CVPR First Aid: Renal embryology Flashcards
Pronephros
Week 4; then degenerates
Mesonephros
Functions as interim kidney for 1st trimester, later contributes to male genital system
Metanephros
Permanent
First appears in 5th week of gestation
Nephrogenesis continues through weeks 32-36
FIRST AIDKidney embryology diagram
562
What is potter sequence syndrome?
Oligohydramnios → compression of developing fetus → limb deformities, facial anomalies (eg, low-set ears and retrognathia, flattened nose), compression of chest and lack of amniotic fluid aspiration into fetal lungs → pulmonary hypoplasia (cause of death)
What is the cause of death in Potter Sequence Syndrome
lack of amniotic fluid aspiration into fetal lungs → pulmonary hypoplasia (cause of death)
Uteric bud is derived from?
Derived from caudal end of mesonephric duct
Uteric bud canalization
fully canalized by the 10th week
Ureteric bud gives rise to
Gives rise to ureter, pelvises, calyces, collecting ducts
Metanephric mesenchyme and ureteric bud interactions
(ie, metanephric blastema)
Uteric bud interacts with this tissue; interaction induces differentiation and formation of glomerulus through to distal convoluted tubule (DCT)
Aberrant interaction between these 2 tissues may result in several congenital malformations of the kidney (eg, renal agenesis, multicystic dysplastic kidney)
Causes of Potter Sequence Syndrome
4 listed
ARPKD
Obstructive uropathy (Eg, posterior urethral valves)
Bilateral ren agenesis
Chronic placental insufficiency
What is ARPKD?
Autosomal recessive polycystic kidney disease
Ureteropelvic junction
Last to canalize → most common site of obstruction (can be detected on prenatal ultrasound as hydronephrosis
Babies who can’t pee in utero develop
Potter Sequence Syndrome
POTTER sequence associated with
Pulmonary hypoplasia
Oligohydramnios
Twisted face
Twisted skin
Extremity defects
Renal failure (in utero)
What is horseshoe kidney?
Inferior poles of both kidneys fuse abnormally
As they descend from pelvis during fetal development, horseshoe kidneys get trapped under inferior mesenteric artery and remain low in the abdomen
Kidneys function normally
Horseshoe kidney is associated with?
5 listed
- Associated with hydronephrosis (eg, ureteropelvic junction obstruction)
- renal stones
- infection
- chromosomal aneuploidy syndromes (eg, Turner syndrome, Trisomies; 13, 18 and 21)
- rarely renal cancer
FIRST AID Identify horseshoe kidney
563
Trisomies associated with Horseshoe kidney
Trisomies; 13, 18 and 21)
Dx of congenital solitary functioning kidney?
Prenatally via ultrasound
What is unilateral renal agenesis?
Ureteric bud fails to develop and induce differentiation of metanephric mesenchyme → complete absence of kidney and ureter
What is multicystic dysplastic kidney?
Ureteric bud fails to develop and induce differentiation of metanephric mesenchyme → complete absence of kidney and ureter
A multicystic dysplastic kidney (MCDK) is the result of abnormal fetal development of the kidney. The kidneyconsists of irregular cysts of varying sizes that resemble a bunch of grapes. A multicystic dysplastic kidney has no function and nothing can be done to save it.
multicystic dysplastic kidney pathophysiology and etiology
Ureteric bud fails to induce differentiation of metanephric mesenchyme → nonfunctional kidney consisting of cysts and connective tissue
Predominantly nonhereditary and usually unilateral
Bilateral leads to Potter Sequence
What is duplex collecting system?
Bifurcation of ureteric bud before it enters the metanephric blastema creates a Y-shaped bifid ureter
Duplex collecting system can alternatively occur through two ureteric buds reaching and interacting with metanephric blastema
Strongly associated with vesicoureteral reflux and/or ureteral obstruction
What are posterior urethral valves
Membrane remnant in the posterior urethra in males
The abnormality occurs when the urethral valves, which are small leaflets of tissue, have a narrow, slit-like opening that partially impedes urine outflow. Reverse flow occurs and can affect all of the urinary tract organs including the urethra, bladder, ureters, and kidneys.
