Week 2 Flashcards
1
Q
For proximal RTA, what is the general pathophysiology of what occurs?
A
- Pathophysiology: defect in proximal HCO3- reabsorption effectively lowering the HCO3- absorption threshold
2
Q
What are the possible mechanisms (4) for the pathophysiology of proximal RTA (defect in proximal HCO3- reabsorption effectively lowering the HCO3- absorption threshold)?
A
- Blocked carbonic anhydrase – blocks formation for CO2 from HCO3- not allowing HCO3- to be reabsorbed
- Blocked luminal Na-H exchanger – H+ is not secreted resulting in HCO3- to remain in the lumen
- Blocked basolateral Na-K-ATPase – cannot produce gradient that drives the Na-H pump
- Blocked basolateral Na-HCO3- cotransporter - HCO3- cannot be reabsorbed into the interstitium
3
Q
What are the labs that will be seen in proximal RTA (urinary and serum)?
A
- Urinary losses (urine stays acidic due to intact distal acidification)
- HCO3- (only if pt. is given HCO3- above the lowered threshold)
- Na+
- K+ (due to charge gradient created by HCO3-)
- Fanconi syndrome: glucosuria, phosphaturia, hyperuricosuria, aminoaciduria
- Due to decreased Na reabsorption
- Non-gap acidosis
- Serum HCO3- in mid-teen range
- Hypokalemia (if pt. given HCO3-)
4
Q
What are some conditions that can cause a proximal RTA?
A
- Etiologies
- Idiopathic
- Genetic
- Fanconi syndrome, glycogens storage disorders (Fabry’s)
- Acquired
- Carbonic anhydrase inhibitors, multiple myeloma. Amyloidosis
5
Q
What is the general pathophysiology of distal RTA?
A
Pathophysiology: impaired distal acid secretory capacity of H+ leading to decreased serum HCO3- because no “new” HCO3- is generated
6
Q
What are the three possible mechanisms of distal RTA? What are some etiologies of each and how do they each work?
A
- Possible defects
- Diminished luminal H-ATPase number or activity
- Not secreting H+ at intercalated cells
- H+-K exchanger will not reabsorb K due to excess potassium → hypokalemia
- Etiology: Sjogren’s: absent H-ATPase
- Increased luminal permeability
- Permeable increases → electrochemical gradients fail → decreased H+ secretion
- Results hypokalemia
- Etiology: Amphotericin B increases permeability
- Diminished Na+ reabsorption at principal cells
- Decreased Na+ reabsorption in principal cells → decreases H+ secretion in intercalated cells
- Results in hyperkalemia
- Diminished luminal H-ATPase number or activity
7
Q
What are the labs associated with distal RTA?
A
- Labs
- Non-gap acidosis
- Very low serum HCO3-
- Urine pH > 6
- Often associated with nephrolithiasis
- Hypercalciuria or hypocitraturia
8
Q
How is distal RTA treated?
A
- NaHCO3
- Potassium citrate
9
Q
What is the general pathophysiology of distal hyperkalemic RTA?
A
- Pathophysiology: aldosterone deficiency → lack of K excretion → hyperkalemia
10
Q
What are the general etiologies of distal hyperkalemic RTA?
A
- Etiologies
- Adrenal insufficiency
- Diabetic nephropathy
- Potassium sparing diuretics
- Congenital adrenal hyperplasia
11
Q
What are the numerical equivalents of the three RTAs?
A
Proximal RTA - Type II
Distal RTA - Type I
Distal Hyperkalemic RTA - Type IV
12
Q
Fill what RTAs for each one.
A
“1” Distal
“2” Proximal
“4” Distal hyperkalemic
13
Q
How can metabolic alkalosis be generated?
