KENdensed Renal Pathophysiology Notes I



KENdensed Renal Pathophysiology Notes I

Glomerular disease thru Acute Renal Failure pgs 62-130 in Renal PPD notes

Glomerular diseases:

Histologic Alterations

1. Glomerular hypercellularity – cellular proliferation, leukocytic infiltration

2. Basement Membrane thickening- thickening of BM, deposition of electron dense material (most common thickening is by extensive subepithelial deposition, as in membranous glomerulonephritis)

3. Hyalinization- accumulation of material that is homogenous, and eosinophilic by LM

4. Sclerosis- Loss of structural detail of Glomerular tuft by increased BM or mesangial matrix, other alterations include fibrin deposition, amyloid, lipid

I. The Clinical Syndromes:

|Syndrome |Clinical Findings |Causes |

|Acute |Hematuria, azotemia, variable proteinuria, |Post streptococcal |

|Nephritic Syndrome |oliguria, edema, HTN |SLE |

| | |Polyarteritis nodosa |

|Rapidly progressive GN |Acute nephritis, proteinuria, ARF |Postinfectious |

| | |Systemics: |

| | |SLE |

| | |Goodpastures |

| | |Vasculitis |

| | |Henoch-Schonlein purpura |

|Nephrotic Syndrome |Proteinuria, hypoalbuminemia, |Membranous GN |

| |hypercholesterolemia, edema |Minimal Change Disease (Lipoid nephrosis) |

| | |FS glomerulosclerosis |

| | |Membranoproliferative GN |

| | |IgA Nephropathy |

| | |Sytemics: |

| | |DM |

| | |Amyloidosis |

| | |SLE |

| | |Drugs ( Gold, penicillamine) |

| | |Infectious (malaria, syphilis, Hep B, HIV) |

| | |Carcinoma |

|Chronic Renal Failure |Azotemia progressing to uremia |Almost any glomerulopathy! |

|Asymptomatic heamturia or |Glomerular hematuria, subnephrotic proteinuria|(incidental finding in routine exam) |

|proteinuria | | |

|Disease |Clinical Presentation |Pathogenesis |Clinical Course |LM |IF |EM |

|Poststrep | | | | | | |

|glomerulonephritis |Acute nephritis |Ab mediated, circulating |Case: young child w/ malaise, fever, |Enlarged, hypercellular bloodless |Granular IgG, C3 in |Subepithelial humps |

| | |or planted Ag |nausea, oliguria, hematuria after sore |glomeruli, |GBM and mesangium | |

| | | |throat. RBC casts in urine, mild |Diffuse proliferation, leukocytic | | |

| | | |proteinuria, periorbital edema, some HTN. |infiltration | | |

| | | |Labs: ASO titer, serum C3 | | | |

| | | |Tx: 95% recover w/ conservative Na/H20 | | | |

| | | |balance therapy | | | |

|Goodpasture’s |RPGN |Anti GBM Ag |RBC casts in urine, moderate proteinuria, |Crescents, formed by proliferation |Granular immune |Distinct ruptures in GBM, |

| | | |variable HTN, edema |of parietal cells and by |deposits |some subepithelial |

| | | | |monocyte/macrophage migration into | |deposits |

| | | |Tx: intensive plasmapheresis, steroids, |Bowman’s space | | |

| | | |cytotoxic agents (these also relieves | | | |

| | | |pulmonary failure) | | | |

|Idiopathic RPGN |RPGN |Anti GBM immune complex |Therapy as with Goodpastures, but results |Proliferation, crescents |Linear IgG, C3 or |Deposits or none |

| | | |not as dramatic | |granular, or none | |

|Membranous |Nephrotic Syndrome |Ab mediated, in situ |Major cause of Nephrotic syndrome in |Uniform, Diffuse capillary wall |Granular IgG, C3 |subepithelial deposits |

|Glomerulonephritis | | |adults: Tumor, ALE, gold, mercury, Drugs, |thickening, BM spikes between | | |

| | | |Hep B, syphilis, schisto, malaria, |deposits | | |

| | | |idiopathic. | | | |

| | | | | | | |

| | | |Case: insidious nephrotic syndrome, | | | |

| | | |hematuria, HTN, w/ increasing sclerosis of | | | |

| | | |glomeruli, rising BUN… notoriously variable| | | |

| | | |course | | | |

|Minimal Change (Lipoid |Nephrotic Syndrome |Unknown |Children w/ massive proteinuria, renal |Normal |Negative |Loss of foot processes |

|nephrosis) | | |function remains good, | | | |

| | | |Tx: corticosteroids | | | |

|Focal Segmental |Nephrotic syndrome, |Unknown |Compared to Minimal change disease: inc |Hallmark is degeneration and focal |Focal IgM and C3 |Loss of foot processes, |

|glomerulo sclerosis |non-nephrotic | |hematuria, red GFR, inc HTN, poor steroid |disruption of visceral epithelial | |epithelial denudation |

| |proteinuria | |response, many progress to chronic GN, IF |cells. Focal and segmental | | |