Complications of Posterior urethral valves
Its persistence can lead to a urethral obstruction
Dx of posterior urethral valves
Can be diagnosed prenatally by hydronephrosis and dilated or thick walled bladder on ultrasound
What Most common cause of bladder outlet destruction
in male infants
posterior urethral valves
What kidney is taken from the donor for transplant
Left kidney is taken during donor transplant because it has a longer renal vein
Describe renal blood flow
Renal artery → segmental artery → arcuate artery → interlobular artery → afferent arteriole → vasa recta/peritubular capillaries → venous outflow
Diagrams pg
564
Describe the course of ureters
Pg 564
Arises from renal pelvis and travels under gonadal arteries → over common iliac artery → under uterine artery/vas deferens (retroperitoneal)
Describe the danger to the ureter from gynecologic procedures
(eg, ligation of uterine or ovarian vessels)
may damage ureter → ureteral obstruction or leak
What prevents urine reflux?
Muscle fibers within the intramural part of the ureter prevent urine reflux
What prevents urine reflux?
Muscle fibers within the intramural part of the ureter prevent urine reflux
VUR AKA
Vesicoureteral reflux (VUR)
Describe the points of constriction of the ureter
3 Listed
Ureteropelvic junction
Pelvic inlet
Ureterovesicle junction
Water (ureters) flows over the iliacs and under the bridge (uterine artery or vas deferens)
Diagram pg 564
What is Vesicoureteral reflux?
is a condition in which urine flows backward from the bladder to one or both ureters and sometimes to the kidneys. … Normally, urine flows down the urinary tract, from the kidneys, through the ureters, to the bladder
Where is [K+] highest?
HIKIN
High K Intracellularly
What is the body water distribution
60-40-20 rule
60% total body water
40% ICF
20% ECF
Describe ICF ion concentrations
K
Mg
Organic phosphates (eg, ATP)
Describe ECF ion concentrations
4 listed
Na+
Cl-
HCO3-
Albumin
Describe ICF ion concentrations
K
Mg
Organic phosphates (eg, ATP)
How can plasma volume be measured?
Radiolabled albumin
How can extracellular volume be measured
Inulin or mannitol
Normal Osmolality of ECF
285-295 mOsm/kg H2O
What is the function of the glomerular filtration barrier
Responsible for filtration of plasma according to size and charge selectivity
The glomerular filtration barrier is composed of
3 listed
Fenestrated capillary endothelium
Basement membrane with type IV collagen chains and heparan sulfate (which is negatively charged)
Epithelial layer consisting of podocyte foot processes
Describe the charge barrier of the glomerular filtration barrier
All 3 layers contain (-) charged glycoproteins that prevent entry of (-) charged molecules (eg, albumin)
Describe the size barrier of the glomerular filtration barrier
Fenestrated capillary endothelium (prevent entry of > 100 nm molecules/blood cells
Podocyte foot processes interpose with basement membrane
Slit diaphragm (prevent entry of molecules > 50-60 nm
Describe 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 (eg, mg/mL
Px = plasma concentration of X (eg, mg/mL)
V = urine flow rate (mL/min)
Interpretation of renal clearance
If Cx < GFR net tubular reabsorption of X
If Cx > GFR net tubular secretion of X
If Cx = GFR no net secretion or absorption
Describe glomerular filtration rate
Inulin clearance can be used to calculate GFR because it is freely filtered and is neither reabsorbed nor secreted
GFR = Uinulin x V/Pinulin = Cinulin
= Kf{[PGC-PBS) - (πGC - πBS)]
GC = glomerular capillary
BS = Bowmans space
πBS usually = 0
Kf= filtration coefficient
What is a normal GFR?
100 mL/min
What is an appropriate measure of GFR
Creatinine clearance is an appropriate measure of GFR but
Slightly overestimates GFR because it is moderately secreted by renal tubules
What do reductions in GFR mean
Incremental reductions in GFR define the stages of chronic kidney disease
What is RPF?
Renal plasma flow
What is eRPF?
effective renal plasma flow
Renal blood flow equation
(RBF) = RPF/(1-Hct)
What is filtration fraction?
FF= GFR/RPF
Normal FF =
20%
Filtered load (mg/min) equation
FL = GFR (mL/min) x plasma concentration (mg/mL)
GFR can be estimated with?
creatinine clearance
RPF is best estimated with?
