B&B Renal: Anatomy & Physiology Flashcards
Germ layer of origin
Kidney Development
Mesoderm
Pronephros
Kidney Development
- 1st embryonic renal structure
- Forms & degenerates by week 4 of gestation
Mesonephros
Kidney Development
- 2nd embryonic renal strucutre
- Acts as interim kidney during 1st trimester
- Contributes to vas deferens in males
Metanephros
Kidney Development
- 3rd embryonic renal structure
- Forms permanent kidney
- Appears during 5th week gestation
- Develops into kidney through weeks 32-26
Kidney Formation
2 key structures
1. Ureteric bud
2. Metanephric mesenchyme
Ureteric bud
Kidney Formation
- Outgrowth of mesonephric (Wolffian) duct
- Forms ureter, renal pelvis & calyces, collecting ducts
Metanephric mesenchyme
Kidney formation
- Mesoderm tissue around ureteric bud
- Interacts with ureteric bud to form glomerulus through distal tubule of nephron
Most common renal malignancy in young children
Wilm’s tumor
Abnormal proliferation of metanephric mesenchyme
* Produces embryonic glomerular structures
* Associated with WT1 mutations
* WT1 is expressed in metanephric mesenchyme
Pathophysiology
Wilms’ tumor
Absence of one or both kidneys at birth
* Unilateral: remaining kidney compensates
* Hypertrophy
* Hyperfiltration
* Risk of FSGS
* Risk of renal failure after decades
* Bilateral:
* Oligohydramnios
* Potter’s syndrome
FSGS: focal segmental glomerular sclerosis
Renal Agenesis
Congenital Anomaly
Renal Agenesis
Pathophysiology
- Ureteric bud fails to develop
- Lack of signals to mesenchyme to trigger differentiation
Renal dysplasia resulting in replacement of kidney with cysts
* No / little functioning renal tissue
* Usually unilateral
Multicystic Dysplastic Kidney
Congenital Anomaly
Multicystic Dysplastic Kidney
Pathophysiology
Abnormal ureteric bud-mesenchyme interaction
- Common cause of single kidney obstruction
- Narrowing in proximal ureter at UPJ
- Often detected in utero
- Can be treated surgical after birth
Ureteropelvic junction (UPJ) obstruction
UPJ obstruction
Complications
- Hydronephrosis
- Poor urinary flow –> kidney stones, UTIs
Duplex Collecting System
Duplicated Ureter
- Occurs when 2 ureteric buds form on right / left side or if a ureteric bud bifurcares during development
- Results in formation of upper / lower kidneys
Duplicated Ureter
Complications
- May lead to poor urinary flow; UTIs
- Hydronephrosis
- Associated with vesicoureteral reflux
- Backward urine flow from bladder to kidneys
- Leads to recurrent UTIs
Vesicoureteral reflux
Abnormal closure of UVJ
* Occurs in children
* Associated with duplex ureters
UVJ = ureterovesical junction; where ureter inserts into bladder
Primary vesicoureteral reflux
Retrograde flow of urine due to high bladder pressure
* Associated with posterior urethral valves
Secondary vesicoureteral reflux
Retrograde flow of urine due to high bladder pressure
* Associated with posterior urethral valves
Secondary vesicoureteral reflux
Loss of fetal cushioning to external forces resulting from decreased / absent amniotic fluid
* External compression of fetus: abnormal face / limb formation
* Alteration in lung liquid movement: abnormal lung formation
* Often fatal
Potter’s syndrome
Potter’s syndrome
Pathophysiology
- Amniotic fluid = fetal urine
- Severe fetal renal malfunction = decreased amniotic fluid
- Limb deformities
- Flat face
- Pulmonary hypolasia
- Often fetal death
Signs
Potter’s syndrome
- Limb deformities
- Flat face
- Pulmonary hypolasia
- Often fetal death
Signs
Potter’s syndrome
Low amniotic fluid levels
Oligohydramnios
Oligohydramnios
Etiology
Causes vary by trimester
* 1st trimester: rare
* 2nd trimester: low fetal urine production
* 3rd trimester: rupture of membranes
1st: 1-12 weeks; 2nd: 13-27 weeks; 3rd: 28 weeks - birth
Potter’s syndrome
Etiology
- Bilateral renal agenesis
- Often detected in utero
- U/S: kidneys not seen by 10-12 wks
- Posterior urethral valve
- Occurs in males
- Valve obstructs bladder outflow
- U/S: dilated bladder, kidneys
- Both kidneys are affected
- Autosomal recessive PKD
- Juvenile cystic kidney disease
