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330 Cards in this Set
- Front
- Back
- 3rd side (hint)
Know healthy, under- and overweight, and obesity BMI definitions.
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Underweight BMI: <18.5
Healthy BMI: 18.5-24.9 Overweight BMI: >= 25 Obesity BMI: >=30 Extreme Obesity >=40 |
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Leptin
source, genetics, 2 fnx, loss of fnx mutation |
Source: adipose tissue
ob gene = leptin db [diabetes] gene = leptin receptor [JAK-STAT] Fnx: high [leptin] 1) suppresses neuropeptide Y --> inhibits anabolic circuits 2) stimulates leptin-melanocortin circuit POMC/CART --> stimulates catabolic pathways, important in thermogenesis Loss of fnx mutation --> early onset severe obesity [3] pro-inflammatory cytokine, regulates hepatopoiesis & lymphopoiesis [4] involved in puberty |
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ob gene
product, fnx |
gene for leptin
1) suppresses neuropeptide Y --> inhibits anabolic circuits 2) stimulates leptin-melanocortin circuit POMC/CART --> stimulates catabolic pathways, important in thermogenesis |
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db gene
fnx |
JAK-STAT leptin receptor
1) suppresses neuropeptide Y --> inhibits anabolic circuits 2) stimulates leptin-melanocortin circuit POMC/CART --> stimulates catabolic pathways, important in thermogenesis |
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MC4R mutation
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important receptor in leptin-melanocortin circuit POMC/CART, normally stimulates catabolic pathways, important in thermogenesis
MC4R mutation in Leptin-POMC pathway --> no satiety signal --> 5% of massive obesity |
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Adiponectin
Source, Fnx |
adipose tissue, produced more in lean individuals
Fnx 1° Directs FA to muscle for oxidation 2° Acts on Liver to inhibit metabolic syndrome: decreases FA influx in liver, decreases TAG content, decreases Gluocse prodxn |
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Ghrelin
Source, Fnx |
THE ONLY GUT HORMONE THAT INCREASES FOOD INTAKE
Source: arcuate nucleus of hypothalamus + empty stomach Fnx: binds growth hormone secretogoge receptor obese individuals not able to fully suppress ghrelin |
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Gut homrone which increases food intake
Source, Fnx |
Ghrelin is the only one
Source: arcuate nucleus of hypothalamus + empty stomach Fnx: binds growth hormone secretogoge receptor obese individuals not able to fully suppress ghrelin |
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Peptide YY
Source, Fnx, Loss of Fnx |
Fnx: ↑ after food intake --> stims POMC/CART neurons in hypothalamus -->satiety signal;
Lost in Prader Willi syndrome --> hyperphagia & obesity |
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Prader Willi syndrome
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Loss of Fnx in Peptide YY
Normally ↑ after food intake --> stims POMC/CART neurons in hypothalamus -->satiety signal; |
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Leptin: melanocortin circuit: catabolic pathway
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POMC/CART [Pro-opiomelanocortin/Cocaine-Amphetamine regulated transcipts] neurons: within hypoathalamic arcuate nucleus. Stimulated by Leptin, Peptide YY to produce alpha Melanocyte-stimulating hormone. aMSH + Melanocortin Receptor 4 MC4R on endocrine/ANS cells --> TRH, CRH --> increases SNS tone, energey expenditure decreases food intake
MC4R mutation in Leptin-POMC pathway --> no satiety signal --> 5% of massive obesity |
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NPY/AgRP pathway
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[Neuropeptide Y, Agouti-related peptide]
ypothalamus stimulated by ghrellin, inhibited by Leptin and Peptide YY; Produce Neuropeptide Y which increases appetite and decreases energy utilization |
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3 consequences of hyperinsulinemia
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→ ↓ [adiponectin] → ↑ [insulin] (+feedback)
→ ↓ IGFBP-1 & -2, (binding proteins) → ↑ free IGF-1 → aging → both IGF-1 & Insulin ↑ cell proliferation & ↓ apoptosis --> CA → sex hormonal changes: ↑ peripheral aromatas activity, estrogen bioavailability, ovarian androgen, ↓ SHBG prodxn --> endometrial & breast CA |
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List all cardiovascular health risks of obesity.
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Coronary Artery Disease ( htn & hyperlipidemia)
CHF: (htn) major cause of death in obese pts Thrombi: htn + inactivity + visceral adipose tissue produces TNFa, IL1, IL6 --> ↑ C reactive protein, ↑ prdxn of PAI plasminogen activator inhibitor + ↑ platelet activation |
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5 features of metabolic syndrome.
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Central Obesity
Insuline Resistance HTN Dyslipidemia: high cholesterol, high TAGs, low HDL +- increases LDL Impaired Glucose Tolerance |
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What is the pathogenesis of hypertension and of thromboembolism related to obesity?
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excess insulin →
retention of sodium --> expansion of blood volume ↑ NE ↑ Smm proliferation w/in arterioles ↓ artery distendability visceral adipose tissue produces TNFa, IL1, IL6 → ↑ C reactive protein, ↑ prdxn of PAI plasminogen activator inhibitor + ↑ platelet activation |
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What are the gastrointestinal risks of obesity?
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Gallstones--> cholecystitis, pancreatitis, gallbladder CA
unfavorable lecithin:cholesterol ratio --> precipitation into gallstones Hernias: Umbilical, abdominal incisional, inguinal, hiatal GERD --> Barret's --> Adenocarcinoma Hemorrhoids Non-EtOH Fatty Liver Disease; Steatosis --> Steatohepatitis --> Cirrhosis |
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What pulmonary and sleep disorders are related to obesity? Describe the sleep disorders.
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Asthma 2* to inflammatory cytokines of abdominal fat
Restrictive Lung Disease --> Pickwickian hypoventilation syndrome Sleep Apnea 2* to neck circumference >=17" M, >=16" F Additl Drowsinesss due to meatbolic change |
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Pickwickian Syndrome
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extreme fat restricts lung expansion --> hypoventilation --> twitching, cyanosis, periodic breathing, 2* polycythemia, Right Heart failure
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Obstructive Sleep Apnea:
best predictor & complications |
50% 2* to neck circumference >=17" M, >=16" F
predisposes to htn, sudden death, postop edema, ARDS |
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What are the musculoskeletal, including Osteopathic complications of obesity?
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Gouty Arthritis
+ Osteoarthritis 2* to weightbearing Knees in women Hips in men Feet & Ankles in both Flattened Thoracic & Lumbosacral curves Sacral extension, L5 anterior to S1 --> bilateral intermittend lumbar radiculopathy --> lumbostacral instability --> pain, weakness in legs --> constant low back pain --> atlanto occiptal muscle contracture headaches |
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Female reproductive risks of obesity
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Menstrual irregularity and amenorrhea
ovulatory infertility polycystic ovarian syndrome increased maternal morbidity -gestation htn, diabetes -increased C section rate -increases risk of pre-eclampsia Increased fetal morbidity -congenital malformations esp NT and heart -macrosomia 2* to daibetes |
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Male reproductive risks of obesity
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Impotence & Infertility
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Renal Effects of Obesity
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DM is the most common cause of renal failure in adults
Htn: 2nd most cause of renail failure in adults Renal insuffieincy not 2* to htn/DM |
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What are psychosocial affects of obesity?
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Depression, worse w/ childhood onset
Bing eating disorder Poor body image, esp white females -- tendency to OVERestimate body size correlates with adolescent obesity Fale expectations for weight loss Social stigmatization for "poor self control" Discrimination: employment, college application, rental, dating |
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What cancers are strongly associated with Obesity? Describe the pathogenesis of obesity-related cancer risk.
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Insulin stimulates growth & IGF-1 release
IGF-1 is mitogenic, anti-apoptotic estrogen syntehd in fat from androgens androgen syned in ovaries, adrenals ↓ sex hormone binding protein prodxn ↓ adiponectin (licenses hyperinsulinemia) Distal Colon Endometrial Prostate Esophageal adenocarcinoma (2* to GERD) Gallbladder (2* to stones) Renal Cell Carcinoma (esp women) |
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What is the overall impact of obesity on mortality
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Increase of all cause mortality 50%+ at BMI >30
13 year reduction in life expectancy |
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What skin lesions are more frequent in obesepatients?
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psoriasis
Funcal infections of skin folds esp taenia cruris (groin-perineum of obese men) panniculitis: bacteiral infection in subcu abdominal fat fourneir's gangrene: necrotizing fasciitis of scrotum |
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What are the diagnostic criteria for diabetes Mellitus?
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Fasting
Normal: <=100 mg/dL Impaired Tolerance 100-125 Diabetic: >126 mg/dL Random Normal: <=140 Impaired 140-199 Random: >=200 mg/dL Hemoglobin A1C Normal: 5% DM: >=6.5 |
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How does HbA1c correlate to average fasting glucose
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Start with HbA1c of 5 ~= average blood sugar at 100
add 35 glucose/1% A1c |
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What is HbA1c
When is it not usefule? |
Glycohemoglobin, glycosylated/glycated hemoglobin
monitoring lab test for average glucose levels over previous few months decreased in sickle cell anemia (HbF) & thalassemia (decreased HbA1 |
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List all causes of diabetes mellitus
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Type 1: Beta Cell Destruction
Type 2: IR w/ relative insluin deficiency Genetic defects of Beta cell fnx: MODY & Mito dysfnx ---MODY = Maturity Onset Diabetes of the Young genes DM 2* to --Pancreatic damage: chronic pancreatitis, CF, pancreatectomy, heomchromatosis --Endocrinopathies: Cushings --Infx : Coxsackie B, CMV --Drugs: glucocorticoids, protase inhibitors, thiazides, beta adrenergics |
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Describe the pathogenesis of type I diabetes mellitus.
What genes are involved |
The fundamental abnormality is a failure in T cell regulation
Insidious autoimmune process presents abruptly after 90% destroyed autoantibodies found in serum, actual damage done by CTL's Genetic susceptibility: 70% twin-corcordance & 6% of 1st degree relatives 20 genes --insulin polymorphism --95% have HLA-DR3, DR4 or both; Class 2 MHC Chrom 6; [DQ8 strongly assoc as well] --CTLA4; PTPN-22 KO's → ↓ T cell inhibition --CD25 ie IL2R KO → ↓ T reg population Coxsackie B, M, M, R, CMV & EBV Hygeine hypothesis |
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What are clinical features of insulin resistance?
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Acanthosis nigricans of skin
Polyps of the skin polycistic ovary syndrome, anovulation, hirsutism high BP ↑ visceral fat in vast majority of IR & majority of BMI>50 have IR |
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Describe the pathogenesis of type II diabetes mellitus.
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Multifactorial: Genetic + Environment
twin concordance > than Type 1(70%), 40+ loci, most strongly beta cell fnx/insulin secretion, NO HLA's Altered insulin signalling pathway --> IR --> postprandial hyperglycemia ↑ visceral fat in vast majority of IR & majority of BMI>50 have IR NEFA's: non-esterified fatty acids; build up and ↓ responsiveness to insulin → , loss of inhibition of hepatic Gng Prohyperglycemia adipokines retinol binding protein 4 RBP4 & resistin Lack of antihyperglycemic adipokines: leptin, adiponectin which normally enhance hepatic & skm AMP-activated protein kinase AMPK to promote FA oxidation. Targetted pathway of metformin Proinflammatory cytokines: TNF, IL6 & M∅ chemoattractant protein 1; create cellular "stress" activates multiple signalling cacades to antagonize insulin Peroxisome proliferator- adtivated receptor gamma PPARG: receptor/transcription factor --> adipocyte differentation, deposition of NEFA in adipose (not liver Muscle) + adiponectin secretion; KO = monogenetic diabetes; stimulated by thiazolidinediones Beta cell dysfnx: genetic predisposition, lipotoxicity from increased NEFA's, accumulation of toxic amyloid in iselts |
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NEFA's
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non-esterified fatty acids; build up in obesity and ↓ responsiveness to insulin → , loss of inhibition of hepatic Gng
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RBP4
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retinol binding protien 4
prohyperglycemic adipokine produced during IR |
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resistin
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prohyperglycemic adipokine produced during IR
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AMPK
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AMP activated Kinase.
stimulated in liver & SkM by adiponectin and leptin → promotes FA oxidiziation leptin, adiponectin signals lost in IR targetted pathway of metformin |
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cellular "stress" of IR
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TNFa, IL1 & M∅ chemoattractant protein 1 induce cellular stress antagonizes insulin
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PPARG
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Peroxisome proliferator- adtivated receptor gamma PPARG: receptor/transcription factor → adipocyte differentation, deposition of NEFA in adipose (not Liver, Muscle) + adiponectin secretion;
KO = monogenetic diabetes; stimulated by thiazolidinediones |
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pathway targeted by metformin
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AMPK: AMP activated Kinase.
normally stimulated in liver & SkM by adiponectin and leptin → promotes FA oxidiziation leptin, adiponectin signals lost in IR |
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pathway targetd by thiazolidinediones
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Peroxisome proliferator- adtivated receptor gamma PPARG: receptor/transcription factor → adipocyte differentation, deposition of NEFA in adipose (not Liver, Muscle) + adiponectin secretion;
KO = monogenetic diabetes; |
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Define MODY, describing genetics, clinical features and characteristics of MODY.
