INP midterm - KIDNEY DISEASE Flashcards
Flashcards for the first half of the INP course. This set will cover KIDNEY DISEASE
Describe the primary functions of the glomerulus.
- Working unit of filtration: blood enters through afferent arteriole, exits through efferent arteriole
- Hydrostatic pressure opposes oncotic pressure
o Oncotic pressure determined by proteins in blood, most notable albumin - Usually a limit to size of molecules that can pass through filtrate (proteins usually too big to be filtered)
Describe the primary functions of the the proximal tube.
- Major site of reabsorption – sodium and glucose
- SGLT 1 & 2 co-transporters
- Sodium/H+ Antiporter – H+ generated from carbonic acid (CO2+H2O, enzyme: carbonic anhydrase)
- Basolateral Na/K-ATPase pump maintains gradient
Describe the primary functions of the loop of Henle.
- Sodium reabsorption – especially in the thick ascending limb (TAL)
- Na/K/2Cl co-transporter
- Na/K-ATPase pump: maintains gradient
Describe the function of the kidney as it relates to sodium.
- kidney maintains sodium concentration via reabsorption/excretion – maintains blood pressure
- Excretion depends on:
o Dietary sodium intake
o Perceived blood volume - Na/K-ATPase pump – maintains electrochemical/concentration gradients that drive reabsorption
Describe the function of the kidney as it relates to water.
Plasma osmolality controls secretion of ADH (released from posterior pituitary)
o ADH: increases permeability of
collecting duct – increases water
reabsorption by kidney
§ Syndrome of Inappropriate ADH: increases blood volume & Hyponatremia
Describe the function of the kidney as it relates to acid/base balance.
- Increased Na reabsorption = Increased H+ excretion à more alkaline (higher pH)
- Bicarbonate: generation requires carbonic anhydrase and glutamine
o majority reabsorbed in proximal tubule –requires sodium and ATP
o Some reabsorbed in distal tubule
o Usually no bicarbonate in urine
- Acid/Base balance affected by:
o Dietary acid load
o Volume contraction
o Ventilatory failure
o Hypokalemia
o Increased aldosterone secretion
Describe the function of the kidney as it relates to potassium (electrolyte).
- Reabsorption highest in proximal tubule and TAL of loop of Henle
- Main sites of regulation = distal tubule and cortical collecting tubule (CCT)
- K+ secretion depends on:
o Delivery of sodium
§ Except when:
· Severely K+ depleted
· Tubule is severely damaged, in which case sodium does not promote excretion of potassium
o Presence/absence of aldosterone – (Aldosterone increases secretion/excretion of K+)
Describe the function of the kidney as it relates to magnesium (mineral).
- Filtered and reabsorbed by kidney – main site of reabsorption = TAL of Loop of Henle
o Na/K/2Cl co-transporter increases electronegative gradient – facilitates voltage-dependent flux of Mg through tight junctions
- Magnesium levels lowered by:
o Diuretics
o Kidney transplantation drugs
o Recovery from kidney failure
o Other drugs
Describe the function of the kidney as it relates to urea.
- Actively transported in kidney
- Kidney failure –> elevated BUN
Describe the function of the kidney as it relates to creatinine.
- Filtered and secreted by kidney
- Bad estimate of eGFR (estimated glomerular filtration rate)
Describe the function of the kidney as it relates to ammonia.
- Generated from glutamine
- Buffers H+ in urine
Describe the function of the kidney as it relates to calcium.
- Majority complexed to phosphate/citrate – some ionized (free)
- Majority reabsorbed in proximal tubule by passive diffusion (60-70%)
- Some reabsorbed in CCT (20%)
o Affected by parathyroid hormone (PTH) and 1,25-OH Vit. D3 (active vitamin D) - Remainder in distal tubule
o Affected by thiazide diuretics, PTH, and 1,25 OH Vit. D3 - PTH levels are dysregulated when kidneys are damaged
Describe the function of the kidney as it relates to phosphate.
