Pathology: Renal Vascular Diseases And Htn

Front 1

What changes happen in the kidney with age?

Back 1

*Thickening of the arterial walls results in decreased renal blood flow.

*There is increased thickness of the glomerular basement membrane and an increase in mesangial cells; increased mesangial matrix.

*There is increased incidence of atherosclerotic changes in renal vessels with age.

*Some glomeruli become nonfunctional due to sclerosis; one expects to find sclerotic glomeruli in the kidney of any elderly person. About one-half of the glomeruli have been lost by age 90 years.

*There is a decrease in mass of the JGA and a corresponding decreased renin release. This is modest and doesn't account for much harm.

Front 2

ID and discuss.

Back 2

*Atherosclerotic Kidney.

*Kidneys are small and scarred as result of slowly progressive ischemia.

*Note circular depressions along with other scars; these also represent ischemic change.

*Similar gross appearance might be seen in chronic pyelonephritis.

Front 3

Discuss Hypertension and the Kidney:

Back 3

*Can result from renal disease.

*Exacerbates or causes renal disease through changes in vasculature.

*A classic example is renal artery stenosis.

Front 4

ID and discuss.

Back 4

*Renal Artery Stenosis.
*An uncommon cause of hypertension.
*Atherosclerosis is usually at the origin of the renal artery.
*More common in elderly or diabetic men.
*Leads to a small kidney with atrophy due to ischemia.

Front 5

Back 5

*"Goldblatt" kidney. Shrunken, atherosclerotic change.

Front 6

Back 6

JUXTAGLOMERULAR CELL HYPERPLASIA in a kidney with a narrowed renal artery.

Left: Hypertrophied JGA cells are on top of and around the black, upside down "V" looking streak.

Right: EM of the JGA cells. Black dots are secretory granules that are sites of renin storage.

Front 7

What are the changes in Renal Artery Stenosis and Hypertension?

Back 7

*Decreased renal blood flow.

*Increased renin production. Increased angiotensin II. Increased aldosterone.

*Vasoconstriction, Na retention, increased blood volume.
*This combination results in hypertension.

Front 8

ID and discuss:

Back 8

Fibromuscular Dysplasia:
*Unilateral or bilateral.
*A heterogeneous group of conditions.
*More common in young women.
*Thickening of one or all three layers by fibrous or muscular tissue. The media is most often involved.

Front 9

Back 9

*Medial Fibroplasia, AKA Fibromuscular Dysplasia. Renal artery. Aorta on the right.

Front 10

Back 10

FIBROMUSCULAR DYSPLASIA WITH MEDIAL HYPERPLASIA.
*Dark pink shows hypertrophied medial muscle fibers.

Front 11

Back 11

FIBROMUSCULAR DYSPLASIA OF RENAL ARTERY WITH MEDIAL HYPERPLASIA (Elastic tissue stain). The media between the two elastic lamina is tremendously thickened. This is the most common type of fibromuscular dysplasia.

Front 12

Back 12

FIBROMUSCULAR DYSPLASIA WITH INTIMAL FIBROPLASIA.

Front 13

Discuss HTN:
What are the 2 kinds?
How is it acquired?

Back 13

*Essential (primary): 95%.

*Secondary: renal, vascular, endocrine, neurogenic.

*Hypertension is the result of altered relationship between blood volume and vascular resistance.

Front 14

What causes essential HTN?

Possible gene defects?

Environmental?

Back 14

*Interaction of genome and environment affecting cardiac output and SVR.

*Possible gene defects:
1) Aldosterone metabolism.
2) Na reabsorption.
3) Transport of Na and Ca across SM membrane.

*Environmental: stress, obesity, smoking, heavy Na intake, physical inactivity.

Front 15

What are 2 hypotheses for causes of essential HTN?

Back 15

1) Cause: defects in renal Na homeostasis. Reduced renal excretion of Na in setting of previous normotension. Result: > blood volume and > cardiac output, vasoconstriction, hypertension. The “Na homeostat” has been reset at a higher level.

2) Cause: increased vascular resistance. This increase in resistance can be caused by either/or:
*Vasoconstriction.
*Hypertrophy and/or hyperplasia of SM cells, resulting in thickening of vascular walls and narrowing of lumens.