Describe MODY2 |
Maturity onset Diabetes of the Young
Autosomal dominant genes, onset <25yo not correlated with: obesity, IR, islet cell autoantibodies 6 genetic defects not relating to T2DM MODY2: glucokinase deficiency: first & RLS of glucose metabolism, transferring P to glucose; mild, non-progressive chronic hyperglycemia half --> gestational DM, accts for 5% of gestational DM remaining MODY's control insulin expression, B cell mass |
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MODY2
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glucokinase deficiency: first & RLS of glucose metabolism, transferring P to glucose; mild, non-progressive chronic hyperglycemia
half --> gestational DM, accts for 5% of gestational DM |
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glucokinase deficiency
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MODY2
glucokinase deficiency: first & RLS of glucose metabolism, transferring P to glucose; mild, non-progressive chronic hyperglycemia half --> gestational DM, accts for 5% of gestational DM |
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Advanced Glycation End Products
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intracellular glucose derived dicarbonyl precurosors + amnio groups of proteins; resistant to protesolytic degredation, rate of prodxn increases in hyperglycemia
AGE can directly crosslink polypeptides, decreases large vessel elasticity, & makess it sticky, trapping LDL's --> atherogenesis Receptors = RAGE; Rage-AGE --> -M∅ release cytokines, growth & procoagulant factors -endothelial cells produce ROS's & procoagulant activity -VSMC proliferate & synth ECM AGE in capillaries & glomeruli traps albumin in basement membrane = diabetic microangiopathy |
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DAG
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metabolic intermediate in the breakdown of FA, backup excess serves as a signalling molecules, activates Protein Kinase C →
increased VEGF (diabetic reitnopathy) decreased NO → vasoconstriction, increasess endothelin deposition of ECM & BM Increased PAI plasminogen activation inhibitor proinflammatory endothelium |
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Polyols
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Ts which do not req insulin for glut transport: nerves, lenses esp
NADPH used in reaction aldose reductase glucose --> sorbitol; NADPH not available regenerate GSH --> ROS damage; glucose neurotoxicity. |
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Pancreatic Morphology
T1DM vs T2DM |
Type 1: reduced size & number of islets, leukocyte infiltration (insulitis)
Type 2: amyloid replacement of islets, subtle reduction in islet cell mass (not readily apparent) Infants of diabetic mothers: increased islet cells |
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List the macrovascular complications of DM
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Accelerated atherosclerosis is the hallmark of DM & most common cause of death M=F
---Metabolic syndrome = independent risk factor MI Strokes Renal artery atherosclerosis --> stenosis --> renovascular htn --> renal failure Hyaline arteriolosclerosis (if severe DM) Gangrene of LE |
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most common cause of death in DM
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accelerated atherosclerosis
(DAG activated PKC → activated endotherlium, AGE's crosslink peptides: reduce elasticity, trap LDL's) |
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What is the frequency and significance of coronary artery disease in DM?
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80% of T2DM deaths
Diabetes same risk as prior MI (DAG activated PKC → activated endotherlium, AGE's crosslink peptides: reduce elasticity, trap LDL's) |
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List the consequences of diabetic microangiopathy
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AGE & PKC
Diffuse thickening of BM's in capillaries and renal tubules. Diabetic capillaires leak plasma proteins causes //this seems backwards, why would thickened BM be more prone to leakage? retinopathy, nephropathy, accelerates neuropathy (diseased vascularization of nerves) Describe the morphologic features and clinical consequences. |
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What are all features of diabetic nephropathy?
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Earliest marker for nerphropathy: Microalbuminuria: albumin in urine >30mg/day but <300 mg/day;
Glomerular lesions produce nephrotic syndrome diffuse mesnagial sclerosis nodular glomerulosclerosis/Kimmelstiel Wilson lesion specific for DM 30% of DM renal atherosclerosis hyaline arteriolosclerosis (nephrosclerosis), both afferent and efferent pyelonephritis with risk for papillary necrosis ~40% of diabetics dvlpt nephropathy. 20 years to renal failure BP control req'd to prevent progression Tx: ACE inhibitors decreases nephropathy & correlated cardiovascular events |
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Hyperglycemia + Microalbuminuria
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Earliest marker for nerphropathy: Microalbuminuria: albumin in urine >30mg/day but <300 mg/day;
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What are the neurologic consequences of DM?
Describe pathogenesus |
Symmetric peripehral neuropaty
both sensory and motor, LE most affected --> diabetic foot ulcers --> infx Charcot joint: lysis of injured bone ANS neuropathy --> sexual impotence, bowel and bladder dysfnx Impaired cognitive fnx from degeneration of brain and cord mononeuropathy affecting one single nerve: obturator, femoral, scietic etc strokes from htn & microangiopathies Hypoglycemic CNS injury |
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Charcot joint
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lysis of injured bone as seen in DM nephropathy
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List GI complications of diabetes mellitus.
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Strongly correlated with glycemic control
--> GI dysmotility, constipation/diarrhea; abd pain, N/V dysphagia, heartburn gallbladder dysfnx: delayed emptying, larger volumes [Pathogenesis: multifactorial] |
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What is the frequency and types of infections in DM? What is the pathogenesis?
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Skin esp foot ulcers
TB/Fungal infx esp necortizing mucor of sinuses pneumonia pyelonephritis (accelerating factor of diabetic nehpropathy) Fournier's gangrene 5% of DM die of infx |
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Ketoacidosis
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glycogen stores depleted, fat metabolism increases --> ketone bodies
counterregulatory hormone actions, glucagon, growth hormone, epinephrine → glucose formed from GNG of AA → hyperglycemia + negative energy balance --> polyphagia; epinephrine blocks residual insulin release, stimulates glucagon. plasma glucose 500+; glycosuria @ >=160 mg/dL --> osmotic duriesis --> polyuria, polydipsia Acetoacetic acid and beta-hydroxybuterate formed more quickly than can be used --> ketonemia, ketonuria; osmotic diuresis --> increases [H+] Nausea/Vomiting, Kussmaul |
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pathogenesis of polydipsia, polyuria, polyphagia
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glycosuria @ >=160 mg/dL --> osmotic duriesis --> polyuria, polydipsia
glycogen stores depleted, fat metabolism increases --> ketone bodies protein metabolism of muscle mass releases amino acids negative energy balance --> polyphagia |
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T1DM correlated disease
(not causal, not complication) |
14 genes shared with Celiac Disease
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Tx T1DM
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Insulin is only pharmacologic therapy. Must be coupled with well regulated diet and regular exercise.
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Clinical Presentation T1DM
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polyuria, polydipsia, polyphagia, weight loss, ketoacidosis
Most new cases <18yo w/ abrupt onset usually 2° to infx 1 year honeymoon "Brittle" glucose intolerance affected by minor changes in diet, physical activity, stress, inefction, vomiting, fluid in/outflow. Risk Ketoacidosis and Hypoglycemic Episodes |
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Hyperosmolar Nonketotic Coma
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failure to adequately compensate for fluid lost through osmotic diuresis;
typical pt elderly, disabled by stroke/infx, unable to drink enough water no nausea, vomiting, respiratory difficulties |
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Tx T2DM
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10% weight loss reverses new onset T2DM
Diet & excersize delay impaired GT Oral Agents: sulfonyrea, glitinides: increases release of insulin metformin: decreases hepatic glucose prodxn thiazolidinediones: decreases insulin resistance GLP1: increases insulin, decreases glucagon, delays stomach emptyig; Glucose control w/o hypoglycemia. ± needs insulin |
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GIP Gastroinhibitory peptide
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GLP glucagon like protein -1
enhances inusline relase metabolized by DPP-4 blocked by sitagliptin --> prolonged elevation of GLP-1 increases insulin release exenatide: GLP-1 like drug from Gilamonsters |
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What are the definition, features and complications of gestational diabetes?
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Definition: Hyperglycemia/Diabetes detected when pt is pregnant
>10% of all pregnancies, most common complication, hispanics more at risk Diagnostic criteria: LOWER THAN FOR DIABETES Fasting 105 Maternal Risk for Post Partum Overt DM ~50% at 5 years Aggressive Tx to Protect Fetus & Mother screen all increased risk for T2DM before pregnancy screen all pregnant women at during 7th month of pregnancy Highest risk: excessive maternal weight gain UA positive for glucose Hx large babies, unexplained fetal loss, family Hx Fetal complications merit their own card |
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Fetal complications of Gestational Diabetes
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childhood obesity & cognitive impairment, metabolic syndrome & T2DM as adult;
macrosomia 2* to growth hormone: risks at delivery: dystocia, fractures, nerve palseis, IUGR (pre-eclampsia) stillbirth malformations: neural tube, cardiac neonatal hypoglycemia 2* to islet hyperplasias increased risk hyaline membrane disease |
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What are the general features of pancreatic endocrine neoplasms?
When are they considered malignant? What is the most common type |
Rare, Adults, Anywhere along Pancreas or in Ectopic Ts;
Carcinoid; ± single/multiple, ± benign/malignant ± hormone prodxn Malignancy if -mets -vascular invasion -gross invasion of adjacent viscera most common islet cell tumor is insulinoma |
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Insulinoma
Frequency, morphology, Sx, lab findings, DDX, Tx |
most common islet cell tumor
gross:solitary, small benign, w/in pancreas micro: monotonous carcinoid cells w/ amyloid deposition Sx: hypoglycemia, Altered mental status, hypoglycemic attacks relieved by glucose lab finding: low fasting blood sugar, high insulin and C peptide Gold standard: 3 day fast w/ glucose insluin & C peptide levesl q6h DDx: diffuse hyeprplasia of islets, hypoglycemia in infants of diabetic mothers; fibrosarcoma paraneoplastic insulin; Tx: surgery |
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Hypoglycemia without hyperinsulinemia
DDx |
Hypoglycemia w/o hyperinsulinemia
diffuse, endstage liver disase inherited glycogenoses drugs- self-induced hypoglycemia |
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Zollinger Ellison syndrome
Sx, Dx, Tx, Px |
Gastrin producing tumor in duodenum, peripancreatic ts or pancreas
peptic ulceration in 90%, intractible to Tx, in unusual locations like jejunum, [duodenal > gastric,] multiple, 1/2 are malignant, 1/2 present with diarrhea Dx: increased serum gastrin (also elevated in atrophic gastritis) Tx: H2 receptor blockers, surgical exision of possible Px: 1/2 invasive metastatic at discovery --> mets to liver, liver fialure in 10 years 25% assoc w/ multiple endocrine neoplasia |
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Glucagonoma
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alpha cell tumors
DM, Migratory necotizing skin erythema, Anemia Perimenopausal women, high plasma glucoagon [rare] |
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Somatostatinoma
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delta cell tumors
DM, Cholelithiasis, Steatorrhea, Hypochlorhydria Hard to localize high serum somatostatin (an IGF) |
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VIPoma
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diarrheogenic islet cell tumor
Vasoactive Peptide Watery diarrhea, hypokalemia, achlorhydria tumors may be invasive &/ metastatic may be caused by neurocrest tumors-neuroblastoma |
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DM, Migratory necotizing skin erythema, Anemia
Perimenopausal women |
Glucagonoma
alpha cell tumors |
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DM, Cholelithiasis, Steatorrhea, Hypochlorhydria
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Somatostatinoma
delta cell tumors Hard to localize high serum somatostatin (an IGF) |
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Watery diarrhea, hypokalemia, achlorhydria
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VIPoma
diarrheogenic islet cell tumor Vasoactive Peptide tumors may be invasive &/ metastatic may be caused by neurocrest tumors-neuroblastoma |
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In general, what labs reflect glomerular function, tubular reabsorption (concentrating ability)?