PAH clearance
Prostaglandins Dilate Afferent arteriole (PDA)
Angiotensin II Constricts Efferent arteriole (ACE)
Bowman’s capsule
Pg 567
Afferent arteriole constriction effect on GFR
↓
Efferent arteriole constriction effect on GFR
↑
↑ plasma protein concentration effect on GFR
↓
↓ plasma protein concentration effect on GFR
↑
Constriction of ureter effect on GFR
↓
Dehydration effect on GFR
↓
Afferent arteriole constriction effect on RPF
↓
Efferent arteriole constriction effect on RPF
↓
↑ plasma protein concentration effect on RPF
-
↓ plasma protein concentration effect on RPF
-
Constriction of ureter effect on RPF
-
Dehydration effect on RPF
↓↓
Afferent arteriole constriction effect on FF
-
Efferent arteriole constriction effect on FF
↑
↑ plasma protein concentration effect on FF
↓
↓ plasma protein concentration effect on FF
↑
Constriction of ureter effect on FF
↓
Dehydration effect on FF
↑
What is FF?
GFR/RPF
Calculation of reabsorption and secretion rate
Filtered load = GFR x Px
Excretion rate = V x Ux
Reabsorption rate = filtered - excreted
Secretion rate = excreted - filtered
FeNa = fractional excretion of sodium
FeNa = Na excreted / Na filtered = (V x Una) / (GFR x Pna)
Where GFR = (Ucr x V/ (PCr) = (PCr x Una) /(Ucr x Pna)
Describe glucose clearance
Glucose at a normal plasma level (range 60-120 mg/dL) is completely reabsorbed in proximal convoluted tubule (PCT) by Na/glucose cotransport
Glucose at a normal plasma level (range 60-120 mg/dL) is completely reabsorbed in proximal convoluted tubule (PCT) by Na/glucose cotransport
In adults at plasma glucose of 200 mg/dL glucosuria begins begins (threshold)
At a rate of 375 mg/min, all transporters are fully saturated (T(m))
Normal pregnancy is associated with ↑GFR
with ↑ filtration of all substances including glucose, the glucose threshold occurs at lower plasma glucose concentrations → glucosuria at plasma concentrations < 200 mg/dL
Glucosuria is an important clinical clue to diabetes mellitus
Splay phenomenon -
Tm for glucose is reached gradually rather than sharply due to the heterogeneity of nephrons (ie, different Tm points); represented by the portion of the titration curve between threshold and Tm
ALL THIS PG 568
Nephron physiology early PCT
Early PCT - contains brush border. Reabsorbs all glucose and amino acids and most HCO3-, Na, Cl, PO4, K, H2O and uric acid
Isotonic absorption
Generates and secretes NH3 which enables the kidney to secrete more H+
PTH inhibits Na/PO4 cotransport → PO4 excretion
ATII - stimulates Na/H exchange → ↑Na, H2O, and HCO3 reabsorption (permitting contraction alkalosis)
65-80% Na reabsorbed
Thin descending loop of Henle
Passively reabsorbs H2O via medullary hypertonicity (impermeable to Na)
Concentrating segment
makes urine hypertonic
Thick ascending loop of Henle
Reabsorbs Na, K and Cl
Indirectly induces paracellular reabsorption of Mg2+ and Ca2+ through (+) lumen potential generated by K backleak
Impermeable to H2O
Makes urine less concentrated as it ascends
10-20% Na reabsorbed
Early DCT
Reabsorbs Na, Cl
Impermeable to H2O
Makes urine fully dilute (hypotonic)
PTH - ↑ Ca/Na exchange → Ca reabsorption
5-10% Na reabsorbed
Collecting tubule
Reabsorbs Na in exchange for secreting K and H (regulated by aldosterone)
Aldosterone - acts on mineralocorticoid receptor → mRNA → protein synthesis
In principal cells ↑ apical K conductance, ↑ Na/K pump, ↑ epithelial Na channel (ENaC activity) → lumen negativity → K secretion
In α-intercalated cells: lumen negativity → ↑H+ ATPase activity → ↑H+ secretion → ↑ HCO3/Cl exchanger activity
ADH - acts at V2 receptor → insertion of aquaporin H2O channels on apical side
3-5% Na reabsorbed
What is SAME?
