Renal Patho Flashcards
prevalence of urinary system congenital malformations and why
- 10% of all newborns
- because you start the process 3 different times so the chance of something going wrong increases
What are the potential 3 sets of kidneys?
- pronphros
- mesonephros
- metanephros
pronephros
- non-functional in humans
- week 4
- functional in lampreys and hagfishes
mesonephros
- briefly functional in humans
- present in fish and amphibians
metanephros
- functional human kidneys
- become functional around week 11
describe the human embryo at the end of week 2 of development
- hollow ball of cells
- 2 layered primordium
- epiblast and hypoblast
when does the embryo progress to 3 layers?
at the end of week 3
- epiblast
- mesoderm
- hypoblast
What do the 3 embryonic tissues develop into?
- epiblast: skin and nervous tissue
- hypoblast: gut lining
- mesoderm: everything else
formation of the urogenital ridge
- after folding (week 4-5) the mesoderm forms a buldge on posterior abdominal wall
- it becomes the urogenital ridge / nephrogenic cord
- reason that kidneys are retroperitoneal
describe the once functional mesophephros in the 5 week embryo
- early mesonephros forms a duct and a vesicle
- they elongate and join to form a single nephron
What is the significant embryologic structure that forms off of the mesonephric duct?
ureteric bud
ureteric bud
- grows out from the mesonephric duct
- starts branching repeatedly into millions of collecting ducts
- so: the entire collecting system of the kidney is form the ureteric bud - a branch of the mesonephric duct
what do the adult kidney tubules originate from?
metanephric mesoderm
kidneys develop mainly from what embryologic structures?
- metanephric diverticulum off mesonephric duct
- metanephric mesoderm
what major change in the kidneys begins around week 9 of development?
- they move from the pelvis region to adult position
- also rotate medially
what happens to the urine produced in the womb?
- urine = amniotic fluid
- swallowed by fetus
- reabsorbed by gut into circulation
- out via placenta
polyhydramnios and cause
- too much amniotic fluid
- esophageal atresia or other obstructions that wouldn’t allow for the fetus to swallow
oligohydramnios and cause
- not enough amniotic fluid
- anything that effects the kidneys/urinary system
ectopic kidney
- a persistant mesonephric kidney
- would be located above the metanephric kidney
- always smaller and can be functional
kidney size vs function
- 0.5% of body weight
- 25% of CO
general functions of the kidney
- excretion
- regulation of water and salt
- maintain pH
- endocrine functions
what is the glomerulus?
-anastomoses of capillaries invested by 2 layers of epithelium
layers of the glomerulus
visceral layer next to the endothelium that is continuous with a parietal layer and Bowman’s space in between
branching of the renal artery
- renal a. enters kidney
- branches to interlobar a. b/w the papilla
- branches into arcuate a.
- branches into interlobular a. in the cortex
- branches into the afferent arteriole into the capillary tuft
- exits as the efferent arteriole
- vasa recta surround the nephron
macula densa
- thick ascending limb of the LoH
- at the transition to the DCT
macula densa cells sense what?
NaCl concentration
decrease in NaCl causes the macula densa cells to:
- decrease resistance to blood flow in afferent arterioles
- this raises hydrostatic pressure in glomerulus - increases renin release from JG cells of afferent and efferent arterioles
an increase in NaCl results in what?
-vasoconstriction of the afferent arterioles and a decrease in JG release of renin
What are all of the layers of the glomerulus that make up a filter?
- fenestrated endothelium
- glomerular basement membrane
- secondary foot processes
- slit diaphragms
fenestra size
70-100 nm (comparison: RBCs 7000 nm)
glomerular basement membrane
- secreted by
- made of
-secreted by epithelial cells
-consists of Type IV collagen
and glycoproteins
secondary foot processes
- where
- size
- embedded in the basement membrane
- separated by 20-30 nm filtration slits
what supports the entire glomerular tuft?
mesangial cells
what do mesangial cells secrete?
- mesangial matrix (BM like)
- may proliferate w/ phagocytic role
what proteins make up the slit diaphragm between the foot process?
nephrin
what happens when there is a defect in the gene for nephrin?
- congenital nephrotic syndrome
- pee protein
diagram of renal corpuscle
a lot of anatomical diagrams on this lecture to review!
in summary, what is filtration based on?
