Renal Flashcards
1
Q
Basic renal functions?
A
- Maintain water balance
- regulate the quantity and concentration of ECF ions
- maintian plasma volume
- A/B balance
- excrete waste product
- secretion of renin, erythropoiertin etc
2
Q
WHat is special about renal vasculature?
A
one way in , one way out, no collateral circulation
kidney vulnerable to change in flow
3
Q
What are the different cell types found in the glomerulus?
A
- Endothelial cells- keep things out by size
- mesangial cell- keep things out based on charge
- podocyte- keep things out on size
4
Q
What is the glomerular basement membrane like?
A
- very thick, continuous
- podocytes sit on top of GBM
- Endothelial cells on side next to capillary bed
5
Q
What should a normal glomerulus have on histology?
A
- Always should b espace outside of bowman’s capsule
- always white, always open
- should always see open space inside capillary itself, inside the bowman’s space
- “darker pink” = glomerular basement membrane
6
Q
Normal histology of cortex?
A
- the glomerulus is a tuft of capillaries within a space called the urinary space or bowman’s space
- glomerulus has been cut through the vascular pole which is seen at 6 oclock
- proximal/distal tubule- in all difference direction
7
Q
Normal histology of medulla
A
- Medulla made up primarily of loop of henle and collecting ducts
- much more homogenous appearance than cortex
8
Q
A
9
Q
What is normal GFR?
A
100-125 mL/min
indication of health of kidney= filtration rate
10
Q
Equation how to find GFR (don’t need to to math, but know what influences for disease state)
A
- GFR= Kf ( HPc- Πc- HPbs)
- HPc- favors filtration
- Πc, HPbs opposes filtration
11
Q
What are the determinants of GFR?
A
- Under normal physiolgic cirucmstances: GFR 100-125 mL/min
- GFR declines with age and in pathology
- Dependent on oncotic pressure, hydrostatic pressure and Kf
- major determinant of GFR is glomerular capillary pressure= blood pressure
12
Q
Autoregulation of kidneys?
A
- Purpose: to maintain constant blood flow through the glomerulus independent of systemic BP
- myogenic mechanism
- tubulo-glomerular feedback (juxtaglomerular apparatus)
13
Q
Review of tubuloglomerular feedback?
A
- Macula densa- sense increase NaCl in distal nephron inhibits renin release; decreased load promotes renin release
- goes to juxtaglomerular cells to release renin into afferent arteriole
14
Q
How does the RAAS system affter blood volume?
A
- Renin–> ang I–> ang II
- Angiotensin II:
- increase blood bolume to increase BP
- Increase in total peripherla resistance (vasoconstriction)–> increase BP (causes hydrostatic pressure to increase and chloride flow to increase in macula densa)
- Angiotensin II:
15
Q
Facts about kidney pathology?
A
- About 1 in 12 people in USA has renal or urinary tract disease.
- 13% of all women ages 20 to 45 will experience a UTI
- 26 million adults >20 years of age have chronic kidney disease.
- 45% of kidney failure is caused by diabetes. High blood pressure is the second leading cause of renal failure.
- Over 87,000 people with kidney failure die each year.
- Kidney disease is America’s ninth leading cause of death.
- there are 367,000 people being kept alive through dialysis
- Over 85,000 patients are on the waiting list for a kidney transplant. Sadly, only 15,000 will get a new kidney this year.
16
Q
Why have incidence rates of ESRD increased so much?
A
increased HTN and DM rates
17
Q
Geographic variaton in ESRD?
A
- largely related to race
- also, access to healthcare, poor diet etc
- Highest rate in black, native american
18
Q
Incident counts of ESRD, tranplant and dialysis
A
19
Q
Mortality rates by modality? HD, PD, tranplant?
A
transplant has best outcomes by far
20
Q
What is acute renal failure?
A
- sudden decrease in GFR (within 1-2 days)
- results in increase in plasma concentraiton of waste products (axotemia) normlaly excreted by kidneys
- causes of ARF are varied and yet treatment depends on identifying the mechanism involved
- ARF almost always evolves in hospital
- 1%-25% of crtiically ill patients
- mortaility in these populations ranges form 28-90%
- other things happening in body to cause ARF
- Characterized by:
- reduced produciton urine, clinically recognized as oliguria or anuria
- retention of water, H, minerlas reuslting in metabolic acidosis
- retention of metabolic waste products in blood, most notably BUN and Cr
21
Q
What 3 different categories is ARF dividided into?
