Nephrology: Renal Physiology and Associated Pathologies

NEPHROLOGY

MEDSCHOOLBRO"
Designed for you to pass USMLE Step 1

Table of Contents

NEPHROLOGY
Renal Embryology
5
Potter Sequence & Related Conditions
6
Renal Anatomy
7
Glomerulus & Renal Physiology
8
Nephron Pharmacology & Tubular Defects
9
RAAS & Renovascular Disease
10
Urinanalysis & Renal Functions Test
11
Nephrotic Syndromes
12
Nephrotic Syndromes Cont.
13
Nephritic Syndromes
14
Nephritic Syndromes Cont.
15
Acid Base Physiology & Renal Tubular Acidosis
16
Acute Kidney Injury
17
Urea Cycle
18
Nephrolithiasis
19
Micturition & Urinary Incontinence
20
Urinary Tract Infection
21
Renal Neoplasms
22
Notes
23
References
24 - 25
About the Author
26

LEGEND

• ! TREATMENT
• RISK FACTORS
• MEMORY TRICKS
• PATHOLOGY

Renal Embryology

PRONEPHROSMESONEPHROSMETANEPHROS
PRO -> MESO -> META = PROTOTYPE -> MIDDLEMAN->MATURE

Mesonephric Duct Development

PRONEPHROS = PROTOTYPE kidney
MESONEPHROS = MIDDLEMAN kidney
METANEPHROS = MATURE kidney

THINK! Renal Development Timing

PRO = 3 letters = week 3
MESO = 4 letters = week 4

Urogenital Sinus

PRONEPHROS
TEMPORARY
Forms in week 3 then
degenerates. A BLUEPRINT
for renal development.

MESONEPHROS

TEMPORARY
Appears in week 4, primary
secretory organ until week 9,
degenerates by week 12. Role in
male reproductive organs.

METANEPHROS

Arises in week 5, canalization
complete by week 10,
progresses to permanent
kidney by week 36 of gestation.

WEEKS of Kidney Development

1
2
3
4
5
6
7
8
9
10
11
12

METANEPHROS Formation

URETERIC BUD interacts with
METANEPHRIC MESENCHYME to become
mature kidney (aka METANEPHROS)!

Mesonephric (Wolffian) Duct

METANEPHRIC
MESENCHYME
Pelvis of
kidney
Kidney calyx
-7
URETERIC
BUD

THINK! Metanephric Mesenchyme Analogy

The Metanephric
mesenchyme are like a
plug connecting with the
uteric bud (socket!)

Metanephric Mesenchyme Structures

Glomerulus through
to the distal
convoluted tubule

Ureteric Bud Structures

Ureter
Pelvises
Calyces
Collecting ducts

! Malformed Kidneys

Dysfunctional/Abnormal
communication between
these embryological
structures can lead
to MALFORMED KIDNEYS
(i.e. Renal agenesis,
Dysplastic kidneys etc.)

METANEPHRIC MESENCHYME Characteristics

These structures
are mesodermal
structures!

URETERIC BUD Characteristics

• METANEPHROS
  PERMANENT
• Contact with bud
  and mesenchyme
  key for kidney
  differentiation

URETEROPELVIC JUNCTION Obstruction

URETEROPELVIC JUNCTION is the
last to canalize which can
cause congenital obstruction.
This can be detected via
PRENATAL ULTRASOUND

Potter Sequence & Related Conditions

OLIGOHYDRAMNIOS Effects

REDUCED CUSHIONING FOR
THE DEVELOPING FETUS
COMPRESSION/TWISTING
OF DEVELOPING FETUS

POTTER Sequence

THINK! Babies who can't Pee develop POTTER Sequence
Bilateral RENAL
AGENESIS or bilateral
MULTICYSTIC
DYSPLASTIC KIDNEYS
Reduced fetal urine
excretion
Oligohydramnios
causing fetal
compression

POTTER Sequence Symptoms

P ulmonary hypoplasia
O ligohydramnios
T wisted face (Flattened nose, low set ears, receding chin)
T wisted skin (wrinkling)
E xtremity defects (Bowed legs, club feet)
R enal failure

CAUSES of Renal Conditions

POLYCYSTIC KIDNEY DISEASE PRESENTS AS: Flank pain, hematuria, HTN, UTI & progressive renal failure
REMEMBER! "Polycystic Kidney" has 16 letters, Most PKD is a due to a defect on CHROMOSOME 16!