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GFR: Glomerular filtration
Proteinuria: Glomerular filtration Urine specific Gravity: Tubular reabsportion (concentrating ability) |
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BUN
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increases before creatinine,
high sensitivity, low specificity; not increased in early nephrotic syndrome Increased in: Dehydration ("pre-renal"), GI bleeding, excess destrxn of cellular proteins ( fever, DM, catabolism --incl. exercise) [From Phys: about half the filtered urea is reabsorbed, and resporption increases when GFR is low] |
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Creatinine
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catabolic end product of creatine in SkM which gave up ATP; prodxn is constant and proportional to muscle mass.
high specificity, low sensitivity for decreased GFR Increased in: dehydration, poor reanl perfusion, most renal disease; [From Phys: freely filtered, almost no resorption/secretion: what you see is what you filtered] |
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Cause of Hyponatremia
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salt wasting renal tubular defect
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Cause of Hyperkalemia
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decreased renal excretion in endstage kidney disease or acidosis
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Cause of Metabolic Acidosis
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renal tubular acidosis: tubular loss of bicarbonate OR decreased tubular excretion of organic and inorganic (phosphates) acids
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Casts
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form in tubules of kidney, indicative of renal disease or dehydration
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Specific gravity
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concentrating ability of kidney, lost in renal tubular disease
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Proteinuria
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ALL glomeular disease results in proteinuria. Urinary protein:Cr ratio >1000mg/g ~= glomerular disease Proteinuria reflects glomeular pressure. Timed urin sample is gold standard for quantitative assessment.
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Albuminuria
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early sensitive marker for many types of kidney disease
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"Spot" urine
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ratio of albumin to creatinine: corrects of hydration. Normal <10mg/g
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compare/contrast nephritic vs nephrotic syndromes utilizing labs
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Nephritic: gross hematuria, <= moderate proteinuria, htn
Nephrotic: >= 3.5g/24h in urine --> hypo-albuminemia, severe edema; hypoproteinemia --> hyperaldosteronemia --> Na+, H2O retention --> worsens edema Lipiduria & hyperlipidemia incl. lipoprotein synth by liver, abnormal transport & decreased catabolism --> increased choleesterold, hyperTAGemia GFR initially increased, BUN & Creatinine normal eventually GFR decreases --> renal insufficiency --> failure proteinuria delivers concentrated cytokines, growth factors, et al mediators to tubules --> interstitial inflam & fibrosis --> tubular/vascular dysfnx |
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selective vs poorly selective proteinuria
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selective: mostly albumin & transferrin
poorly selective: albumin + globins --> lost IgG = Infx, lost AT3 & antiplasmin --> thrombosis/thromboembolism |
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What two labs predict chronic kidney disease and its progression? What is the GFR that defines chronic kidney disease, stage 2?
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-proteinuria + creatinine (? I guess)
GFR = best measurement of renal fnx, estimated by Creatinine clearance or estimated Cr clearance from serum Creatinine Chronic kidney disease defined as reduced kidney fnx for >3 mo stage 1: kidney damage + proteinuria, GFR >=90 stage 2: GFR <90 stage 3: GFR< 60 Stage 4: GFR <30 Stage 5: GFR <15 = Kidney Failure, req's dialysis [there is a lot more about staging, not in obj] |
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Define azotemia. How is renal azotemia differentiated from pre- and postrenal azotemia? What are causes of pre-renal azotemia? Postrenal azotemia?
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Azotemia: elevated BUN + Creatinine: indicative of decreased GFR
Renal cause BUN:Cr ratio 12-20:1; if disproportional, look for non-renal cause of increased BUN; Prerenal azotemia: hypeoperfusion w/o parenchymal damage BUN/Cr > Causes: hemorrhage, shock, dehydration, CHF Postrenal azotemia: outblow obstrx Causes: Stones, prostate, tumor etc. Relief of obstrx corrects azotemia. |
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Uremia labs
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Hct ↓, Cr ↑, BUN ↑, Ca2+ ↓ Uric acid ↑, Proteinuria
--Hyperphosphatemia (normally excreted), hypocalcemia (normally absorbed) --> stones & also 2* increased PTH w/--> renal osteodystrophy --Anemia: normocytic normochromic w/ burr cells (NcyNch Acanthrocytes); EPO low, serum iron low; Bleeding due to platelet dysnfx --> low Hct --uremic retinopathy: atherosclerotic (silver wire arteries, hemorrhages) hypertensive: cotton wool exudates, flame shaped hemorrhages, papilledema) --Uremic respiratory disease: hilar pneumonitis "bat wint" opacity on x ray" Kussmall respiration, urine smell to breath, plural effusions --CV: HTN --> CHF --> Pulmonary Edema, Fibrinous Pericarditis --GI: N/V, inflammation w/ ulcerations: Bleeding (low platelets), constipation <--> diarrhea; Coated tongue ammoniacal/unpleasant taste --Neuromuscular: myopathy, peripheral neuropathy, encephalopathy --Dermatologic: Sallow (grey-yellow), pruritis, dermatitis, edema, purpura, exocriations (sloughing), rarely "uremic frost" --CNS: HA, drowsiness/insomnia, muscle fasiculation/weakness, convulsions, coma |
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Cardio: Htn, dizziness, friction rub, cardiomegaly
GI: N/V, hematochezia/melena Respiratory: dyspnea on exerction, burning retrosternal pain worse on inspiration; rales Dermal: sallow, excoriations, bruises, pitting edema` |
Uremia
--Hyperphosphatemia (normally excreted), hypocalcemia (normally absorbed) --> stones & also 2* increased PTH w/--> renal osteodystrophy --Anemia: normocytic normochromic w/ burr cells (NcyNch Acanthrocytes); EPO low, serum iron low; Bleeding due to platelet dysnfx --> low Hct --uremic retinopathy: atherosclerotic (silver wire arteries, hemorrhages) hypertensive: cotton wool exudates, flame shaped hemorrhages, papilledema) --Uremic respiratory disease: hilar pneumonitis "bat wint" opacity on x ray" Kussmall respiration, urine smell to breath, plural effusions --CV: HTN --> CHF --> Pulmonary Edema, Fibrinous Pericarditis --GI: N/V, inflammation w/ ulcerations: Bleeding (low platelets), constipation <--> diarrhea; Coated tongue ammoniacal/unpleasant taste --Neuromuscular: myopathy, peripheral neuropathy, encephalopathy --Dermatologic: Sallow (grey-yellow), pruritis, dermatitis, edema, purpura, exocriations (sloughing), rarely "uremic frost" --CNS: HA, drowsiness/insomnia, muscle fasiculation/weakness, convulsions, coma |
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bilateral renal agenesis
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Potter's syndrome: bilateral total agensis, incompatible with life; failure to produce urine --> oligohydramnios --> flat facies, limb defects, hypoplastic lungs; amnion nodosum
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unilateral renal agenesis
|
hypertrophied singular, risk for glomerular sclerosis
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renal hypoplasia
|
bilateral hypoplasia --> childhood renal failure
unilateral hypoplasia, usuallyl atrophy 2* to infx |
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Ectopic Kidney
|
Ectopic: commonly in pelvis or just above pelvic brim
Risks: UTI, obstrx 2* to tortuous ureter |
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Horseshoe kidney
|
fusion of poles acorss midline; 1/500; risks: UTI, obstrx 2* to tortuous ureter;
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Multicystic renal dysplasia:
|
sporatic
enlarged cystic kidney/flank mass, present at birth disorganized architecture: cartilage, undifferentiated mesenchyme, immature collecting ductules, abnormal lobular organization; unilateral or bilateral, assoc with abnormalities lower down |
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adult polycystic kidney disease
genetics, pathogenesis, morphology, progression, presentation, complications, comorbidities, dx, Px |
- Inheritance: AD, Penetrance increases with age, Frequency: Common 1/700; 10% of transplants
- Morphology: Large, multicystic kidney, liver cysts, berry aneurysms - Outcome: chronic renal failure beginning ~50 ± 10, Initially focal always progress to bilateral. - Polycystin located in primary cilium of tubule cells & influences mechanocensing --> intracellular Ca2+ --> influences cell-cell & cell-matrix interactions --> altered tubular growth --> cyst --> cysts detach and enlarge by fluid secretion --> glomerular vascular damage, interstitial inflam/fibrosis. 3 separate genes: Majority are PKD1 on Chrom 16 which produces polycystin 1, PKD2 ≈ delayed onset - Presenting sx: 50 yo w/ renal colic from passing clots 2* to dilation & hemorrhage; bilateral abdominal masses, hematuria, proteinuria, polyuria, htn - Complications: Hematuria, flank pain, UTI, Stones, HTN Comorbidities: defective basement membranes: 40% have polycystic liver disease, 30% have berry aneurysm in circle of willis, mitral valve prolase - Dx: US, CT Px: Slowly progressive azotemia → death from HTN: CVA, Ruptured aneurysm |
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50 yo, renal colic, bilateral abdominal masses
hematuria, proteinuria, polyuria, htn |
Adult Polycystic Kidney Disease
- Inheritance: AD, Penetrance increases with age, Frequency: Common 1/700; 10% of transplants - Morphology: Large, multicystic kidney, liver cysts, berry aneurysms - Outcome: chronic renal failure beginning ~50 ± 10, Initially focal always progress to bilateral. - Polycystin located in primary cilium of tubule cells & influences mechanocensing --> intracellular Ca2+ --> influences cell-cell & cell-matrix interactions --> altered tubular growth --> cyst --> cysts detach and enlarge by fluid secretion --> glomerular vascular damage, interstitial inflam/fibrosis. 3 separate genes: Majority are PKD1 on Chrom 16 which produces polycystin 1, PKD2 ≈ delayed onset - Presenting sx: 50 yo w/ renal colic from passing clots 2* to dilation & hemorrhage; bilateral abdominal masses, hematuria, proteinuria, polyuria, htn - Complications: Hematuria, flank pain, UTI, Stones, HTN Comorbidities: defective basement membranes: 40% have polycystic liver disease, 30% have berry aneurysm in circle of willis, mitral valve prolase - Dx: US, CT; Px: Slowly progressive azotemia → death from HTN: CVA, Ruptured aneurysm |
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childhood polycystic kidney disease
frequency, inheritance, pathogenesis, morphology, Px |
Rare, AR
PKHD1: fibrocystin: membrane protein of primary cilium of tubular cells; most cases are compound heterozygotes; Morphology: parallel cylindrical cysts in cortex and medulla at right angles to cortical surface Perinatal most common: rapid renal failure Infantile assoc w/ congenital Juvenile: hepatic fibrosis, liver disease w/ increasing age |
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medullary sponge kidney
morphology, complications |
Morph: multiple small cystic dilations of cuboidal transitional/cell lining in medullary collecting ducts
Complications: calcifications in dilated ducts, hematuria (presenting sx) Renal fnx: normal |
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Sulfanamides
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Trimethoprim/Sulfamethoxazole (Bactrim, Septra)
Sulfisoxazole (Gantrisin) Sulfisoxasole/Erythromycin (Pediazole) Silver Sulfadiazine (Silvadene) **Topical form Sulfacetemide (Cetamide) **Opthalmic drops |
Use:
broad spectrum, use for UTI, increase fluids SE: GI, skin rash, phototox, super-infections, hyperkalemia, blood dyscrasias, stevens johnson syndrome, anaphylaxis |
|
Adult onset medullary cystic disease
inhereitance, morphology, complications, Px |
Inheritance: AD
Morph: corticomedullary jxn cysts, corticotubular atrophy & interstital fibrosis, shrunken kidneys Complications: salt wasting polyuria Outcome: chronic renal failure beginning in adulthood |
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most common genetic cause of endstage renal disease in children, young adults
|
Complex variants of Nephronophthisis
Familial or sporadic familial AR manifests in chilhood familial AD in adults Gene: NPH (7 variants) for nephrocytin = ciliary protein sodium wasting polyuria with tubular acidosis --> terminal renal failure in 5 years Dx: biopsy shows chornic tubulointerstitial nephritis |
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What are the features of dialysis-associated acquired cystic disease?
inhereitance, morphology, complications, outcome |
Inhertiance: None
Morph:Cortical and Medullary Cysts Tubules obstrcted by interstital fibrosis or oxalate crystals Complications: increased risk of renal cell tumors, +-hematuria Outcome: dialysis |
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simple cysts
inhereitance, morphology, complications, outcome |
Freq: common
Inheritance: None Morph: 1+ cysts in normal sized kidney up to 10cm Complciations: microscopic hematuria, occasional hemorrhage: rapid distention & pain, DDX: cystic renal cell carcinoma Outcome: benign |
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Recognize the gross and microscopic morphology of benign nephrosclerosis. Know associations and significance.