Syndrome of apparent mineralocorticoid excess
Describe renal defects in Fanconi syndrome
Generlized reabsorption defect in PCT → ↑ excretion of amino acids, glucose, HCO3 and PO4 and all substances reabsorbed by the PCT
Describe renal defects in Bartter syndrome
Resorptive defect in thick ascending loop of Henle (affects Na/K/2Cl cotransporter)
Presentation of renal defects in Gitelman syndrome
Reabsorption defect of NaCl in DCT
Describe renal defects in Liddle syndrome
Gain of function mutation → ↑ activity of Na channel → ↑ Na reabsorption in collecting tubules
Describe the renal defects in Syndrome of apparent mineralocorticoid excess
In cells containing mineralocorticoid receptors 11β-hydroxysteroid receptors, 11β-hydroxysteroid dehydrogenase converts cortisol (can activate these receptors to cortisone (inactive on these receptors)
Hereditary deficiency of 11β-hydroxysteroid → excess cortisol → ↑ mineralocorticoid activity
Presentation of the effects of the renal defect in Fanconi syndrome
May lead to metabolic acidosis (proximal RTA)
hypophosphatemia
osteopenia
Describe the effects of the renal defect in Bartter syndrome
3 listed
- Metabolic alkalosis
- Hypokalemia
- hypercalciuria
Describe the effects of the renal defect in Gitelman syndrome
4 listed
- Metabolic alkalosis
- Hypomagnesemia
- Hypokalemia
- Hypocalciuria
Describe the effects of the renal defect in Liddle syndrome
4 listed
- Metabolic alkalosis
- Hypokalemia
- Hypertension
- ↓ aldosterone
Describe the effects of the renal defect in Syndrome of apparent mineralocorticoid excess
Metabolic alkalosis
Hypokalemia
Hypertension
↓ serum aldosterone level
Cortisol tries to be SAME as aldosterone so ↑ cortisol levels
Causes of Fanconi syndrome
Hereditary defects
(eg, Wilson disease, tyrosinemia, glycogen storage disease)
Ischemia
Multiple myeloma
Nephrotoxins/drugs (eg, ifosfamide, cisplatin, expired tetracyclines)
Lead poisoning
Causes of Bartter syndrome
Autosomal recessive
Causes of Gitelman syndrome
Autosomal recessive
Causes of Liddle syndrome
Autosomal dominant
Causes of SAME
Autosomal recessive
Can acquire disorder from glycyrrhtinic acid (present in licorice) which blocks activity of 11β-hydroxysteroid dehydrogenase
Special considerations of Bartter syndrome
Presents similarly to chronic loop diuretic use
Special considerations of Gitelmen syndrome
Presents similarly to lifelong thiazide diuretic use
Less severe than Bartter syndrome
Special considerations of Liddle syndrome
Presents similarly to hyperaldosteronism but aldosterone is nearly undetectable
Treatment of Liddle syndrome
Amiloride
What is amiloride?
The potassium-sparing diuretics are competitive antagonists that either compete with aldosterone for intracellular cytoplasmic receptor sites, or directly block sodium channels (specifically epithelial sodium channels (ENaC) by amiloride).