AUTOSOMAL DOMINANT Polycystic Kidney Disease

Multiple cysts in the renal cortex
& medulla. 85% due to PKD1
mutation, 15% due to PKD2
mutation.
HTN and CKD common.
ASSOCIATED WITH: Berry aneurysms,
hepatic cysts, MVP and diverticulosis
TREATMENT: ACEi

AUTOSOMAL RECESSIVE Polycystic Kidney Disease

Subtype that can cause POTTER
Sequence!
Cystic dilation of ducts which appears
during infancy.

MULTICYSTIC DYSPLASTIC KIDNEY

Abnormal interaction
between ureteric
bud and metanephric
mesenchyme
creating a cystic, non
functional kidney.
> Largely
non-hereditary &
unilateral, but bilateral
leads to POTTER
Sequence!

RENAL AGENESIS

Ureteric bud does
not develop
fails to differentiate
into metanephric
mesenchyme leading
to complete absence of
kidney & ureter.

CHRONIC PLACENTAL INSUFFICIENCY

Hydronephrosis

POSTERIOR URETHRAL VALVE

Dilated ureter
Urinary reflux
Tissue remnant
in the posterior
urethra leading
to obstruction of
urine outflow.
Most common
cause of bladder
outlet obstruction
in MALES.
Distended bladder
Urethra obstructed
by posterior
urethral membrane
· Diagnosed via.
U/S & Voiding
cystourethrogram.

Renal Anatomy

Adrenal
Aorta
Kidney

Renal Pelvis

1
Renal pelvis
Metanephros
Renal
pelvis
Ureter

POINTS OF URETHRAL OBSTRUCTION

1 Ureteropelvic junction
2 Pelvic inlet
3 Ureterovesical junction

! HORSESHOE KIDNEY

FAILURE TO ASCEND CAN BE DUE TO HORSESHOE KIDNEY
HORSESHOE KIDNEY
> Kidneys fail to ascend as
they get stuck under the
INFERIOR MESENTERIC ARTERY
-> Fusion of inferior poles
> Increased incidence of
UTI's, Hydronephrosis,
Renal stones, & Renal
Cancer
> Higher incidence in
chromosomal aneuploidy
(i.e. Turners, Trisomies 13,
18, 21)

URETER Blood Supply

Despite receiving roughly 20% of our
bodies entire cardiac output, the renal
medulla receives less blood flow than
the cortex making it prone to ischemia!

THINK! Ureter Course

"Water (URETERS) flows OVER the iliac & UNDER
the bridge (uterine artery or vas deferens)!"

URETER BLOOD SUPPLY Details

Renal artery
(PROXIMAL)
Gonadal artery
Aorta
MIDDLE
Common iliac artery
Internal iliac artery
- Superior vesical artery
Uterine artery
Middle rectal artery
Vaginal artery
- Inferior vesical artery *in males

RENAL BLOOD FLOW Pathway

1 Renal artery
2 Segmental artery
3 Interlobar artery
4 Arcuate artery - interlobular artery
NOT SHOWN ....:
5 Afferent arteriole
6 Glomerulus
7 Efferent arteriole
8 Vasa recta
9 Venous outflow
Left renal vein is Longer,
and receives additional
tributaries via the Left
gonadal and
suprarenal veins

Kidney Anatomical Location

Kidvvnd to their anatomical
location at T12-13 by week 9 of
gestation

Glomerulus & Renal Physiology

Renal Equations

RENAL CLEARANCE
Effective clearance of substance
(X) from plasma (Px) to urine (Ux).
x
If Cx < GFR: net tubular
reabsorption and/or not
freely filtered.
If Cx > GFR: net tubular
secretion of X.
If Cx = GFR: no net
secretion or reabsorption

EFFECTIVE RENAL PLASMA FLOW (eRPF)

Para-aminohippuric acid (PAH) can be
used to estimate eRPF.
The amount of PLASMA filtered by the blood.
eRFP = U
PAH
PAH
e GFR
Estimated ability for kidneys to filter.
NOTE:
Pregnancy is
associated with
increased GFR!

