Pathology Flashcards
(84 cards)
1
Q
What is acute kidney injury? How might patients present? Is it reversible?
A
- a sudden onset of rapidly reduced GFR with an accompanying increase in nitrogenous wastes in the body
- oliguria may or may not be present
- is potentially reversible
- (originally called acute renal failure)
- vs. chronic renal disease: slow, progressive, irreversible loss of renal function
2
Q
Why is chronic renal failure considered insidious?
A
- because 75% of the kidney tissue can be destroyed before symptoms from the loss of function are even noticeable
3
Q
What is the most common cause of kidney injury?
A
- antibody-mediated injury (immune complex deposition)
- most common kidney disorder is IgA nephropathy
4
Q
What are the three main nephrotic syndromes? What are two major causes of secondary nephrotic syndrome?
A
- minimal change disease (MCD)
- focal segmental glomerulosclerosis (FSGS)
- membranous nephropathy
- secondary: diabetes, amyloidosis
5
Q
What are the four main nephritic syndromes?
A
- post-strep glomuerular nephritis (PSGN)
- rapidly progressive glomerulonephritis (RPGN)
- IgA nephropathy
- alport syndrome
6
Q
What are the two glomerular diseases that are both nephritic and nephrotic?
A
- mebranoproliferative glomerulonephritis (MPGN)
- diffuse proliferative glomerulonephritis (DPGN)
- (these are severe nephritic syndromes that can present as nephrotic if enough damage to the GBM is done)
7
Q
What is the hallmark of nephrotic syndrome? What are the other signs and symptoms of this syndrome?
A
- nephrotic syndrome is characterized by massive proteinuria (greater than 3.5 g/day)
- hypoalbuminemia (albumin is main protein lost)
- generalized edema (because of drop in oncotic pressure)
- hypercoagulability (because of loss of antithrombin III)
- hypogammaglobulinemia (increased risk of infection)
- hyperlipidemia and hypercholesterolemia (hypoalbuminemia results in increased synthesis of lipid and cholesterol to try and “fatten” the blood back up to normal)
8
Q
What is the hallmark of nephritic syndrome? What are the signs and symptoms of this syndrome?
A
- nephritic syndrome is characterized by glomerular inflammation
- inflammation results in hematuria and RBC casts in the urine
- azotemia and oliguria
- hypertension (due to salt retention)
- proteinuria (but less than 3.5 g/day)
9
Q
What is minimal change disease? Which patients is it most commonly seen in? What do we see on light microscopy, electron microscopy, and immunofluorescence?
A
- (MCD is a nephrotic syndrome)
- excessive cytokines damage to the podocytes, resulting in the effacement/flattening of the podocyte foot processes
- this effacement increases the permeability of the glomerulus, resulting in SELECTIVE proteinuria (only albumin is lost)
- 90% of MCD occurs in children (“Michelin babies”)
- LM: no change; glomeruli are normal
- EM: podocyte foot process effacement
- IF: negative
10
Q
What is minimal change disease associated with? How is it treated?
A
- MCD may be triggered by a recent infection, immunization, or other immune stimulus
- it may also be associated with Hodgkin lymphoma (as this lymphoma releases lots of cytokines!)
- MCD is unique in that it is really the only glomerular disease that responds very well to steroids
11
Q
What is focal segmental glomerulosclerosis (FSGS)? Which patients is it most commonly seen in? What four things is it associated with? What do we see on light microscopy, electron microscopy, and immunofluorescence?
A
- (FSGS is a nephrotic syndrome)
- certain portions of certain glomeruli are sclerosed with connective tissue, causing foot process effacement
- most commonly seen in blacks and Hispanics
- associated with HIV*, IVDU (heroin, especially), sickle cell anemia, and extreme obesity
- LM: segmental sclerosis and hyalinosis
- EM: podocyte foot process effacement
- IF: negative
12
Q
What percent of cases of FSGS respond to steroid treatment? What percent will progress to renal failure within ten years? What about within just two years (malignant course)?
A
- only 10-20% of cases of focal segmental glomerulosclerosis respond well to steroids
- 50% of cases progress to renal failure within 10 years
- 20% will progress within 2 years
- (this is not a good glomerular disease to have!)