A
- Generation of metabolic alkalosis
- Etiology: Loss of H+, gain of HCO3-, aldosterone excess, hypercapnia
- Volume depletion
- Generation: Decreased ECF (activates RAAS) → decreased GFR → decreased filtered NaHCO3
- Also, due to RAAS pathway → increased NaHCO3 reabsorption → increased K+/H+ excretion (persistent hypokalemia)
- Maintenance: This process continues as long as RAAS is activated
- Generation: Decreased ECF (activates RAAS) → decreased GFR → decreased filtered NaHCO3
- Volume depletion
- Etiology: Loss of H+, gain of HCO3-, aldosterone excess, hypercapnia
14
Q
How is metabolic alkalosis maintained?
A
- Volume contraction
- Persistent hypokalemia
- In states where patients are hypokalemic, K+ is preferentially reabsorbed at the collecting duct via K+/H+ ATPase → results in H+ excretion → metabolic alkalosis
- Reduced Cl- delivery to collecting tubules
- At intercalated-alpha cells, Cl is co-secreted with H+
- At intercalated-beta cells, Cl is exchanged for HCO3- at the luminal membrane
- Decreased Cl- in the lumen, results in decreased HCO3- secretion → metabolic alkalosis
15
Q
List chloride responsive alklalosis etiologies and what it generally has to do with.
A
- Chloride responsive alkalosis – has to do with volume depletion
- GI losses: vomiting, nasogastric aspiration – H+ loss
- Renal losses
- Diuretics
- Nonabsorbable anions (e.g. carbenicillin)
- Post hypercapnia
- Recovery from lactic and ketoacidosis (overshoot)
- K+ deficiency
16
Q
List chloride resistant alklalosis etiologies and what it generally has to do with.
A
- Chloride-resistant alkalosis – has to do with mineralocorticoid excess not volume depletion
- Primary aldosteronism
- Cushing syndrome (pituitary, adrenal adenoma, ectopic)
- Renal artery stenosis
- CKD + alkali
- Adrenal enzyme defects
- Apparent mineralocorticoid excess
- Liddle, Bartter, Gitelman syndromes
17
Q
What is the importance of anion gap and differentiate between gap acidosis and non-anion gap acidosis.
A
- Importance: anion gap is used to differentiate production of organic anions versus acidosis that is not associated with organic anion production
- Anion gap acidosis: adding organic acids reduces HCO3- and increases the anion gap
- Non-anion gap acidosis: adding non-organic acids (i.e. HCl) reduces the HCO3- and increases the Cl with no effect on the anion gap
18
Q
How is the anion gap calculated? What is the exact equation and the normal? What if the patient is hypoalbuminemic (less than 4)?
A
- Anion gap: the difference between positive and negative ions
- An increase in this often means extra anions have been added
- Equations
- Anion Gap (AG) = Measured cations – measured anions
- In a normal patient
- AG = Na – (Cl + HCO3-)
- Normal AG is 12
- When a patient is hypoalbunemic
- AG = (Na-(Cl+ HCO3-)) + (2.5 x (4-albumin))
19
Q
What can cause an elevated anion gap acidosis?
A
- Elevated anion gap acidosis
- Increased production of organic acids like: ketones and lactic acid
- Exogenous acids: like: methanol
- Decreased excretion of phosphates and sulfates
20
Q
What can cause a decreased anion gap?
A
- Decreased anion gap
- Due to hypoalbuminemia
21
Q
How can you have a normal anion gap acidosis?
A
- Normal anion gap acidosis
- Due to loss of bicarbonate
- Occurs in diarrhea, proximal RTA, and ureteral diversion
- Decreased renal acid excretion
- Distal RTA
- Distal hyperkalemic RTA
- Chronic kidney disease (CKD)
- Severe CKD will lead to elevated anion gap acidosis
- Due to loss of bicarbonate
22
Q
What is albumin’s affect on acid-base processes?
A
- Albumin is a protein that carries negative charges → when it decreases in the body, H+ cannot bind to the albumin → acidemia
For this reason, you must correct for it using the equation above
23
Q
What are the 4 steps to elucidate acid-base disorders?
