Renal Flashcards
Potter Sequence (Syndrome)
Oligohydramnios (too little amniotic fluid) leads to compression of developing fetus leading to limb deformities, facial anomalies (low-set ears and retrognathia), compression of chest and lack of amniotic fluid aspiration into fetal lungs.
This leads to pulmonary hypoplasia (cause of death)
Causes ARPKD, obstructive uropathy (posterior urethral valves), bilateral renal agensis.
Babies who can’t P in utero develop Potter Sequence
P = Pulmonary hypoplasia O = Oligohydramnios (trigger) T = Twisted Face T = Twisted Skin E = Extremity defects R = Renal failure (in utero)
Kidney embryo
1) Pronephros - week 4; then degenerates
2) Mesonephros - functions as interim kidney for 1st trimester; later contributes to male genital system
3) Metanephros - permanent; first appears in 5th week of gestation; nephrogenesis continues through 32-36 weeks of gestation.
- Ureteric Bud - derived from caudal end of mesonephric duct; gives rise to ureter, pelvises, calyces, collecting duct; fully canalized by 10th week
- Metanephric mesenchyme - ureteric bud interacts with this tissue; interaction induces differentiation and formation of glomerulus through to distal convoluted tubule (DCT)
- Aberrant interaction btw these 2 tissues may result in several congenital malformations of the kidney
4) Ureteropelvic junction - last to canalize. Most common site of obstruction (hydronephrosis) in fetus.
Horseshoe kidney
Inferior poles of both kidneys fuse. As they ascend from pelvis during fetal development, horseshoe kidneys get trapped under inferior mesenteric artery and remain low in the abdomen.
Kidneys function normally.
Associated with ureteropelvic junction obstruction, hydronephrosis, renal stones, infection, chromosomal aneuploidy syndromes (Edwards, Down, Patau, Turner), and rarely renal cancer.
Multicystic dysplastic kidney
Due to abnormal interaction between ureteric bud and metanephric mesenchyme.
Leads to a nonfunctional kidney consisting of cysts and connective tissue.
If unilateral (most common), generally asymptomatic with compensatory hypertrophy of contralateral kidney.
Often diagnosed prenatally via ultrasound
Duplex collecting system
Bifurcation of ureteric bud before it enters metanephric blastema creates Y-shaped bifid ureter.
Can alternatively occur when 2 ureteric buds reach and interact with metanephric blastema.
Strongly associated with vesicoureteral reflux and/or ureteral obstruction, higher risk of UTIs.
Which kidney is taken from donor before transplant?
Left.
It has a longer renal vein.
Ureters - course
Ureters pass under uterine artery and under ductus deferens (retroperitoneal)
Gyn procedures involving ligation of uterine vessels traveling in cardinal ligament may damage ureter leading to ureteral obstruction or leak.
Fluid compartments
HIKIN - High K intracellularly
60-40-20 rule (% of body weight for avg person):
60% total body water
40% ICF
20% ECF
Plasma volume measured by radiolabeled albumin
Extracellular volume measured by inulin
Osmolality = 285-295 mOsm/kg H2O
Normal fluid volumes
Normal person is 70kg (70L)
.6 (70) = 42L of total body water
.4 (70) = 28L of non water mass
Of the 42L water mass - 1/3 is extracellular, 2/3 is intracellular
OR 20% of overall = ECF, 40% of overall = ICF
.33 (42) or .2 (70) = 14 L ECF
.67 (42) or .4 (70) = 28 L ICF
Extracellular = Interstitial fluid + plasma
Intracellular includes RBC volume
Blood volume is about 6 L. Of these 6L, 45% is hematocrit (RBC). .45 (6) = 2.8 L of RBC (intracellular) and 3.2 L is plasma (extracellular)
Glomerular filtration barrier
Responsible for filtration of plasma according to size and net charge.