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Kidney of benign htn: sclerosis of renal arterioles & small arteries
assoc w/ age, diabetes, htn & African Americans Pathogenesis: intimal thickening + Hyaline deposition from extravasated plasma --> narrowing of lumens --> patchy ischemic tubular atrophy with intestitial fibrosis; glomeruli become sclerotic Finely granular cortical surface Clinical presenation: GFR >= Normal, mild proteinuria, increased risk of renal failure |
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What are the clinical and morphologic features (gross and microscopic) of kidney and of retina in malignant hypertension. Define malignant hypertension and list causes.
|
Malignant HTN: BP >200/120
Causes: complication of any htn; most likely htnsive young black men, or scleroderma with nephropathy essential htn 2* htn: --endocrine disease: pheochromocytomas --renal vascular disease --acute and chronic renal disease |
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What are common complications of hypertension?
|
Concentric LV hypertrophy: CHF
MI, Strokes, Cerebral Hemorrhage, Aortic dissection, Chronic renal failure Morphology: fibrinoid necorsis of arterioles --> onionskin hypertorphy Renal vascular damage --> fibrosis & low perfusion --> AT2 secret'n --> renal vasoconstrxn --> further injury also low perfusion --> aldosterone --> salt retention --> Focal hemorrhages = "flea bitten" shrunken overtime Retinas: flame-shaped hemorrhages, cotton wool exudates, papilledema |
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Causes of HTN w/ Hypokalemia
|
Malignant hypertension
Primary hyperaldosteronism hyperaldosteronism 2* to renovascular disease Cushing syndrome Endocrine Thiazide/diuretic Rx's Rule out renal vascular disease with duplex US [Pheochromocytoma --> VMA/metanephrines in urine from catecholamines] |
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Describe the pathogenesis of renovascular hypertension using unilateral stenosis model.
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Constriction of artery --> ischemic kidney --> renin secretion increased --> AT2, Aldosterone --> maintenance of HTN by sodium
Shrunken "Goldblatt" Kidney |
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What diseases cause renovascular hypertension and what are the features and morphology of each?
|
Causes:
-Majorty are Atherosclerosis: atheromatous plaque at origin of renal artery -Fibromuscular dysplasia Women 20-40 yo: beaded appearang vessel on x ray from fibro-eslatic ts or VSMC thickening Morphology: -Contralateral hyaline arteriosclerosis -End stage kidney shrunken, inflammed atrophied, fibrotic Clinical features: HTN with hyperreninemia, responds to ACE inhibitors Dx via arteriography Tx via interventional radiology |
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Review the pathogenesis and list of thrombotic microangiopathies.
|
Typical HUS: childhood HUS following bloody diarrhea
Atypical huse: no diarrhea, acquired or familial TTP: Idiopathic trhombocytic throbocytoepnic purpura |
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What are the peripheral blood and renal morphologic findings of these thrombotic microangiopathies?
|
Thombosis in capillaries and arterioles
microangiopathic hemolytic anemia thrombocytopenia +- renal failure Morphology: platelet/platelet fibrin thrombi in small arteries and glomeruli: |
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What are the causes/clinical features of typical HUS?
|
Typical HUS:
-follows diarrhea or "flu" +- hematemesis, melena Shiga toxin damages endothelium --> intravascular thrombosis --> schistocytes Sudden onset of oliguria w/ hematuria, microangiopathic hemolytic anemia, +-nerologic disease Tx: dialysis Px: 5% mortality, high % persistent abnormal renal fnx --> chronic renal failure |
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What are the causes/clinical features of atypical HUS?
|
adults with inherited deficiency of complement regulatory proteins, esp factor H
else: -antiphospholipid syndrome, post-partum renal failure, renal vascular disease 2* to malignant htn or systemic sclerosis, CA chemotherapies or renal radiation [?Sudden onset of oliguria w/ hematuria, microangiopathic hemolytic anemia, +-nerologic disease Tx: dialysis Px: poor |
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What factor is deficient in TTP?
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Nerologic Sx! + microangiopathic hemolysis thrombocytopenic purpura; renal failure; fever
Activated vWF multimers 2* to deficiency of protease ADAMTS-13: acquired or familial, familial is chronic/relapsing Females <40 |
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What renal diseases are related to atherosclerosis? Atheroemboli (recognize morphology 20-43)
|
Atherosclerotic ischemic renal disease
bilateral --> renal insufficiency +- htn Atheroebolic enral disease --> acute renal failure, cholesterol crystals in lumen |
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What are all associations of papillary necrosis of the kidney (table 20-9).
|
See table, have made chart
Sickle cell disease nephropathy: papillary necoris, hematuria, diminished concentration Homozygoes 30% have proteinuria, +- nephrotic w/ glomerular lesions |
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What are associations and consequences of diffuse cortical necrosis?
|
follow septic shock & abruptio placenta ie obstretric emergencies.
Sudden onset aneuria + uremia Bilateral = poor prognosis |
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What are causes and morphology of renal infarcts?
|
Kidney is the most common site of infraction, mostly due to embolism
Infarcts are wedge shaped, pale & produce scare silent infarct presents as costovertebral angle pain & hematuria may cause htn |
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|
What are the seven categories of systemic manifestations for chronic kidney disease and uremia
|
Fluid & Electrolytes
Calcium Phosphate & Bone Hematologic Cardiopulmonary GI Neuromuscular Dermatologic |
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|
What are the four stages of renal failure?
|
1. Diminished renal reserve- GFR 50% normal; no increase in BUN, Creatinine, aSx
2. Renal insufficiency- GFR 20-50% normal; azotemia w/ anemia and hypertnesion, polyria, nocturia 3. Renal Failure GFR <25% normal +- edema, acidosis, hypocalcemia, uremia 4. End Stage Renal Disease GFR <5% normal, uremia |
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What are the three groups of glomerular diseases? (Table 20-2)
|
Primary glomerulopathies- kidney predominate as only organ
2ndry--due to systemic disseases Hereditary disorders |
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What are the five major glomerular syndromes? (Table 20-3)
|
Nephritic Syndrome: hematuria, azotemia, +- proteinuria, oliguria, edema, htn
Rapidly progressive Glomerulonephritis: acute nephritis, proteinuria, acute renal failure; Nephrotic Syndrome: >3.5 gm proteinuria, hypoalbuminemia, hyperlipidemia, lipiduria Chornic rneal fialure: Azotemia --> uremia Isolated urianry abnormaliteis: glomerular hematuria, subnephrotic proteinuria |
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What are the four basic tissue reactions in glomerulonephritis?
|
Glomerular hypercellularity: proliferative: mesangial, endothelial, infiltrative: PMN, M0, lymphos
Crescents: accumulation of cells composed of proliferating epithlial cells and infiltrating lymphos Basement membrane thickening: --LM: thicked capillary was --EM: thickened BM's, depsoition of amorphous electron dense material Hyalinization and Sclerosis --LM: accumulation of homogenous eosinophilic mateiral --EM: extracellular amorphous substance |
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Define wrt the Glomerulus
Diffuse, Global, Focal, Segmental |
Diffuse- involving all glomeruli
Global- involving the entire glomerulus Focal- involving a certain portion of the Segmental- involving only certain portions of each glomerulus |
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Diffuse, linear immunofluorescent pattern of glomerular immune complex despition
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Anti-GBM nephritis: Goodpasture Syndrome: Severe damage & Rapid renal failure
Antibodies directed against intrinsic GBM antigens Cross reacts with other BM's esp lung alveoli |
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immunofluorescence pattern is granular and interrupted of glomerular immune complex despition
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Heymann's nephritis
antibodies to bursh border antigens EM: numerous electron dense depsoits in subepithelial aspect of BM |
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granular heterogenous pattern on immunofluroescence of glomerular immune complex despition
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Planted Antiens
ab's react in situ with non-glomerular ag's |
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granular deposits on BM &/ on mesangium of glomerular immune complex immunofluorescence
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Circulating Immune Complex Nephritis
Trapping of cirgulating immune complexes within glomerul --> complement activation --> damage EM: electron dense deposits in mesangial, subendothelial (between endothelial cells & GBM), subepithelial (btw podocytes & outer surface of GBM, rare) |
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Using figure 20-5 identify the four areas of localization of immune complexes.
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?
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What happens when glomerular epithelial cells are injured
|
Morphologic changes: loss of food processes, vacuolization, etraction and detachement from GBM; functional proteinuria
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focal segmental glomerulosclerosis
|
due to adaptive change in unaffected glomeruli --> compensatory hypertrophy & hemodynamic changes. Htn + increased permeability --> accumulation of proteins in mesangial matrix, proliferation of mesangial cells, infiltration by macorcytes, ECM deposition. --> sclerosis --> proteinuriaglobal
[podocytes unable to increase in number, streteched too thin --> unopposed intracapillary pressure --> fibrous attachemnt of bulgin gcapillary to bowmans capsule --> contineud sclerosis] |
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tubulointerstitial ifnalmmation and fibrosis:
|
better correlated with decline in renal fnx than severity fo glomerular damage
protein causes direct injury to and activation of tubular cells. |
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Explain renal ablation focal segmental glomerulosclerosis (Fig. 20-8).
|
(Fig. 20-8).
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Know the entire table 20-5 with the summary of major primary glomerulonephritides except for the pathogenesis column.
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I made a chart!
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Syndrome of Acute Nephritis
|
Hematuria, red cell casts, azotemia, oliguria, mild to moderate htn; proteinuria and edema lesss than in nephrotic syndrome; may occur in multisystem disease; typically characteristic of acute proliferative glomeulonephritis and srescentif GN;
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Acute proliferative GN
Poststreptococal, Postinfectious |
immunologically mediated GN w/in a mo after certain GABHS strains;
enlarged hyperceullar glomeruli, diffuse proliferation of mesangial, endotheial cells, diffuse infiltration of PMN,s M0's; tubules will have RBC casts, +- interstitial edema/inflam IF: granular deposits of IgG, IgM and C3 in mesangium and along BM EM: discrete amorphous electron dense deposits on epithelial side of BM --"humps" of C3 Clinical: young child w/ abrupt onset of malaise & hematuria w/in mo after recovering from sore throat RBC casts, milkd proteinuria, periorbital edema, mild htn adult onset atypical Lab findings: elevated anti-streptococcal ab titers, low serum C3, cryoglobins in serum Most children recover totally. 2% slow progression to chronic GN, <1% rapidly progressive GN Only 2/3 adults recover completely |
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Rapidly Progressive Glomerulonephritis = RPGN
|
Crescents of proliferted parietal cells and infiltrating M0 into Bowman's space (obliterate space); Fibrin between layers of crescent;
EM: rupture in GBM +- deposits ImmunoF: Post-infx: granular Goodpasture: linear Ideopathic: granular, linear or none Serum analysis for Anti-GBM, antinuclar ABS' and ANCA's Clinical: Hematuria w/ red cell casts, proteinuria variable htn & edema rapid loss of renal fnx w/ oliguria, death w/in weeks if unTx Goodpasture: recurrent hemoptysis or life trheatening pulmonary ehmorrhage Tx: goodpastrues: plasmapharesis, cytotoxic agents, steroids Non-goodpasture: steroids, cytotoxic agents |
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Types of Rapid Progressive glomerulonephritis
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Type 1: Goodpastures: Antibodies vs BM, esp glomerulus and lungs
IF: linear; tx: plasmapheresis, cytotoxic agents, steroids Type 2: IC mediated IF: granular pattern Tx: underlying disease Type 3: pauci-immune type: Most C-ANCA or P-ANCA, lack of anti-GBM abs/IC's, either idiopathic or part of systemic vasculitis Tx: steroids, cytotoxic agents Idiopathic RPGN: IF: granular, linear or none 1/4 = Type 1, 1/4 = Type 2, 1/2 = Type 3 |
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Define the nephrotic syndrome (four features). What are the major primary glomerular diseases that present with the nephrotic syndrome (Table20-7)? Which is most common in children? In adults?