13
Q
What is membranous nephropathy? Which patients is it most commonly seen in? What is the disease associated with? What is the major complication of this disorder? What do we see on light microscopy, electron microscopy, and immunofluorescence?
A
- (a nephrotic syndrome); it is diffuse
- immune-complex deposition in the glomerular basement membrane (SUB-EPITHELIAL) results in the diffuse thickening of the capillary walls and membrane itself
- most common in whites
- associated with SLE* (the most common glomerular disease seen in SLE, however, is diffuse proliferative glomerulonephritis), HBV, HCV, and certain drugs
- patients with membranous nephropathy have a high risk of thromboembolic events involving the renal vein (for some reason this risk is highest in this disorder)
- LM: diffuse thickening of capillaries and basement membrane
- EM: sub-epithelial deposits; “spikes and domes”
- IF: granular (indicates immune complex deposition)
14
Q
What percentage of cases of membranous nephropathy undergo spontaneous remission? Result in persistent proteinuria? Develop into progressive renal failure? What about in IgA nephropathy?
A
- 30% for each in both disorders
- membranous nephropathy is nephrotic, so 30% will have persistent proteinuria
- IgA nephropathy is nephritic, so 30% will have persistent hematuria
15
Q
What are the two types of membranoproliferative glomerulonephritis? Which is more common? Where are the immune complex deposits in each?
A
- (MPGNs are nephritic syndromes that can also present with nephrotic syndrome)
- immune-complex deposition results in the proliferation of the mesangial cells and increased mesangial matrix, thickening the basement membrane
- type I (more common): immune complex deposits are SUB-ENDOTHELIAL
- type II: immune complex deposits are INTRA-MEMBRANOUS
- both have granular IFs (immune complexes) and a “tram-track” appearance (a double contour of the BM); type II also has “dense deposits”
16
Q
What is each type of membranoproliferative glomerulonephritis associated with?
A
- type I MPGN associated with HBV and HCV
- type II MPGN associated with C3 nephritic factor (C3NeF), an auto-antibody that STABILIZES C3 convertase, over-acting the complement system (this also results in lowered C3 serum levels)
17
Q
Where are the immune complex deposits in membranous nephropathy? What about in type I membranoproliferative glomerulonephritis? Type II? IgA nephropathy? Poststreptococcal? Diffuse proliferative?
A
- type I MPGN: sub-endothelium
- type II MPGN: intra-membranous
- membranous nephropathy: sub-epithelium
- IgA nephropathy: mesangium
- DPGN: sub-endothelium
- PSGN: sub-epithelium
18
Q
How can diabetes mellitus lead to a nephrotic syndrome? What percent of diabetics will be afflicted? What characteristic finding do we see on light microscopy?
A
- (diabetic glomerulonephropathy is a nephrotic syndrome)
- non-enzymatic glycosylation damages the basement membrane, increasing its permeability and its thickness
- NEG also affects the efferent arteriole more so than the afferent, resulting in increased glomerular pressure, resulting in hyperfiltration and eventually nephrotic syndrome (eventually, the afferent will also get hyalinized and then GFR will decrease)
- affects 30-40% of diabetics
- LM: mesangial expansion, basement membrane thickening, and Kimmelstiel-Wilson lesions (eosinophilic nodules of sclerosis)
19
Q
What is amyloidosis? What characteristic finding do we see on light microscopy?
A
- (a secondary cause of nephrotic syndrome)
- a systemic disease resulting in amyloid deposits (misfiled proteins) throughout the body (commonly affects the kidneys)
- the misfolded proteins deposit in the mesangium, eventually resulting in nephrotic syndrome
- LM: Congo red stain reveals apple-green birefringence under polarized light
20
Q
What is postsreptococcal glomerulonephritis? Which infections can it follow? How do patients classically present? Is the prognosis good or bad? What do we see on light microscopy, electron microscopy, and immunofluorescence?