Treatment of SAME
Treat with K-sparring diuretics (↓ mineralocorticoid effects)
Or
Corticosteroids (exogenous corticosteroid ↓ endogenous cortisol production →↓ mineralocorticoid receptor activation
Renal tubular defect that presents similarly to chronic loop diuretic use
Bartter syndrome
Renal tubular defect that presents similarly to lifelong thiazide diuretic use
Gitelmen syndrome
Renal tubular defect that presents similarly to hyperaldosteronism but aldosterone is nearly undetectable
Liddle syndrome
Describe the relative concentrations along the proximal convoluted tubule
571
Tubular inulin ↑ in concentration (but not amount) along the PCT as a result of water reabsorption Cl- reabsorption occurs at a slower rate than Na in early PCT and then matches the rate of Na reabsorption more distally
Thus its relative concentration ↑ before it plateaus
Describe the factors that stimulate renin secretion
Secreted by juxtaglomerular cells in response to:
↓ renal perfusion pressure (detected by renal baroreceptors in afferent arteriole)
↑ renal sympathetic discharge (β1 effect)
↓ NaCl delivery to macula densa cells
ATII
Helps maintain blood volume and blood pressure
Affects baroreceptor function; limits reflex bradycardia which would normally accompany its pressor effects
ANP & BNP
Release from atria (ANP) and ventricles (BNP) in response to ↑ volume; may act as a “check” on renin-angiotensin-aldosterone system; relaxes vascular smooth muscle via cGMP → ↑ GFR. ↓renin
Dilates afferent arteriole
Constricts efferent arteriole
Promotes natriuresis
ADH
Primarily regulates serum osmolality; also responds to low blood volume states
Stimulates reabsorption of water in collecting ducts
Also stimulates reabsorption of urea in collecting ducts to maintain corticopulmonary osmotic gradient
Aldosterone
Primarily regulates ECF volume and Na content; responds to low blood volume states
Responds to hyperkalemia by ↑ K excretion
Diagram 572
572
Describe the juxtaglomerular apparatus
Consists of mesangial cells
JG cells (modified smooth muscle of afferent arteriole)
Macula Densa (NaCl sensor located in at the distal end of loop of Henle
JG cells secrete renin in response to
↓ renal perfusion pressure (detected by renal baroreceptors in afferent arteriole)
↑ renal sympathetic discharge (β1 effect)
↓ NaCl delivery to macula densa cells and cause efferent arteriole vasoconstriction → ↑ GFR
JG cells are what kind of cells?
(modified smooth muscle of afferent arteriole)
What is the macula densa?
(NaCl sensor located in at the distal end of loop of Henle)
JG cells secrete renin in response to
↓ renal perfusion pressure (detected by renal baroreceptors in afferent arteriole)
↑ renal sympathetic discharge (β1 effect)
↓ NaCl delivery to macula densa cells and cause efferent arteriole vasoconstriction → ↑ GFR
How is GFR maintained?
The JGA maintains GFR via renin-angiotensin-aldosterone system
ANP and BNP effect on Renin
decrease renin by increasing GFR
my assumption^
Β-blockers and RAAS
In addition to vasodilatory properties β-blockers can decrease BP by inhibiting β1 receptors of the JGA →↓ renin release
What are the kidney endocrine functions?
4 listed
- Erythropoietin
- Calciferol
- Prostaglandins
- Dopamine
Describe kidney erythropoietin
Released by interstitial cells in peritubular capillary bed in response to hypoxia
Stimulates RBC proliferation in bone marrow
Chronic kidney disease and EPO
EPO is often supplemented in CKD
Describe kidney calciferol
PCT cells convert 25-OH vitamin D3 to 1, 25- (OH) vitamin D3 (calcitriol, active form)
PTH and Vitamin D
PTH activates 1α-hydroxylase to convert to active form calcitriol
Describe kidney prostaglandins
Paracrine secretion vasodilates the afferent arterioles to ↑ RBF
NSAIDS block renal-protective prostaglandin synthesis → constriction of afferent arteriole and ↓ GFR; this may result in acute renal failure in low renal blood flow states
Describe kidney dopamine effects at low doses
At low doses
Promotes natriuresis
Dilates interlobular arteries, afferent arterioles and efferent arterioles →↑ RBF
Little or no change in GFR
contraction alkalosis
ATII - stimulates Na/H exchange → ↑Na, H2O, and HCO3 reabsorption
in the PCT
Describe kidney dopamine effects at high doses
At higher doses
acts as a vasoconstrictor
Dopamine is secreted by what in the kidney?
Secreted by PCT cells
Hormones acting on the kidney
574
Where does Angiotensin II act in the nephron?
Proximal convoluted tubule
Where does PTH act in the nephron?
Proximal convoluted tubule
DCT
Where does ANP act in the nephron?
Distal convoluted tubule
Where does aldosterone work in the nephron?
Distal convoluted tubule and collecting ducts
Where does Vasopressin work in the nephron?
Collecting duct
ADH is secreted in response to?
