Renal Flashcards
Pronephros
Early embryologic kidney (Week 4)–> degenerates
Mesonephros
Interim kidney for 1st trimester
- Contributes to male genitalia
Metanephros
Permanent kidney structure; appears in 5th week
- Nephrogenesis until 32-36 weeks gestation
Structures within metanephros:
- Ureteric bud
- Metanephric mesenchyme (mesoderm)
Intermediate mesoderm
Forms urogenital ridge–> nephrogenic cord–> mesonephros:
- Wolffian duct in males
- Gartner’s ducts in females
Ureteric bud
Caudal end of mesonephros; canalized by week 10 Collecting system: - Collecting duct - Major/minor calyxes - Renal pelvis - Ureters
Metanephric mesoderm
Kidney structures:
- Glomerulus
- Bowman’s space
- Proximal tubule
- Loop of Henle
- Distal and collecting tubule
** formed through interaction/induction with ureteric bud
Ureteropelvic junction
Last part of kidney to canalize–> most common site of obstruction (hydronephrosis) in fetus
Potter’s syndrome
Oligohydramnios–> compressed fetus–> limb/facial deformities, pulmonary hypoplasia (death)
can’t Pee–> Potters
Causes:
- ARPKD
- Posterior urethral valves
- Bilateral renal agenesis
Horseshoe kidney
Inferior poles of kidneys fuse
- Ascend–> trapped under inferior mesenteric artery
Normal function
* Associated with Turner’s syndrome (46XO)
Multicystic dysplastic kidney
Abnormal interaction between ureteric bud and metanephros–> nonfunctional kidney (cysts and connective tissue)
- Unilateral= asymptomatic, contralateral kidney hypertrophies to compensate
Prenatal diagnosis with ultrasound
Fluid balance
60% total body water
- 2/3 (40% total) Intracellular (ICF)
- 1/3 (20% total) extracellular (ECF): 1/4 plasma, 3/4 interstitial
Plasma volume= measured by radiolabeled albumin
ECF= measured by inulin (freely filtered, fully cleared)
Glomerular filtration barrier
Vessel: fenestrated capillary endothelium (size barrier)
Glomerulus:
- Basement membrane (fused) with heparin sulfate= negative charge barrier
- Epithelial layer= podocyte foot processes
** charge barrier lost in nephrotic syndrome–> albuminuria, hypoproteinemia, generalized edema, hyperlipidemia
Renal clearance
Clearance (x)= Urine[x]*Urine flow (V)/ Plasma[x]
Cx=UxV/Px
Cx < GFR: reabsorption
Cx > GFR: secretion
Cx = GFR: no net secretion or reabsorption
GFR
Inulin clearance used to calculate GFR= completely cleared
GFR= U[inulin]*V/P[inulin]= C[inulin]
** Creatinine clearance is approximate measurement of GFR (slightly overestimates as renal tubules secrete):
Creatinine= Non-protein waste product of skeletal muscle metabolism
Clearance= 15-25 mg/kg/day= proportional to muscle mass; Serum concentration dependent on:
- Excretion (glomerular filtration)
- Secretion into lumen
Changes in creatinine excretion have hyperbolic relationship with GFR:
- jump from 1 to 2 mg/dL–> 50% loss of nephrons
Effective renal plasma flow
Estimate using PAH clearance: filtered and actively secreted in proximal tubule
- All entering kidney–> excreted
ERPF= U[PAH] * V/P[PAH}
** underestimates by ~10%
Filtration
Filtration fraction= GFR/RPF
- Normal = 20%
- Filtered load= GFR * plasma concentration
- Prostaglandins dilate Afferent arteriole–> increased RPF, GFR–> constant FF)
- Blocked by NSAIDs
- Angiotensin II constricts Efferent arteriole–> decreased RPF, increased GFR–> increased FF
- Blocked by ACE-I
Glucose clearance
Completely reabsorbed in proximal tubule: Na+/glucose cotransport
- 160 mg/dL–> glucosuria
- 350 mg/dL–> transporters fully saturated (Tm)
Pregnancy: decreased reabsorption of glucose, amino acids–> glucosuria, aminoaciduria
Amino acid clearance
Reabsorbed in proximal tubule:
Na+-dependent transporters
Hartnup’s= deficiency of neutral aa (tryptophan) transporter–> pellagra
Urea excretion
Freely filtered at glomerulus
- Passively reabsorbed in proximal tubule, inner medullary collecting duct
- Passively secreted by thin loop of Henle
10-70% excreted depending on urinary flow, concentration
PTH in kidney
Acts on interstitial side of tubules
Proximal tubule: inhibits Na/Phosphate cotransporter–> excrete phosphate
- enhances activity of enzyme (1-alpha-hydroxylase) that converts 25-OH to 1,25-OH2 Vit D
DCT: increases Ca+2/Na+ exchange–> increased Ca+2 reabosorption
Angiotensin II
Maintains blood volume and BP
Within kidney:
- Constricts efferent arteriole
- PCT: stimulates Na+/H+ exchange on luminal side–> increased Na+, H2O, HCO3- reabsorption (compensatory Na+ resorption with water vs ADH)
* Contraction alkalosis (dehydrated–> more ATII–> more bicarb resorption)
Adrenal gland:
- Synthesis of aldosterone
Vasculature:
- AT1 receptors on smooth muscle–> vasoconstriction–> increased BP
Posterior pituitary:
- ADH secretion–> H2O absorption via aquaporin in medullary collecting duct
Hypothalamus:
- Thirst
Cardiac:
- Limits reflex bradycardia that normally accompanies increased BP
Aldosterone
decreased blood volume–> renin–> angiotensin II production–> Aldosterone in adrenal gland
- Also secreted in response to elevated [K+]
Cortical Collecting duct:
- Mineralocorticoid receptor–> insert Na+ channel on luminal side–> increase Na+, water resoprtion
- Na+/K+ pump insertion on interstitial side
- upregulates K+ channels, intercalated H+ channels–> K+ and H+ excreted–> can cause metabolic alkalosis
** Directly blocked from receptor by spironolactone; effects blocked by amiloride, triamterine (K+-sparing diuretics)
ADH
decreased blood volume–> renin–> angiotensin II production–> ADH in posterior pituitary
Regulates osmolarity
Responds to low blood volume (overrides osmolarity)
Collecting tubule
- Acts on V2 receptor
- Inserts aquaporin channel on luminal side
ANP
Released from atria in response to increased blood volume
- “Checks” RAAS
- Relaxes vascular smooth muscle: increased cGMP–> increased GFR–> decreased renin–> Na+ and H2O loss
