Renal diseases & Blood Vessels Disorders

Question 1

What is the clincal presentation of someone with Benign hypertensive nephrosclerosis?

Answer 1

• Usually normal or slight reduced GFR
• long standing history of hypertension
• Slowly progressive elevation in serum Creatinine
• Mild proteinuria (<1 g/day)
• No microscopic hematuria
• Few progressing to ESRD

Risk factors for ESRD: - Blacks ( 8- fold) - Higher blood pressure - Second underlying CKD (diabetes)

Question 3

What is the benign hypertensive nephrosclerosis map?

Answer 3

Question 4

What occurs to the vasculature, glomerulus, and Tubules/interstitium in Benign hypertensive?

Answer 4

* Vascular: medial & intimal thickening ( response to hemodynamic changes) * Hyaline arteriolosclerosis ( due to extravasation
of plasma proteins through injured endothelium)

*Glomerular: • Global sclerosis (ischemic injury)…leading to
nephron loss • FSGS( adaptive injury), compensatory
hyperfiltration due to nephron loss *

Tubules & interstitium: • Tubular atrophy • Interstitial fibrosis (ischemic mediated)

Question 5

What are the main features of Malignant hypertensive nephrosclerosis?

Answer 5

• Renal disease associated with marked increases in blood pressure
generally >180/120mmHg/(diastolic >130mmHg)

• Develops in patients with pre-existing essential hypertension, secondary hypertension { pheochromocytoma, primary hyperaldosteronism)
• Most common in young black males

Question 6

What is the Malignant hypertensive nephrosclerosis pathogenesis map part1?

Answer 6

Question 7

What is the Pathogenesis Map of Malignant hypertensive nephrosclerosis part 2?

Answer 7

Question 8

Malignant hypertensive CRISIS requires what type of therapy?

Answer 8

Intravenous anti-hypertensive medications to avoid irreversible organs damage

• Renal failure + other organs involved: Brain, eye, heart, lungs, large vessels

Question 9

Hemolytic uremic syndrome (HUS)
Thrombotic thrombocytopenic purpura (TTP)

what are the clincial path?

Answer 9

• Disorders characterized by abnormal platelet aggregation leading to thrombosis in arterioles & capillaries throughout the body
• Thrombosis in small vessels results in mechanical injury to circulating RBCs with resultant“microangiopathic hemolytic anemia”
• Clinically: microvascular thrombi lead to ischemic injury to target organs: kidney, brain, heart

Question 10

HUS/TTP: Diagnosis?

Answer 10

• Microangiopathic hemolytic anemia ( schistocytes in peripheral blood smear)
• Thrombocytopenia
• Purpuric rash
• Acute renal failure (mild to moderate proteinuria, hematuria)
• Neurological abnormalities: headache, confusion, seizure, stroke
• Fever

Question 11

What is the clinical presentation of someone with HUS?

Answer 11

• Classically seen in children (one week after episode of bloody diarrhea caused by enterohemorrhagic E. coli ( 0157:H7)
• More severe renal failure, less pronounced CNS involvement
• Associated with other infections: viral, Shigella, Salmonella
• Drug induced: Quinine (tonic water), Gemcitabine, Cyclosporine, Ticlopidine, Oral contraceptives
• Microangiopathic hemolytic anemia, purpric rash, acute renal failure

Question 12

What are the common features of someone with Renal artery stenosis (RAS)?

Answer 12

• Narrowing of one or both renal arteries
• 75-90% due to occlusion by atheromatous plaque
• 10-25% fibromuscular dysplasia
• Others: Takayasu’s arteritis, aortic/renal artery dissection

Question 13

What are some of the Renal consequence- ischemic nephropathy seen in RAS?

Answer 13

• Diffuse ischemic atrophy in kidney of affected RA stenosis

• Crowded glomeruli
• Atrophic tubules
• Interstitial fibrosis • No significant arteriolosclerosis in kidney of affected RA stenosis:
• Arterioles “protected” from transmission of high pressure due to stenotic renal artery
• Hypertensive arteriosclerosis in contra-lateral kidney due to increased systemic pressure

Question 14

What is the clinical presentation of someone with Renal artery stenosis ?

Answer 14

Physical Exam/Labs: • Flank or epigastric bruit • ARF

History: - Onset of HTN age <30 or >55 - Sudden onset of uncontrolled HTN in previously well controlled patient - Accelerated/ malignant hypertension - Intermittent pulmonary edema with normal LV
function

Question 15

What is the TTP- clinical presentation?

Answer 15

• CNS involvement more pronounced , renal failure less severe

Fever

Renal failure

Purpuric Rash

• Microangiopathic hemolytic anemia

Question 16

What is the common features of Autosomal dominant polycystic kidney disease ?

Answer 16

• Characterized by development of multiple fluid filled cysts…leading to increased kidney size

90% have Abnormal Chromosome 16p13.3 (PKD1 gene)

10% - Abnormal Chromosome 4q21 (PKD2 gene) **Milder phenotype: •Later onset of cysts •Fewer & smaller cysts •Slower progression •Later age of ESRD

Question 17

WHat is the pathogenesis map for ADPKD?

Answer 17

Question 18

How does ADPKD cause Renal Failure?

Answer 18

• Proposed mechanism: “Growth of cysts leads to”:

• 1- Compression & destruction of normal
  adjacent parenchyma
• 2- Glomeruli are overperfused

BUT: - Small number of nephrons <5% involved - No evidence of FSGS

Question 19

What are the renal manifestation of someone with ADPKD?

Answer 19

• Hypertension 50-70% = Cysts →compression of renal vessels–> renin, aldosterone
• Hematuria 50-60% = Rupture of cysts in collecting system
• Flank pain 60% = Stretching of renal capsule
• Nephrolithiasis 30% = >50% uric stones, calcium oxalate

Question 20

What are the Extra-renal manifestations of someone with ADPKD?

Answer 20

• Hepatic cysts • Cerebral aneurysms • Pancreatic cysts • Cardiac valve disease (MVP, AR) • Colonic diverticular disease • Abdominal wall & inguinal hernia

• Prevalence increases with age • 80% over age 30 • Usually asymptomatic & mild • Synthetic liver function intact • May cause pain due to distension on liver
capsule

Question 21

What are the common features of someone with Childhood Polycystic kidney?

Answer 21

• Autosomal recessive

• Genetically homogeneous “Gene PKHD1 (chromosome 6p21-23)”
{Protein fibrocystin}
• Enlarged, cystic kidneys at birth

• Cysts arising from collecting ducts
• Hepatic fibrosis
• Typical outcome: variable {death in infancy or childhood}

Question 22

Common Features of Alport’s syndrome?

Answer 22

• Defects in Collagen IV synthesis basement
• Mutations { COL4A4 & COL4A5 genes }
• X-linked (80%) / AR & AD (20%)
• 5-20 yr ( M>F)
• Nephritis ( hematuria, proteinuria, renal failure)
• Nerve deafness 55%
• Eye disorders 15-30% (juvenile form)
• Hematologic disorders rare (thrombocytopenia) membrane

Question 23

What is seen in the LM,IF, and EM of someone with Alport Syndrome

Answer 23

LM: Variation of the thickness of BM & FSGS

IF: negative & ** negative / Segmental stain for alpha 3, 4, 5 collagen GBM

EM: - Thin BM ( <150nm ) - Splitting & lamination