A
- Prerenal (decreased renal perfusion)
- post renal (obstruction to urine flow)
- parenchymal renal disease (within kidney)
Note: NOT muslaly exclusive, all three of them may b epresent at the same time. THerfore, it is important, even if it seems obvious why the renal funciton is falling, to look for evidence of all three
22
Q
Pathogenesis of prerenal ARF?
A
- Any process that sharply decreases renal perfusion
- hypotension
- volume depletion (fluid loss, bleeding)
- primary cardiac pump failure
- decreased SVR (Sepsis)
- response to renal hypoperfusion
- decrease in GFR–> increase in ang II, increase ADH, increase aldosterone
- Na and water retnetion- bad because already not filtering much urine. build up toxins
- increase in BUN/Cr levels (20/1 is normal)
- BUN= reabsorb
- Cr= secretion
- both will go up in ARF. however BUN will increase more than Cr (ratio will be >20:1)
- decrease in GFR–> increase in ang II, increase ADH, increase aldosterone
- Pre-renal failure is best treated by imporving renal perfusion: volume replacement, dialysis
- all compensatory mechanisms are just going to make prerenal ARF worse
23
Q
Common causes of intrarenal (parenchymal) ARF?
A
- ATN- acute tubular necrosis
- cortical necrosis
- acute glomerulonephritis
- malignant HTN
- disseminated intravascular coagulation
- renal vasculitis
- allograft rejection
- drug allergy
- infection
- tumor
most are reversible
24
Q
What are causes of postrenal ARF?
A
- Tubular obstruciton
- insult (ischemia) cuases sloughing of cells and cast formation. obstruction in the tubule then cauess a retrograde increase in pressure and reduced the GFR
- Tubular backleak
- backward flow of filtrate
- causes: ie prostate, UTI, tumor, kidney stone
25
Q
What is early phase of postrenal obstruction?
A
- Reflex adaptation to maintain GFR despite rising tubular hydrostatic pressure
- afferent arteriolar dilitation, enhances glomerular perfusion
- this phase lasts only 12-24 hours
26
Q
Late phase of postrenal obstruction?
A
- After 12-24 hours, the afferent vasodilatation ceases
- progressive fall in renal perfusion: glomerular blood flwo and GFR drop
- may result in anuria
- this phase continues until the obstruction is relieved
- if rpolonged, the ischemia leads to progressive permanent nephron loss
27
Q
Recovery phase after postrenal obstruction relieved?
A
- With release of pressure, the pre-renal vessels relax, perfusion restored and GFR increases in the nephrons which survive
- tubular pressure returns to normal
- dilation of the calyces and collecting system may remain permanently
28
Q
What is BUN/Cr ratio with postrenal damage?
A
10-20/1 (normal range)
29
Q
What is BUN/Cr ratio with prerenal failure?
A
>20/1
- Reduced blood flow causes elevated creatinine and BUN
- additionally, BUN reabsorption is increased because of the lower flow
- BUN is disproportionately elevated relative to creaitnine
30
Q
What is BUN/Cr ratio with intrarenal renal failure?
A
<10/1
- Renal damage causes reduced reabsorption of BUN, therefore lowering the BUN/Cr ratio
- something is wrong in kidney, see reduction in BUN/Cr
31
Q
What is Chronic kidney disease?
A
- Gradual and progressive loss of the ability of the kidneys to excrete waste, concentrate urine and conserve electrolytes d/t diseases affecting the kidney either
- Primarily:
- chronic glomerulonephritis
- interstitial nephritis
- Secondarily
- HTN vascular disease
- diabetes
- partial urinary tract obstruction
- Progression may continue to ESRD
32
Q
What is relationship b/w GFR and Cr?
A
GFR= 1/Pcr
lower the GFR, higher the plasma Cr
33
Q
What is the progression of CRF?
A
- Reduced renal reserve- we have tons more nephrons than we need
- Renal insufficiency <30% left, GFR= 30%
- GFR is reduced and mild azotemia, nocturia, mild anemia
- Renal failure <20% functioning, start to feel symptoms
- azotemia, acidosis, impaired urine dilution, severe anemia, hypernatruima, hyperkalemia
- End stage renal failure
- near absence of GFR, all organ systems are affected
34
Q
What are clinical manifestations of uremia?