- Cysts form in kidneys & biliary tree
- Both kidneys are affected
- Severe: oligohydramnios
- Less severe: renal failure & HTN in childhood
PKD = polycystic kidney disease
Fused inferior poles of kidneys
* Kidneys cannot ascend from pelvis to retroperitoneum
* Trapped by inferior mesenteric artery
Horseshoe kidney
Horseshoe kidney
Presentation
- Most pts are asymptomatic
- A/w Turner & Down syndromes
- A/w vesicoureteral reflux
- Embryologic structure that connects dome of bladder to umbilicus
- Becomes obliterated at birth & becomes median umbilical ligament
Urachus
Urachal remnants
Failed / incomplete obliteration of urachus
* Patent urachus: urine can leak from umbilicus
* Failed obliteration of urachus
* Urachal cyst / sinus / diverticulum
* Incomplete obliteration of urachus
* Can lead to infections
Urachal remnants
Complications
Can lead to adenocarcinoma of the bladder
* Key feature: tumor at dome of bladder
* Presentation: adult with painless hematuria
Kidney
Anatomy
3 major regions
1. Cortex: outer region
2. Medulla: middle region
3. Collecting system: inner region
Renal cortex
Anatomy
- Outer region of kidney
- Nephron structures:
- Glomeruli
- Proximal tubules
- Distal tubules
Renal medulla
Anatomy
- Middle region of kidney
- Consists of renal / medullary pyramids
- Nephron structures:
- Loop of Henle
- Collecting ducts
Collecting system
Anatomy
- Calyx: collects urine draining from medullary pyramid
* Minor calyx: collects urine from one medullary pyramid
* Major calyx: collects urine from several minor calyces - Papilla: junction between medullary pyramid & calyx
- Pelvis: collects urine draining from all major calyces
Renal vasculature
Anatomy
- Renal artery
- Segmental arteries
- Interlobar arteries
- Arcuate arteries
- Interlobular arteries
- Glomeruli
Glomerular blood flow
Anatomy
- Interlobular artery branches into series of afferent arterioles
- Each afferent arterioles supplies a glomerular capillary bed
- Blood leaves glomerular capillaries via efferent arterioles
- Blood from efferent arteriole enters peritublar capillaries
- Blood from peritublar capillaries drains into renal vein via series of venules
Afferent & efferent arterioles
Anatomy
Afferent & efferent arterioles allow body to control blood flow into and out of glomerular capillaries via 2 mechanisms:
* Vasoconstriction of afferent arteriole (AA)
* Reduces blood flow into glomerulus
* Decreases GFR
* Vasoconstriction of efferent arteriole (EA)
* Reduces blood flow out of glomerulus
* Blood spends more time in glomerular capillaries
* Increases GFR
Fluid Compartments
Physiology
- Extracellular (ECF): 1/3 of TBW
- Plasma: 1/4 of ECF
- Interstitial fluid: 3/4 of ECF
- Intracellular (ICF): 2/3 of TBW
Body composition: total body water (TBW) = 60%; Non-water: 40%
Fluid Compartment Shifts
Physiology
- Plasma osmolarity = 300 mOsm/kg
- Equilibrium between cells & ECF
- Fluid shifts only occur if there is difference in osmolarity between ICF & ECF
Addition / loss of isotonic fluid
Fluid Compartment Shifts
Change in ECF volume; no change in ICF volume
* Example: hemorrhage
* Loss of ECF volume
* No change in ICF volume
* Example: infusion of normal saline
* Increase in ECF volume
* No change in ICF volume
Isotonic = same osmolarity as plasma
Addition of hypotonic fluid
Fluid Compartment Shifts
Increase in ECF volume & ICF volume
* Decreases plasma osmolarity
* Osmotic gradient drives ECF into cells
* Example: infusion of 5% dextrose
Hypotonic = lower osmolarity than plasma
Addition of hypertonic fluid
Fluid Compartment Shifts
Increase in ECF volume; decrease in ICF volume
* Raises plasma osmolarity
* Osmotic gradient pulls fluid out of cells into ECF
* Example: mannitol infusion
Effective Circulating Volume (ECV)
Physiology
Volume of ECF contained in arterial system
* Maintains tissue perfusion
* Modified by: volume, CO, SVR
Low ECV
Physiology
Low ECV leads to low BP
* Low ECV activates: SNS, RAAS
* Conditions with low ECV:
* Volume depletion: low ECV & TBW
* Heart failure: low ECV, high TBW
* Cirrhosis: low ECV, high TBW
HF = low CO; cirrhosis = low SVR