Front 16

What are the Renal Causes of Secondary Hypertension?

Back 16

*Vascular disease.

*Glomerular diseases –-> volume expansion.

*Chronic renal diseases such as pyelonephritis or interstitial nephritis.

*Chronic renal failure by increasing blood volume through salt and water retention.

*Tumors of JG apparatus --> increased renin.

Front 17

What are the CV Effects Of Hypertension?

Back 17

*Functional and structural changes in small arteries and arterioles.

*Atherosclerosis affects larger elastic and muscular arteries.

*HTN indirectly affects these vessels by ACCELERATING atherosclerosis.

Front 18

Discuss Hyaline Arteriolosclerosis:

Back 18

*Gk. Hyalinos: made of crystal or glass.

*Kidney is small or normal size, fine nodularity on the surface, thin cortex.

*Seen most commonly in hypertension. THIS IS A HALLMARK OF PEOPLE WITH ESSENTIAL HTN!

*Also in diabetes and the elderly.

Front 19

Back 19

L: Hypertensive renal disease.
R: Normal kidney disease.

*Disregard color ∆. Note that normal kidney is smooth and glistening. On hypertensive kidney, capsule was adherent; this is why you see pocking, scarring, granularity. This is typical of uncomplicated hypertensive renal disease.

Front 20

Back 20

L: Hypertensive renal disease. Cortical region is quite thin. This is due to tubular atrophy and fibrosis.

R: Normal kidney disease.

Front 21

Back 21

*FOCAL CORTICAL ATROPHY (HYPERTENSION).
*Note some normal tubules in lower right. Note wedge-shaped area depressing down; this is fibrosis/scarring; this is what causes the gross granularity.

Front 22

Back 22

*HYALINE ARTERIOLOSCLEROSIS.
*Note dramatically reduced lumen, due to massive thickening of arteriolar wall. THINK HTN!!!

Front 23

ID and discuss this image.

Back 23

*HYALINE ARTERIOLOSCLEROSIS.
*The lesions are characterized by glassy thickening of arterial and arteriolar walls. In this section an involved arteriole (arrow) is adjacent to a sclerotic glomerulus (asterisk). Though seen in other conditions, hyaline arteriolosclerosis is most common and most severe in hypertensive patients.

Front 24

What is the pathogenesis of Hyaline Arteriolosclerosis?

Back 24

*Glassy thickening is due to plasma components leaking across injured endothelium and to increased ECM production by SM.

*Consists of plasma proteins, fibrin, collagen, and basement material.

*Clinically referred to as “benign nephrosclerosis.”

Front 25

Discuss Malignant Hypertension:

Back 25

*Usually, this is superimposed on essential or secondary HTN. Less frequently, it will be the first manifestation of HTN.

*Associated with HYPLERPLASTIC arteriolosclerosis, AKA Malignant nephrosclerosis.

Front 26

Back 26

*Gross kidney in malignant HTN.
*Note brownish red areas on kidney surface; these represent areas of hemorrhage in the renal tissue.

Front 27

Back 27

*Cut surface of kidney of a 23 y/o man. Cerebral hemorrhage. Malignant hypertension. Note hemorrhages in pelvis and sinus.

Front 28

Back 28

*Malignant hypertension, gross, high magnification.
*Pinpoint hemorrhages represent glomeruli. Note hemorrhagic streaks in medulla. Histology showed fibrinoid necrosis of arteriolar walls.

Front 29

Discuss and describe Hyperplastic Arteriolosclerosis:

Back 29

*Associated with malignant hypertension.

*Thick laminated walls with narrow lumen.
*EM shows abundant SM cells in intima.
*Fibrinoid necrosis when severe.
*Sometimes mucoid changes in wall.

*These lesions occur in other organs.

Front 30

Back 30

Hyperplastic Arteriolosclerosis. Increased number of SM cells in a concentric arrangement.

Front 31

Back 31

Hyperplastic Arteriolosclerosis. Note laminar arrangement in vascular wall, “onion skin lesion”.

