-
Functions of kidneys
- Excretion of waste products of metabolism
- Regulation of the body's concentration of water & salt
- Maintenance of appropriate acid balance of plasma (7.2-7.4)
- Secretion of hormones
-
Hormones secreted by the kidneys
- Renin- regulates BP
- Erythropoietin- increases RBC formation
- Prostaglandins- mediators of inflammation
-
4 Compartments of the kidneys
- Glomerulus
- Tubules
- Interstitial tissue
- Kidney vessels
-
Diseases of kidney glomerulus are almost always caused by _____.
Immune system pathologies
-
The kidney tubules are mainly affected by ______ & _______.
Toxins, infections
-
Kidney interstitial tissue is mainly affected by ______ & _____.
Toxins, infections
-
Kidney vessels are mainly affected by ________.
Cardiovascular pathologies
-
Glomerulus
- Bundle of capillaries located within a Bowman's capsule
- Highly permeable to water
- Contains a network of afferent & efferent arterioles
-
3 layers of the capillaries of the glomerulus
- Endothelial cells
- Basement membran
- Epithelial cells
-
Endothelial cells of the capillaries of the glomerulus
Innermost layer of capillary; have holes called pseudofenestrations between them
-
Epithelial cells of the capillaries of the glomerulus
- aka podocytes or visceral epithelial cells
- Outermost layer of the capillaries with filtration slits between them
-
Nephrin
Glycoprotein located between the podocyte slits of the capillaries of the glomerulus that aids in selective filtration
-
Parietal epithelial cells
Similar in nature to the podocytes, but they line the internal surface of the Bowman's capsule
-
Mesangial cells
Fill in the spaces b/w bordering vessels in the glomeruli- account for scar tissue in the healing process
-
Juxtaglomerular cells
- Located in the area where the afferent arterioles enters the glomerulus
- Function is to regulate BP
- Produces renin when BP decreases
-
Glomerulonephritis (GMN) or NephrItic syndrome
Inflammation of all 3 layers of the glomeruli capillaries
-
GMN/NephrItic syndrome is characterized by:
- Hematuria
- Oliguria
- Azotemia
- Hypertension
-
Hematuria
- Change in the permeability of the arterial wall in the glomerulus
- Results in blood & RBC casts in the urine
-
Oliguria
Decreased urine production resulting from decreased GFR
-
Azotemia
- Nitrogen in the blood
- Waste products of metabolism are not able to go from the bloo to the urine due to oliguria
- Is a biochemical abnormality (not clinical) characterized by increased levels of creatine & blood urea nitrogen (BUN) in the bloodstream
- There are no clinical symptoms until the process becomes advanced, in that case, it is referred to as uremia
-
Hypertension due to GMN/NephrItic syndrome
- Juxtaglomerular cells release renin due to a decrease in GFR
- Renin-> angiotensinogen-> angiotensin 1-> angiotensin 2 (vasoconstrictor)-> increased BP
- Angiotensin 2 also stimulates the release of aldosterone (increases salt & water reabsorption)-> increased BP
-
3 main pathogenic mechanisms of GMN
- 1. Circulating immune complex deposition GMN
- 2. Anti-Glomerular basement membrane GMN
- 3. Heyman GMN
-
Circulating immune complex deposition GMN
- Type 3 hypersensitivity reaction
- Antigen & antibody are both present in flowing blood-> binding takes place in circulating blood to form an immune complex-> immune complex settles in tissue
- Phagocytes try to engulf the complex & release destructive enzymes against it
- The immune complex is protected because it has settled within the wall of the glomerulus-> more enzymes are released which eventually begin to digest the wall of the glomerulus
- Vasculitis occurs locally
-
Anti-glomerular basement membrane GMN
- Type 2 hypersensitivity reaction
- BM becomes "non-self"-> the antigens are fixed & antibodies are released by the immune system-> an immune complex forms on the BM
- Phagocytic cells cannot engulf this complex so they release destructive enzymes that destroy the BM & the immune complex
-
Heymann GMN
- Not a specific type of hypersensitivity
- Marked by an autoimmune reaction against the podocytes as well as some antigens located wthin the podocytes-> leads to destruction of the podocytes
-
Specific Causes of GMN
- 1. Acute proliferative (post strep infectious) GMN
- 2. Rapidly progressive crescentic GMN
