increased serum creatinine bun level and retention of urea and other introgenous F u ther dam a g e of th e ne p h r on 8 -90 % dam a g e C FR 10-20%. Tha n lead t o ch r o n i c r enal fa i lu r e.

39. PATHOGENESIS

40. CLINICAL MANIFESTATION OF CHRONIC RENAL FAILURE

41. Alterations in Fluids and Electrolytes

42. Alterations in Fluids and Electrolytes

43. METABOLIC ACIDOSIS

44. ANEMIA

45. HEMATOLOGIC CHANGES ANEMIA, FATIGUE, WEAKNESS, COLD INTOLERANCE AS KIDNEYS ARE TO PRODUCE ERYTHROPOIETIN BLEEDING TENDENCIES AS ACCUMULATION OF UREMIC INTERFERE WITH PLATLET ADHESIVENESS. HEMOLYSIS, CLOTTING ABNORMALITIES.

46. Firstly: kidney fail to excrete phosphate. Hyperphosphatemia 4 - RENAL OSTEODYSTROPHY Secondary : high parathyroid hormone levels.

47. Early stages (1-2-3) hyperphosphate mia Hy p o c a lc a emia Later stages( 4-5) decreased synthesis of 1α-hydroxylase 4 - RENAL OSTEODYSTROPHY by negative feedback.

48. RENAL OSTEODYSTROPHY

49. RENAL OSTEODYSTROPHY

50. OSTEOPOROSIS OSTEOSCLEROSIS OSTEOMALACIA OSTEITIS FIBROSA RENAL OSTEODYSTROPHY

51. INTEGUMENTORY CHANGES:- SKIN-VERY DRY BECAUSE OF ATROPHY OF SWEAT GLAND. PRURITIS-EXCORIATED SKIN. SKIN COLOR-UROCHROMS PIGMENTS. MUEHRCKE’S LINE UREMIC FROST

52. RESPIRATORY CHANGES PULMONARY EDEMA. UREMIC LUNG METABOLIC ACIDOSIS AS A RESULT OF RESPIRATORY CHANGES TO HYDROGEN IONS .

53. C OMPLICATIONS OF UREMIA Uremia-induced platelet dysfunction Uremic pe r ic a rd i tis Uremic enc e ph a l o pathy Increased tendency to bleed and ecchymosis Ecchymosis, GI bleeding Chest pain, malaise H e ad a ches, confusion, coma Per i c a r d ia l friction rub

54. L O S S O F EX CR E T O R Y R E N A L F UNC T I O N S D E C R EASE D LI B IDO INFERTILITY D E L A YE D H E ALI NG INFECTION A D V A N C E D A T H E R O S C LE R O SIS E R R A TIC BL O O D G L U C O S E LE V EL A N E M IA , P AL L OR DECREASED CALCIUM ABSORPTION:- OSTEODYSTR O PHY AND HYPOCALCE M IA DISTU R B A N C ES IN REPRODUCTION IMM UNE DISTU R B A N C ES IN C REA SED PRO D U C TION O F LIPI D S IM P AIRED INS U LI N ACTION F AI L U R E T O PRO D U C E ERYTHROPOIETIN F AI L U R E T O C O N V E R T INA C TI V E FOR M S OF CALCIUM

55. LOSS OF NON-EXCRETORY RENAL FUNCTIONS METABOLIC ACIDOSIS DECREASED HYDROGEN SECRETION AND DECREASED BICARBONATE REABSORPTION HYPERPHOSPHATEMIA→DECREASED CALCIUM ABSORPTION→ HYPOCALCEMIA→ HYPER-PARATHYROIDISM→ DECREASED POTASSIUM EXCRETION→ HYPERLKALEMIA DECREASED PHOSPHATE EXCRETION HYPERKALEMIA DECREASED POTASSIUM EXCRETION WATER RETENTION CAUSING HYPERTENSION, HEART FAILURE, EDEMA DECREASED SODIUM REABSORPTION IN TUBULE UREMIA CAUSING INCREASED BUN, CREATININE, URIC ACID, PROTEINURA, PERIPHERAL NERVE CHANGES, PERICARDITIS, PRURITIS, CNS CHANGES, BLEEDING TENDENCIES DECREASED EXCRETION OF NITROGENOUS WASTE

56. C HRONIC K IDNEY CLINICAL MANIFESTATIONS And C OMPLICATIONS OF UREMIA

57. DIAGNOSTIC EVALUATION History taking. Physical examination. Blood testing. Urine testing. Electrocardiogram. Imaging test. Kidney biopsy. Renal function test.

58. AIM OF TREATMENT

59. P REVENTION OF FURTHER DETERIORATION T REAT COMPLICATION 3. E STABLISHMENT OF TREATMENT STRATEGY FOR ESRD AIM OF TREATMENT

60. DIETARY INTERVENTIONS FLUID ALLOWANCE 500-600ml (or) MORE THAN THE PREVIOUS DAY 24hrs Urine Output. Carbohydrate & Fat Intake 40 - 50kcal/Kg/Day. Diet Restriction Protein 1g/Kg/Day. Vitamin Supplements.

61. ADMINISTRATION OF Anti-hypertensives Erythropoietin Iron Supplements Phosphate Binding Agents Calcium Supplements Adequate Dialysis

62. HYPERKALEMIA Dialysis Therapy Potassium Removal Potassium Restricted Diet

63. SURGICAL MANAGEMENT