A
- Step 1: Check pH to see if acidotic or alkalotic.
- Step 2: Is it metabolic or respiratory acidosis?
- 2a: Is it gap or non-anion gap acidosis?
- Step 3: Is the compensation appropriate?
- Use equations and shit
- Step 4: For anion gap metabolic acidoses, is there another underlying disorder?
24
Q
What equations do you use to check for compensation for a patient with respiratory alkalosisand what are you looking for?
A
- Respiratory alkalosis
- If HCO3- falls more than expected, you also have a metabolic acidosis
- If HCO3- falls less than expected, you also have a metabolic alkalosis
25
What equations do you use to check for compensation for a patient with respiratory acidosis and what are you looking for?
* Respiratory acidosis
* If HCO3- rises more than expected, you also have a metabolic alkalosis
* If HCO3- rises less than expected, you also have a metabolic acidosis
26
What equations do you use to check for compensation for a patient with metabolic alkalosis and what are you looking for?
* Metabolic alkalosis:
* PCO2 = 40 + 0.7 (HCO3- - 24) +/- 2
* If PCO2 higher than expected, you also have a respiratory acidosis
* If PCO2 is lower than expected, you also have a respiratory alkalosis
27
What equations do you use to check for compensation for a patient with metabolic acidosis and what are you looking for?
* Metabolic acidosis:
* PCO2 = 1.5 (HCO3- + 8) +/- 2
* If PCO2 higher than expected, you also have a respiratory acidosis
* If PCO2 is lower than expected, you also have a respiratory alkalosis
28
How do you determine metabolic alkalosis/acidosis based on bicarb and the anion gap?
* In an elevated anion gap, we would expect the elevation of the anion gap to be a 1:1 ratio with the decline in HCO3-
* If the HCO3- fell less than the amount of anion gap elevation, you also have a metabolic alkalosis
* If the HCO3- fell more than the amount of anion gap elevation, you also have a metabolic acidosis
29
What are the 5 main characteristics of nephrotic syndrome?
**Neprhr**_o_**tic Syndrome:**
* Glomerular disorder characterized by pr**_o_**teinuria \> 3.5 gm/day resulting in:
* Hypoalbuminemia – pitting edema
* Hypogammaglobulinemia – increased risk of infection
* Hypercoagulable state – due to loss of antithrombin III
* Hyperlipidemia and hypercholesterolemia – fatty casts in urine
30
What are the 6 main characteristics of nephritic syndrome?
**Nephr**_i_**tic Syndrome:**
* Glomerular disorders characterized by glomerular **_i_**nflammation and bleeding:
* Limited proteinuria (\< 3.5 gm/day)
* Oliguria and azotemia
* Salt retention with periorbital edema and hypertension
* RBC casts and dysmorphic RBCs in urine
* Biopsy reveals inflamed, hypercellular glomeruli (influx of inflammatory cells)
31
Recognize primary glomerular diseases.
* Acute diffuse proliferative glomerulonephritis (GN), Post-infectious (Strep or non-Strep), Crescentic (rapidly progressive) glomerulonephritis, Membranous nephropathy, Minimal change disease, Focal segmental glomerulosclerosis, Membranoproliferative glomerulonephritis, IgA nephropathy, Chronic glomerulonephritis
32
Name 4 systemic diseases that can cause glomerular disease
* Lupus, Diabetes mellitus, Amyoidosis, Goodpasture syndrome
33
What are the 3 mechanisms of glomerular injury?
Antibody mediated injury, cell mediated injury (activated macrophages and T cells), activation of alternative complement pathway (C3 nephritic factor)
34
What are the three mechanisms of antibody mediated glomerular injury?
How can it be diagnosed?