- Phosphorous usually elevated in kidney disease
o Hyperphosphatemia can be treated by increasing Ca++ intake – binds phosphate - Regulated by dietary calcium intake
- Majority reabsorbed in proximal tubule (Na/PO4 co-transporter)
o Expression of co-transported modulated by:
§ dietary phosphorous intake
§ FGF23 (fibroblast growth factor)
§ PTH
What are the endocrine functions of the kidney as discussed in class?
- renin secretion
- erythropoietin synthesis
- 1-hydroxylation of 25-OH vitamin D à 1,25-OH Vit. D
- insulin metabolism
What is renin?
- an enzyme secreted in response to decreased Na, sensed by the macula densa cells, which implies low blood volume/low GFR
- results in increased Na+/water reabsorption
Explain erythropoietin synthesis in the kidney.
o Synthesized by peritubular cells of kidney in response to hypoxia
o Binds to EPO receptor on red cell precursors in bone marrow
o Kidney failure –> dec. EPO –> Anemia
What does insulin metabolism have to do with kidney?
- insulin is reabsorbed at the proximal tubule and degraded to oligopeptides
- some insulin is reabsorbed at the distal tubule, which stimulates the reapsorption of
- sodium
- phosphate
- glucose
- kidney failure prolongs insulin action (T1/2)
1-hydroxylation of 25-OH vitamin D –> 1,25-OH Vitamin D.
Explain.
o Activity increased by:
§ Hypocalcemia
§ Hypophosphatemia
§ Increased PTH
§ Increased GH
o Activity decreased by:
§ Kidney failure
§ High FGF23
o People with kidney failure given supplement of active vitamin D
o 25 hydroxylation takes place in liver
What are the primary symptoms and complications of nephritis (a glomerular disease)?
- Ex. Post-infectious (esp post- strep infection), SLE (lupus), etc.
- Hallmark: Inflammation of glomerular capillary – usually acute onset
- Usually resolves with time or treated with steroids
- Symptoms
o Urinary casts/hematuria
o HTN/Edema
What are the nutritional considerations for nephritis?
o NO protein restriction
o Volume retention treated with diuretics + salt restriction (2g/day)
§ may increase ADH –> hyponatremia
o possible benefits from omega-3 fatty acids (not definitively proven):
§ Fish oils & IGA nephropathy
§ Flaxseed oil & SLE (lupus) nephritis
What are the primary symptoms and complications of nephrosis (a glomerular disease)?
- Diagnosis (must have at least 3 of the following symptoms for nephrotic syndrome diagnosis)
o >3.5 g proteinuria/m^2/day (anything > 500 mg is abnormal)
o HTN
o HLD
o Edema
o Hypoalbuminemia - Hallmark: loss of podocyte foot processes on electron microscopy + subsequent leaking of protein due to loss of filtration barrier
o Foot processes prevent protein leakage - hypoalbuminemia, hypercholesterolemia, edema
- loss of anti-thrombin 3/ other clotting factors à, thrombotic disorders
- HTN and kidney insufficiency/failure can develop
What are the nutritional considerations for nephrosis?
o Hypoproteinemia – high protein diet (1.5g/kg/day) à increased urinary protein excretion
§ Protein restriction has been tried (.8-1.0 g/kg/day) à decreased urinary protein excretion without compromising muscle mass
§ Elimination diets in kids (gluten or dairy) – mixed results
o Edema: (secondary to low oncotic pressure)
§ Sodium restriction may help, but risk of hyponatremia
o HLD: (mech. Unclear)
§ One thought is that liver increases production of cholesterol along with albumin
§ Or loss of sterol regulatory elements
§ Likely: increased PCSK9, decreased LDL receptors
§ Dietary fat restriction (<30%, <10% saturated fat) + conventional lipid lowering therapy (statins/ ezetimibe)
· Shouldn’t use statins to lower cholesterol when albumin is low
§ Other approaches: fish oils (DHA/EPA), plant sterols/stanols
What is the definition of acute kidney injury?
Deterioration of kidney function that occurs over hours to days and results in accumulation of nitrogenous wastes
What is acute tubular necrosis?
o most common type of acute kidney injury
o Requires multiple insults to kidney
o Recovery over weeks to months if underlying disease is treated
