Renal basic science

Physiology

Anatomy

structure

kidney

glomerulus

renal pelvis(腎盂)

ureter

renal vein

medullary pyramids(腎錐体)

renal artery>segmental artery>interlobar artery>arcuate artery(弓状動脈)>interlobular artery

cortex/ medulla

podocyte

macula densa

Mesangial cells

juxtaglomerular cell

Bowman capsule

distal convolunted tubule

efferent arteriole>affernet arteriole

left kidney is taken during transplantation (longer renal vein)

course of ureters

3 constriction of ureter

renal pelvis→travel under gonadal artery→ocer common iliac artery→under uterine artery/vas deferens(精管)

ureteropelvic junction(腎盂尿管移行部)

pelvic inlet(骨盤入口)

ureterovesical junction(尿管膀胱接合部)

Physiology

fluid compartment

non water (40%)

total body water(60%)

ECF (20%)

ICF (40%); RBC (4%)

plasma (5%)

interatitial fluid (15%)

osmolality=285-295 mOsm/kg H₂O

glomerular filtration barrier

components

basement membrane with type 4 collagen chains and heparan sulfate

epithelial layer consisting of podocyte foot process

fenestrated capillary endothelium

barrier

charge barrier: all layers charge -, so prevent entry of - charged protein

size barrier: fenestrated capillary endothelium(100nm); podocyte(50-60nm)

renel clearance

Cx=(Ux×V)/Px; volume of plasma from which the substance is completely cleared per unit time

Cx<GFR→net tubular reabsorption of X

Cx>GFR→net tubular secretion of X

Cx=GFR→none

glomerular filtration rate(GFR)

inulin clearance can be used to calculate GFR

GFR=Cinulin=Kf{(Pgc-Pbs)-(πgc-πbs)}

normal GFR=100mL/min

creatinine clearance is an aproximate measure of GFR, slightly over estimate

effective renal plasma flow

renal blood flow(RBF)=RPF/(1-Hct); usually 20-25% of CO

plasma volume=TBV(全循環血流量)×(1-Hct)

eRPF can be estimated using para-aminohippuric acid(PAH) clearance

filtration

filtration fraction(FF)=GFR/RPF; normally 20%

filtered load=GFR×plasma concentration

Pはこちら側から向こう側への圧力,πはこちら側に引き込む圧力

changes in glomerular dynamics

↑plasma protein concentration: ↓GFR, ↓FF

↓plasma protein concentration: ↑GFR, ↑FF

efferent constriction: ↑GFR, ↓RPF, ↑FF

constriction of ureter: ↓GFR, ↓FF

afferent constriction: ↓GFR, ↓RPF

dehydration: ↓GFR, ↓↓RPF, ↑FF

calculation

excretion rate=V×Ux

reabsorption rate=filtered-excreted

filtered load=GFR×Px

secretion rate=excreted-filtered

Fena=fractional excretion of sodium

glucose clearance

at 200mg/dL, glucosuria begin, at 375mg/min (cotransporter), all transporters are fully saturated

Tm for glucose is reached gradually

at normal level, glucose is completely reabsorbed in PCT by Na/glucose cotransport

nephron physiology

early DCT

collecting tubule

thin descending loop of Henle

thick ascending loop of Henle

early PCT

generate and secret NH₃, which enables the kidney to secrete more H⁺

PTH→inhibit Na/PO₄ cotransport→PO₄ excretion

isotonic absorption

AT Ⅱ→stimulate Na/H exchange→↑Na, H₂O, HCO₃⁻ reabsorption

all glucose and amino acids and most HCO₃⁻,Na⁺, Cl⁻,PO₄³⁻, K⁺, H₂O, and uric acid

passive reabsorb H₂O via medullary hypertonicity

impermeable H₂O

10-20% Na is absorbed

indirectly induce paracellular reabsorption of Mg, Ca

reabsorbe Na, K, Cl

PTH→Ca reabsorption

5-10% Na reabsorption

impermeable to H₂O

reabsorb Na, Cl

aldosterone→on mineralcorticoid receptor→protein synthesis; ↑K conductance, Na/K pump, K secretion, HCO₃⁻/Cl exchanger