|
Massive proteinuria >3.5 g/day
hypoalbuminemia <3g/dL generalized edema hyperlipidemia & lipiuria assoc. w/ primary & systemic GN most common in children: minimal change disease most common in adults: focal segmental glomerulosclerosis |
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membranous GN
LM, EM, IF Causes, Px |
LM: diffuse, uniform thickening of capillary wall; silver stain shows spikes of BM between deposits
IF: granular deposits of IgG and C3 EM: irregular dense subepithelial deposits, foot processes lost Causes: 85% idiopathic; rest: drugs, malignant tumors, SLE, infx, autoimmune disorders Clinical: insidious onset of nephrotic syndrome, indolent; proteinuria does not repsond to steroids; proteinuria persists in 60$; 40% dvlp renul insufficiency in 10 years. only 10% reach renal failure in 10 years. |
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Minimal change disease
|
aka lipoid nephrosis
most common cause of nephrotic syndrome in children LM: lipid in tubles EM: no deposits, uniform and diffuse effacement of food processes Rapid repsonse to steroids nephrotic phase may recurr (come back to the rest) |
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|
What are the two hereditary syndrome of isolated hematuria?
|
Alport Syndrome
Thin Membrane Disease-- most common cause of benign familial hematuria |
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What are the manifestations of Alport Syndrome and the clinical course?
|
Defective GBM syntehsis is 1* lesion
Nephritis + nerve deafness & eye disorders males more freq & severe, heterogenous inheritance EM: GBM shows irregular foci of thickening or attenuation, pronounced splitting ClinicaL: hematuria starting age 5, renal failure sometime after age 20 |
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What are the clinical and morphologic features of Thin Basement Membrane Disease? What is the other name for Thin Basement Membrane Disease?
|
most common cause of benign familial hematuria
diffuse thinning of GBM renal fnx normal, prognosis good |
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Which GN’s are likely to progress to chronic GN? Not likely to progress? (Figure 20-21). What are the gross and microscopic features of chronic GN? What is the clinical course?
|
Kidneys symetrically contracted, diffusely granular cortical surfaces
hyaline obliteration of glomeruli, acellular eosinophilic PAS positive masses atrophy of tubules, interstitial fibrosis, lymphocytic infiltrate Extrarenal morphology: uremia: pericarditis, gastroenteritis, 2* hypoparathyroidism w/ neprhocalcinosis & renal osteodystrophy; LV hypertorphy 2* to htn, Pulmonary DAD Clincial: insidious progression to death most pts htn, clinical manifestation may be cerebral or cardiovascular must be maintained on dialysis or receive transplant Most likely to progress: Crescentic GN, PSGN, membraneous, Focal Segmental Glomeruloscleorsis, Membranoproliferative GN, IgAN |
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What are the three morphologic changes that occur in the glomeruli of diabetics? What is the other term for nodular glomerulosclerosis? Describe the clinical progression of renal disease in diabetics?
|
arteriolar sclerosis, papillary necoris, tubular lesions
AGE's --> thicken GBM & increase mesangium Hemodynamic htn --> glomerular hypertrophy --> diffuse mesangial sclerosis nodular glomerulosclerosis: aka Kimmelstiel Wilson Disease = spherical laminated hyaline masses at periphery; PAS+, lipid, fibrin Clincal progression increased GFR --> microalbuminuria proteinuria --> nephrotic progressive loss of GFR --> end stage renal filure systemic hypertension dialysis, transplants, may recur Preventable w/ control of blood sugar; delayed progression w/ ACE inhibitors |
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spherical laminated hyaline masses at periphery; PAS+, lipid, fibrin
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Kimmelstiel Wilson Disease
aka nodular glomerulosclerosis: |
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What are the two major groups of processes which affect the tubules and interstitium?
|
1. Ischemic/toxic tubular injury = acute kidney injury aka actue tubular necrosis AKI/ATN
2. Inflam rxn of tubules & interstitium: tubulointerstitail nephritis |
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|
FIGURES:
|
20-23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 37
TABLES: 20-8, 9, 10 |
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What are the major morphologic and clinical features of acute kidney injury? What is the most common cause of acute renal failure? Is AKI reversible? What are the two patterns of AKI? What are the two critical events in AKI?
|
Morph: destrx of tubular epithelial cells
Clinical: acute suppressed renal fnx, most common cause of acute renal failure Diagnostic criteria: an absolute increase in serum Creatinine >= 0.3 mg/dl, a percentage increase in serum creatinine of >= 50% or a reduction in UO < 0.5 ml/kg/h for >6h AKI is by definition a reversible lesion Two types of AKI: Ischemic & Nephrotoxic Two critical events: tubular injury + persisten & severe disturbance in blood flow ( decreased GFR) |
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|
Acute renal failure:
|
acute suppression of renal function and urine flow falling w/in 24 h to less than 400 ml
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|
What are the two main morphologic features of both types of AKI (Fig. 20-24)?
|
Ischemic morphology:
focal tubular epithelial necoris + apoptosis at multle points along nephron with skin areas, +- reuptured BM's, occlusion of tubular lumens by casts affects traight portion of proximal tubule adn ascending thick limb of Henle Toxic morphology: acute tubular injury in proximal convoluted tubules distinctive patterns with ?[mercuric chloride, carbon tetrachloride, ethylene glycol, calcium oxalate] Both types +- eosinophilic hyaline casts & pigmented granular gasts in distal tubules & collecting ducts; casts principally Tamm-Horsfall protein-urinary glycoprotein secreted by cells of ascending thick limb & distal tubules +- interstitial edema/inflam epithelal regeneration = flattened epithelal cells w/ hyperchormatic nuclei & mitotic figures |
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What are the three phases of classic AKI? Describe each phase. What is the prognosis for AKI?
|
1. Initiating: slight decline in urine 36 hours after inciting event
2. Maintenance: sustained decrease to 40-400 ml/day, Na+H2O overload, rising BUN, hyperkalemia, metabolic acidosis; keep pt alive with dialysis 3. Recovery: steady increase in urine volume to 3L/day; tubules still damaged, w/ Na+H2O wasting & increased risk of infx Px: 50% mortality with burn or spesis related shcok; recovery if other organs not seriously damaged |
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Nonoliguric ATN
|
more benign clinical course
|
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|
What features distinguish acute and chronic tubulointerstitial nephritis? What distinguishes TIN from glomerular disease?
|
Acute: acute onset, focal tubular necrosis, w/ inflam & edema
Chronic: Mononuclear cells, fibrosis, widespread atrophy Tubuloinsterstial Nephritis will not have nephritic/nephrotic syndrome, and will have defects in tubular fnx manifest as: impaired concentration: polyuria, nocturia salt wasting metabolic acidosis isolated defects in tubular resorption of secretion |
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|
What parts of the kidney does pyelonephritis affect? What are the two forms of peylo? Characterize each. What is the most common organism causing urinary tract infections? Where do the infecting organisms come from?
|
Bacterial infx 2* to UTI
Tubules, Interstium & Renal Pelvis Forms: Acute & Chronic Acute: Chronic: + other factors (?the hell does that mean) 1* Gram Negative Bacilli: E Coli, Proteus, & Kleb (by freq respectively) Organisms from GI tract, reflux up UTI Tranplanted Kidneys at risk for Polymoavirus, PMV, & Adeno |
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|
What are the two pathways by which bacteria can reach the kidney? (Fig. 20-26) What are the five steps in ascending infection of the kidney? What is vesicoureteral reflux (Fig. 20-27)? What is it most often due to?
|
Ascending (most common) & Hematogenous
1. Colonoization of distal urethra and intraoitus by coliform bacteria, req's P fimbrae w/ ability to adhere to uroepithelium 2. Entry to bladder via instrumentation or women (shorter urethras, no antibacterial prostatic fluid, hormanal influence on adherence, intercourse) 3. Multiplication in bladder; Usually flushed out. Req's stasis: BPH, tumors, calculi 4. Vesicoureteral reflux: incompetance of vesicoureteral valve: most often congenital inherited absense or shortening of intravesical portion of ureter; acquired due to spinal cord injury --> spinal cord injury 5. intrarenal reflux through papillae into poen ducts: demonstrate with voiding cystourethrogram. w/o reflux infx remains localized to bladder |
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|
What are the three hallmark morphologic features of acute pyelonephritis? What are three serious complications which may occur with acute pyelo?
|
Morphology: patchy interstitial suppurative inflam, intratubular aggregates of PMN's and tubular necrosis
Complications: Papillary necorsis esp in diabetics & obstrux, usually bilateral, affects any number ofpyramids, tips of pyramids have grey white necrosis grossly, on micro: coagulative infarct necrosis Pyelonephrosis: supprative exudate can drain & fills renal pelvis --> total or complete obstrx Perinephric abscess: extension of suppurative inflam through capsule into perinephric tissue [Healing pyelo: scarring w/ fibrous depressions on cortical surface w/ fibrosi & deformation of underlying calyx & pelvis] |
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|
What are the predisposing conditions for acute pyelo?
|
Obstrx
Pregnancy Preexisting renal lesions Immunovulnerable Vesicoureteral reflux 1st year = anatomical anomolies, after 1 year; Women <40, Men >40 (prostatic hypertrophy & instrumentation) DM |
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|
Sudden onset CVA pain, fever, malaise
dysuria, frequency, urgency, Pyuria; wbc casts |
acute pyelo
Tx: antibiotics Px: generally benign course |
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|
What pathogen may cause pyelo in kidney allografts? Treatment?
|
Polyoma virus: latent infx widespread in general, takes advantage of immunosuppression; Tx: back off immunosuppression.
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|
What are the two forms of chronic pyelo? Which is more common?
|
Chornic pyelo: chronic inflam & scarring w/ involvement of calyces & pelvis
2 forms: chronic obstructive & reflux nephropathy Chronic obstructive: recurrent infx superimposed on obstructive lesions Reflux nephropathy is more common form: early childhood superimposed UTI's on congenital vesicoureteral & intrarenal reflux |
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|
What are the gross morphologic features of chronic pyelo? What part of the kidney is involved by chronic pyelo which leads to distinctive changes (Fig. 20-32)?
|
Morph:
Kidneys are irregularly scarred, asymmetrically so if bilateral (contast w/ GN) Hallmark is coarse, discrete corticomedullary scar overlying blunted dilated calyx Tubules shot atrophy * hypertrophy +- colloid casts (thyroidization); fibrosis in cortex and medulla; |
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How do chronic pyelo patients present? What complication may occur which leads to proteinuria?
|
Insidiously else acute w/ back pain, fever, pyruia and bacturia
Reflux neuropathy = the common cause of htn in children if proteinuria, mild focal segmental glomerulosclerosis = poor prognositc change |
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|
In what three ways can toxins and drugs produce renal injury?
|
1. Trigger Immune Reaction
2. Acute Renal Failure 3. Subtle, cumulative injries --> chronic renal insufficiency |
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|
What groups of drugs cause acute drug-induced interstitial nephritis (ADIIN)? What are the four clinical features? When do they occur after drug exposure? What complication occurs in 50 % of cases? What types of leukocytes are present in the interstitium?
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synthetic penicillins, sulfonamides
onset 15 days after exposure fever, eosinophilia, rash + renal: hematuria, eosinophil leukocyturia, mild proteinuria 50% dvlp rising creatinine or Acute Renal Failure interstitial edema w/ mononuclear infiltrate +- large # eosinophils & PMNs. |
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Is the immune response in ADIIN dose related? Does withdrawal of the drug always lead to recovery?
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most likely hapten in combo w/ tubular cells
onset not dose related withdrawal of drug always followed by recovery (check this fact-cat on book right now) |
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Analgesic nephropathy is caused by what? What are the two morphologic features? What analgesic is implicated ? In what sequence do the morphologic features occur? What do the papillae show microscopically?
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excessive intake of analgesics
morph: chronic tubulointerstitial nephritis w/ renal papillary necrosis papillary necrosis occurs first then cortical tubulointerstitial nephritis acetaminophan injurs by covalent binding and oxidative damage aspirin potentiates by inhbiting vasodilatory effects of prostaglanding gross: depressed areas of cortical atrophy overlying necrotic papillae in various stages of necosis --> calcification --> fragmentation --> sloughing microscopically papillae show patchy to full necosis; cortex tubular atrophy, interstitial iflam/fibrosis |
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Analgesic nephropathy is prevalent in what group of patients? Does drug withdrawal lead to recovery? What complication may occur in a small percentage of patients? Is papillary necrosis specific for analgesic nephropathy (Table 20-9)?