A
- (PSGN is a nephritic syndrome)
- nephritic syndrome developing about 2 weeks after an infection with group A beta-hemolytic strep (strep throat OR skin infection)
- patients are classically children presenting with peripheral and facial/periorbital edema, dark urine, and hypertension
- the prognosis is great in children (resolves spontaneously), but progression into RPGN is not uncommon in adults
- LM: enlarged and hypercellular glomeruli
- EM: sub-epithelial immune complex humps
- IF: granular (IC deposits); “starry sky” appearance
21
Q
What is rapidly progressive glomerulonephritis? Why is it a medical emergency? What will we see on light microscopy, electron microscopy, and immunofluorescence?
A
- (RPGN is a nephritic syndrome)
- progresses into renal failure in a matter of weeks/months, making it a medical emergency
- LM: crescents of inflammatory debris (fibrin, complement, proteins, macrophages) in Bowman’s space
- EM: n/a
- IF: 3 possibilities; can be negative, linear (Goodpasture), or granular
22
Q
Which three disease processes can result in rapidly progressive glomerulonephritis? Which is the major one and how do patients initially present?
A
- Goodpasture syndrome: linear IF; the main one; Ab against the type IV collagen in the glomerular and alveolar basement membranes, patients present with hemoptysis and eventually hematuria and eventually liver failure via RPGN
- granulomatosis with polyangiitis (Wegener): negative IF; c-ANCA
- microscopic polyangiitis: negative IF; p-ANCA
23
Q
What is diffuse proliferative glomerulonephritis? Which patients is it most commonly seen in? What will we see on light microscopy, electron microscopy, and immunofluorescence?
A
- (DPGN is a nephritic syndrome that can present also as nephrotic)
- it his highly associated with SLE, and is the MC glomerulonephritis in SLE patients (it is also the MCC of death in these patients, as it usually develops into chronic renal failure)
- LM: “wire looping” of capillaries
- EM: SUB-ENDOTHELIAL IgG immune complexes
- IF: granular
24
Q
What is IgA nephropathy? What is it also known as? What is it the most common cause of in children? How do patients classically present? What disease it is seen with? What will we see on light microscopy, electron microscopy, and immunofluorescence?
A
- (IgA nephropathy is a nephritic syndrome)
- also known as Berger disease
- IgA immune complexes deposit in the mesangium
- this is the most common nephropathy overall and is the most common cause of chronic glomerulonephritis in children
- patients classically present with episodic hematuria, usually following a mucosal infection
- seen with Henoch-Schonlein purpura
- LM: mesangial proliferation (focal)
- EM: mesangial IgA immune complex deposits
- IF: granular
25
What is alport syndrome? What other symptoms do we see in this disorder?
- (alport syndrome is an INHERITED nephritic syndrome)
- X-linked recessive (MC) defect in type IV collagen, resulting in the thinning and splitting of the glomerular basement membrane
- patients present with glomerulonephritis, hearing loss, and ocular disturbances
26
Horseshoe Kidney
- congenital kidney disease
| - the kidneys are conjoined (usually at the lower pole)
27
What is the most common congenital renal anomaly?
- horseshoe kidney
- the inferior poles of the kidneys fuse together; the conjoined kidneys are too large to ascend normally during development, and so are usually found in the abdomen
28
What are the effects of oligohydramnios? What are these effects collectively called? When does oligohydramnios develop?
- lung hypoplasia (breathing amniotic fluid in and out is necessary for proper lung development)
- flat face, low set ears (w/o fluid, the face can push up against the uteran wall)
- defects of the extremities
- this is known as Potter's sequence/syndrome
- oligohydramnios develops with in-utero bilateral renal failure (bilateral renal agenesis, juvenile polycystic kidney disease, bilateral multicystic dysplastic kidneys)
29
What is multicystic dysplastic kidney (AKA cystic dysplasia)? Is it inherited? Is it usually bilateral or unilateral?
- a NON-inherited congenital malformation of the renal parenchyma (abnormal metanephric differentiation); occurs in utero
- characterized by the replacement of functional tissue with numerous cysts and connective tissue
- vast majority of cases are unilateral and therefore asymptomatic
30
What is ADPKD? Is it bilateral or unilateral? Which genes are involved? What is it associated with?