| | | |shows deposits. |sclerosis, collapse of BM, inc | | |

| | | |Rare spontaneous remission. |mesangial matrix and hyalinosis | | |

|Disease |Clinical Presentation |Pathogenesis |Clinical Course |LM |IF |EM |

|Membranoproliferative GN| | | | | | |

|Type I |Nephrotic Syndrome |Immune complex |Older children, young adults. Some patients|Large hypercellular glomeruli, |IgG, C3, C1, C4 |Subendothelial deposits |

| | | |develop crescents, and RPGN, 50% develop |Mesangial proliferation, GBM | | |

| | | |CRF. |thickening, splitting, some | | |

| | | |Tx of steroids, immunosuppressive agents |crescents | | |

| | | |not very effective. | | | |

|Membranoproliferative GN| | | | | | |

|Type II |Hematuria, CRF |AutoAb, alternative |Older children, young adults. Some patients|Large hypercellular glomeruli, |C3, some IgG |Dense deposits |

| | |complement pathway |develop crescents, and RPGN, 50% develop |Mesangial proliferation, GBM | | |

| | | |CRF. |thickening, splitting, some | | |

| | | |Tx of steroids, immunosuppressive agents |crescents | | |

| | | |not very effective. | | | |

| | | |Recurrence is common in Type II | | | |

|IgA Nephropathy |Recurrent hematuria and |Unknown |Affects children/young adults in 1-2 days |Focal proliferative GN; mesangial |IgA, IgG, IgM, C3 in|Mesangial and |

|(Berger’s disease) |/or proteinuria | |of mucosal infections of Resp, GI or |widening |mesangium |paramesangial dense |

| | | |urinary tracts, slowly progressive disease | | |deposits |

|Chronic |CRF |Variable |Insidious development slowly progresses to |Hyalinized glomeruli |Granular or negative|none |

|glomerulonephritis | | |death in uremia. Most patients have HTN, | | | |

| | | |manifested by cerebral or cardio symptoms. | | | |

Chronic renal failure:

Major Causes of CRF

1. Glomerulopathies

2. Hypertension

3. Obstructive uropathy

4. Interstitial nephritis

5. Hereditary (PCKD)

I. Intact Nephron hypothesis – nephrons in damaged kidneys operate at a higher functional level so that gross kidney function is preserved

II. Discrimination between ARF and CRF

1. H & P- Previous serum Creatinine, nocturia, history of foray urine, edema, orthostatic HTN, muscle tenderness, etc

2. Kidney size – small, CRF

3. Renal Osteodystrophy – yes- CRF

4. Carbamylated HgB – yes- CRF

5. Anemia – no- ARF

Stages of renal failure

1. Decreased renal reserve – excretory regulatory capacity intact, GFR dec. but labs normal

2. Renal insufficiency – mild azotemia, impaired concentrating ability, nocturia, anemia

3. Renal failure – anemia inc, hypocalcemia, hyperphosphatemia, hyponatremia, impaired concentrating ability, nocturia, isothenuria, metabolic acidosis

4. Uremia – constellation of signs/symptoms

a. Signs and symptoms of uremia:

i. Nervous- stupor, coma, fatigue, malaise, insomnia, memory, speech slurred, tics, dementia, headache, cramps

ii. GI – hiccup, parotitis, gastritis, anorexia, pancreatitis, ulcer, nausea/vomiting

iii. Hematology – anemia, bleeding

iv. Immunology – inc infection/ cancers

v. Cardio – pericarditis, atheromatosis, edema HTN, cardiomyopathy

vi. Pulmonary – pleuritis, edema

vii. Skin –pruritus, nail atrophy, melanosis

viii. Endocrine – glucose intolerance, hyperlipidemia, hyperPTH, hypogonadism, growth retardation

ix. Bone – renal osteodystropy, amyloidosis

x. Misc – thirst, weight loss, uremic fetor, hyperthermia

Functions of the Kidney

1. Fluid-electrolyte balance, acid/base homeostasis

a. Types of filtrate products

i. Non regulated – plasma concentration falls w/GFR (creatinine, BUN)

ii. Partial regulation – balanced until GFR < 30-40 ml/min

(Hydrogen ion, uric acid, phosphate, calcium)

iii. Complete regulation – balance maintained until GFR < 10-15 ml/min (Na+, K+, H20)

b. CRF loss of renal concentrating ability

i. At max urine output, CRF patients make less urine than normal and at higher osmolarity—more Na+ loss

ii. At min urine output, CRF patients make more urine than normal—and at less osmolarity—unable to excrete enough Na+

c. Signs of abnormal fluid balance

i. Abnormal concentration

• Nocturia

• Volume depletion/hypernatremia w/o access to H20 or impaired thirst

ii. Abnormal dilution

• Hyponatremia

• Greater susceptibility to H20 intoxication

d. Na+ excretion with CRF

i. CRF patients excrete same amount of Na+ as normal patients, but they have dec GFR, so they lose higher % of Na+

ii. Regulation of Na+ by CRF patients

• Adaptation occurs in distal tubule

• Aldosterone levels normal to high

•ANP inc

iii. Uremic symptoms from abnormal Na+

•Hypernatremia-- edema, CHF, hypertension

• Hyponatremia—volume contraction, ARF

e. e. K+ excretion with CRF

i. K+ regulation with CRF

f. • Maintained until GFR ................
................

In order to avoid copyright disputes, this page is only a partial summary.

Google Online Preview   Download