* Antibody-mediated injury
* Circulating immune complexes deposited in glomeruli
* 3 mechanisms:
* Circulating: antibody/antigen circulate and plant together
* Fixed: antigen intrinsic to GBM, antibody attaches
* Planted: antigen plants, antibody attaches
* Diagnosis:
* The right image shows a linear scan in which the antibody is present everywhere (i.e. on the basement membrane) → seen in circulating and planted
* The left image shows a granular scan in which the antibody is present in certain areas (i.e. foot processes) → seen in fixed
35
What is nephrotic syndrome characterized by?
* Characterized by the following:
* Abnormal GBM
* Leakage of plasma proteins and lipoporteins into urine → compensatory hyperlipidemia
* Depletion of serum albumin leading to generalized edema
36
What do you see in the following for nephrotic syndrome?
* complications (4 main)
* Complications
* Sodium and water retention:
* Due to reduction in osmotic pressure gradient as proteins are filtered into kidney
* Hyperlipidemia
* Increased hepatic synthesis of lipoproteins because they are being excreted
* Infection
* Increased excretion of immunoglobulins
* Hypercoagulability/pro-thrombotic state
* Increased excretion of anti-coagulant factors and antiplasmins
37
What do you see in the following for nephrotic syndrome?
* urinalysis
* epidemiology
* Urinalysis
* Fatty cast and oval fat body
* Maltese cross appearance under polarized light
* Epidemiology
* In kids, NS is typically primary NS
* Minimal change disease is the most common cause
* In adults, NS is both primary and secondary NS
* Membranous nephropathy and Focal segmental glomerulosclerosis (FSGS) is most common primary glomarular diseases
*
38
What cast is this?
Fatty
39
For Minimal change disease:
* Characteristics/Pathophys
* Epidemiology
* Labs
* Characteristics:
* Foot processes become flat and disappear → disrupted filtering
* Process of disappearing is cytokine mediated
* Epidemiology:
* Children ages 2-6 y/o – most common cause of NS
* Labs:
* Urinalysis: albumin present, lack of blood, oval fat bodies present, protein present
40
For minimal change disease:
* Imaging/Histology
* Clinical features seen
* Treatment
* Imaging/Histology:
* Normal H&E Stain
* On electron microscopy, effacement (flattening) of podocytes can be seen
* Clinical features
* Can be triggered by recent infection/immunization
* In adults, may be associated with Hodgkins or NSAID use
* Despite massive albuminuria, renal function remains good w/o HTN and hematuria
* Treatment: Corticosterioids → rapid improvement in children
41
What is this disease?
Minimal change disease
42
For focal segmental glomerulosclerosis:
* Imaging/histology
* Treatment
* Imaging/histology
* Histology
* Collapse of portion of tuft → not many open capillary loops → sclerosis (left arrow)
* Accumulation of eosinophilic material → form nodular pink regions → hyalinosis (right arrow)
* Immunofluorescence
* Non-specific trapping of IgM and C3 in sclerotic segments
* Electron microscopy
* Effacement of foot processes
* Treatment
* May not response to steroid therapy
* Since the disease decreases renal function/mass, increased workload at glomerulus causes damage
* Therefore, RAAS drugs can be used to decrease workload
43
For focal segmental glomerulosclerosis:
* Characteristics
* Epidemiology
* Labs
* Clinical Features
* Characteristics
* Hyalinosis and sclerosis
* Primary/idiopathic: most likely cytokine involvement
* Secondary: HIV, heroin abuse, obesity, HTN
* Epidemiology
* Children and adolescents
* Labs
* Can have few RBCs in urine (no RBC casts), proteinuria
* Clinical features
* Higher incidence of hematuria, reduced GFR, and HTN
* Worse prognosis than minimal change disease
44
What disease is this?