- autosomal dominant polycystic kidney disease (AKA adult)
- an inherited (A.D.) disorder that leads to the formation of bilateral renal cysts in young adulthood
- 85% involves PKD1 gene (chromosome 16), 15% involves PKD2 gene (chromosome 4)
- cysts are also present in liver, pancreas, and spleen; associated with berry aneurysms, MVP, diverticulosis, RCC
31
What is ARPKD? Is it bilateral or unilateral? Which genes are involved? What is it associated with?
- autosomal recessive polycystic kidney disease (AKA juvenile)
- an inherited (A.R.) disorder that leads to formation of bilateral renal cysts during development (cysts are present at birth)
- due to mutation in PKHD1 gene (chromosome 6)
- associated with congenital hepatic fibrosis, Potter syndrome if severe
32
What is medullary cystic kidney disease? Is it inherited? Is it bilateral or unilateral? How do patients present?
- an inherited (A.D.) defect resulting in bilateral cysts developing in the medullary collecting ducts (not in the cortex as well as seen in PKDs, and MCDK)
- patients present with progressive renal insufficiency with inability to concentrate urine
- poor prognosis
33
What issue with the ureters might you find in a patient with ectopic kidneys?
- (ectopic kidneys are a congenital disorder; the kidneys develop in abnormally low sites such as the pelvis)
- the ureters might be kinked as a result of the low placement of the kidneys
- this will lead to obstruction and backflow
34
What is the hallmark of AKI? What is it often accompanied with? How common is each general cause of AKI?
- AKI: acute kidney injury (acute renal failure)
- azotemia: an increase in nitrogenous waste (BUN and creatinine) products in the blood
- oliguria is also often present
- pre-renal:60-70%
- renal: 25-40%
- post-renal: 5-10%
35
What is the normal BUN:creatinine ratio of blood? Explain.
- the normal ratio is 15
- the blood usually has higher levels of BUN because it is reabsorbed from the tubule back into the plasma, while creatinine is not
36
In pre-renal AKI, what happens to the BUN:creatinine ratio? Why?
- the ratio increases (usually to be greater than 20)
- this is because as blood flow to the kidney decreases (due to the pre-renal anomaly), RAAS is activated because renal BP is low, causing an increase in Na+ reabsorption. this increase in Na+ reabsorption causes a subsequent increase in H2O reabsorption as well, and as more H2O diffuses across the lumen into the plasma, more BUN will diffuse across as well (because its concentration in the lumen will increase as H2O leaves)
37
Compare serum BUN/Cr, FENa, urine sodium, and urine osmolality in pre-renal, renal, and post-renal acute kidney injury.
- pre-renal: BUN/Cr is greater than 20 (because decreased GFR), FENa is less than 1%, urine sodium is less than 20 (because decreased renal blood flow), urine osmolality is greater than 500 (because parenchyma is still functioning)
- renal: BUN/Cr is less than 15, FENa is greater than 2%, urine sodium is greater than 40, urine osmolality is less than 350 (all because of damaged parenchyma)
- post-renal: BUN/Cr is greater than 15 (because decreased GFR from obstruction), FENa is greater than 1% (greater than 2% if severe), urine sodium is greater than 40, urine osmolality is less than 350 (prolonged obstruction damages parenchyma, eventually BUN/Cr can decrease as in renal)
38
What are the two general causes of intra-renal AKI? Which is more common? What can cause each? Which is worse?
- acute tubular necrosis (ATN): more common; due to ischemic (MCC is untreated pre-renal azotemia) or nephrotoxic injury (toxins such as aminoglycosides, radiocontrast agents, lead; crush syndrome; etc.)
- tubulo-interstitial nephritis: MCC is acute pyelonephritis; drugs (especially Methicillin)
- ischemic damage is worse because this also damages the tubular basement membrane, impairing successful regeneration
39
What is the hallmark finding in acute tubular necrosis? What complications may occur in the maintenance phase of ATN? What about in the recovery phase?