Evaluating renal function
Physiology
- Glomerular filtration rate (GFR)
- Renal blood / plasma flow (RBF/RPF)
- Filtration fraction (FF): GFR / RBF
Capillary fluid exchange
Physiology
- Hydrostatic pressure: fluid pushing against walls of vessels
- High pressure drives fluid toward low pressure
- Oncotic pressure: solutes (albumin) pulling fluid into vessels
- High pressure draws fluid away from low pressure (osmotic graident)
Determinants of GFR
Physiology
- Hydrostatic pressure (P): P-GC vs. P-BC
- Oncotic pressure (π): π-GC vs. π-BC
GC = glomerular capillary; BC = Bowman’s capsule
Dilate afferent arteriole
Changes in GFR
More blood flow into glomerular capillary
* RPF: increases
* P-GC: increases
* GFR: increases
* FF: no change
Constrict efferent arteriole
Changes in GFR
Less blood flow out of glomerular capillary; blood pools behind constricted EA
* RPF: decreases
* P-GC: increases
* GFR: increases
* FF: increases
Increase plasma proteins
Changes in GFR
Less blood drawn out of glomerular capillary into proximal tubule
* RPF: no change
* GFR: decreases
* FF: decreases
Ureteral obstruction
Changes in GFR
Urine backs up behind obstruction & hydrostatic pressure in Bowman’s capsule increases; less blood flow from capillary into Bowman’s capsule
* RPF: no change
* P-BC: increases
* GFR: decreases
* FF: decreases
Constrict afferent arteriole
Changes in GFR
Less blood flow into glomerular capillary
* RPF: decreases
* P-GC: decreases
* GFR: decreases
* FF: no chanfe
Renal autoregulation
Physiology
Maintains constant GFR / RBF (FF) over range of blood pressures
1. Myogenic mechanism
2. Tubuloglomerular feedback
Myogenic mechanism
Autoregulation
- Afferent arteriole constricts w/ high BP
- Responds to changes in stretch
- High blood pressure causes stretching of arterioles
- Result: maintenance of normal GFR/RPF
- Vasoconstriction decreases RPF
Tubuloglomerular feedback
Autoregulation
- Increased GFR:
- Increased flow into proximal tubule
- Increased NaCl in distal tubule
- NaCl is detected by macula densa
- Macula densa stimulates vasoconstriction of AA
Macula densa = part of juxtaglomerular (JG) apparatus
Renal clearance
Renal Function
C = (U x V) / P
* Clearance (C): volume of blood cleared of substance; excreted volume of blood containing substance
* Urine concentration of substance (U)
* Plasma concentration of substance (P)
* Volume flow of urine (V)
Creatinine
Renal Function
Creatine clearance is used to estimate GFR
* Product of muscle metabolism
* Closest naturally occurring substance to inulin
* Inulin: all filtered goes out; no secretion / resorption
* Creatinine: all filtered goes out; small amount secreted
* Using Cr to estimate GFR
* Secreted Cr is counted as filtered
* Slightly overestimates GFR
Estimating GFR
Renal Function
Cockcroft-Gault formula
GFR = [(140-age) x weight (kg)] / (P-Cr x 70 kg)
* If female, multiply estimated GFR by 0.85
Serum creatinine (P-Cr) & GFR
Renal Function
C-Cr = (V-Cr x U-Cr) / P-Cr = GFR
* Body produces and excretes the same amount of creatinine everyday
* V-Cr x U-Cr = constant
* P-Cr & GFR are inversely proportional
* Increase in GFR = decrease in P-Cr
* Decrease in GFR = increase in P-Cr
High serum creatinine
Renal Function
Impaired renal function
* Decreased GFR
Prostaglandins (PGs) & NSAIDs
Renal Function
- PGs dilate afferent arterioles: increase RPF
- NSAIDs block production of PGs
- Vasoconstriction of afferent arterioles
- Decrease RPF
- Decrease GFR
- Clinical effects of NSAIDs:
- Acute renal failure
- Acute heart failure
ACE inhibitors
Renal Function
- Ang II promotes vasoconstriction of efferent arterioles
- ACEi block production of Ang II
- Vasodilation of efferent arterioles
- Decrease GFR
- Increase RPF
- Decrease FF
Secretion & Absorption
Renal Function
E = F - R + S
* Amount filtered (F) = GFR x P
* Amount excreted (E) = V x U
* Amount resorbed (R) = F - E
* If F > E
* Amount secreted (S) = E - F
* If F < E
Regulated solutes: Na+, K+
Solutes in Renal Failure
- Renal failure: decreased GFR
- Plasma concentration (P-Na, P-K): no change