Secreted in response to ↑ plasma osmolarity and ↓ blood volume
Describe the effects of ADH in the nephron
Binds to receptors on principal cells causing ↑ number of aquaporins and ↑H2O reabsorption in the collecting duct
Stimuli for aldosterone secretion
2 listed
Secreted in response to ↓ blood volume (via AT II) and ↑ plasma [K+]
Effects of aldosterone
causes ↑Na reabsorption, ↑K secretion, ↑H+ secretion in the DCT and collecting ducts
Describe the effects of ANP in the nephron
Secreted in response to ↑ atrial pressure
Causes ↑ GFR and ↑ Na filtration with no compensatory Na reabsorption in the distal nephron
Net effect Na loss and volume loss
Describe the effects of AT II in the nephron
Synthesized in response to ↓ BP
Causes efferent arteriole constriction → ↑GFR and ↑ FF but with compensatory Na reabsorption in proximal and distal nephron
Net effect: preservation of renal function (↑FF) in low-volume state with simultaneous Na reabsorption (both proximal and distal) to maintain circulating volume
Describe the effects of PTH
Secreted in response to ↓ plasma [Ca], ↑ plasma [PO4] or ↓ plasma 1, 25-(OH)2 D3
Causes ↑Ca reabsorption in the DCT and ↓ PO4 reabsorption in the PCT and ↑1, 25(OH)2 D3 production leading to ↑Ca and PO4 absorption from the gut via vitamin D
Describe the effects of aldosterone in the nephron
Secreted in response to ↓blood volume (via ATII) and ↑plasma [K+]
Causes ↑Na reabsorption ↑K+ secretion ↑H+ secretion
Digitalis potassium shift
Digitalis (blocks Na/K+ATPase) causing shift of K+ out of cell causing hyperkalemia
Hyperosmolality effect on potassium
Shifts K+ out of cells causing hyperkalemia
Cell lysis effect on potassium
Shifts K+ out of cells causing hyperkalemia
Examples of processes that can cause cell lysis
crush injury
Rhabdomyolysis
Tumor lysis syndrome
Alkalosis effect on potassium
Shifts K+ into cells causing hypokalemia
Acidosis effect on potassium
Shifts K+ out of cells causing hyperkalemia
β-adrenergic agonist effect on potassium
↑Na/K ATPase causing shift of K into cells causing hypokalemia
β-blocker effect on potassium
↓ Na/K ATPase activity
Shifts K+ out of cells causing hyperkalemia
Insulin effect on potassium
↑ Na/K ATPase causing K+ shift into cells causing hypokalemia
High blood sugar effect on potassium
Insulin deficiency causes ↓ Na/K ATPase leading to K+ shift out of cells causing hyperkalemia
Insulin potassium mnemonic
Insulin shift K into cells
Succinylcholine effect on potassium
↑ risk of burns/muscle trauma causing shift of K+ out of cells causing hyperkalemia
Hyperkalemia Mnemonic
Hyperkalemia? DO LAβSS
Digitalis
HyperOsmolality
Lysis
Acidosis
β-Blocker
High blood Sugar
Succinylcholine
Conn Syndrome AKA
Primary hyperaldosteronism
Symptoms of low serum [Na+]
4 listed
Nausea and malaise
Stupor
Coma
Seizures
Symptoms of high serum [Na+]
3 listed
Irritability
Stupor
coma
Symptoms of low serum [K+]
5 listed
U waves and flattened T waves on ECG
Arrhythmias
Muscle cramps
Spasm
Weakness
Symptoms of high serum [K+]
3 listed
Wide QRS and peaked T waves on ECG
Arrhythmias
Muscle weakness
Symptoms of low serum [Ca2+]
5 listed
Tetany
Seizures
QT prolongation
Twitching (Chvostek sign)
Spasm (Trousseau sign)
Symptoms of high serum [Ca2+]
5 listed
Stones (renal)
Bones (pain)
Groans (abdominal pain)
Thrones (↑ urinary frequency)
Psychiatric overtones (anxiety, altered mental status)
Symptoms of low serum [Mg2+]
4 listed
Tetany
Torsades de pointes
Hypokalemia
Hypocalcemia (when [Mg2+] < 1.2 mg/dL)
Symptoms of high serum [Mg2+]