A
- Uremia refers to a number of symptoms caused by a decline in renal function with the accumulation of toxins
- causes unknown, and it appears that urea and creatinine build up plays little to no role
- symptoms
- anorexia, nausea, vomiting, diarrhea, weight loss, edema and neuro changes
-
uremia is umbrella term meaning “urine in blood”
- accumulation of other toxins in body
35
Q
Sodium and water blanace in body?
A
- Sodium must be regulated within narrow limits
- the nephron is very efficient at reabsorbing sodium
- when GFR declines, a decreased fraction of filtered Na and water must b ereabsorbed- keeps them in balnace
- CRF kidneys become less flexible
- typically, our kidneys can regulate high Na content very easily. We loose this ability to regulate in renal failure
- urinary dilution and concentration are impaired
36
Q
Calcium balance in body with renal failure?
A
- Normally (without any condition) Calcium, in general, is reabsorbed in body
- In renal failure, Vitamin D levels decrease (because not activating it in the kidney)
- Diminished absorption of calcium from the gut (because no vit D)
- overproduciton of parathyroid hormone (because low Ca in blood)
-
Plasma phosphate levels increase because of the decrease in GFR
- phosphate levels bind to plasma calcium levels, further decreases calcium levels
37
Q
Potassium balance in renal failure?
A
- Aldosterone-mediated potassium transport unable to function at such a low GFR
- Hyperkalemia results
- the risk increases as the diseas progresses and must be controlled by dialysis
38
Q
A/B balance in renal failure?
A
- Kidneys secretes acids in large amounts
- as the kidney fails, ammonia synthesis decrease
- there is compensation, but must be treated with dialysis if severe
- if K didn’t cause patient to go on dialysis, the a/b problems would
39
Q
What is renal osteodystrophy?
A
- bone pain because of bone resorption
- high risk fracture and osteoporosis
- elevated sreum phosphate levels
- decreased serum calcium levels
- impaired activation of Vit D
- hyperparathyroidism
40
Q
Hematologic alterations in renal failure?
A
- Decrease in the produciton of erythropoietin, thus an inadequate produciton of RBC
- Normochromic normocytic anemia- normal size and normal shape of RBC, just not enough because no erythropoietin
- anemia presents with
- letharge
- dizziness
- low HCT
- Also associated with left ventiricular hypertrophy
- long term anemia leads to LVH (heart has more strain because it needs to pump faster/harder to make up for loss in RBC)
41
Q
Cardiovascular system funciton in renal failure?
A
- HTN resulting from excess fluid volume and sodium levels
- elevated renin
- Dyslipidemia
- not well understood, seen in liver dysreuglation of lipoprotein in blood
- not as much HDL, increase amount of LDL
- Constitues the most frequent cause of death in this population
- increase risk atherosclerosis
42
Q
Neural function in renal failure?
A
- Mild sleep disorders, impaired concentration, memory loss, and impaired judgment may occur in some individuals
- some may experience frequent hiccups, muscle cramps, and twitching (potassium/Ca dysregulation)
- caused by alterations in electrolyte and metabolic product elevation
43
Q
Endocrine function and reporduciton in renal failure?
A
- Uremic males and females have decrease in sex steroids
- amenorrhea and inability to maintain a pregnancy in females
- decreased libido and impotence in mena nd sometimes infertility
- with dialysis, can get better
44
Q
Immunologic dysregulation in renal failure?
A
- Gneralized immunosuppression d/t unknown reasons
- increases susceptibilyt to infection
- deficient resposne to vaccinations
- impaired wound healing
- dialysis needed
- “toxins” buildup may be contributing cause
45
Q
GI tract funciton in renal failure?
A
- Non-specific GI complications including anorexia, nausea and vomiting, along with a metallic taste in mouth
- Uremic gastroenteritis<only most severe ESRD
- bleeding ulcerations along that mucosa that results in sig blood loss
- Uremic fetor
- form of bad breath caused by urea breakdown by salivary enzymes
- symptoms alleviated with dietary protein is restriction or institution of regular dialysis
- decrease protein, decreas nitrogenous waste, and decrease symptoms
71
Q
What is nephrotic syndrome?
A
- First thing that happens with altered glomerular permeability–> increased filtration of plasma proteins and proteinuria
- edema forms
- get reduction in blood volume, activate renin, furthering edema
- hepatic synthesis of lipoproteins is triggered from hypoalbuminemia
- unsure of why this happens.