- size of fenestra
- glomerular basement membrane
- filtration slits
- slit diaphragm
- charge
absorption at the proximal tubules
-PCT absorbs about 2/3 of glucose, K, phosphate, aa, proteins, and toxins
why are the PCTs more prone to damage?
most exposure to toxins
define acute renal failure
- abrupt onset of not being able to produce urine
- oligo/anuria w/ azotemia
- follows rapidly progressing glomerulonephritis or ATN
- usually reversible
azotemia
elevation in BUN
ATN
acute tubular necrosis
-MC cause: hypotensive shock
oliguria
- <05 ml/kg/hr of urine output
- 400-500 ml/d
what to suspect in asymptomatic hematuria or proteinuria
mild glomerular disease (ex: from DM) all the way to cancer
nephrotic syndrome
- heavy proteinuria
- > 3.5 gm/d
- hypoalbumen
- edema
acute nephritic syndrome
gross hematuria/proteinuria and HTN secondary to post-strep glomerulaonephritis
chronic renal failure
occurs over years, not reversible, and usually secondary to systemic disease
diminished renal reserve
- GFR >50%
- nl BUN/Cr
renal insufficiency
- GFR 20-50%
- azotemia
- anemia
- HTN
renal failure
- GFR about 20%
- loss of regulation of water, pH, salts
- edematous
- metabolic acidosis
- hypocalcemia***
- hyperkalemia***
end stage renal disease
- GFR about 5%
- terminal
most causes of glomerular injury result from what?
- immune mechanisms (70%)
- other 30% is from DM and toxins
What are the two in situ types of immune mediated glomerular disease?
- anti-GBM
2. heymann model
anti-GMB (masugi’s model) of glomerular dz
- auto antibodies to type IV collagen w/i the BM
- immune binding clogs the GBM and decreases GFR
- less than 5% have this
heymann model of glomerular dz
- auto antibodies to glycoprotein on foot processes of visceral epithelium
- clots filtration slits and GBM
What is the condition called when you make auto-abs against type 4 collagen?
good pasture syndrome
what are the triggers for the development of auto-antibodies?
- toxins like mercuric chloride
- “planted antigens” such as bacterial debri
- graft vs. host dz
in the circulating model (as opposed to the 2 in situ models) of glomerular dz, what is the process?
- the antibody antigen complex is already formed and that is what clogs the system
- there is no immunologic specificity for glomeruli
what are the 2 types of complexes in the circulating complexes model?
- endogenous
- exogenous
endogenous complexes
- think autoimmune diseases
- SLE
- dsDNA is worst offender
exogenous complexes
complexes to bacterial/viral products
-ex: strep
what are common viral triggers for the circulating complex model?
- hep B and C
- mumps
- mono
- varicella
what are common bacterial triggers for the circulating complex model?
- group A hemolytic strep
- meningococcus
- strep pneumo
- syphillis
- staph (endocarditis)
what is the pathophys behind the circulating complexes concept?
- complexes form in mesangial matrix and subendothelially
- this activates immune system
- infiltration of leukocytes and proliferation of mesangial cells
- once deposited, can be cleared by phagocytosis (unless chronic like in SLE)
Ddx when pt presents w/ fever, N/V, HTN, periorbital edema, oliguria, hematuria w/ dark-colored urine 1-2 weeks after strep
post-strep AGN
pathognomonic for AGN
RBC casts
labs in AGN
UA:
- RBC casts
- proteinuria
-elevated ASO titer
prognosis of post-strep AGN
- > 95% recover w/ conservative water/electrolyte management
- hematuria and proteinuria may last weeks - months
- about 3% will progress to acute/chronic renal failure
- so treat strep throat!!
puffy face, think ______
nephritic syndrome
diabetic nephropathy
-30% of DM1 develop end-stage renal dz
-50% of DM1 and DMII have proteinuria 10-20 yrs after onset –>
signals progression of chronic renal failure w/i 4-5 yrs
diabetic mechanisms that have a role in kidney damage
- GBM thickening
- glomerulosclerosis
- GFR increase and subsequent decrease
- accelerated atherosclerosis
GBM thickening
- when
- process
- as early as 2 yrs after onset
- secondary to non-enzymatic glycosylation of proteins
- glucose stimulates increase in type IV collagen
glomerulosclerosis
- associated w/ GBM thickening
- from hemodynamic change
- produces glomerular hypertophy secondary to increased mesangial cells and matirx
in summary, what are the 3 main things to think about with relating DM to kidney issues?
- GBM thickening
- glomerularsclerosis
- arteriosclerosis
how to help DM effects on kidney
- tight glucose control
- ACE inhibits to decrease glomerular capillary pressure
- STOP smoking!