6 listed
↓DTRs
Lethargy
Bradycardia
Hypotension
Cardiac arrest
Hypocalcemia
Symptoms of low serum [PO43-]
Bone loss
Osteomalacia (adults)
Rickets (children)
Symptoms of high serum [PO43-]
Renal stones
Metastatic calcifications
Hypocalcemia
BP in Bartter syndrome
Normal
BP in Gitelman syndrome
normal
BP in Liddle syndrome
↑
BP in SAME
↑
BP in SIADH
Normal/↑
BP in Primary hyperaldosteronism
↑
BP in Renin-secreting tumor
↑
Plasma renin in Bartter syndrome
↑
Plasma renin in Gitelman syndrome
↑
Plasma renin in Liddle syndrome
↓
Plasma renin in SAME
↓
Plasma renin in SIADH
↓
Plasma renin in Primary hyperaldosteronism
↓
Plasma renin in Renin-secreting tumor
↑(important differentiating feature)
Aldosterone in Bartter syndrome
↑
Aldosterone in Gitelman syndrome
↑
Aldosterone in Liddle syndrome
↓(important differentiating feature)
Aldosterone in SAME
↓(important differentiating feature)
Aldosterone in SIADH
↓
Aldosterone in primary hyperaldosteronism
↑(important differentiating feature)
Aldosterone in Renin-secreting tumor
↑
Serum Mg2+ in Gitelman syndrome
↓
Urine Ca2+ in Bartter syndrome
↑ (important differentiating feature)
Urine Ca2+ in Gitelman syndrome
↓(important differentiating feature)
pH in metabolic acidosis
↓
pH in metabolic alkalosis
↑
pH in respiratory acidosis
↓
pH in respiratory alkalosis
↑
PCO2 in metabolic acidosis
↓
PCO2 in metabolic alkalosis
↑
PCO2 in Respiratory acidosis
↑(1° disturbance)
PCO2 in Respiratory alkalosis
↓(1° disturbance)
[HCO3-] in metabolic acidosis
↓ (1° disturbance)
[HCO3-] in metabolic alkalosis
↑ (1° disturbance)
[HCO3-] in respiratory acidosis
↑
[HCO3-] in respiratory alkalosis
↓
Compensatory response to metabolic acidosis
Hyperventilation (immediate)
Compensatory response to metabolic alkalosis
Hypoventilation (immediate)
Compensatory response to respiratory acidosis
↑ renal [HCO3-] absorption (delayed)
Compensatory response to respiratory alkalosis
↓ renal [HCO3-] absorption (delayed)
Henderson-Hasselbach equation
pH=6.1 + log ([HCO3-]/0.03PCO2)
How to predict the respiratory compensation for a simple metabolic acidosis
Can be calculated using the Winter’s Formula
If measured PCO2 > predicted CO2 → concomitant respiratory acidosis
If measured PCO2 < predicted CO2 → concomitant respiratory alkalosis
PCO2 = 1.5[HCO3-] + 8 +/- 2
Acidosis and alkalosis flow chart
576
Common causes of respiratory acidosis
Airway obstruction
Acute lung disease
Chronic lung disease
Opioids
Sedatives
Weakening of respiratory muscles
Common causes of ↑ anion gap metabolic acidosis
MUDPILES
Methanol (formic acid)
Uremia
Diabetic ketoacidosis
Propylene glycol
Iron tablets or INH
Lactic acidosis
Ethylene glycol
Salicylates (late)
Common causes of normal anion gap metabolic acidosis
HARDASS
Hyperalimentation
Addison disease
Renal tubular acidosis
Diarrhea
Acetazolamide
Spironolactone
Saline infusion
Common causes of respiratory alkalosis
Hyperventilation
Anxiety/panic attack
Hypoxemia (eg, high altitude)
Salicylates (early)
Tumor
Pulmonary embolism
Common causes of metabolic alkalosis
H+ loss/HCO3- excess
Loop diuretics
Vomiting
Antacid use
Hyperaldosteronism
Anion gap equation
Na - (Cl+HCO3) = AG
What is renal tubular acidosis
Disorder of renal tubules that causes normal anion gap (hyperchloremic) metabolic acidosis
Types of renal tubular acidosis
Distal renal tubular acidosis (type 1)
Proximal renal tubular acidosis (type 2)
Hyperkalemic tubular acidosis (type 4)
What is Type 1 renal acidosis
Distal renal tubular acidosis
What is type 2 renal acidosis?