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women with recurrent headaches & muscle pain: factory workers,, psychoneurotic pts
[inability to concentrate urine, HA, anemia, GI sx, htn, UTI in 50% entire tips of necortic papillae may be excreted: gross hematuria w/ renal colic] drug withdrawal and proper infx tx may stabalize or improve else chronic renal failure; rare complication: transitional papillary carcinoma |
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What are the NSAID associated renal syndromes?
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Hemodynamically induced acute renal failure
actue hypersensitivity interstitial nephritis acute intersitial nephritis and lipoid nephrosis Membranous GN [slide on chinese herb nephropathy] |
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What three types of nephropathy can occur in patients with hyperuricemic disorders?
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Acute uric acid nephropathy: precipitation of uric acid crystals in renal tubules, obstrx of nephrons, actue renal failure, esp in leukemia lymphoma pts during chemo
Chronic urate nephroathy (gouty nephropathy) depsoition of monosodium urate n distal tubules: microscopically distinctive bireringement needlelike cyrstals in tubular lamina/intersitium --> giant cell enclosed trophus Nephrolitiasis: uric acid stones |
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What four factors contribute to renal damage in multiple myeloma? What are the clinical renal manifestations?
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Bence Jones Light Chains directly toxic to epithelium, combine with Tamm Horsfall urinary glycoprotein to form tubular casts that obstruct lumin and induce peritubular inflam
Amyloidosis Light chain nephropathy hyhpercalcemia, hyperuricemia morphology: pink-blue amorphous masses of Benc Jones tubular casts filling & distending tubular lumens ± multinucleated giant cells Clinical: mostly chronic renal failure, some acute renail failure; bence jones proteinuria in 70% |
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[ Hypercalcemia and Nephrocalcinosis, Acute phosphate nephroapthy, Renal involevement by nonrenal neoplasms]
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Hypercalcemia --> stones --> tubulointerstitial
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What are three consequences of urinary tract obstruction?
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infection
calculus hydronephrsosis, hydroureter --> kidney atrophies under pressure |
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List congenital anomalies causing obstruction.
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stricture, meatal stenosis
posterior ruerthral valves in male infants: valves arise from verumontanum, bladder wall hypertrophy; mucosal surface trabeculated. ureteral pelvic jnx narrowing --> veicourteral reflux 1st sign may be pyelonephritis |
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What other conditions cause obstruction? Which are most likely to cause bilateral obstruction?
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urinary calculi; in bladder will cause bilateral obstrx
benign prostatic hyperplasia -bilateral obstrx inflamation: prostatisis, ureteritis, urethritis w/ strix, retroperitoneal fibrosis Tumors: prostate, urothelial, lymphoma, cervical carcinoma Pregnancy uterine prolapse & cystocele retroperitoneal fibrosis Papillary necrosis: diabetes, pyelonephritis, sickle cell, analgesic abuse nephroapthy (phenacetin), obstrx w/ infx Blood Clots Functional Disorders: neurogenic (spinal cord injury), diabetic neuropathy |
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pain
renal colic back pain at costophrenic angle Dx, Tx, Px |
clinical presentation of urinary tract obstruction
renal colic: due to stone, clot, papillae in distended ureter back pain at costophrenic angle from renal capsular distention nocturia and urgency if prostatic enlargement Dx: US/Imaging |
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urinary obstrx
complete vs partial, unilateral vs bilateral |
Unilateral or partial: may be silent until irreversible hydronephrosis
Partial bilateral-->tubulointerstitial lesions: --decreased concentrating ability, salt wasting --> distal tubular acidosis, htn --calculi form in stagnant urine --scarring Complete bilateral obstrx Causes: prostatic hyperplasia, posterior urethral valves, urethral strix, bladdder stones, neoplasms of bladder/pelvis Sx: oliguria/anuria MUST BE RELIEVED TO PREVENT DEATH, Relief => Massive Diuresis |
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List 4 types of common urinary calculi. Which is most common. Know causes of each, listing by frequency. Contrast as to:
pH of urine in which they form radiolucent vs radio-opaque on plain film of abdomen Know any unique morphology |
calcium oxalates/Calcium Phosphates, highest frequency, pH ~7, radioopaque
Magnesium ammonium phosphate stone, urease bacteria alkaline urine, Radio-opaque, staghorn calculi Uric Acid Stones Acid Urine Radio-lucent Cystine Stones Urinary pH: Acidic, Mildly Radiodense (visible) |
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calcium oxalates/Calcium Phosphates
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Frequency: Majority of stones
Urinary pH: near neutral/acidic pH Radio-opaque Morphology: Causes by freq: Ideopathic hypercalciuria, uric acidemia, no metabolic defect, hypercalciuria 2* to hypercalcemia, hypercalciuria 2* to renal tubular reabsorption defects, familial/vegan hyperoxaluria, hypocritraturia 2* to chornic diarrhea/acidosis |
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Magnesium ammonium phosphate stone
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Causes: urea splitting proteus or staph --> ammonia --> alkaline urine
Urinary pH: alkaline Radio-opaque Morphology: any size/location --> grow to staghorn calculi: large, branching, take shape of calyces & pelvis |
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Uric Acid Stones
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Causes: mostly from elevated uric acid: gout, leukemia/lymphoma
, else hyperuricemia, uricosuria 2* to Rx's: Vitamin C, thiazides, etc Urinary pH: Acid Urine Radio-lucent Morphology |
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Cystine Stones
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Genetic defect in renal reabsorption of Amino-Acids
Frequency: Uncommon Urinary pH: Acidic Mildly Radiodense (visible) Morphology |
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Staghorn calculi
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Magnesium ammonium phosphate stone
Causes: urea splitting proteus or staph --> ammonia --> alkaline urine Urinary pH: alkaline Radio-opaque Morphology: any size/location --> grow to staghorn calculi: large, branching, take shape of calyces & pelvis |
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Stone in alkaline urine
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Magnesium ammonium phosphate stone
Causes: urea splitting proteus or staph --> ammonia --> alkaline urine Urinary pH: alkaline Radio-opaque Morphology: any size/location --> grow to staghorn calculi: large, branching, take shape of calyces & pelvis |
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Radio-lucent kidney stones
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Uric Acid Stones
Causes: mostly from elevated uric acid: gout, leukemia/lymphoma , else hyperuricemia, uricosuria 2* to Rx's: Vitamin C, thiazides, etc Urinary pH: Acid Urine Radio-lucent Morphology |
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Most common kidney stones
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calcium oxalates/Calcium Phosphates
Frequency: Majority of stones Urinary pH: near neutral/acidic pH Radio-opaque Morphology: Causes by freq: Ideopathic hypercalciuria, uric acidemia, no metabolic defect, hypercalciuria 2* to hypercalcemia, hypercalciuria 2* to renal tubular reabsorption defects, familial/vegan hyperoxaluria, hypocritraturia 2* to chornic diarrhea/acidosis |
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Causes and consequences of hypercalcemia:
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- hyperparathyroidism
-carcinoma met'd to bone -homrone producing lung/renal CA -granulomatous disease: sarcoidosis, TB/Coccy -Hypervitamin-A/D-oses -Addison Disease |
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What are symptoms, labs, common locations of urinary calculi? Review consequences of obstruction.
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Sx: hematuria w/ cramping, colicky pain
Consequences: obstrx assoc w/ smaller stones --> hydroureter, hydronephrosis Ulceration & bleeding; obstrx & trauma --> Infx Common sites: passing brim of pelvis, entry into urinary bladder |
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Review and recognize all consequences of lead toxicity. What are the nephrotoxicities of lead?
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Pull out previous cards ofr led toxicity
Chronic tubulointerstitial renal disease Acute Toxicity: damage to proximal tubules --> aminoaciduria, phosphaturia, glycosuria (Fanconi syndrome) Chornic Toxicity: Diffuse interstitial Fibrosis: proteinuria, hyperuricemia, htn, gouty arthritis +- --> chronic renal failure -Htn -Renal Cell Carcinoma |
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What are the nephrotoxcity and the CNS toxicity of mercury?
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methyl mercury & ethylmercury do not respond to chelation
acute expsoure: proximal tubular necorsis chornic low dose exposure: mild renal dysfnx CNS Toxicity: Minamata disease aka Mad Hatter: Muscle Tremors, Dementia, Gingivitis, Cerebral palsy, Mental retardation |
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What are the nephrotoxicity and malignancies associated with cadmium exposure?
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pulmonary toxicity: obstructive lung disease
nephrotoxicity: concentrates in proximal convoluted tubules acute toxicity: proteinuria chornic toxicity: hypercalciuria, osteopenia, fractures, prostate and renal CA |
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Describe angiomyolipoma of the kidney by histology, behavior. What are characteristics of the associated syndrome?
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blood vessesl, smm, fat
--> tuberous sclerosis AD familal TSC1 or TSC2 Skin lesions: ash leaf macules, periungual fibromas cerebral cortex lesions: siezures, +- retardation ~half have angiomyolipoma |
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What is the appearance and association of oncocytoma? Is it benign or malignant?
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brown liver-like cut surface
cuboidal mitos rich eosinophlic cells benign, tho may reach ~10 cm in size |
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Know risk factors for renal cell carcinoma. What two gene defects are associated with these neoplasms?
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Males 50-70
Tob smoking Obesity (unopposed estrogen) asbestos petroleum industry Htn chornic renal failure dialysis (cystic kidney) Genetics (1/20 of cases) ---Von Hippel Lindau: hemangioblastomas of cerebellum & retina; 2/3 develop multiple bilateral RCC --Non-syndromal defects in VHL gene --Hereditary papillary carcinoma = MET oncogene |
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Stratify the 4 listed types of renal cell carcinoma by 1) most frequent; 2) good prognosis; 3) poor prognosis; 4) origin
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Clear Cell Carcinoma: most frequent, Origin: tubular epithelial cells
Papillary adenocarcinoma Chromophobe renal cell carcinoma; best prognosis Prognosis Excellent Origin collecting duct intercalated cells (Bellini) Collecting Duct Carcinoma: Least Frequent, worst prognosis Origin: renal medulla, |
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VHL gene
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tumor suppressor [ubiquintin ligase complex:] normally downregulates downregulates HIF-alpha, promotes VEGF, EPO & other growth factors--> pro-angiogenic [hemangioblastomas, polycythemia vera, renal cysts & renal cell carcinoma] assoc w/ 80% of RCC Clear Cell type; chrom 3
VHL inhibits insulin like growth factor (anti-apoptotic) |
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What is the gross and microscopic appearance of clear cell carcinoma of the kidney?
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solitary, unilateral if psortaic
multiple bilateral in VHL Spherical 9 cm (+- 6) yellow mottled surface w/ gray-white necrosis Vascular w/ areas of hemorrhage histology: clear/granular cytoplasm + for glycogen |
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What are the clinical presentation; paraneoplastic syndromes, pattern of metastases of renal cell carcinoma.?
to where is it most likely to met? |
Hematuria (not paraneoplastic) +
Polycythemia, Hypercalcemia, Htn metastatic sites: most to lungs by renal vein extension 33% to bones: osteoclastic "lytic" mets [Endocrine dysnfx: cushings; feminization/masculinization Hepatic dysfnx eosinophilia, leukemoid rxns] [else Mets regional LN's, Liver, Adrenals, Brain] 5 years survival ~half, better if no mets on discovery (present in 1/4) |
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Hematuria, Polycythemia, Hypercalcemia, Htn
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paraneoplastic syndromes, pattern of metastases of renal cell carcinoma.
metastatic sites: most to lungs by renal vein extension 33% to bones: osteoclastic "lytic" mets 5 years survival ~half, better if no mets on discovery (present in 1/4) |
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What are the risk factors, growth pattern and presenting symptoms of urothelial carcinoma of the kidney? What diagnostic studies are employed; how does the prognosis compare with renal cell carcinoma? What is the gross and microscopic morphology?
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Arises from renal pelvic transitional cell epithelium
Presenting sx: may be multiple locations along urinary tract, 10% of kidney carcionma prsesenting sx: hematuria, obstrx (flank pain, hydronephrosis), Risks: Tob, analgesic nephropathy, balkan nephropathy Diagnostic procudres: Urine cytology for atypical cells [imaging, retrograde pyelography, cytbrush of lesion] Morphology: papillary transitional cell carcinoma [or invasive] prognosis dependent upon depth of invasive Superficial >50%, Invasive ~10% at 5 yr, Tx: nephrectomy |
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Where do calculi lodge in ureters?