INULIN & GFR Estimation

Freely filtered

CYSTATIN C & GFR Estimation

CAN USE

CREATININE & GFR Estimation

Slightly overestimates
GFR since
creatinine is moderately
secreted by kidneys

FILTRATION FRACTION (FF)

Percentatge of plasma that is filtered.
Filtration fraction (FF) = GFR/RFP.
Normal range of FF is roughly 20%

Glomerular Filtration Barrier Components

MADE UP OF:
> Basement membrane
(TYPE IV COLLAGEN)
Podocyte foot processes
A
BBDO
FP FP

Glomerular Filtration Barrier Filters

FILTERS PLASMA BASED ON:
SIZE:
Endothelium prevents
molecules > 100 nm from
being filtered. Slits b/w the
podocytes and basement
membrane prevent entry of
molecules >50-60 nm.
CHARGE:
Layers of the Glomerulus are
all negativley charged which
prevent negatively charged
molecules (i.e. ALBUMIN) from
being filtered.

NSAIDS & Afferent Arteriole

MAIN AREA FOR FILTRATION
Prostaglandins
preferentially dilate
afferent arteriole
(1 RPF, 1 GFR, so no 4 FF)
PDA: Prostaglandins
Dilate Afferent

BLOOD Filtration

Bowman capsule
(parietal layer)
Bowman space
Podocytes
(visceral layer)
Basement membrane
Filtered
Excreted
Reabsorbed
Secreted

THINK! ACE Inhibitors

ACE: Angiotensin II
Constricts Efferent

EFFERENT ARTERIOLE Constriction

Angiotensin II
ACE INHIBITORS -OH preferentially constricts
efferent arteriole
(IRPF, 1 GFR, so TF)

CHANGES IN GLOMERULAR DYNAMICS

GFR
RPF
FF (GFR/RPF)
Afferent arteriole constriction
-
Efferent arteriole constriction
1
1
T plasma protein concentration
plasma protein concentration
1
-
8
Dehydration
->

THINK! Plasma Dynamics

PLASMA
AFFERENT ARTERIOLE
x V/P
= CPAH*
PAH*
Constriction of ureter

Nephron Pharmacology & Tubular Defects

* = RENAL TUBULAR DEFECTS

PROXIMAL CONVOLUTED TUBULE

HCO,
Na+
Ca2+
1
H2O

Acetazolamide

MOA: Carbonic anhydrase inhibitor
OTHER USES: Glaucoma, metabolic
alkalosis, altitude sickness
AEs: "Acid" azolamide causes acidosis, can
cause sulfa allergy

Fanconi Syndrome

Reabsorption defect in the PCT -> excretion of
AA's, glucose, HCO2 & PO,3- - > metabolic acidosis
Fanconi Flushes nutrients down the PCT drain!

CORTEX & MEDULLA

CORTEX
MEDULLA

DESCENDING LIMB

Mannitol

Na*
K*
2CI-
Osmotic diuretic (increases tubular fluid osmolarity)
MOA: Elevated intracranial pressure
AEs: Dehydration, contraindicated in CHF & anuria!

THICK ASCENDING LIMB

Loop Diuretics

I.E .: Furosemide, Bumetanide,
Torsemide
MOA: Inhibits Na+/K+/2Cl-
cotransporter -> disrupts
hypertonicity of medulla
AEs: Ototoxicity, hypocalcemia/
hypomagnesemia
Loops Loose Ca2+ ->
THINK! can precipitate calcium
oxalate stones!