- Now have hyperlipoproteinemia
- makes LDL and VLDL–> increase risk for atherosclerosis
- decreased immunoglobluins- can’t fight off infection
- hypercoaguable state– loose anticoagulants (more so than coagulants) so now we are hypercoaguable
73
Q
What does the histology of membranous glomerulonephritis show?
What is immunofluoresence?
A
- Glomerulus is normocellular
- increase in extracellular substance, especially in the form of thickened capillary loops
- nice bowman’s space, normocellular, but lots of pink stuff (glomerular basement mbemrane)
- lots of extra from antibodies
- no big, open capillary visualized
- feature is diffuse in a glomerulus and all glomeruli would show this change (generalized)
- diffuse granular fluorescence for IgG is a capillary loop pattern
- immunofluoresence= take antibody with fluorescent marker, once it finds something, it fluoreses, showing antibodies/antigen complex
- immune system in this disease is affecting everywhere within glomerulus
76
Q
Specfic histological changes in membranoproliferative glomerularnephritis?
A
Top pic:
- The glomerular tufts are diffusely hypercellular
- Increase in mesangial cell number
- more purple dots (more mesangial cells, got bigger)
- GBM grew
- less bowman’s space
Bottom pic:
- The glomerular capillary loops show two basement membranes giving the loops a “tram track” appearance (arrow)
77
Q
Pathophys behind membranoproliferative glomerularnephritis?
Treatment?
A
- Same as membranous glomerulonephritis
-
Treatment: steroids, immunosuppressant to stop antigen-ab immune complex
- decrease immune system, gets better
78
Q
Population, histology and mechanism of minimal change disease? Treatment?
A
-
Population- young children (2-6), more common in males
- usually after recent respiraotyr infection or after receiving routin immunizations
-
Histology: unknown etiology
- potentially a change in GBM charge
- causes fusion of foot processes
- potentially a change in GBM charge
- Treatment= steroids
- Podocytes are lined with proteoglycans that are charge (negatively). These charges repel and keep podocytes away from eachother*
- In minimal change dx, they think the proteoglycans are killed or the disease changes the charg. Now, we no longer have negative charges repelling. Get “blobs and giant holes” that allow filtration of proteins*
- Speculate that this also changes the charge of the GBM (typically negative). If neutral charge, won’t keep proteins out based on charge*
79
Q
What are some speicifc histological changes in minimal change disease?
A
Top pic:
- The glomeruli appear normal on light microscopic examination
- despite the absence of structural abnormalities, the glomerular capillary basement membranes are leaky to low molecular weight proteins such as albumin, due to alteration in the electrical charge
- nuclei- black
- inside cells- pink
-
connective tissue (fibrosed protein)- blue
- only outside glomerulus
- never connection tissue inside glomerulus, only outside, connecting tubules
bottom:
- the visceral epitherlial cells shows fusion of foot processes
- blob of foot processes, no speicifc podocyte seen
80
Q
What is focal segmental glomerulosclerosis histology?
A
Top pic:
- One half of glomerular tuft is sclerosed
- the other half of the glomerular tuft (left) is normal showing patent capillary loops
- filtration capacity not functioning
bottom
- lesions are frequently positive for IgM
- The IgM deposits are not blieved to be immune complexes but instead serum proteins that have been entrapped by the sclerosing process
- Ab doesn’t appear to play role in disease process
- Steroids not helpful to dx
- no known treatment
85
Q
Hisotlogy behind post-streptococcal glomerulonephritis?
A
top pic:
- The increase in cellularity is due to neutrophils and to proliferation of endogenous endothelial cells and mesangial cells
- TONS of cells in glomerulus (purple)
bottom pic:
- large subepithelial deposits (arrow)
- a neutrophils (PMN) is noted in the mesangium in the lower right corner
87
Q
Histology of IgA nepropathy?
A
top pic
- The glomerulus is architectually not very remarkable except for mild mesangial expansion (arrow)
- the expansion is due to the increased numbers of mesangial cells
bottom
- electron micrograph shows many discrete electron dense deposits located in the mesangium (on of these deposits is demarcated by arrow)
89
Q
Histology of chronic glomerulonephritis?