- 3. IgA nephropathy
- 4. Alport syndrome
-
Acute proliferative (post strep infection) GMN
- Type 3 hypersensitivity
- Occurs predominantly in children; 99% recover if treated on time
- Caused by beta hemolytic streptococcus group A
- Antibodies are produced & form a complex w/ the antigen that settles in the glomerular tissue in the subentimal layer of the membrane (layer b/w BM & endothelium)
- Adults recover in 50% of cases (the other 50% switch to chronic GMN)
-
Rapidly progressive crescentic GMN
Group of disorders marked by hyperplasia of the parietal cells of the Bowman's capsule that merge to form a crescent shape-> the increased amount of cells compress the glomerulus & lead to pressure atrophy-> development of oliguria & death if not treated within weeks or months
-
3 types of rapidly progressive crescentic GMN
- Type 1 anti-GBM
- Type 2 immune complex deposition
- Type 3 pauci-immune
-
Type 1 anti-GBM (rapidly progressive crescentic GMN)
- Type 2 hypersensitivity
- Goodpastures syndrome
-
Goodpastures syndrome
- Development of antibodies against alveolar & glomerular basement membranes; in the lungs there is the accumulation of RBC's & hemoptosis
- Idiopathic in more than 50% of cases
-
Type 2 immune complex deposition (rapidly progressive crescentic GMN)
- Type 2 hypersensitivity
- idiopathic
- SLE
- Henoch-Schonlein purpura
-
Systemic lupus erythromatosis (SLE)
- Occurs in young women (3x more common in black women)
- Kidneys are most involved organ
- Butterfly rash on face
- Anti-nuclear antibodies are produced against double stranded DNA
- Exposure to UV radiation can trigger an episode
- Also includes joint involvement (like RA) & hypertension
- May also be triggered by post strep infection
-
Henoch-Schonlein purpura (aka hemorrhagic vasculitis)
- Develops in late adolescent males
- 4 manifestations
- Formation of purpura (subcutaneous hemorrhages) on the legs, abdomen, & buttocks
- Duodenitis & gastritis
- Arthritis
- Nephritic syndrome (most dangerous)
-
Type 3 pauci-immune (rapidly progressive crescentic GMN)
- Not related to a specific type of hypersensitivity
- Idiopathic vasculitis
- Wegner's granulomatosis
-
Wegner's Granulomatosis
- Mostly affects middle-aged males
- Anti-neutrophil cytoplasmic auto-antibodies are produced
- Necrotic granulomas of the upper/lower respiratory tract
- Necrotic vasculitis of arteries, arterioles, & capillaries
- Facial bones may be destroyed (decay)
-
Polyarteritis (periarteritis) nodosa
- This used to be considered a type of rapidly progressive GMN type 3, but it has been found that this disease does NOT cause GMN
- Vasculitis of middle & small arteries only w/o any aretriole or capillary involvement in all parts of the body except lungs
- Involves pouching of the vascular walls
- Kidney is the organ MC involved -> leads to destruction of vessels, ruptures/hemorrhages, microinfarction causing decreased lumen size, compression of surrounding tissue, & wet gangrene
-
IgA nepropathy aka Berger's disease
- Do NOT confuse w/ BUERGER's disease
- MC cause of GMN in the world
- Manifested as hematuria 1-2 days after a common cold, UTI, or intestinal infection
- Caused by overproduction of IgA (which is normally only present in mucous membranes) -> immune complexes found in mesangial cells
- Not related to a specific type of hypersensitivity
-
Buerger Disease
- Do NOT confuse with BERGER's disease
- aka thromboagitis obliterans
- Segmental thrombosing vasculitis of middle & small arteries AND veins & nerves in the vicinity
- Has an affinity for the tibial & radial nerves
- Strong association w/ smoking
- Classic symptom is instep claudication- pain after walking
-
Alport syndrome
GMN w/ other symptoms such as lens dislocation, cataracts, corneal dystropy, & hearing/ear problems
-
Chronic Glomerulonephritis
- Typically the end stage of any glomerular disease
- The kidney is not able to function properly because the functional tissue has been replaces w/ connective scar tissue-> a contracted kidney may develop-> the kidney becomes yellow, pale, & coarsely granular-> ends w/ the development of chronic renal failure
- Symptoms may include crystal deposits on the skine, ammonia breath, nausea, CNS problems, secondary hyperparathyroidism leading to osteoporosis
|
|