- "muddy brown" granular casts in urine; these casts are made up of the necrotic cells
- maintenace phase (oliguric phase): risk of hyperkalemia and metabolic acidosis
- recovery phase (polyuric phase): risk of hypokalemia
40
What do we see in patients with tubulo-interstitial nephritis? Which drugs are associated with this disorder?
- (TIN is largely a DRUG induced hypersensitivity reaction in the renal interstitium and tubules; resolves with recession of the drug)
- patients develop a rash, fever, and *eosinophiluria and eosinophilia*
- associated with the 4 P's: Pee (diuretics), Pain-killer (NSAIDs), Penicillins (especially methicillin), and rifamPin
- 1st 2 and ACE-inhib: triple whammy
41
What are the two pathways for the spread of a UTI? Which is more common? Which UTI is the most common?
- ascending infection (way more common)
- hematogenous infection
- CYSTITIS is the most common UTI!
42
Which UTI presents with dysuria, supra-pubic pain, and increased urgency and frequency of urination?
- cystitis
| - systemic signs of infection are usually NOT present
43
Which UTI presents with fever, chills, flank pain, WBC casts, dysuria, supra-pubic pain, and increased urgency and frequency of urination?
- pyelonephritis
| - systemic signs of infection are present here
44
What are the major risk factors for developing a UTI?
- sexual intercourse, urinary stasis, catheters
- females
- increasing age (mainly for men because of BPH)
45
What will a UTI show on urinalysis? On dipstick analysis? What does the presence of nitrites on a dipstick test indicate?
- (urine will be cloudy)
- urinalysis: greater than 10 WBCs/hpf (hpf = high powered field)
- dipstick: positive leukocyte esterase (indicates pyuria) and nitrites (bacteria convert nitrates into nitrites)
46
What pathogen is the most common cause of UTIs?
- E. coli (80% of all UTIs)
47
What are the three most common causes of sterile pyuria?
- Chlamydia trachomatis*
- Neisseria gonorrhea
- M. tuberculosis
- (these are all obligate/facultative intracellular parasites)
48
What is VUR? What does it increase the risk for?
- vesicoureteral reflux (backflow from the bladder to the kidneys)
- increases the risk for pyelonephritis
49
Type I Fimbrae
- the most important virulence factor of UPEC
- these are long polymeric organelles (pili) that are highly attracted to D-mannose residues, which are found in urethral tissue
50
What are the common causes of AKI?
- hypoperfusion, drug toxicity, and acute tubular necrosis (ATN)
51
Oliguria vs. Anuria vs. Polyuria
- oliguria: urine output less than 400 ml/day
- anuria: urine output less than 100 ml/day
- polyuria: urine output greater 2500 ml/day
52
Why are the renal tubules so sensitive to ischemia?
- because the medulla is already essentially anaerobic as a result of the peritubular capillaries off-loading most of its oxygen in to the tubular cells in the cortex and upper medulla
53
4 Types of Nephrolithiac Stones (in order from most common to least)
- calcium oxalate (MC)/calcium phosphate stones (80%)
- ammonium-magnesium-phosphate/AMP/triple stones (15%)
- uric acid stones (5%)
- cysteine stones (1%)
54
Calcium Oxalate / Calcium Phosphate Stones
- result from increased calcium in the urine (hypercalciuria)
- hyperparathyroidism, Chrons disease, diffuse bone disease, sarcoidosis, and general hypercalcemia are other causes
55
Ammonium-Magnesium-Phospate (AMP/Triple) Stones
- result from alkalinization of the urine due to urease positive organisms (urease converts urea to ammonia = alkaline urine)
- form staghorn caliculi
56
Staghorn Caliculus
- massive and impassable kidney stone that sits in the calyces/pelvis
- associated with AMP stones and cysteine stones
57
Uric Acid Stones
- result from acidic urine, hot & arid climates, decreased urine volume
- commonly seen in patients with hyperuremia (urine is acidic here) such as patients with gout and leukemia
- are NOT radiopaque on X-ray (can't be seen on X-ray)
58
T or F: kidney stones are radiopaque on X-ray.
- true and false!