Composed of:
1) Fenestrated capillary endothelium (size barrier)
2) Fused basement membrane with heparan sulfate (negative charge barrier)
3) Epithelial layer consisting of podocyte foot processes
Charge barrier is lost in nephrotic syndrome leading to albuminuria, hypoproteinemia, generalized edema, hyperlipidemia
Renal Clearance
Cx = UxV/Px = volume of plasma from which the substance is completely cleared per unit time.
Cx = Clearance of X (mL/min) Ux = Urine concentration of X (mg/mL) Px = Plasma concentration of X (mg/mL) V = urine flow rate (mL/min)
Cx
Net tubular reabsorption of X
Cx > GFR
Net tubular secretion of X
Cx = GFR
No net secretion or reabsorption
Glomerular Filtration Rate
Inulin clearance can be used to calculated GFR bc it is freely filtered and is neither reabsorbed nor secreted
UV/P for inulin:
GFR = (U inulin)V/(P inulin) = C inulin
GFR = Kf [(Pgc - Pbs) - (pi gc - pi bs)]
gc = glomerular capillary
bs = bowman space
Pi bs normally = 0
Normal GFR = 100 mL/min
Creatinine clearance is an approximate measure of GFR. Slightly overestimates GFR bc creatinine is moderately secreted by renal tubules.
Incremental reductions in GFR define the stages of chronic kidney disease.
Effective Renal Plasma Flow
eRPF can be estimated using para-aminohippuric acid (PAH) clearance bc it is both filtered and secreted in the proximal collecting tubule, resulting in near 100% excretion of all PAH entering kidney
eRPF = U pah V / P pah = C pah
RBF = RPF / (1 - Hct)
eRPF underestimates true renal plasma flow (RPF) by about 10%
Filtration
Filtration fraction (FF) = GFR/RPF
Normal FF = 20%
Filtered load (mg/min) = GFR (mL/min) x Plasma concentration (mg/mL)
GFR can be estimated with creatinine clearance. RPF is best estimated with PAH clearance.
Changes in glomerular dynamics
1) Afferent arteriole constriction:
Lower GFR, Lower RPF, no change FF (GFR/RPF)
2) Efferent arteriole constriction:
Higher GFR, Lower RPF, Higher FF
3) Higher plasma protein concentration:
Lower GFR, Flat RPF, Lower FF
4) Lower plasma protein concentration:
Higher GFR, Flat RPF, Higher FF
5) Constriction of ureter:
Lower GFR, Flat RPF, Lower FF
Prostaglandin effects on glomerulus
Preferentially dilates afferent arteriole (higher RPF, higher GFR, flat FF)
NSAIDs inhibit this
Angiotensin II effects on glomerulus
Preferentially constricts efferent arteriole (Lower RPF, Higher GFR, Higher FF)
ACE Inhibitors inhibit this
Calculation of reabsorption and secretion rate
Filtered Load = (GFR) (Px)
Excretion rate = (V)(Ux)
Reabsorption = filtered - excreted Secretion = excreted - filtered
Glucose clearance
Glucose at a normal plasma level is completely reabsorbed in PCT by Na/Glucose cotransport
At plasma glucose of 200, glucosuria begins (threshold).
At 375, all transporters are fully saturated (Tm)
Glucosuria is an important clinical clue to diabetes mellitus
Normal pregnancy may decrease ability of PCT to reabsorb glucose and amino acids leading to glucosuria and aminoaciduria.
Amino acid clearance
Na-dependent transporters in PCT reabsorb amino acids
Hartnup Disease
Auto recessive
Deficiency of neutral amino acid (like tryptophan) transporters in proximal renal tubular cells and on enterocytes leads to neutral aminoaciduria and lower absoprtion from the gut.
This lowers tryptophan for conversion to niacin leading to pellagra-like symptoms.
Treat with high protein diet and nicotinic acid
List the Renal Tubular Defects (5)
The kidneys put out FABulous Glittering LiquidS.