Proximal renal tubular acidosis
What is type 3 renal acidosis?
IDK?
What is type 4 renal acidosis?
Hyperkalemic tubular acidosis
Describe the defect in Distal renal tubular acidosis
Inability of α-intercalated cells to secrete H+ → no new HCO3- is generated → metabolic acidosis
Describe the defect in proximal renal tubular acidosis
Defect in PCT HCO3- reabsorption → ↑ excretion of HCO3- in urine → metabolic acidosis
Urine can be acidified by α-intercalated cells in the collecting duct, but not enough to overcome the increased excretion of HCO3- → metabolic acidosis
Describe the defect in Hyperkalemic tubular acidosis
Hypoaldosteronism or aldosterone resistance;
Hyperkalemia → ↓ NH3 synthesis in PCT →↓ NH4+ excretion
Describe urine pH in distal renal tubular acidosis
> 5.5
Describe urine pH in Proximal renal tubular acidosis
<5.5
Describe urine pH in Hyperkalemic tubular acidosis (type 4)
< 5.5 (or variable)
Serum K in distal renal tubular acidosis
↓
Serum K in proximal renal tubular acidosis
↓
Serum K in hyperkalemic tubular acidosis
↑
Causes of distal renal tubular acidosis
4 listed
Amphotericin B toxicity
Analgesic nephropathy
Congenital anomalies (obstruction) of urinary tract
Autoimmune diseases (eg, SLE)
Causes of proximal renal tubular acidosis
Fanconi syndrome
Multiple myeloma
Carbonic anhydrase inhibitors
Causes of hyperkalemic tubular acidosis
↓ aldosterone producton (eg, diabetic hypereninism, ACE inhibitors, ARBs, NSAIDs, heparin, cyclosporine, adrenal insufficiency)
Or aldosterone resistance (eg, K+ sparring diuretics, neprhopathy dut to obstruction, TMP-SMX)
Distal renal tubular acidosis associations
↑ risk for calcium phosphate kidney stones (due to ↑ urine pH and ↑ bone turnover)
Proximal renal tubular acidosis associations
↑ risk for hypophosphatemic rickets (in Fanconi syndrome)
What are casts in urine?
Presence of casts indicates that hematuria/pyuria is glomerular or renal tubular origin
Are there urine casts in bladder cancer or kidney stones?
No
ATN AKA
Acute tubular necrosis
What is reabsorbed in the PCT?
9 listed
Reabsorbs all glucose and amino acids and most HCO3-, Na, Cl, PO4, K, H2O and uric acid
PTH and phosphate
PTH inhibits Na/PO4 cotransport → PO4 excretion
PTH reduces the reabsorption of phosphate from the proximal tubule of the kidney, which means morephosphate is excreted through the urine. However,PTH enhances the uptake of phosphate from the intestine and bones into the blood. … The absorption of phosphate is not as dependent on vitamin D as is that of calcium.
ATII and contraction alkalosis
ATII - stimulates Na/H exchange → ↑Na, H2O, and HCO3 reabsorption (permitting contraction alkalosis)
Thick ascending loop of Henle resorbs?
Reabsorbs Na, K and Cl
Indirectly induces paracellular reabsorption of Mg2+ and Ca2+ through (+) lumen potential generated by K backleak
Impermeable to H2O
Makes urine less concentrated as it ascends
Thick ascending loop of Henle % Na resorbed
10-20%
Na reabsorption in early PCT
65-80% Na reabsorbed
Thick ascending loop of Henle Reabsorbs?
Reabsorbs Na, K and Cl
Indirectly induces paracellular reabsorption of Mg2+ and Ca2+ through (+) lumen potential generated by K backleak
Aldosterone acts on what in the where?
Aldosterone - acts on mineralocorticoid receptor → mRNA → protein synthesis
in the collecting duct
Principal cells of the CD
In principal cells ↑ apical K conductance, ↑ Na/K pump, ↑ epithelial Na channel (ENaC activity) → lumen negativity → K secretion
Describe α-intercalated cells in the CD
lumen negativity → ↑H+ ATPase activity → ↑H+ secretion → ↑ HCO3/Cl exchanger activity
ADH actions in the CD
ADH - acts at V2 receptor → insertion of aquaporin H2O channels on apical side