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Points of narrowing: ureteropelvic jnx, crossing iliac arteries, entry to bladder
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Review list of causes of ureteral obstruction. (Table 21-1)
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Calculi, strictures, tumors, blood clots, neurogenic
pregnancy, periureteral inflam, endometriosis, tumors |
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Define and list complications of :
Exstrophy of the urinary bladder |
Bladder opens anteirorly through abdominal wall. high risk for infection, intestinal metaplasia with risk for adenocarcinoma, surgically correctable.
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Define and list complications of :
Patent urachus |
fistulous tract from bladder to umbilicus may closet to bladder diverticulum, may persist as urachal cyst.
Site of adenocarcinoma of the bladder |
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Define and list associations and complications of sclerosing retroperitoneal fibrosis?
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fibrous proliferative inflammation which bilaterally obstructs ureters and causes hydronephrosis;
>= middle age, assoc. w ergot, beta adrenergics & beta blockers, fibrosis elswhere: Reidel's struma (thuroid). most are idiopathic possbly autoimune |
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List types of cystitis.
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Bacteira
Schistosoma haematobum in middle east Cyclophosphamide: hemorrhagic cystitis radiation cystits +- hemorrhagic Hemorrhagic & Intersitial |
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What are the characteristics of interstitial cystitis?
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painful form of chronic cystitis associated with SLE & autoimmunities, (females)
Intermittent severe suprapubic pain, frequency, urgency, dysuria, hematuria Sterile urine hunner ulcers in mucosa inflammation with mast cells & fibrosis of all layers |
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What is malakoplakia and its associations?
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chronic e coli infx in an immunosuppressed pt
gross: soft, yellow raised mucosal plaques micro: infiltrate of foamy M0 w/ PAS+ cytoplasm |
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List associations of urethritis.
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gonococcal: urethritis is 1st manifestation, produces uretheral strictures in males
nongonococcal: e coli, other coliforms; venereal: chlamydia trachomatis, mycoplasma assoc. prostatitis in males, cystitis in females |
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Metaplastic lesions of urothelium:
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Metaplastic: common w/ no adverse associations
--Cystitis cystica, cystitis glandularis Metaplastic 2* to injury: --squamous emtapolasa, nephrogenic adenoma (forms a nodule) |
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List the spectrum of urothelial neoplasms. Compare morphology, risk of recurrence, survivals. What is the most important determinant of prognosis for urothelial carcinoma?
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Papilloma = benign
Non invasive papillary (//sessile) tumors range form low malignant potential to high carcinoma in situ: flat but high grade Low grade papillary urothelial carcinoma aka Grade I papillary transitional cell carcionma mild nuclear atypia/pleomorphism; 50% risk of recurrence, low 10% invasivenss, low risk progression, excellent prognosis. high grade urothelial carcinoma: may be papillary, nodular, flat (in situ) or flat invasive; pleomorphic anaplastic cells with frequent mitoses, loss of polarity and cohesions. Px ~= depth of invasion; muscularis = worst. "superficial" tumors likely to have invasive areas. high risk of recurrence 40% 10 year survival. Carcinoma in situ: high grade flat neoplasm within epithelium. usually accompanies other transitional cell carinoma. aggressive with high risk for invasion, 60% invade if unTx. |
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Papilloma = benign
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Non invasive papillary (//sessile) tumors range form low malignant potential to high
carcinoma in situ: flat but high grade |
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Low grade papillary urothelial carcinoma aka Grade I papillary transitional cell carcionma
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mild nuclear atypia/pleomorphism; 50% risk of recurrence, low 10% invasivenss, low risk progression, excellent prognosis.
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high grade urothelial carcinoma
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may be papillary, nodular, flat (in situ) or flat invasive;
pleomorphic anaplastic cells with frequent mitoses, loss of polarity and cohesions. Px ~= depth of invasion; muscularis = worst. "superficial" tumors likely to have invasive areas. high risk of recurrence 40% 10 year survival. |
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Carcinoma in situ
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high grade flat neoplasm within epithelium. usually accompanies other transitional cell carinoma. aggressive with high risk for invasion, 60% invade if unTx.
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What are the causes and significance of squamous cell carcinoma of the urinary bladder?
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chronic bladder irritaiton, eg schistosoma haematobum; deeply invasive ad discovery, poor prognosis: 70% mortality at 1 year.
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What conditions are associated with adenocarcinoma of the urinary bladder?
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rare, histologically identical to GI tract tumors
arises from bladder epithlium: urachal remnants, exstrophy, etc. |
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What agents are risk factors for urothelial carcinoma?
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Cigarette smoking
industrial arylamines: 2-naphthylamine strongest 10+ years after exposure; pelvic radition betel nuts Shistosoma hematobium analgesic abuse phenacetin cyclophosphamide immunosuppressant long term heavy use cases hemorrhagic cystitis and risks transitional cell CA [molecualr alterations not an objx] |
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What is the clinical presentation and behavior, in general, of carcinoma of the bladder?
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painless hematuria is most common presenting complaint
+- obstruction --> pyelo, hydronephrosis; 50% are single localized to bladder, but likely to recur at any site along urinary tract, likely to crop up multifocally. |
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How is carcinoma of the bladder diagnosed?
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Dx via cytoscopy w/ biopsy;
Retrograde pyelography w/ contrast (x ray procedure) urine cytology: atypical cells w/ non-visualized tumor on cytoscopy suggests ureteral or kidney lesions flow cytometry for DNA, other markers [tx no in objex] |
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What mesenchymal tumors involve the urinary bladder
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rarely benign leiomyomas
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What is the nature of mesenchymal tumors that involve the urinary bladder
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malignantly: embryonal rhabdomyosarcoma (sarcoma botryoides): occur in infnacy/childhood, large mass protruding into lumen of bladder
[no objx for 2ndry bladder tumors] |
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What are causes, clinical features and morphology of bladder neck obstruction?
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Bladder neck obstruction, causes
congential narrowings, structures prostate hyperplasia/prostatitis immediately postpartum fibrosis bladder any tumor bladder calculi, foreign bodies neurogenic cystocele in women Clinical features: acute obstrx, distended bladder w/ thinned wall chronic obstrx; hypertrophied wall, trabeculations & diverticula Bilateral hydrophenosis in either |
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What two tumors involve the urethra of older females. What is the morphology of the more common?
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urethral carbuncle: vascular proliferation w/ inflammatory cells produces small painful nodule at extenrla meatus. sx: local pain & bleeding; more common
squamous cell carcinoma. sx: local pain & bleeding, distal urethra w/ poor prognosis. |
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How many cell layers are the normal prostate glands lined by?
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2 cell layers: basal layer of low cuboidal cells + columnar mucous secreting cells
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What three pathologic processes affect the prostate with any frequency? Which is the most common?
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Inflammation
Benign Nodular Enlargement - most common Tumors |
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What three categories can prostatitis be divided into?
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Acute Bacterial
Chornic - insidious, hx of UTI's Chronic abacteiral - insidious no hx of UTI's Granulomatous 2* to intentionall innoculation of BCG into baldder to tx CA |
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What causes acute bacterial prostatitis?
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Acute Bacterial prostatitis
E coli & gram neg rods fever, chills dysuria clinically tender & boggy, dx via urine cultures & clinical features |
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What are the symptoms of acute bacterial prostatitis?
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morpholgoy: minute disseminated abscesses, large coalescent areas of necrosis
diffsue edema, congestion boggy suppration of entire gland, eventual scarring |
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What are the clinical presentations of chronic bacterial prostatitis? What common clinical setting is found?
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chronic: insidious presentation: low back pain, dysuria, aSx
Hx of recurrent UTI's w/ same organism Dx: leukocytosis & positive bacteiral cultures in prostatic secretions |
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Why is chronic bacterial prostatitis difficult to treat?
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Difficult to treat because antibiotics seed prostate poorly
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How is chronic bacterial prostatitis diagnosed?
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morphology: aggregates of lymphos, plasma cells, M0's & PMNs
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What is the most common form of prostatitis ? What history is lacking as compared to chronic bacterial? How is it diagnosed?
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Chronic abacterial
no recurrent UTI's clinically same as chronic bacterial w/o Hx of UTI's: insidious presentation: low back pain, dysuria, aSx Caused by Chlamydia trachomatis, ureaplasma urealyticum prostatis secretions contain >10 WBC/high powered field |
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BPH is common in men over what age? What androgen is implicated? What drug is used to counteract the androgen?
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50 yo
DHT, 5 reductase inhibitor will reduce conversion of testosterone to DHT, estorgens may aid process |
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What is the tension of prostate smooth muscle mediated by? How can alpha-adrenergic receptor antagonists help in BPH?
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tension in prostate smooth muscle mediated by alpha 1 receptors
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What are the gross features of BPH? What are the hallmark microscopic features?
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hallmark feature is nodularity
prostatic nodules ~80 gms (+-20) originating in periurethral & transitional zones. nodules may compress urethra nodes easily identified on cross section glandular: yellow, soft, milkey fibrious- pale grey, tough no fluid no true capsule bilayered (inner columnar, outer cuboidal) epithlium predominates with aggregates of small & large cystically dilated glands epithlium thrown into numerous papillary buds and infoldings |
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What two secondary effects account for the clinical symptoms of BPH?
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compression of urethra: difficulty voiding
retention of urine: distention, hypertrophy & infections of bladder |
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What are the clinical symptoms of BPH?
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LUTS:
-frequency -nocturia -difficulty stopping & starting -overflow dribbling -dysuria -2ndry changes in bladder |
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Is BPH a premalignant lesion?
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Hyperplasia is not a premalignant condition
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What treatments are available for BPH?
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Tx: alpha blockers decrease smooth msucle tone, 5alpha reductase inhibitors reduce DHT, estrogen antagonizes DHT: shrinks prostate.
Noninvasive: TURP, US, laser therpay, hyperthermia, stents & radiofrequency |
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What is the most common form of cancer in males? Where does it rank in terms of cancer death in men?
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Prostate cancer: 1/6 men;
2nd leadign cause of CA death. that said: 90% indicental at autopsy: most men die with cancer rather than from the cancer. |
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Prostate cancer is usually a disease of men over what age?
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50's
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What are the five risk factors of prostate cancer?
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Ethnicity: Blacks
Age: 75% found >65 Family Hx High Fat Diet Genetics: androgen receptor AR gene amplification: related to CAG repeats: short repetaes ahve increased sensitivity to androgen (accts for ethnic variation) |
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What is the most common genetic alteration seen in prostate cancer?
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>90% show hypermethylation of GSTP1 glutathione S transferase gene promotor 1; GSTP1 important to prevent damage from carcinogens, hypermethylation turns it off.
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Where do most cases of cancer arise in the prostate?
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70% posterior lcoations, palpable through rectum
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Describe the gross features f prostate cancer?
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gritty & firm
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Describe the bony metastases of prostate cancer? What bone is most frequently involved?
|
spreads via direct invasion into seminal vesicles, bladder, spreads hematogenously to lumbar spine, spreads lymphatically to obturator nodes
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What are the hallmarks of malignancy?
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Hallmarks of malignancy: capsular invasion, perineural invasion
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What are the histologic features of prostate cancer? How many cell layers are present?
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Most are adenocarcinomas w/ well defined gland patterns
only one cell layer: outer basal layer absent; malignant acini smaller & closely spaced w/ little intervening stroma, may see papillary cribiform pattern; nuclei large, vaculolated 2/ 1+ nucleoli |
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What is PIN?
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Prostate intraepithelial neoplasia
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Is PIN a presumptive precursor lesion to carcinoma?
|
Seen in 80% of CA's
architecturally benign prostatic acini lined by cytolicocally atypical cells w/ prominent nucleoli no invasiaon, basal cell layer intact or fragmented intraacinar proliferation of cells w/ nuclear anaplasia similar molecular changes in PIN & invasive CA presumptive precursor lesion for carcinoma |
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What is the best known grading system? How many grades are in the system?
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Gleason grades 1-5
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How is a score obtained?
|
assign primary grade to dominant pattern, 2ndry grade to subdominant pattern, add 2 together to get gleason score
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Why is grading important?
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Low score = well diffrentiated, high score = poorly differentiated
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What staging system is used?
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Grading is good predictor for prognosis
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What is the significance of incidental cancers? What is the difference in outcome between a T1a and a T1b?
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TNM staging system is important for Tx
T1 = incidental finding on TURP T1a no progression over 10 years T1b 40% progress w/in 5 years |
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Do most cancer patients present with urinary symptoms?