FSGS
45
For membranous nephropathy:
* imaging/histology
* Clinical features
* Treatment
* Imaging/histology
* Electron microscopy
* Spikes and domes (deposits) of new GBM material → thickening of GBM
* Histology
* Thickened basement membrane
* Immunofluoroscence: granular (IgG deposits)
* Clinical features
* Primary: idiopathic
* Secondary: infection, lupus, diabetes, inorganic salts, drugs (NSAIDS), malignancies
* Treatment
* Associated with spontaneous remission
* However, if gone untreated, 1/3 patients develop ESRD
46
For membranous nephropathy:
* Characteristics/pathophys
* Epidemiology
* Labs
* Characteristics
* Phospholipase A2 receptor (PLA2R) highly expressed on podocytes → deposit at subepithelial border → causes thickening of the GBM
* This is planted antigen-circulating antibody mediated pathophysiology
* Epidemiology
* Adults
* Labs
* Albuminuria, no RBCs in urine, proteinuria
47
For **Membranoproliferative glomerulonephritis**:
* Imaging/Histology:
* Clinical features
* Imaging/histology
* Histology:
* H&E stain: Large subendothelial deposits seen as thick pink wire loops (arrows)
* Silver stain: tram-track appearance of GBM around each capillaries
* Electron microscopy
* Deposits at the subendothelial area
* Immunofluorescence
* Granular: Circulating immune complexes that deposit in subendothlium
* Clinical features
* Systemic diseases with MPGN pattern: Lupus, Hepatitis B and C
* Some have only hematuria or only proteinuria, but some present with a combined nephrotic-nephritic picture
48
For **Membranoproliferative glomerulonephritis**:
* Characteristics/pathophys
* Epidemiology
* Labs
* Characteristics
* Forms:
* Antigen-antibody mediated → activation of classic complement pathway
* See immunoglobulins and complement proteins on immunofluorescence
* Complement mediated → C3NF causes persistent activation of alternate complement pathway
* Only see complement protein on immunofluorescence
* A subtype: dense deposit disease, notable for ribbon-like transformation of GBM
* Epidemiology
* Small percentages of cases of NS in children and adults
* Labs
* Urine: proteinuria
* Elevated creatinine
* Decreasing serum C3 and C3NF
49
What disease?
* **Membranous nephropathy**
50
What disease is this?
* **Membranoproliferative glomerulonephritis**
51
What disease is this?
Membranoproliferative glomerulonephritis
52
For diabetic glomerulopathy:
* Pathophys
* Clinical
* Risk factors
* Histology
* Most common cause of ESRD
* Pathophysiology: glycosylation of circulating and intrarenal proteins
* Clinical: HTN and renal hyperfiltration
* Risk Factors: FHx, Diabetes, HTN, tobacco use
* Histology: GBM thickening, Kimmelstiel-Wilson nodules (indicated by \*)
53
What disease:
Glomerular nephropathy
54
For renal amyloidosis:
* What is the pathophys
* Histology
* Pathophysiology: abnormal folding of proteins → deposits in renal tissues as fibrils
* Histology:
* Apple green birefringence on Congo-Red Staining
* Electron microscopy: randomly oriented fibrils
55
Acute proliferative glomerulonephritis
labs, clinical, imaging/histology,
* Labs
* Hematuria (rare RBC casts), proteinuria, azotemia (elevated BUN)
* Clinical
* Oliguria, mild to moderate HTN
* Imaging/Histology
* Histology
* Glomerular inflammation
* Proliferation of endothelial/mesothelial cells à causes compression of capillary loops
* Global proliferation (aka involves all lobules of the glomerulus)
* Immunofluorescence
* Granular IgG and C3 deposits
56
Acute post-infectious glomerulonephritis
clinical, epidemology, imaging/histology, treatment
* Clinical
* Occurs 1-2 weeks after strep throat infection
* Epidemiology
* Common in children ages 6-10 y/o
* Imaging/Histology
* Electron microscopy: Very large (“like fucking huge” – Arsh) subepithelial deposits
* Treatment
* 95% of children recover spontaneously
* Conservative management otherwise
57
IgA nephropathy
clinical, epidemiology
* Clinical
* Very common cause of gross and microscopic hematuria
* Hematuria may occur within a day or two of respiratory, GI, or urinary infection
* Can be a result of: Henoch-Schönlein purpura (HSP), a systemic disease characterized by a purpuric skin rash, arthritis, abdominal pain and nephritis.