Front 32

Back 32

MALIGNANT HYPERTENSIVE NEPHROPATHY. Hyperplastic Arteriolosclerosis. Onion skinning; lumen of vessels is essentially obliterated.

Front 33

Discuss Fibrinoid Necrosis:

Back 33

*Necrosis of arteriolar walls.
*Occurs when hypertension is very severe.
*Lesions contain fibrin, Gammaa Globulins, albumin, and complement.
*Rarely, there are inflammatory cells; this is called "necrotizing arteriolitis."
*EM shows electron-dense deposits.

Front 34

Back 34

Fibrinoid Necrosis. Inflammatory cells are present, so this is necrotizing arteriolitis.

Front 35

Back 35

A. FIBRINOID NECROSIS OF AFFERENT ARTERIOLE
B. HYPERPLASTIC ARTERIOLITIS

Front 36

Back 36

Maternal vessel in HTN as part of eclampsia.

Front 37

Discuss Renal Arterial Embolism:

Back 37

*Causes infarcts.
*Embolus comes from heart, aorta, or renal arteries.
*Rarely, paradoxical embolism (originates in venous blood, but due to patent foramen ovale, crosses into arterial circulation).
*Recent infarcts are pale and wedge-shaped; surrounded by red border.
*Old infarcts pale depressed white V-shaped scars.

Front 38

Back 38

*Orientation: Aorta on left. RA has been opened to show embolus.
*Pale red embolus occludes renal artery at origin. The rest is propagated thrombus. RHD with MS.

Front 39

Back 39

*Renal Infarcts. A classical pale wedge-shaped renal infarct with the base of the triangle on the capsule. They may be solitary or multiple, unilateral or bilateral. They are surrounded by a congested, red border. This is coagulative necrosis.

Front 40

Back 40

Shows a repeated renal emboli. There are fibrosed remnants of old infarcts. Note depressions. The point: an isolated renal infarct won't kill you, but these things can keep on happening.

Front 41

Back 41

*ATHEROMATOUS (atherosclerotic) EMBOLUS in an artery branching off from the renal artery. This is a chunk of atherosclerotic plaque that popped off a patient during a cardiac catheterization.

Front 42

Back 42

*AORTIC ATHEROSCLEROSIS. This is just to show that catheterization can pop off these plaques, and they can embolize...including to the kidney.

Front 43

Discuss ATHEROMATOUS EMBOLI to the kidney:

Back 43

*More likely in Elderly persons.
*Occur with manipulation of aorta at surgery or catheterization or ballooning.
*Embolization occurs from fragments of plaques from aorta or renal artery or aortic valve.

Front 44

What are some miscellaneous diseases With Renal Vascular Involvement?

Back 44

*Lupus erythematosis.
*Polyarteritis nodosa.
*Scleroderma.
*Wegener’s granulomatosis.
*Microscopic polyangiitis.

Front 45

Discuss Renal Vein Thrombosis:

What causes it? Who do you see it in?

Back 45

*A result of compression, phlebitis, renal tumors, amyloidosis, and hypercoagulation syndromes.
*Sometimes seen in fetuses of diabetic mothers.
*Or in infants with severe gastroenteritis.
*Hemorrhagic cortical infarction.
*Nephrotic Syndrome.

Front 46

Back 46

Renal vein thrombosis. Looks pretty much like any other thrombus; just need to be able to tell that this is in a vein.

Front 47

Discuss Papillary Necrosis:

What causes it? Who do we see it in?

Back 47

*Characterized by impaired blood flow in vasa recta; results in necrosis of papilla.

*Acute pyelonephritis.
*UT obstruction.
*Diabetes mellitus.
*Sickle cell nephropathy.
*Analgesic nephropathy.

Front 48

Back 48

Papillary necrosis in a case of diabetes. Yellow areas represent necrosis of the papillae.

Front 49

What are Thrombotic Microangiopathies?

What do they have in common? Where do you see them? 3

Back 49

*A group of diseases not easily differentiated.

*Characterized by endothelial injury and/or platelet activation/aggregation.

*You see thrombi in interlobular arteries, afferent arterioles, and glomerular capillaries.

Front 50

What are the changes in the blood that you see in Thrombotic Microangiopathies?