Bartter Syndrome

Reabsorption defect in the thick
asc. loop -> metabolic alkalosis
Bartter's BF is Furosemide
because they are twins

DISTAL CONVOLUTED TUBULE

Thiazide Diuretics

I.E .: Hydrochlorothiazide,
chlorthalidone, metolazone
MOA: Inhibits NaCI reabsorption
-> decreases Ca2+ excretion
AEs: THINK! HyperGLUC
HyperGlycemia
HyperLipidemia
HyperUricemia
HyperCalcemia

Gitelman Syndrome

Reabsorption defect of NaCl in
DCT -> metabolic alkalosis
Gitel is a man whose
mistaken for Thai(azide)

COLLECTING DUCT

Na+
K+ Sparing Diuretics
K
H+
I.E .: Spironolactone, Eplerenone,
Amiloride, Triamterene
MOA; Aldosterone receptor
antagonists
OTHER USES:
· Spironolactone: anti-androgen,
hepatic ascites
> Amiloride: nephrogenic DI
AEs: Hyperkalemia

Liddle Syndrome

* Liddle Syndrome
Mutation causing decreased
Na+ channel degradation ->
Increases Na+ reabsorption in
collecting tubules
Liddle but Dominant ->
Autosomal Dominant

S.A.M.E. (SYNDROME OF APPARENT MINERALOCORTICOID EXCESS)

* S.A.M.E
(SYNDROME OF APPARENT
MINERALOCORTICOID
EXCESS)
Decreased conversion of cortisol
to cortisone -> increases cortisol
-> increases mineralocorticoid
receptor activity
TREATMENT: K+ sparing
diuretics or corticosteriods

Na+ & CI- Transport

Na+
CI-
Sugars
Amino acids
Na+

RAAS & Renovascular Disease

Afferent Arteriole

MACULA DENSA

Chemoreceptor lined cells in the distal
convoluted tuble
Detects changes in concentraction of
NaCl and secretes PROSTAGLANDINS

JUXTAGLOMERULAR CELLS

Baroreceptor lined cells around the
afferent arterioles
> Detects decreases in renal perfusion
pressure

SYMPATHETIC ACTIVATION

> Detects low systemic BP & releases
norepinephrine

GLOMERULUS

Efferent arteriole
AT Il also
R
C
R
R
R
R
R
R
R
R

RENIN Conversion

RENIN converts Angiotensinogen
in the liver to Angiotensin I

JUXTAGLOMERULAR CELLS Secretion

JUXTAGLOMERULAR CELLS
to secrete RENIN into the
blood stream

Angiotensin II Effects

Increases GFR via
vasoconstriction of the
EFFERENT ARTERIOLES
&
Increases Na+, HCO3;,
& H2O reabsorption at
the PCT

KIDNEYS

a-INTERCALATED CELLS

Increase in H+/ATPase >
Increases H+ secretion

EFFECT OF ANGIOTENSIN II ON:

Synthesis of :
ALDOSTERONE in the
ADRENAL GLANDS

PRINCIPAL CELLS

ADRENALS
Nat absorption/K+ secretion
(via ENaC) & Increased H20
reabsorption (via aquaporins)

Angiotensin II Receptors

Binds to receptors
AT II receptors in the
hypothalamus
Promotes ADH secretion
at the posterior pituitary
> increases thirst + H20
reabsorption

Renovascular Disease

O Most common cause of secondary hypertension in adults.

CAUSES of Renovascular Disease

MOSTLY CAUSED BY:
Long-standing atherosclerosis on the
proximal 1/3 of the renal artery
> Classically in elder males who smoke!
Fibromuscular dysplasia of the distal 2/3
of the renal artery/segmental branches
4 Classically in young-middle aged women!

Renovascular Disease Manifestations

CAN CAUSE:
UNILATERAL
STENOSIS
Asymmetric kidney size.
Venous sampling will
show increased renin
in affected kidney and
decreased in unaffected.
BILATERAL
STENOSIS
Sudden increase in
Creatinine following
administration of ACEi,
ARB, or renin inhibitor.
Decreased
renal
perfusion
Increase in
renin
Increase in
Angiotensin
HYPERTENSION

Angiography Findings

"String of beads" on angiography

Systemic Vasoconstriction

THESE 3
ALL ACTIVATE:
causes
systemic
vasoconstriction
leading to an
increase in BP!

Angiotensin I Conversion

Angiotensin I is then converted
to ANGIOTENSIN II (AT ID) via
ACE primarily in the vascular
endothelial cells of the lungs

HYPOTHALAMUS Role

BOTH
WILL
CAUSE
Proximal
convoluted
tubule