* Epidemiology
* Most common in adolescent or young adult males
58
IgA nephropathy
lab, imaging/histology
* Lab
* Proteinuria, RBC, No cellular casts, minor proteinuria
* Normal creatinine and BUN
* Histology/Imaging
* H&E stain: Mesangial cell proliferation
* Immunofluorescence/ Electron microscopy
* IgA in mesangial stalks
59
Rapidly progressive/crescentic Glomerulonephritis
histology/imaging, labs, clinical
* Histology/Imaging:
* Will see crescent formation of cells à
* Labs:
* Urine: Albuminuria, hematoruira, numerous RBCs/WBCs, granular casts, renal tubular epithelial cells, RBC casts noted
* Anti-GBM positive
* Clinical
* Rapid progressive decline in renal function
* Poor prognosis
60
Rapidly progressive/crescentic Glomerulonephritis
describe type 1, 2, 3
talk about immunoflourence
* Type I (anti-GBM disease, in situ IC formation)
* Associated with Good Pasture syndrome
* Can cause pulmonary hemorrhage due to antibodies to renal and alveolar basement membranes
* Immunofluorescence: Anti-GBM linear
* Type II (deposition of circulating ICs)
* Associated with Post-infectious GN and lupus
* Immunofluorescence: immune complex - granular
* Type III (pauci immune disease)
* Most are ANCA associated: granulomatosis with polyangitis
* Immunofluorescence: NONE.
61
Chronic glomerulonephritis
END RESULT OF ALL PROGRESSIVE GLOMERULAR DISEASE
Associated with scarring and sclerosis and HTN
62
Rapidly progressive/crescentic Glomerulonephritis
63
IgA nephropathy
64
Acute proliferative glomerulonephritis
65
Acute post-infectious glomerulonephritis
66
Define the three components of routine urinalysis
gross features
dipstick analysis
Microscopic examination of urine sediment
67
Name six characterisitics that describe the gross features of urine
* Turbidity
* Cloudiness can be caused by excessive cellular material and protein
* Color
* Normal: pale yellow
* Abnormal: red/brown (hematuria, drugs, foods)
* Volume
* Anuria \< 100 ml/day, Polyuria \> 2.5 L/day
* pH
* Normal range: 4.5 – 6.5
* Specific Gravity
* Measurement of urine density compared against density of water
* Reflects ability of kidney to concentrate/dilute urine
* Normal: 1.001 -1.040
* Osmolality
68
Dipstick analysis
what protien is it sensitive for?
* Simple and rapid test used to determine levels of various compound like protein, leukocytes, ketone, and glucose in urine
* Only sensitive for albumin
69
What are sources of WBC and RBC in urine
* RBCs
* Hematuria
* Glomerular sources
* Glomerular diseases resulting in RBC casts and possible proteinuria
* Extra-glomerular sources
* Kidney stones/bladder stones
* Infection/tumor/injury
* WBCs
* Pyuria
* Usually neutrophils and indicates infection
70
describe and identify each of the casts
* Hyaline cast → not indicative of disease
* Solidified Tamm-Horsfall mucoprotein
* Fatty cast (maltese cross) → nephrotic syndrome
top to bottom
71
describe and identify each of the casts
* Granular or waxy/broad cast → advanced renal failure
* Cellular cast
* RBC casts → pathognomonic for glomerulonephritis, vasculitis
* WBC casts → pyelonephritis, tubulointerstitial nephritis
* Epithelial cell cast → acute tubular necrosis
* aka Muddy Brown casts
top to bottom
72
where are casts formed
Formed in the DCT and collecting duct
73
Describe how and why different methods are used to assess proteinuria.