ADH→act at V₂ receptor→insertion of aquaporin H₂O channel

reabsorb Na/ secreting K and H

3-5% Na reabosorbed

renal tubular defect

Gitelman syndrome

Liddle syndrome

Bartter syndrome

syndrome of apparent mineralocorticoid excess(AME syndrome)

Fanconi syndrome

metabolic acidosis, hypophosphatemia, osteopenia

hereditary defect, multiple myeloma, drug

reabsorption defect in PCT→↑excretion of amino acids, glucose, HCO₃⁻, PO₄⁻, etc

metabolic alkalosis, hypokalemia, hypercalciuria

defect in ascending loop of Henle

metabolic alkalosis, hypomagnesemia, hypokalemia, hypocalciuria

reabsorption defect of NaCl in DCT

metabolic alkalosis, hypokalemia, hypertension, ↓aldosterone

↑Na reabsorption in collecting tubules

metabolic alkalosis, hypokalemia, hypertension

defect in conversion from cortisol to cortisone→excess cortisol

relative concentration along proximal convoluted tubules

CL⁻ reabsorption occurs at a slower rate than Na in early PCT and then match the rate of Na reabsorption more distally

TF/P; >1→less quickly than water, =1→same rate as water, <1→more quickly than water

renin-angiotensin-aldosterone system

↓BP, ↓NaCl, ↑sympathetic tone→renin (JG cell)

angiotensinogen→(renin catalyze)angiotensin1→(ACE catalyze)angiotensin2→aldosterone, ADH

angiotensin2→↑BP(vasoconstriction), preserve GFR(↑FF), Na⁺, HCO₃⁻, H₂O reabsorption, thirst(hypothalamus)

aldosterone→H⁺ secretion, Na⁺ reabsorption, K⁺secretion

ADH→H₂O reabsorption

ANP and BNP check on renin-angiotensin-aldosteron system; dilate afferent, constrict efferent, promote natriuresis

juxtaglomerular apparatus

JG cells secrete renin in response to ↓renal blood pressure, ↑sympathetic tone

macula densa cells sense ↓NaCl delivery to DCT

consists of mesangial cells, JG cell, macula densa

maintain GFR

kidney endocrine

calciferol (vitaminD)

prostaglandin

erythropoietin

dopamine

released by interstitial cells in peritubular capillary bed in response to hypoxia

stimulate RBC proliferation in bone marrow

PCT cells convert 25-OH vitamin D₃ to 1,25-(OH)₂ vitamin D₃ (activate)

paracrine secretion vasodilate the afferent arterioles

NSAIDs block

secreted by PCT cell, promoting natriuresis

↑RBF, no cjange in GFR

hormones acting on kidney

aldosterone

ADH

angiotensin2

parathyroid hormone

ANP

secreted in response to ↑atrial pressure

cause ↑GFR and ↑Na filtration with no compensatory Na reabsorption in distal nephron

Na loss and volume loss

in response to ↓BP

cause efferent constriction→↑GFR and ↑FF with compensatory Na reabsorption in proximal and distal nephron

in response to ↓plasma[Ca], ↑[PO₄], ↓[activated vitamin D]

cause ↑Ca reabsorption(DCT), ↓PO₄ reabsorption(PCT) and ↑activated vit.D production

