NURS 337 Pathophysiology Nephrology

Functions of the kidneys

-Filter and clean the blood of toxic buildup

-Make urine

-Keep salts and minerals in balance

-Maintain blood pressure and blood volume

-Vitamin D production

-Hormone production: Erythropoietin

-Plasma pH balance

How can the Kidneys fail?

-The filters in the kidney stop working (glomerular disease)

-The blood vessels

-Trauma

-Urine backup

Oliguria

Decreased urine production (less than 500 mL/day)

Anuria

The absence of urine production (less than 50 mL/day)

Azotemia

Excess of nitrogenous product of protein metabolism in the blood (Increased blood urea nitrogen [BUN])

-BUN level: 7 - 20 mg/dL

Uremia

increase level of urea in the blood

"Normal" Creatine Level

0.6 - 1.3 mg/dL

-Pitfall: Dependent on muscle mass

-Pitfall: Falsely elevated by medications

Glomerulonephritis

Inflammation of the glomerulus

-Primary: Isolated to Kidney

-Secondary: Caused by a systemic disease (ex. Type 2 diabetes, hypertensive crisis)

-Immune Mechanisms: Main etiology for primary and secondary injury

Primary Glomerular Diseases

-Minimal-change Disease

-Focal Segmental Glomerulosclerosis

-Membranous Nephropathy

-Acute Postinfectious Glomerulonephritis

-Membranoproliferative Glomerulonephritis

-IgA Nephropathy

-Dense Deposit Disease

-C3 Glomerulonephritis

Glomerulopathies Secondary to Systemic Diseases

-Lupus Nephritis (Systemic Lupus Erythematosus)

-Diabetic Nephropathy

-Amyloidosis

-Glomerulopathy secondary to Multiple Myeloma

-Goodpasture Syndrome

-Microscopic Polyangiitis

-Granulomatosis with Polyangiitis

-Henoch-Schonlein Purpura

-Bacterial Endocarditis-Related Glomerulonephritis

-Thrombotic Microangiopathy

Hereditary Disorders for Glomerulonephritis

-Alport Syndrome

-Fabry Disease

-Podocyte/Slit-Diaphragm Protein Mutations

Glomerulonephritis Archetype

Acute poststreptococcal glomerulonephritis

Pathophysiology of Glomerulonephritis

-Presence of antistreptococcal (ASO) antibodies

-Formation of an antigen-antibody complex

-Activates complement system

-Inflammatory response in glomeruli

• Increased capillary permeability-leakage of protein and erythrocytes

• Congestion and cell proliferation

• Decreased GFR-retention of fluid and wastes

What are the Two Major Signs of Glomerulonephritis?

-Hematuria with red blood cell casts (Dark Urine)

-Proteinuria exceeding 3 to 5 g/day with albumin (macroalbuminuria) as the major protein

Other Manifestations of Glomerulonephritis

-Oliguria

-Hypertension (renin and aldosterone are secreted, causing vasoconstriction and fluid retention to compensate for fluid loss)

-Edema: Generalized, Facial, Periorbital

-Metabolic acidosis

-Flank or Back Pain - Edema and stretching of renal capsule

-General signs of inflammation

Broad or Waxy Cast

Chronic Renal Failure

Hyaline Case

Exercise, Diuretics, and Concentrated Urine

Fatty Cast

(Oval Fat Bodies) Nephrotic Syndrome

WBC Cast

Interstitial Nephritis, Pyelonephritis

RBC Cast

Glomerulonephritis

Renal Tubular Epithelial Cell Cast

Caused by Acute Tubular Necrosis (ATN)

Granular Cast

Chronic Renal Failure, Muddy Brown = ATN

Diagnosis of Glomerulonephritis

-Blood Tests:

• Elevated serum urea and creatinine levels

• Elevation of anti-DNase B, streptococcal antibodies, antistreptolysin, anti-streptokinase

• Complement levels decreased (use in renal inflammation)

-Urinalysis

• Proteinuria

• Hematuria

• Erythrocyte casts

• No evidence of infection

Treatment of Glomerulonephritis

-Low sodium diet

-Protein and fluid intake decreased in severe cases

-Drug Treatment:

• Glucocorticoids (prednisone) to reduce inflammation

• Antihypertensives

• Antibiotics

Nephrotic Syndromes

Caused by glomerular injury/damage (non-immune/non-inflammatory)

-Loss of Proteins:

• Proteinuria > 3.5 g/day

• Hypoalbuminemia < 3.5 g/dL

-Hyperlipidemia and Lipiduria (Liver will compensate for kidneys not working, and will produce lipoproteins)

-Edema

-Vitamin D Deficiency

-Hypocalcemia

Nephritic Syndromes

Inflammation of the Glomeruli

-Hematuria - Dysmorphic red blood cells

-Red blood cell casts

-Azotemia

-Hypertension

-Oliguria

-Variable proteinuria (usually < 3 g/day)

-Berger’s disease (IgA Nephropathy): most common cause of primary glomerulonephritis

Acute Kidney Injury (AKI)

Sudden/abrupt (within hours) decline in kidney function that encompasses both injury (structural damage) and impairment (loss of function)

-Decrease in glomerular filtration

-Decrease in urine output

-Accumulation of nitrogenous waste products in blood

Prognosis of Acute Kidney Injury (AKI)

-Renal insufficiency

-Renal failure

-End-stage Kidney Disease

Pathophysiology of Acute Kidney Injury (AKI)

-Autoregulation - renal blood flow and glomerular filtration rate - held constant

-Decreased perfusion -> Dilate afferent arteriole, constrict efferent arteriole

• Afferent dilation mediated by prostaglandins

• Efferent constriction effected by angiotensin II

-Sudden/severe decrease in renal perfusion -> sudden decrease in GFR -> renal injury

Acute Kidney Injury - Prerenal

Most common cause of Acute Kidney Injury

Caused by IMPAIRED RENAL BLOOD FLOW

-Decreased intravascular fluid volume (burn, diarrhea)

-Decreased cardiac output (MI, IHD, CHF)

-Renal artery occlusion

-Renal vasoconstriction (NSAIDs, contrast)

-GFR declines because of the decrease in filtration pressure

ex. marathon runners due to the sympathetic nervous system activation (vasoconstriction) resulting in decreased blood flow to the kidneys

Acute Kidney Injury - Intrarenal

Most common cause - Acute Tubular Necrosis (ATN)

Pathogenesis:

-Post-ischemic events

-Nephrotoxin

• Drugs - Aminoglycosides, amphotericin-B, chemo-agent

• Metals - Lead, aluminum

• Contrast

ex. alcoholics who drink antifreeze

• Antifreeze metabolizes to crystals and is toxic to the kidney

Acute Kidney Injury - Post-Renal

Urinary Tract Obstruction

-Interference with the flow of urine at any site along the urinary tract

-Etiology: Kidney stones, Prostate enlargement, Compressive, Tumor

Chronic Kidney Disease (CKD)

Progressive loss of renal function that affects nearly all of the organ systems

Etiology: Associated with Type I and II diabetes, hypertension, and intrinsic kidney disease

Diagnosis of Chronic Kidney Disease

GFR < 60 mL/min x 3 months

Fluid and Electrolyte Imbalance in Chronic Kidney Disease (CKD)

-Sodium excretion increases, leading to sodium deficit and volume loss

• Concentration and dilution ability diminishes

-Potassium Imbalance

• Hypokalemia - early

• Late + Oliguria -> Hyperkalemia

-Metabolic Acidosis when GFR < 30%

-Decreased Vitamin D

-Hypocalcemia

-Anemia of chronic disease - Low Erythropoietin

Characteristics of Chronic Kidney Disease (CKD)

-"Frost"

-"Red Eye"

-Anorexia, nausea, vomitting

-Hypertension, pericarditis, heart failure

-Pleurisy, dyspnea on exercise

-Epistaxis

-Anemia

-Sallow Pigmentation

-Urea Crystals (Pruritic excoriations)

-Bruising

-Amenorrhea, Impotence infertility

-Myopathy (muscle weakness)

-Peripheral Neuropathy

-Edema

-Nail Changes

-Bone Pain

Treatment of Chronic Kidney Disease (CKD)

Treat the disease by managing the underlying cause(s)

-Diabetes mellitus: Improved glucose control will improve major kidney outcomes in Type II Diabetes

-Hypertension

• Keep Blood Pressure < 130/80 mmHg = critical

• Angiotensin-converting enzyme inhibitor (ACEI) (Lisinopril)

• Angiotensin II receptor blocker (ARB)

-Dialysis if needed

-Transplant list

Acute Renal Failure

Causes: Severe shock, Burns, Nephrotoxins, Massive exposure, Acute bilateral kidney infection or inflammation

Onset: Sudden, acute

Early Signs: Oliguria, increased serum urea

Progressive Signs: Recovery-increasing urine output, if prolonged failure - uremia