* Dipstick analysis is not sensitive to all protein types
* Other tests like Sulfosalicylic acid are used to detect all proteins
74
Types of proteinuria
* ![]()Glomerular proteinuria
* Increased filtration of protein that can be detected by dipstick
* Tubular proteinuria
* Abnormal excretion of smaller protein due to dysfunctional reabsorption at PCT (cannot be diagnosed by dipstick)
* Overflow proteinuria
* Increased production of low MW proteins which are normally filtered
* Saturates reabsorption mechanisms at the PCT leading to excretion of the excess
* Some proteins like Ig light chains, multiple myeloma, myoglobin, free hemoglobin
75
Microalbuminuria
* Normal albumin excretion (\<20 mg/day) below dipstick detection limit
* Early clinical sign of some renal diseases
76
Interpret urine protein-to-creatinine ratio.
* Large changes in GFR “early” in renal disease cause small changes in BUN or creatinine
* Small changes in GFR late in renal disease cause big changes in BUN or serum creatinine
77
Compare and contrast different methods for assessing GFR and renal function.
* Creatinine, BUN
* Serum Cystatin C
* Low MW protein that is freely filtered
* Not reabsorbed nor secreted but metabolized by tubule
78
List functions of the tubulointerstitium. (4)
* Main source of EPO production in the kidney
* Contains immune cells: macrophages, lymphocytes
* Produces hormones, such as renin and adenosine
* Contains fibroblasts that produce collagen
79
acute pyelonephritis
descritpion, epidemiology, pe/symptoms,
* Description: inflammation of the tubular interstitium due to bacterial infection
* Epidemiology: young, sexually active women; often secondary to UTI
* Physical Exam/Symptoms: CVA tenderness, fever, tachycardia, chills, vomiting
80
acute pyelonephritis
labs, histology, diagnosis, tx
* Labs: urine analysis shows +nitrite, +leukocyte, +blood, and +culture
* Histology: scattered neutrophils in interstitium (rare to see this b/c not biopsied)
* Diagnosis: Based on physical exam and symptoms; do NOT perform biopsy
* Treatment: 10-14 days of ABX (i.e. Ciprofloxacin, bactrim)
81
Chronic pyelonephritis
causes
* Multiple bouts of acute pyelonephritis à scarring
* Vesicoureteral reflux (Rahul)
82
acute interstitial nephritis
descritpion, etiology, pe/symptoms
* Description: acute renal failure resulting from immune-mediated tubulointersitital injury, often initiated by medications, and other causes (Sjogren’s and sarcoidosis)
* Etiology
* Drugs: penicillin, sulfa drugs
* Physical Exam/Symptoms: classical triad of rash, peripheral eosinophilia, and renal failure
83
acute interstitial nephritis
labs, epidemiology, histology, diagnosis, tx
* Labs:
* Urine: positive WBC (sterile pyuria), negative culture, eosinophils
* Epidemiology
* Commonly seen in patients
* Histology:
* Eosinophilia with interstitial edema
* Diagnosis
* Biopsy
* Treatment
* Stop drugs or start patient on high-dose steroids
84
Distinguish the pathology of acute interstitial nephritis and NSAID induced interstitial nephritis
* NSAID-related interstitial nephritis is a subset of acute interstitial nephritis
* Histology
* Will see epithelioid granulomas rather than diffuse eosinophils
85
Analgesic Nephropathy
description/ pathology
* Description: chronic kidney disease caused by excessive ingestion of certain analgesics
* Have to ingest something like 2 FUCKING KGs of Aspirin over three years
* Pathology: shrinkage of the papilla (location where collecting ducts convene)
86
Transplant Rejection