A
top pic
- atrophic kidney with thin cortex from a patient at autopsy with chornic renal failure
-
can’t see difference in cortex/medulla/columns because whole kidney just atrophies
- lots of fat (yellow) in kidney filling where functional space used to be
bottom pic
- the glomeruli have been transformed into solidified spherical structures
- there is extensive parenchymal scarring with interstitial fibrosis and tubular atrophy
- the atrophic tubules have markedly thickened basement membrane
- no functioning glomerulus
- Kf decreases which decrease GFR
-
pic has one glomerulus and bunch of tubules
-
some are white, some thick pink
- white- healthy
-
pink- tubular cast- when tubule is associated with dead glomerulus, it will die and 2 things will happen
- tubule falls in on itself OR
- calcification on outside of the normal self
- patient very quickly progresses into ESRD to dialysis to kidney transplant
-
some are white, some thick pink
91
Q
What are the 2 types of tubulointerstitial nephritis?
What are the 2 ways you can get either pyelonephritis?
A
- acute pyelonephritis
- chornic pyelonephritis and reflux nephropathy
Both:
- often caused by bacterial infection
- starts in pylon and then move up
- affects tubules and interstitial; glomeruli spared
- renal pelvis is prominently involved (pyelonephritis)
- Two ways to get infection
- hematogenous infection (aka blood borne)- less common and results form seeding of the kidneys d/t septicemia or bacterial endocarditis
- vesicoureteral reflux (aka- ascending UTI)- occurs more readily with an uretheral obstruction or cystitis as the urinary bladder pressure is increased and the normal vesicoureteral valve is compromised
94
Q
What is histology of acute pyelonephritis?
A
top
- kidneys of a 2 yo child born with multiple anomalies including hydrocephalus
- kidneys show patchy lighter colored areas (arrows) when compared to normal, darker colored areas
- big, white filled areas- pus filled as WBC attempt to eradicate bacterial infection
- pus filled nodules all over kidney
bottom
- there is acute and chronic inflammation affecting the renal parenchyma
- the interstitium is widened by inflammatory cells
- there are inflammatory cells consisting largely of neutrophils in the tubular lumens (arrows)
- lots of neutrophils, WBC, attempting to kill bacteria (purple dots)
97
Q
Histological changes of chronic pyelonephritis?
A
top
- the cystic appearing structures are actually dilated calyces, reflecting hydronephrosis
bottom
- many tubules are dilated with hyaline casts giving the kidney a thyroid-like appearance
- pathcy areas of collected chronic inflammatory cells are present
- a couple of glomeruli are noted in the mid lower field
- every time infection occurs, kills nephrons, lose Kf, lose GFR, lower kidney function
99
Q
Histological changes with benign nephrosclerosis?
A
top
- sclerosis of renal arterioles and small arterioles
- medial and intimal thickening, as a response to hemodynamic changes, genetic defects
- “onion skin” in arteries
-
with atherosclerosis, diff layers vessel wall get thicker and thicker
- usually medial/intimal portion of wall
-
not much blood getting thorugh, ischemic changes
- low blood, low pressure to maintain GFR, low O2
bottom
- few glomeruli may undergo ischemic wrinkling
- not enough O2, glomerulus wrinkles in on itself
- no filtration
- glomerulus can’t function
- with continues HTN, more glomerulus will look liek this
- eventualyl nothing can pass through arteries and everything downstream will die
101
Q
Histologic changes seen in malignant HTN and malignant nephrosclerosis?
A
top
- thickening of arterial wall is associated with a hyperplastic arteriolosclerosis
- this arteriole has a n onion skin appearance
bottom
- glomeruli: the glomeruli will be completely fibrotic
103
Q
Histological changes in diabetic nephropathy?
A
Left- glomerular capillaries
- glomeruli get smaller
- thick, pink glomeruli with huge amoutn of GBM
- sclerosis noted
Right- arteriole
- thickening of vessel wall (atherosclerosis noted)
- will see ischemia, decrease in blood coming to glomeruli
109
Q
Histological changes in autosomal recessive (childhood) PKD)_
A
TOP
- autopsy specimens from a child who died in infancy from complications associated with PKD
- A cross section of kidney shows the typical pattern of fusiform, cylindrical channels that occupy most of the kidney parenchyma
- kidney like a sponge of cysts
- need immediate kidney transplant
- usually know in utero
- bottom*
- These cysts are massively dilated terminal branches of collecting ducts