- Filterered load (GFR x P): decreases
- Excretion: no change
- Fractional excretion: increases
Can adjust K+, Na+ secretion / resorption; filtered load can fall
Unregulated solutes: Cr, Urea
Solutes in Renal Failure
- Renal failure: decreased GFR
- Plasma concentration (P-Cr, P-Urea): increases
- Filtered load (GFR x P): no change
- Excretion: no change
- Fractional excretion: no change
Can only eliminate Cr, Ur via filtration; must maintain filtered load
Renal Hormones
Renal Endocrine Function
- Released by kidney:
- Erythropoietin
- Renin (enzyme)
- 1,25-Vit D
- Act on kidney:
- Angiotensin II (Ang II)
- Atrial natriuretic peptide (ANP)
- Antidiuretic hormone (ADH)
- Aldosterone
- Parathyroid hormone (PTH)
JG apparatus
Renin
- JG cells: modified smooth muscle of afferent arteriole; secrete renin
- Macula densa: part of distal tubule
RAAS
Renal Endocrine Function
- Angiotensinogen (plasma protein; from liver)
Renin (from JG cells in kidneys) - Ang I
ACE (in lungs) - Ang II
Stimuli for renin release
RAAS
- Low perfusion pressure
- Low BP or low ECV
- Sensed by afferent arteriole –> renin release
- Low NaCl delivery
- Sensed by macula densa –> renin release
- Also constricts afferent arteriole: TGF
- Sympathetic activation
- Renal B1-receptors –> renin release
- Renal A1-receptors –> constricts arterioles
- Decreases GFR to limit Na/H2O excretion
TGF: tubuloglomerular feedback
Activates RAAS
* Converts angiotensinogen to Ang I
RAAS
Renin
Ang II
RAAS
- Efferent arteriole vasoconstriction
- RPF: decreases; less renal blood flow
- GFR: increases; more Na/H2O filtration
- Increased Na/H2O reabsorption
- Proximal tubule: increases Na+ resorption via capillary effect, Na+/H+ exchange
- Stimulates aldosterone release
Capillary effect
Proximal Tubule
Efferent arteriole constriction increases NaCl resorption
* Ang II induces efferent arteriole constriction
* Efferent arteriole constriction decreases blood flow beyond constriction
* Decreased RBF reduces hydrostatic pressure in peritubular capillaries
* Favorable gradient for reabsorption of Na & H2O in proximal tubule: capillary effect
* Efferent arteriole constriction increases GFR
* More fluid is filtered from glomerular capillaries into Bowman’s capsule leaving concentrated plasma proteins
* Increased oncotic pressure favors reabsorption of Na & H2O
Collecting duct effects
* Resorption of Na+, H2O
* Excretion of K+, H+
RAAS
Aldosterone
Lower blood pressure
* Block converstion of Ang I to Ang II
RAAS Drugs
ACE-inhibitors
Lower blood pressure
* Block effects of Ang II
RAAS Drugs
Ang II receptor blockers (ARBs)
Beta-Blockers
RAAS Drugs
Lower blood pressure
* Block sympathetic stimulation of JG apparatus
* Inhibit renin release
Lower blood pressure
* Block effects of aldosterone
* Increase serum K+ & H+ (reduce pH)
RAAS Drugs
Aldosterone antagonists
* Spironolactone
* Eplerenone
Lower blood pressure
* Inhibit ENaC
* Inhibit Na+ & H2O resorption
* Inhibit K+ secretion
Potassium-sparing diuretics
* Triamterene
* Amiloride
Natriuretic peptides
Hormones Acting on Kidneys
Hormones released by the heart that act on the kidneys
* Response to increased cardiac volume
* Increased volume causes myocyte stretch
* ANP: released by atrial myocytes
* BNP: released by ventricular myocytes
* Opposite effects of RAAS
* Relax VSM via cGMP
* Vasodilation: reduces SVR
* Increased diuresis: decreases ECV
PTH
Hormones Acting on Kidneys
Maintains Ca2+ levels
* Released by chief cells of parathyroid gland
* Stimulus: low serum [Ca]
* Net effects:
* Increases plasma [Ca]
* Decreases plasma [PO4]
* Increases urine [PO4]
Renal effects of PTH
Hormones Acting on Kidneys
- DCT: increased Ca2+ resorption
- PTH stimulates Na/Ca2+ exchanger
- PCT: decreased PO4 resorption
- PTH inhibits Na/phosphate cotransporter
- PCT: increased production of 1,25-(OH)2-Vit D
- PTH stimulates 1a-Hydroxylase
Erythropoietin (EPO)
Renal Hormones
Stimulates RBC in bone marrow
- Produced by interstitial cells of peritubular capillaries
- Released in response to hypoxia
- Decreased production in renal failure
- Results in normocytic anemia