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In CA urinary sx present late if at all
some present with back pain |
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The finding of osteoblastic bone mets in bone in virtually diagnostic of what?
|
finding osteoblastic mets is diagnostic for prostate cancer
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How are the cancers detected? What is required to confirm the diagnosis ?
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Digital rectal, transrectal ultrasound for early detection
transperineal/rectal biopsies to confirm CT/MRI to evaluate extent of disase (nodes), bone scane |
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Is PSA produced by normal glands? What is a common laboratory cutoff value for PSA? Is PSA cancer specific? Organ specific?
|
produced by normal and neoplastic endoethlium
sensitive not specific for CA, also elevated in BPH, prostatitis, infarct, instrumentation 30% of pts w/ CA have psa <4 |
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What things besides cancer can cause an elevated PSA?
|
PSA <4ng/ml normal
PSA 4-10ng/ml <50% risk for CA 10-20 >50% risk for CA >20ng/mL = frank CA |
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What four refinements have been proposed in the estimation and interpretation of PSA values?
|
PSA density: takes ratio between serum SPA adn volume of prostate gland
PSA velocity: rate of change in PSA with time Age specific range references |
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When is the use of per cent free PSA the most valuable? Are serial measurements of PSA useful?
|
Age specific range references
Ratio of free to unbound BSA: useful in discriminating when in 4-10ng/mL grey zone |
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What are the five types of therapy for cancer? What is the treatment for metastatic disease?
|
Watchful waiting
Surgery (radical, perineal, nerve sparing) Radiotherpay (external or brachytherapy) Cryotherapy Hormonal manipulation - orchiectomy, agonists of LHRH, mainstay of tx for metastatic disease |
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What is the role of PSA in screening currently?
|
controversial
|
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|
What is the expected specific gravity of first voided urine?
|
1.025
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What is “low, fixed specific gravity” and what is the significance?
|
end stage renal disease produces low, fixed specific gravity ~1.010
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What is the renal threshold for glucose? List causes of glycosuria.
|
180 +-20 = 160-200
Endstage kidney w/ normal blood sugar DM hyperglycemia: adrneal cortical/endocriend disease renal disease alters renal trheshold Rx: diuretics, birth control pills fever in children |
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List causes of ketonuria
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poorly controlled insulin dependent diabetes
anorexia nervosa/acute dieting prolonged vomiting GI diseases |
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What are the causes of proteinuria?
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renal disease: glomerular, tubulointerstitial, vascular
microalbuminuria 30-300mg first sign of diabetes Bence-Jones proteinuria of multiple myeloma only detected by immunoelectrophoresis, negative by dipstick w/o disease: usually trace to 1+ strenuous exercise exposure to extreme cold psychologic stress non-urinary disease: usually trace to 1+ hemorrhage systemic infections heart failure dehydration, starvation |
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What defines nephrotic urine? What are the other lab findings of nephrotic
syndrome. List causes. |
>3.5 gm protein/24 hours
oval fat bodies is the other cuase other lab findings lipiduria w/ fatty casts oval fat bodies hyperlipidemia hypoalbuminemia most common cause in childhood: minimal change disease other causes: henoch schonlein purpura adutls: daibetict neropathy focal segmental glomerulaosclerosis Systemic amyloidosis membraneous glomeurlonephritis 1* or 2* to: NSAIDs, Penicillamine, carcinoma of lung or colon, Hep B & C, Syphilis, SLE Urinary tract disease |
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What are the causes of hematuria / hemoglobinuria(by dipstick)?
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hematuria:
strenuous exercise produces transient glomerular defect disorders of uterus, vagina (menses) prostatitis, prostatic CA (late sign) disorders of urinary tract --tumors both malignant and benign: renal cell carincoma, urothelial carcinomas --glomerulonephritis --pyelonephritis --renal calculi --polycystic kidney, medullary sponge kidney --bleeding disorders incl anticoagulatnt herapy False negative with vitamin C |
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What is the significance of RBCs plus casts in urine?
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renal disease usually nephritic
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RBC's without proteinuria?
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bleeding distal to keyney
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Dysmorphic RBCs are seen in:
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suggestive of glomerulonephritis
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When would urine demonstrate hemoglobinuria but no RBCs on microscopic
examination? |
myoglobin:
after severe physical exercise rhabdomyolysis of all causes hemoglobin: hemolysis of RBC's within urinary tract intravascular hemolysis, hemolytic anemia, transfusion reaction |
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RBC casts
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bleeding from kidney
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WBC casts
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pyelonephritis
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RTE casts
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renal tubular damage- toxic or ischemic ATN
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Fatty casts-
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lipiduria: nephrotic syndrome
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Waxy casts:
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acute & chronic renal failure w/ severe tubular destruction
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Bile casts
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hepatorenal syndrome
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Red casts, no RBCs
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Myoglobin: rhabdomyolysis of all causes, extreme exercise
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What are the associations of positive nitrite? Can a UTI be present when nitrite
is negative? |
bacteriuria: only certain species: E Koli, Kleb, proteus, staph pseudomonas
yes: yeasts, enterococci, false negative from low vegetable diet |
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What does esterase detect? What diseases are associated with positive esterase?
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leukocytes pyuria
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List causes of leukocyturia.
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UTI, renal disease, renal calculi, ladder tumors, prostatitis urethririts
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glitter cells:
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PMNs in hypertonic solution
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One or more photomicrographs of crystals will be presented on exam. Recognize morphology and correlate with urinary tract pathology. Use drawing as reference and know uric acid, calcium oxalate, cystine, triple phosphate
crystals. |
shit
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What is the significance of increased renal tubular epithelial cells in urine? When
is ethylene glycol poisoning suspected? |
RTE + Oxalate = ethylene glycol
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What is the significance of :
Atypical cells ? |
malignant transitional epithelal cells = renal cell carcinoma, urothelal cell carcionma
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What is the significance of > 8 / hpf Squamous epithelial cells
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vaginal contamination of urine
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What is the urinalysis of endstage kidney disease? Review all lab findings
of uremia/ |
low volume, low fixed specific gravity, proteinuria, glycosuria, grace blood few rbcs & wbc's waxy casts
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GSPT1
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the most common genetic alteration seen in prostate cancer?
>90% show hypermethylation of GSTP1 glutathione S transferase gene promotor 1; GSTP1 important to prevent damage from carcinogens, hypermethylation turns it off. |
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The most common cuase of htn in children
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Reflux neuropathy
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nodular prostate
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hallmark feature of benign hypertrophy
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embryonal rhabdomyosarcoma
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malignant mesenchymal tumor in the bladder; occur in infnacy/childhood, large mass protruding into lumen of bladder
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hunner ulcers
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in mucosa of bladder assocaited with interstitial cystitis, mostly from autoimmunity aka chronic pelvic pain syndrome
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EM: uniform diffuse effacement of foot processes
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Minimal change disease aka lipoid nephrosis
most common cause of nephrotic syndrome in children LM: lipid in tubles EM: no deposits, uniform and diffuse effacement of food processes Rapid repsonse to steroids nephrotic phase may recurr (come back to the rest) |
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Glomerular disease responds to steorids
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Minimal change disease aka lipoid nephrosis
most common cause of nephrotic syndrome in children LM: lipid in tubles EM: no deposits, uniform and diffuse effacement of food processes Rapid repsonse to steroids nephrotic phase may recurr (come back to the rest) |
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cystitis cytica
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metaplastic cystic lesion with no adverse assocations
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cystitis glandularis
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metaplastic cystic lesion with no adverse assocations
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liver toxicity with obstructive lung disease, bone disorder
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cadium
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Finely granular cortical surface
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of benign nephrosclerosis.
Kidney of benign htn: sclerosis of renal arterioles & small arteries assoc w/ age, diabetes, htn & African Americans Pathogenesis: intimal thickening + Hyaline deposition from extravasated plasma --> narrowing of lumens --> patchy ischemic tubular atrophy with intestitial fibrosis; glomeruli become sclerotic Finely granular cortical surface Clinical presenation: GFR >= Normal, mild proteinuria, increased risk of renal failure |
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Circulating IC Nephritis EM
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Trapping of cirgulating immune complexes within glomerul --> complement activation --> damage
EM: electron dense deposits in mesangial, subendothelial (between endothelial cells & GBM), subepithelial (btw podocytes & outer surface of GBM, rare) |
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LM: diffuse uniform thickening of capullary wall
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membranous GN
LM: diffuse, uniform thickening of capillary wall; silver stain shows spikes of BM between deposits IF: granular deposits of IgG and C3 EM: irregular dense subepithelial deposits, foot processes lost Causes: 85% idiopathic; rest: drugs, malignant tumors, SLE, infx, autoimmune disorders Clinical: insidious onset of nephrotic syndrome, indolent; proteinuria does not repsond to steroids; proteinuria persists in 60$; 40% dvlp renul insufficiency in 10 years. only 10% reach renal failure in 10 years. |
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EM: irreglar dense subepithelial deposts, foot processes lost
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membranous GN
LM: diffuse, uniform thickening of capillary wall; silver stain shows spikes of BM between deposits IF: granular deposits of IgG and C3 EM: irregular dense subepithelial deposits, foot processes lost Causes: 85% idiopathic; rest: drugs, malignant tumors, SLE, infx, autoimmune disorders Clinical: insidious onset of nephrotic syndrome, indolent; proteinuria does not repsond to steroids; proteinuria persists in 60$; 40% dvlp renul insufficiency in 10 years. only 10% reach renal failure in 10 years. |
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granular deposits of IgG, IgM and C3 in mesangium along BM
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acute proliferative (post-strep)immunologically mediated GN w/in a mo after certain GABHS strains;
enlarged hyperceullar glomeruli, diffuse proliferation of mesangial, endotheial cells, diffuse infiltration of PMN,s M0's; tubules will have RBC casts, +- interstitial edema/inflam IF: granular deposits of IgG, IgM and C3 in mesangium and along BM EM: discrete amorphous electron dense deposits on epithelial side of BM --"humps" of C3 Clinical: young child w/ abrupt onset of malaise & hematuria w/in mo after recovering from sore throat RBC casts, milkd proteinuria, periorbital edema, mild htn adult onset atypical Lab findings: elevated anti-streptococcal ab titers, low serum C3, cryoglobins in serum Most children recover totally. 2% slow progression to chronic GN, <1% rapidly progressive GN Only 2/3 adults recover completely |
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humps of C3
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acute proliferative (post-strep)immunologically mediated GN w/in a mo after certain GABHS strains;
enlarged hyperceullar glomeruli, diffuse proliferation of mesangial, endotheial cells, diffuse infiltration of PMN,s M0's; tubules will have RBC casts, +- interstitial edema/inflam IF: granular deposits of IgG, IgM and C3 in mesangium and along BM EM: discrete amorphous electron dense deposits on epithelial side of BM --"humps" of C3 Clinical: young child w/ abrupt onset of malaise & hematuria w/in mo after recovering from sore throat RBC casts, milkd proteinuria, periorbital edema, mild htn adult onset atypical Lab findings: elevated anti-streptococcal ab titers, low serum C3, cryoglobins in serum Most children recover totally. 2% slow progression to chronic GN, <1% rapidly progressive GN Only 2/3 adults recover completely |
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flea bitten kidney
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focal hemmorhages
complications of htn |
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fibrocystin
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childhood polycystic kidney disease
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parallel cylindrical cysts at right angles to cortx
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childhood polycystic kidney disease
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MET oncogene & renal CA
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papillary carcinoma
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gut hormone binds growth hormone secretogogue receptor
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Ghrelin
THE ONLY GUT HORMONE THAT INCREASES FOOD INTAKE Source: arcuate nucleus of hypothalamus + empty stomach Fnx: binds growth hormone secretogoge receptor obese individuals not able to fully suppress ghrelin |
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Stones caused by thiazides
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uric acid
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patchy interstitial suppurative finlam, intratubular aggreagates of PMN's and tubular necrosis
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hallmark morphology of acute pyelonephritis
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stone caused by too much vitamine C
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acidic Ca2+ oxalate
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stones caused by uric acidemia
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uric acid
Ca2+ oxalate (acidic & forms nidus) |
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CA originating from Tubular epithelial cells
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Clear Cell Carcinoma
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CA originating from duct intercoloating cells
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Chromophobe
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CA originating from Collecting Ducts
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Belllini Collecting Duct Carcinoma
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