- most stones are radiopaque and can be seen on X-ray as a result
- uric acid stones are radiolucent and are therefore NOT visible via X-ray
59
Cysteine Stones
- result from acidic urine via increased cysteine concentrations in the urine
- usually due to a genetic defect in renal reabsorption of amino acids
- rare, but affect children more commonly than adults
- form staghorn caliculi
60
How do we treat Calcium Oxalate / Calcium Phosphate Nephrolithiasis?
- we use a calcium sparing diuretic
61
How do we treat AMP Nephrolithiasis?
- surgically remove the impassable staghorn caliculus and eradicate the infectious pathogen
62
How do we treat Uric Acid Nephrolithiasis?
- treat with hydration and alkalinization of the urine (via potassium bicarbonate)
63
How do we treat Cysteine Nephrolithiasis?
- surgical removal of the staghorn caliculus
| - hydration & alkalinization of the urine (via potassium bicarbonate)
64
ESRF
- end-stage renal failure
| - chronic kidney disease/renal failure eventually leads to ESRF
65
What are the top three causes of Chronic Kidney Disease?
- diabetes mellitus, hypertension, and glomerular disease
66
What is the main hallmark symptom of Chronic Kidney Disease?
- uremia (excessive urea in the blood) as a result of progressively increasing azotemia
67
Symptoms of Uremia
- pericarditis, platelet dysfunction, encephalopathy (a degenerative neuro disorder), asterixis (flapping tremor), deposition of urea crystals in the skin, nausea, anorexia
- (uremia inhibits platelet activation & aggregation)
68
Other than uremia, what other symptoms are associated with Chronic Kidney Disease?
- edema, hypertension, hyperkalemia & acidosis, anemia, hypocalcemia, and renal osteodystrophy (bone damage)
69
Fanconi Syndrome
- disease of the proximal renal tubules
- inability to reabsorb glucose, amino acids, uric acid, phosphate, and bicarbonate
- dehydration (glucose), tubular acidosis (bicarb), rickets (phosphate)
70
Congenital Cystinosis
- a deformity causing the buildup of cysteine within cells, resulting in cell death
- leads to Fanconi syndrome if it occurs in the kidney
71
Three Complications of Acute Pyelonephritis
- papillary necrosis: seen in diabetics and in patients with urinary tract obstruction
- pyonephrosis: pus builds up in the renal pelvis
- perinephric abscess
72
What criteria are needed for Pyelonephritis to be considered chronic?
- the inflammation must involve the calyces and renal pelvis
73
What are the two causes of chronic pyelonephritis? Which is more common?
- reflux nephropathy (MC)
- chronic obstruction
- (both result in repeated bouts of acute pyelonephritis)
74
What is the leading cause of CKD and ESKD in children?
- congenital anomalies of the kidney and urinary tract
75
Duplex System
- each kidney and ureter gets a "twin"
| - a result from the failure to suppress 1 of the 2 active ureteric buds during development
76
In a Duplex System, which kidney's ureter is larger? Where does it insert in the bladder? Where does the smaller ureter insert?
- the upper kidney's ureter is larger (called a megaureter); it inserts in the bladder neck
- the lower kidney's ureter is thinner and inserts high up in the bladder
77
What is the most common congenital bladder outlet obstruction?
- posterior urethral valves (PUV)
- it is only seen in boys
- 40% of cases develop into ESKD
78
Branchio-Oto-Renal Syndrome
- a branching defect in the neck, ears, and kidneys
79
Explain the mechanism behind Diabetic Keto-Acidosis.
- the lack of insulin in diabetics results in the burning of fatty acids for energy, and this creates an abundance of acidic ketone bodies
80
What is the physiological hallmark of ATN?
- the inability to concentrate urine
81
Pathophysiology of Diabetic Nephropathy
- diabetic HTN --> hyperfiltration --> thickening of GBM --> nephrotic syndrome
82
What is the most significant early clinical sign of diabetic nephropathy?
- microalbuminuria
83
Why does a post-renal urinary obstruction decrease GFR?
- the back-pressure build up will increase the hydrostatic pressure in the Bowman's space
84
Hydronephrosis
- dilation of the pelvis, renal calyces, and papillae
| - a result of high pressures secondary to a urinary obstruction
