Pathophysiology ARF and CKDARF to CRF Overview

Precipitating FactorsPrerenal causes (~55%)Intrerenal causes (~40%)Postrenal causes (~5%)Predisposing FactorsAgeDMHeredity/GenesPrimary hypertensionCardio and peripheral vascular diseasesSLEAIDS

PhenomenonLegend:

Manifestation/s

Abrupt deterioration of renal structural integrityDirection of Pathogenesis (P)

Renal function compromisePossible Direction of P

Stages- Fluid and Electrolyte imbalances- Impaired wound healing- Increased susceptibility to infections- Acidosis- Gastrointestinal complications- Anemia- Increased incidence of pericarditis- Uremic encephalopathy- Platelet dysfunction

Major manifestations show:

Sustained renal damages or destruction

- Fluid and Electrolyte imbalances- Metabolic changes- Hematologic changes- Gastrointestinal changes- Immunologic changes- Changes in medication metabolism- Cardiovascular changes- Respiratory changes- Musculoskeletal changes- Integumentary changes- Neurologic changes- Reproductive chnges- Endocrine changes - Psychosocial changes

Multisystem involvement:End Stage renal Disease

Total GFR decreased

Serious inability of the kidneys to rid body of all waste productsRenal damage advances

Pathophysiology: ARF Concentration

1st Precipitating FactorsPrerenal Causes:-Volume depletion (from hemorrhage, renal losses, GI losses)-Impaired cardiac efficiency resulting from MI, heart failure, dysrhythmias, cardiogenic shock-vasodilation from sepsis

All Known Predisposing Factors

Hypovolemia

Increased osmolality of exracecellular fluidFalling O2 levels, High CO2 and H ions

Reduced arterial (e.g. carotid sinus) and cardiac baroreceptors

Excites vasomotor centerExcites osmoreceptors located @ anterior hypothalamus

Excites supraoptic nucleiIntrinsic kidney secretions causes: (Allows) vasomotor center to send vasoconstriction signals

Causes posterior pituitary to release Vasopressin ArginineProtein molecules to split causing

Almost all arterioles to constrictSmall and large veins constrictHeart stimulated to enhance pumping

Acts on the basolateral membrane of tubulesRenin release into kidney and the bloodstream

Activates the enzyme adenyl cyclase

Reacts with Angiotensinogen in liver

Causes formation of cyclic adenosine monophosphate (cyclic AMP) in cytoplasm

Angiotensin 1 released

Continues to persist in the bloodDiffuses to the laminal sideCauses mild vasoconstriction

Development of elongated vesicular structuresReacts with ACE in the lungs

Becomes Angiotensinogen 2

Fuses to the laminal membrane

Thirst mechanism activated

Inactivated by AngiotensinaseGeneral thirst sensationLaminal membrane becomes highly permeable to H2O

General constriction of arterioles

H2O moves to the inside of the cell

H2O proceeds to basolateral membrane

Causes adrenal glands to secrete AldonsteroneDecreased kidney blood flow

Drinking of H2OH2O proceeds to interstitial tissueDecreased blood flow in peritubular capillaries

Increased tubular reabsorption of sodium

Decreased fluid filters from glomeruli to tubulesRapid osmotic reabsorption of fluid from tubules

H2O conservation

Increase arterial pressure

Isovolemia or Homeostasis restoredAdequate mechanism

Possibilities

Decreased O2 delivery to proximal tubulesDecreased renal perfusionInadequate mechanism

Cycle repeats

Decreased GFR

Decreased cellular ATP

Decreased tubular flow

2nd Precipitating FactorsIntrarenal Causes:-Prolonged parenchymal ischemia from pigment nephropathy, myoglubinuria, hemoglobinuria-nephrotoxic agents- aminoglycosides, radiopaque contrast agents, heavy metals and solvents, NSAIDs, ACE inhibitors, infectious processesAll Known Predisposing Factors

1st stage

Damaged tubules

Renin-angiotensin-aldosterone reactivationInability to conserve sodium

2nd oliguric

Some cell deathMore vasoconstriction

Less fluid filteredSome tubular necrosisDecreased renal perfusion

Large numbers of excretory substances in tubules of functional nephrons

Throughout the stages: increased BUN and creatinine

3rd diuretic

Acts as osmotic diuretic pulling water with it

Rapid fluid flushing

4th recovery

Gradual improvement in metabolic waste removalToo rapid tubular fluid

Possibilities

Disruption of concentrating and diluting mechanisms

3rd Precipitating FactorsPostrenal Causes:-Urinary tract obstruction-Calculi-tumors-BPH-Strictures-Blood clotsAll Known Predisposing Factors

Obstruction @ lower urinary tract

Backing up of urine to the kidneys

Tubular damageIncreased pressure in collecting ducts and tubulesOverloading of urinary secretions

More nephrons are destroyed progressively

Pathophysiology: CRF Concentration

Precipitating FactorUntreated Acute Renal FailureAll Known Predisposing Factors

More nephrons are destroyed progressively

Decreased GFR

Inability to reabsorb electrolytesHypertrophy of remaining nephrons

Sodium wastingInadequate urine concentration

H2O wasting

Thickening or an increase in the amount of collagen in basement membrane of small vessels/tubules

Sluggish/impaired blood flow

Glomerulosclerosis

Decreased GFR

Increased vascular volumeSodium and water balance disturbedStage IDIMINISHED RENAL RESERVEGFR 50%

Edema and hypertension

More than 75% damage of nephrons

Potassium balance disturbed

Hyperkalmeia

Stage IIRenal InsufficiencyGFR 20-50%

PericarditisAccumulation of nitrogenous wastes

UremiaBUN, creatinine levels continue to rise

Skin disorders

Remaining nephrons undergo changes to compensate for those damaged nephrons

Gastrointestinal Manifestations

Filtration of more concentrated blood by the remaining nephrons

Neurologic Manifestations

Hypertrophy of nephrons

Sexual dysfunctionIntolerance and exhaustion of the remaining nephrons

Erythropoeitin production impaired

Anemia

Further damage of the nephrons

Skeletal BufferingAcid-base imbalances80-90% damage

AcidosisStage III RENAL FAILUREGFR 10-20%

OsteodystrophiesVitamin D activation impaired

Impaired kidney function and Uremia

Vitamin D activation impaired

Hyperparathyroidism

Stage IV End-Stage Renal DiseaseGFR 20% and below

Phosphate accumulation