Chronic Renal Failure

Causes: Nephrosclerosis, Diabetes mellitus, Nephrotoxins, Long-term exposure, Chronic bilateral kidney inflammation or infection, Polycystic disease

Onset: Slow, insidious

Early Signs: Polyuria with dilute urine, Anemia, Fatigue, Hypertension

Progressive Signs: End-stage failure or uremia, Oliguria, Acidosis, Azotemia

Acid-Base Balance

-Carefully regulated via multiple mechanisms

• Small changes significantly alter biologic processes

If [H+] is high,

the pH is low (acidic: pH<7.35)

If [H+] is low,

the pH is high (alkaline - pH > 7.45)

Alkalosis vs. Acidosis

-Alkalosis means INCREASED pH (Alkaline/Basic)

-Acidosis means DECREASED pH (Acidic)

Blood

-Good buffer

• carbonic acid-bicarbonate system

-Proteins have negative charges, so they can serve as buffers for H+

Organs that manage acid-base balance

• Lungs (Respiratory)

• Kidneys (Metabolic)

  • Only organ system that can remove acids

Normal (neutral) Arterial Blood pH

7.35-7.45

-Obtained by arterial blood gas (ABG) sampling

Acidosis

-Systemic increase in H+ concentration or decrease in bicarbonate (base)

Alkalosis

-Systemic decrease in H+ concentration or increase in bicarbonate

Acidemia

Decrease in the blood pH

Alkalemia

Increase in the blood pH

What are the four categories of acid-base imbalances?

-Respiratory Acidosis

-Respiratory Alkalosis

-Metabolic Acidosis

-Metabolic Alkalosis

Respiratory Acidosis

Elevation of pCO2 as a result of ventilation depression

-CO2 + H2O: increased

-H+: Increased

-HCO3-: increased

-Respiratory Compensation: none

-Renal Compensation or Correction: Increased HCO3- reabsorption (compensation)

Respiratory Alkalosis

lowered pCO2 as a result of alveolar hyperventilation

-CO2 + H2O: decreased

-H+: Decreased

-HCO3-: decreased

-Respiratory Compensation: none

-Renal Compensation or Correction: decreased HCO3- reabsorption (compensation)

Metabolic Acidosis

reduced HCO3- or an increase in non-carbonic acids

-CO2 + H2O: decreased

-H+: Increased

-HCO3-: decreased

-Respiratory Compensation: Hypoventilation

-Renal Compensation or Correction: Increased HCO3- reabsorption (correction)

Metabolic Alkalosis

increased HCO3- usually caused by an excessive loss of metabolic acids

-CO2 + H2O: increased

-H+: Decreased

-HCO3-: increased

-Respiratory Compensation: Hypoventilation

-Renal Compensation or Correction: increased HCO3- excretion (correction)

Causes of Respiratory Acidosis (decrease pH, increase CO2)

Hypoventilation

• Airway obstruction

• COPD

• Pneumonia

• Atelectasis

• Chest trauma, neuromuscular disease

• Pulmonary edema

• Decrease respiratory stimuli (Anesthesia, Drug overdose)

Causes of Metabolic acidosis (decrease pH, decrease HCO3-)

-Diabetic ketoacidosis

-Salicylate OD (aspirin)

-Severe diarrhea (losing bicarbonate)

-Renal failure

-Sepsis

-Shock

Potassium Levels in Acidosis

Potassium levels go up in Acidosis

Causes of Respiratory Alkalosis (increase pH, decrease CO2)

Hyperventilation

• Anxiety

• High altitudes

• Pregnancy

• Fever

• Hypoxia

• Initial stages of pulmonary emboli

Causes of metabolic alkalosis (increase pH, increase HCO3-)

-loss of gastric juices (vomiting loses acid)

-potassium wasting (diuretics, increase loss of H+)

-overuse of antacids

Causes of Metabolic Acidosis 2

-Increased H+ Production (DKA, Hypermetabolism)

-Decreased H+ Elimination (Renal Failure)

-Decreased HCO3 Production (Dehydration, Liver Failure)

-Increased HCO3 Elimination (Diarrhea, Fistulas)

Causes of Respiratory Alkalosis 2

-Hyperventilation (Anxiety, PE, Fear)

-Mechanical Ventilation

Causes of Metabolic Alkalosis 2

-Severe vomiting

-Excessive GI Suctioning

-Diuretics

-Excessive NaHCO3