in response to ↓blood volume, ↑plasma K

cause Na reabsorption, K secretion, H secretion

in response to ↑plasma osmolarity, ↓blood volume

cause ↑number of aquaporins and H₂O reabsorption

potassium shift

K into cell

K out of cell

hypoosmolarity, alkalosis, β-adrenergic agonist, insulin

digitalis, hyperosmolarity, lysis of cell, acidosis, β-blocker, high blood sugar

electrolyte disturbance

PO₄³⁻

-: nausea, malaise, stupor, coma, seizure

+: irritability, stupor, coma

-:U wave and flattened T wave, arrhythmias, muscle cramps, spasm, weakness

+: wide QRS and peaked T wave, arrhythmias, muscle weakness

-: tetany, seizure, QT prolongation, twitching, spasm

+: stone, bone pain, abdominal pain, urinary frequency, psychiatric overtone

-: tetany, TdP, hypokalemia, hypocalcemia

+: ↓DTRs, lethargy, bradycardia, hypotension,

-: bone loss, osteomalacia(骨軟化症), rickets

+: renal stone, metastatic calcification, hypocalcemia

acid-base physiology

metabolic alkalosis:↑[HCO₃⁻]→compensatory hypoventilation

respiratory acidosis:↑Pco₂→↑ reneal[HCO₃⁻] reabsorption

metabolic acidosis:↓[HCO₃⁻]→compensatory hyperventilation

respiratory alkalosis:↑Pco₂→↓ reneal[HCO₃⁻] reabsorption

Henderson-Hasselbalch equation: pH=6.1+log([HCO₃⁻]/0.03×Pco₂)

Pco₂=1.5[HCO₃⁻]+8±2

cidosis and alkalosis

pH>7.45 (alkemia)

pH<7.35 (acidemia)

Pco₂<36mmHg

HCO₃⁻>28mEq/L

respiratory alkalosis

metabolic alkalosis

Pco₂>44mmHg

HCO₃⁻<20mEq/L

respiratory acidosis

metabolic acidosis

↑anion gap

normal anion gap

renal tubular acidosis

hyperkalemic tubular acidosis (type4)

distal renal tubular acidosis (type1)

disorder of the renal tubules that causes normal anion gap

proximal renal tubular acidosis (type2)

pH>5.5

↓ serum K

inability of α-intercalated cells to secrete H⁺→no new HCO₃⁻ is generated→metabolic acidosis

defect in PCT HCO₃⁻ reabsorption→metabolic acidosis

pH<5.5

↓ serum K

hypoaldosteronism or aldosterone resistance; hyperkalemia→↓NH₃→↓NH₄ excretion

pH<5.5

↑ serum K

Embryology

pronephros: week4; then degenerate

metanephros

mesonephros: function as interim kidney for 1st trimester; later contribute to male genital system

ureteric bud (尿管芽)

metanephric mesenchyme(後腎組織)

permanent; first appears in 5th week of gestation; nephrogenesis continues through weeks 32-36 of gestation

aberrant interaction result in congenital malformation of the kidney (eg. renal agenesis, multicystic dysplastic kidney)

from caudal end of mesonephric duct

give rise to ureter, pelvis, calyx, collecting duct

fully canalized by 10th weeks

bud interact with tissue

interaction induce differentiation and formation of glomerulus through to DCT

ureteropelvic junction: most common site of obstruction

Potter sequence

ARPKD

renal failure(obstructive uropathy, bilateral renal agenesis, chronic placental insufficiency)

compression of chest and lack of amniotic fluid aspiration into fetal lung→pulmonary hyperplasia

facial anomalies

oligohydramnios(羊水過少症)→compression of developing fetus→limb deformities

horseshoe kidney

get trapped under inferior mesenteric artery and remain low in the abdomen

hydronephrosis, renal stone, infection, chromosomal aneuploidy syndrome, renal cancer

inferior poles of both kidney fuse abnormally

congenital solitary functioning kidney

unilateral renal agenesis: complete absence of kidney and ureter

multicystic dysplastic kidney(多嚢胞性異形成腎): nonfunctional kidney consisting of cysts and connective tissue

only one functioning kidney, compensatory hypertrophy of contralateral kidney

duplex collecting system

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associated with vesicoureteral reflux and ureteral obstruction, ↑ risk for UTIs

bifurcation of ureteric bud→Y-shaped bifid ureter

posterior urethral valves

lead to urethral obstruction

mambrane remnant in the posterior urethra in males