B68 End stage kidney and renal failure

Question 1

Define uremia and azotemia

Answer 1

Uremia is a clinical syndrome

Azoetmia is elevated BUN (>9mM) and creatinine (> 120uM)

Uremia is azotemia and clinical symptoms

Question 2

What are the clinical symptoms of Uremia?

Answer 2

1. Decreased GFR -> RAS activation
   
   • secondary hyperaldosteronism
   • Salt and water retention
   • Hypertension
   • Edema
2. Metabolic acidosis
   
   • ​​Decreased H+ secretion,
   • reduced bicarbonate reabsoprtion,
   • Hyperkalemia
3. Renal failure related osteodystrophy
   
   1. ​Phosphate retention and hyperphosphatemia
      
      • Induces FGF23 and inhibits Vitamin D
        
        • FGF23 inhibits PTH secretion
        • Inhibits vitamin D/calcitriol activation by kidney 1 alpha hydroxylase
        • Increases activtiy of 24 alpha hydroxylase, the vitamin D inactivating enzymes
      • Causes Calcium precipitation, directly decreasing free calcium levels.
4. Secondary Hyperparathyroidism
   
   • Increased bone resorption, but persistent hypocalcemia due to the other causes
5. Cardiopulmonary decompensation due to hypervolemia
   
   • ​​decompensate heart failure
   • induce pulmonary edema causing ARDS
6. Pericarditis directly due to uremia
7. Anemia
   
   • ​​deficient EPO production
8. Uremic gastroenteritis
9. Skin disorders
   
   1. Skin disorders are very prevalent in uremic patients, nearly all.
   2. ​Urea crystals are often visible as white deposits on the skin and scalp.
   3. skin bullae, half-and-half nail discolorations red-brown distally and white proximally. hemosiderin deposition outside of the legs.
   4. Pruritis
10. Encephalopathy with asterixis *flapping tremor of extended hands. Due to the toxin acumulation.
    
    • Eventual Coma
11. Nausea and anorexia

Question 3

What are the causes of End Stage Renal Failure?

Answer 3

3 most common: Diabetes, Hypertension, and Glomerular disease

Glomerular diseases:

• Glomerulonephritis
• Interstitial nephritis
• Polycystic kidney disease
• Chronic pyelonephritis
• Chronic vesiculouretal reflux and hydronephrosis

Question 4

What are the molecules that cause toxicity during uremia?

Answer 4

It is not the BUN and creatinine, these are very good indicators of uremia but not the toxic agents. The toxins that accumlate are termed uremic toxins.

The toxicity is mostly caused by:

Middle-Weight Uremic toxins:

Products of Nucleic Acid breakdown, including Beta 2 microglobulin

and Aliphatic Amines

3 categories of uremic toxins (there are man specific uremic toxins)

● Small, water-soluble, non-protein-bound compounds, such as urea

● Small, lipid-soluble and/or protein-bound compounds, such as the phenols

● Middle Weight Molecules >500 daltons, *notttttt kilodaltons

others:

• homocysteine
• hippurate
• Beta 2 microglobulin

Question 5

Where is what cells produce EPO?

Answer 5

Renal Peritubular Interstitial Cells