What are the 3 types I need to know?

Back 50

*Microangiopathic hemolytic anemia, thrombocytopenia, thrombi formation, and acute renal failure are present.

*Classification: HUS and TTP:
1) Typical hemolytic-uremic syndrome
2) Atypical hemolytic-uremic syndrome
3) Thrombotic thrombocytopenic purpura.

Front 51

Discuss Typical HUS. What causes it? What does it look like? What can it result in?

Back 51

*Most common in children.
*A toxin from infection by E. coli, 0157:H7 or Shigella dysentery.

*GI symptoms or flu-like syndrome at onset.

*Bleeding, oliguria, hematuria, neurological changes.

*Microangiopathic hemolytic anemia and acute renal failure.

Front 52

Discuss toxin role in Typical HUS:

Back 52

*The Shiga toxin is carried by neutrophils in the circulation.

*It acts on the endothelium of the glomerular capillaries to increase adhesion of leukocytes, increase production of endothelin, and decrease nitric oxide. DAMAGE TO ENDOTHELIUM IS KEY!!!

*It can also enter the cells and cause cell death.

Front 53

What pathological traits do HUS and TTP have in common?

Back 53

*Cortical necrosis, subcapsular petechiae.
*Thick glomerular capillary walls.
*Mesangial matrix can become disrupted.
*Platelet-fibrin clots are present in capillary lumens. THIS IS KEY!
*Fibrinoid necrosis in walls of small arteries and afferent arterioles.

Front 54

Back 54

HEMOLYTIC UREMIC SYNDROME (FIBRINOID NECROSIS OF HILAR ARTERIOLE). Irregular pinkish areas represent fibrinoid necrosis.

Front 55

Back 55

HEMOLYTIC UREMIC SYNDROME. Fibrinoid necrosis visible within the glomerulus.

Front 56

Back 56

TTP WITH STAIN FOR FIBRIN; the red thrombin is totally occluding the capillary lumina. NOT GOOD! REMEMBER THIS SLIDE.

Front 57

DISCUSS Atypical HUS:
Who does it affect? What characterizes it?

Back 57

*Most common in adults.
*No Diarrhea, or not much.
*Not related to Shiga toxin.
*Can occur in a number of clinical settings.

Front 58

What kinds of causes are to blame for Atypical HUS? 6

Back 58

1) Mutations in complement genes:
*Commonly factor H which normally protects cells from complement activation.

2) Pregnancy or post-pregnancy complications:
*Postpartum renal failure after uncomplicated pregnancy and delivery.
*After placental abruption.

3) Antiphospholipid antibodies.

4) Vascular diseases affecting the kidney:
*Systemic sclerosis.
*Malignant hypertension.

5) Chemotherapy or immunosuppression: Mitomycin, cyclosporine, et al.

6) Radiation of the kidney.

Front 59

What is Postpartum Renal Failure?

Back 59

*It is renal failure and microangiopathic hemolytic anemia within 10 days following an uncomplicated pregnancy.

*This entity is distinct from renal failure following abruption, PP hemorrhage, AF embolism, puerperal sepsis.

Front 60

Back 60

*POSTPARTUM RENAL FAILURE (Atypical HUS).
*No platelets are visible!
*RBCs are small and "helmeted."

Front 61

Discuss Thrombotic Thrombocytopenic Purpura (TTP):
What symptoms?
Who does it occur in?
What's the differential?
What's the pathogenesis?

Back 61

*Rare disease, most common in young women.

*Fever, neurological changes, hemolytic anemia, thrombocytopenia, and renal failure.

*Differential diagnosis from adult HUS; severe neurological manifestations and less severe renal disease favor TTP.

Front 62

What is the pathogenesis of TTP?

Back 62

*Different pathogenesis from HUS (which results from endothelial injury and activation).

*TTP due to acquired defect in proteolytic cleavage of von Willebrand Factor (vWF) multimers (can be autoimmune, can be due to drugs).

*Rarely, hereditary.
*The defect is in a vWF protease, ADAMTS 13, a disintegrin and metalloprotease.

*WEIBEL-PALADE BODIES SECRETE MULTIMERS!!!!!!!