FA = Fanconi Syndrome is the 1st defect (PCT) B = Bartter Syndrome is next (Thick Ascending loop) G = Gitelman Syndrome is after Bartter (DCT) L = Liddle Syndrome is last (collecting tubule) S = Syndrome of apparent mineralocorticoid excess (collecting tubule)
Fanconi Syndrome
Generalized reabsorptive defect in PCT
Associated with higher excretion of nearly all amino acids, glucose, Bicarb, Phosphate.
May result in metabolic acidosis (prox renal tubular acidosis)
Causes include:
1) hereditary defects (Wilson disease, tyrosinemia, glycogen storage disease)
2) Ischemia
3) Multiple myeloma
4) Nephrotoxins/drugs (expired tetracyclines, tenofovir), lead poisoning
Bartter Syndrome
Reabsorptive defect in thick ascending loop of Henle.
Autosomal recessive
Affects Na/K/2Cl cotransporter
Results in hypokalemia and metabolic acidosis with hypercalciuria
Gitelman Syndrome
Reabsorptive defect of NaCl in DCT
Auto recessive
Less severe than Bartter. Leads to hypokalemia, hypomagnesemia, metabolic alkalosis, hypocalciuria
Liddle Syndrome
Gain of function mutation leading to higher Na reabsorption in collecting tubules (increased activity of epithelial Na channel)
Auto Dominant
Results in HTN, hypokalemia, metabolic alkalosis, lower aldosterone
Tx = Amiloride
Syndrome of apparent mineralocorticoid excess
Hereditary deficiency of 11B-hydroxysteroid dehydrogenase, which normally converts cortisol into cortisone in mineralocorticoid receptor-containing cells before cortisol can act on the mineralocorticoid receptors
Excess cortisol in these cells from enzyme deficiency leads to increased mineralocorticoid receptor activity.
This leads to HTN, hypokalemia, metabolic alkalosis.
Low serum aldosterone levels
Can acquire disorder from glycyrrhetic acid (present in licorice), which blocks activity of 11B-hydroxysteroid dehydrogenase
Renin-Angiotensin-Aldosterone System
Triggers:
1) Lower BP (JG Cells)
2) Low Na delivery (Macula Densa Cells)
3) Higher sympathetic tone (B1 receptors)
What happens?
These triggers increase secretion of Renin
Renin converts Angiotensinogen (from liver) to Angiotensin I
AT I is converted to Angiotensin II via ACE (from lungs and kidney). NOTE!!! ACE also breaks down bradykinins
AT II acts at a lot of places:
1) Acts at AT II receptor type 1 on vascular smooth muscle.
- This leads to vasoconstriction leading to increased BP
2) It constricts efferent arterioles of glomerulus.
- This leads to higher FF to preserve renal function (GFR) in low volume states (i.e. when RBF falls)
3) It triggers aldosterone release from adrenal gland.
- This increases Na channel and Na/K pump insertion in principal cells
- Enhances K and H excretion by way of principal cell K channels and alpha-intercalated cell H ATPases
- All this creates a favorable Na gradient for Na and H2O reabsorption
4) Triggers release of ADH from posterior pituitary
- Increases aquaporin insertion in principal cells (these dudes are in the collecting ducts)
- Leads to H2O reabsoprtion
5) Increases PCT Na/H activity
- leads to Na, Bicarb, H2O reabsorption (can permit contraction alkalosis)
6) Stimulates hypothalamus
- stimulates thirst
Angiotensin II
Affects baroreceptor function; limits reflex bradycardia, which would normally accompany its pressor effects. Helps maintain blood volume and blood pressure.
AT II acts at a lot of places:
1) Acts at AT II receptor type 1 on vascular smooth muscle.
- This leads to vasoconstriction leading to increased BP
2) It constricts efferent arterioles of glomerulus.
- This leads to higher FF to preserve renal function (GFR) in low volume states (i.e. when RBF falls)
3) It triggers aldosterone release from adrenal gland.
