MPP II 2.7 - RENAL PHYSIOLOGY: CKD I

Renal Physiology - CKD

• Acute Kidney Injury (AKI) develops quickly within 48 hours and is usually treatable with no other complicating issues.
• Chronic Kidney Disease (CKD) develops over multiple years and triggers a progressive and irreversible loss of nephrons.
• In CKD, reduced clearance of solutes are primarily excreted by the kidney, resulting in retention in the body fluids.
• CKD is rarely reversible, leading to a continuous decline in renal function.
• Prerenal failure has a profound drop in GFR and occurs because of lessened renal blood flow and glomerular perfusion pressure.
• Prerenal failure normally occurs secondary to shock and ischemia.

Pathophysiology

• A reduction in renal mass triggers hypertrophy of the remaining nephrons.

Nephrons

• Increased hyper-filtration occurs as GFR in nephrons is increased, putting a burden on remaining nephrons
• This can lead to progressive glomerular sclerosis and interstitial fibrosis.

Stages of CKD

• Stage 1: Kidney damage with normal kidney function, GFR is 90 or higher.
• Stage 2: Kidney damage with mild loss of kidney function and a GFR of 89-60.
• Stage 3a: Mild to moderate loss of kidney function, GFR is 59-45.
• Stage 3b: Moderate to severe loss of kidney function, GFR is 44-30.
• Stage 4: Severe loss of kidney function and a GFR of 29-15.
• Stage 5: Kidney failure, GFR is less than 15.

Normal GFR numbers

• Age 20-29: 116
• Age 30-39: 107
• Age 40-49: 99
• Age 50-59: 93
• Age 60-69: 85
• Age 70+: 75

Clinical Manifestations

• Integumentary: Bruises, pruritus, dry skin, skin color changes ashen gray to yellowish, dry brittle hair and nails.
• Cardiovascular: High blood pressure, increased heart rate, dysrhythmias, electrocardiographic changes, abnormal heart sounds, retinopathy, fluid retention with peripheral edema, and/or pulmonary edema.
• Musculoskeletal: Renal osteodystrophy, decreased calcium, vitamin D impairment, hyperparathyroidism, pathological fractures.
• Neurological: Peripheral neuropathy, restless legs, change in level of consciousness, lethargy, confusion, encephalopathy, altered motor function.
• Hematological: Anemia, weakness, fatigue, bleeding, lethargy due to impaired platelet aggregation.
• Respiratory: Increased respiratory rate, Kussmaul respirations, crackles, and decreased P02.
• Renal: Decreased urine output, azotemia, proteinuria, hematuria, and hyperuricemia.
• Gastrointestinal: Anorexia, nausea, vomiting, halitosis, metallic taste in mouth, and bleeding in gastrointestinal tract.
• Immune: Increased risk of infection

Endocrine Hallmarks

• Endocrine Hallmarks: Normal Kidney regulates phosphate and calcium homeostasis
• In CKD the kidney no longer performs this function correctly

CKD results in these hormonal changes

• FGF23 rises
• PTH rises
• Vitamin D decreases
• Phosphate rises

FGF23

• FGF23 - "Pi Wasting Hormone"
• Acts on the kidneys via co-receptor Klotho, and increases the excretion of Pi.
• Decreases the expression of Na+-Pi II cotransporters.
• Limits Vitamin D, and inhibits 1a-hydroxylase.

PCT (Proximal Convoluted Tubules)

• SGLT2 (apical): high capacity load
• SGLT1 (apical): low capacity, high affinity
• Acetazolamide inhibits carbonic anhydrase
• Carbonic anhydrase is a mild diuretic
• The most mild diuretic is not usually good for HF/HIN
• Usually good for altitude sickness & glaucoma.

Loop Diuretics

• Steep osmotic gradient that is driven by the corticopapillary osmotic gradient.
• DTL uses H20 reabsorption through AQPS.
• There’s no AQPs in TAL (no H20 reabsorption) but salt is excreted.
• Furosemide, torsemide, and burmetanide are loop diuretics
• Loop Diuretics inhibit Na+/K+/Cl- cotransporter and are massive & quick diuretics used in acute vol. overload.

TAL

• TAL reabsorption results in a hypo-osmotic solution of urine compared to plasma in that segment.
• Atrasen is in the basolateral side.
• Na/Cl/ K+ apical cotransporter, diuretic target.

DCT (Distal Convoluted Tubule)

• Imported by hormones, such as PTH, Aldosterone, and Ang. II

Diuretics

• Thiazides inhibit Na/Cl cotransporter in DCT.
• DCT is near the bowman’s capsule and has macula densa cells for tubuloglomerular feedback.
• BL(Basolateral): Na/ K+ atpase
• Increase expression and activity of TRPVS
• increases reabsorption and storage of Calicum.

Principal cells of the late DCT

• Target site for aldosterone, which causes lower BV MAP and hyperkalemia

Collecting ducts

• Water reabsorption and/or secretion depend on the body.
• Spironolactone and triamterene/amlaride inhibits aldosterone effects in late DCT.

Intercalated cells

• d: Bicarb. thru Bl mem. of absors.
• P: mores bicarb. wetrafiltrate to a bicarb. feeretur.

Kidney Dialysis

• Blood is pumped into a dialyzer, and is exposed to a semipermeable membrane to remove waste, salt, and extra water, while keeping safe K+, Na+ and bicarb levels.
• Cleansed blood is returned to the body via the circuit.
• Ultrafiltration occurs by increasing the hydrostatic pressure across the dialyzer membrane, with removal of excess fluid in a 4 hours session.
• Kidney dialysis does not replace endocrine function of the kidney, such as erythropoietin, renin, and vit D.
• Dialysis helps keep potassium, sodium and bicarbonate levels safe