description, histology, labs
* Description: renal failure due to a graft vs host reaction
* Types: T-cell mediated and antibody mediated
* Labs: creatinine increases and proteinuria occurs
* Histology: interstitial inflammation and tubilitis
* If very severe, you may get vasculitis
87
tumor lysis syndrome
pathogenisis, types, complications, diagnosis/labs
* Pathogenesis: tumor lyses à release of uric acid, potassium, and phosphorus
* Types:
* Acute: due to Tumor Lysis Syndrome
* Chronic: due to gout
* Complications/Histology
* Uric acids deposits and damages tubules à interstitial inflammation and fibrosis à uric acid nephropathy
* Diagnosis/Labs
* Cairo-Bishop Criteria
* Uric Acid (\>8 mg/dL), Potassium (\>6 mEq/L), Phosphorus (\>4.5 mg/dL), Calcium (\<7 mg/dL)
88
tumor lysis syndrome
prevention, tx
* Prevention
* IV hydration: prevents uric acid deposition in tubules
* Allopurinol: xanthine oxidase inhibitor
* Rasburicase (synthetic urate oxidase):
* urate oxidase – converts uric acid to allantonin for urinary excretion
* Treatment
* Management of electrolyte disturbances
* Severe may require dialysis
* Only treat hypocalcemia if symptomatic
89
acute pyelonephritis.
90
acute interstitial nephritis
91
NSAID induced interstitial nephritis
92
Analgesic Nephropathy
93
uric acid nephropathy secondary to tumor lysis syndrome
94
what type of tumor is Renal Cell Carcinoma (RCC)
An immunogenic tumor – which means it activates the immune system
95
explain RCC staging and treatment for each
* Stage I
* Small (\<7 cm) and restricted to the kidney
* Therapy: nephrectomy and active surveillance
* Stage II
* Large (\>7 cm) but still restricted to kidney
* Therapy: nephrectomy, active surveillance, +/- sunitinib
* Stage III
* Big or small, escape from local environment, but not Gerota’s fascia (fascia around the kidneys); +/- nodal involvement
* Therapy: nephrectomy, active surveillance, +/- sunitinib
* Stage IV
* Invasion of tissues beyond Gerota’s fascia; +/- nodes; +/- metastasis
* Therapy: nephrectomy + resection of metastases, active surveillance,
* Clear cell – nivolumab and cabozantinib (preferred)
* Non-Clear cells – sunitinib (preferred)
96
What is Kidney resection
Partial or radical can be accompanied with radiation or not
97
Explain the use of NIBs
and examples
* NIBS
* Block intracellular kinase receptors (VEGFR, PDGFR)
* Examples: sunitinib, sorafenib
98
Explain the use of MABs
and examples
* MABS
* Blocks extracellular ligands (VEGF, PDGF)
* Examples: Bevacizumab
99
Explain the use of mTOR inhibitors
and examples
* Block mTOR from stimulating HIF
* Examples: temsirolimus, everolimus
* \*\*\* Different from tacrolimus (cyclosporine) and sirolimus (rapamycin)
* Sirolimus – comes from the precursor drug temsirolimus
* Also used in transplants
* Tacrolimus – calcineurin inhibitor
* Used in transplants
100
Explain the use of immune inhibitors (2 types)
and examples
* PD-1 Inhibitor
* PD-1 normally causes apoptosis of the T-cell
* Example: nivolumab
* CTLA-4 Inhibitor
* CTLA-4 normally downregulates immune responses of T-cells
* Example: ipilimumab
101
Explain the use of IL-2 and IFN-alpah
* IL-2
* Activates lymphoid cells to attack tumor cell
* SE: fluid retention, inflammation, hypotension, arrhythmias
* Interferon-alpha
* Anti-proliferative effects on tumor cells
102
explaijn the use of chemo in RCC
Chemotherapy
RCC is generally resistant to chemo because of a high expression of P-glycoprotein MDR pumps – pumps chemo drugs out of tumor cells