- This increases Na channel and Na/K pump insertion in principal cells
- Enhances K and H excretion by way of principal cell K channels and alpha-intercalated cell H ATPases
- All this creates a favorable Na gradient for Na and H2O reabsorption
4) Triggers release of ADH from posterior pituitary
- Increases aquaporin insertion in principal cells (these dudes are in the collecting ducts)
- Leads to H2O reabsoprtion
5) Increases PCT Na/H activity
- leads to Na, Bicarb, H2O reabsorption (can permit contraction alkalosis)
6) Stimulates hypothalamus
- stimulates thirst
ANP, BNP
Released from atria (ANP) and ventricles (BNP) in response to an increase in volume
May act as a “check” on renin-angiotensin-aldosterone system
Relaxes vascular smooth muscle via cGMP leading to an increased GFR, and lower renin
ADH
Primarily regulates osmolarity; also responds to low blood volume states
- Increases aquaporin insertion in principal cells (these dudes are in the collecting ducts)
- Leads to H2O reabsoprtion
Aldosterone
Primarily regulates ECF volume and Na content; responds to low blood volume states
- This increases Na channel and Na/K pump insertion in principal cells
- Enhances K and H excretion by way of principal cell K channels and alpha-intercalated cell H ATPases
- All this creates a favorable Na gradient for Na and H2O reabsorption
Juxtaglomerular apparatus
Consists of mesangial cells, JG Cells (modified smooth muscle of afferent arteriole) and the macula densa (NaCl sensor, part of DCT)
JG cells secrete renin in response to decreased renal blood pressure and increased sympathetic tone (B1)
Macula densa cells sense reduced NaCl delivery to DCT leading to adenosine release which causes vasoconstriction.
JGA maintains GFR via renin-angiotensin-aldosterone system
B-Blockers can decrease BP by inhibiting B1-receptors of the JGA leading to decreased renin release
Substances released by the Kidney (Kidney endocrine function)
1) Erythropoietin
2) 1,25-(OH)2D3
3) Renin
4) Prostaglandins
Erythropoietin
Released by interstitial cells in peritubular capillary bed in response to hypoxia
1,25-(OH)2D3
PCT cells convert 25-OH vitamin D to 1,25-(OH)2 Vitamin D (active form)
The enzyme that does this is 1alpha-hydroxylase
This enzyme is inhibited by PTH
Renin
Secreted by JG Cells in response to lower renal arterial pressure and increased renal sympathetic tone (B1 effect)
Prostaglandins
Paracrine secretion vasodilates the afferent arterioles to increase RBF
NSAIDs block renal-protective prostaglandin synthesis leading to constriction of afferent arteriole and lower GFR
This may result in acute renal failure
What causes a shift of K out of cells leading to hyperkalemia?
1) Digitalis
2) HyperOsmolarity
3) Lysis of cells (crush injury, rhabdomyolysis, cancer)
4) Acidosis
5) B-blocker
6) high blood Sugar (insulin deficiency)
trick = “DO LABS” on patients with hyperkalemia
What causes a shift of K into cells leading to hypokalemia?
1) Hypo-osmolarity
2) Alkalosis
3) B-adrenergic agonist (increases Na/K ATPase)
4) Insulin (Increases Na/K ATPase)
“IN”sulin shifts K “IN”to cells
Angiotensin II - where does it act? what does it do? Part 2
Made in response to lower BP
Causes efferent arteriole constriction leading to increased GFR and increased FF but with compensatory Na reabsoprtion in proximal and distal nephron
Net effect: preservation of renal function (higher FF) in low-volume state with simultaneous Na reabsoprtion (both proximal and distal) to maintain circulating volume
Parathyroid hormone
Secreted in response to:
1) lower plasma Ca
2) high plasma PO4
3) low plasma 1,25-(OH)2D3
Causes/leads to:
1) increased Ca reabsorption (DCT)
2) lower PO4 reabsorption (PCT)
3) higher 1,25-(OH)2D3 production (higher Ca and PO4 absorption from gut via vitamin D)
