kidney pathophysiology

8/13/2019 Kidney pathophysiology

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ANATOMY

KIDNEYS:

1./ Capsule

2./ Renal cortex:

Nephron: (Cortical 85 %, Juxtamedullar 15 % /reach into the medulla)

Bowmans capsule

Glomerulus:

Afferent arteriole (artery to the glomerulus)

Capillary:

Endothelial cells

Basement membrane

Podocyte foot processes

Efferent arteriole (artery from the glomerulus):

This vessel supplies the tubules, as well.

The efferent arteriole ends in capillaries, the capillaries arejoined into venules and the venules return to the renal vein.

Mesangial cells

Tubule: Proximal convoluted tubule

Loop of Henle: Descending limb of loop of Henle

Ascending limb of loop of Henle

Distal convoluted tubule JGA / Juxtaglomerular apparatus

Collecting tubule

3./ Renal medulla

4./ Renal pyramid

5./ Renal pelvis

URETERS

BLADDER

URETHRA


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STRUCTURE OF GLOMERULUSSTRUCTURE OF GLOMERULUS

http://herkules.oulu.fi/isbn9514264290/html/x782.html

http://www.colorado.edu/intphys/Class/IPHY3430-200/image/19-4d.jpg


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PHYSIOLOGY:KIDNEYS:

Urine formation:As a result of glomerular function - Filtration / Filtrate formation

As a result of tubule function - Reabsorption- Secretion / Excretion

- Concentration and dilution

Removal of pathological metabolic productsHormone production:Renin-Angiotensin-Aldosterone System, Erythropoietin,

Prostaglandins, Hydroxylation of Vitamin-D

Regulation of salt and water homeostasisRegulation of acid-base balance

URETERS: Forward urine

BLADDER: Store urine

URETHRA: Void urine

FUNCTION OF GLOMERULUSFUNCTION OF GLOMERULUS --FILTRATIONFILTRATION

Proximal convulated tubule

Intersticial pressure 10 mmHg

Bowmanscapsule

Glomerulus

Afferent arteriole Efferent arteriole

Hydrostatic pressure75 mmHg

Tubular pressure10 mmHg

EffectEffectvvfiltrationfiltrationpressurepressure7575--3030--1010--10=2510=25 mmHgmmHg

Oncotic pressure30 mmHg

FUNCTION OF THE NEPHRONFUNCTION OF THE NEPHRON

H+, K+, NH3NaCl, water, K+,COLLECTING DUCT

reninNaCl, K+, Ca2+, Mg2+,

NH4+,

DISTAL TUBULE

waterLOOP OF HENLE

H+, NH4+, organic anion,

organic cation

NaCl, water, K, glycose,

Aminoacids, PO43-,

HCO3-, Ca2+, Mg2+,

urate, urea

PROXIMAL TUBULE

SECRETIONSECRETIONREABSORPTIONREABSORPTIONTUBULUSTUBULUS

FILTRFILTRCICIGLOMERULUSGLOMERULUS

FFIILLTTRRAATTIIOONN


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GGLLOOMMEERRUULLAARR DDIISSEEAASSEESS

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MAIN POINT: Lesion of nephrons:

1./ Glomerular lesion:

a./ Increased permeability:

Due to lesion of filtration barrier

(Components: endothel, BM and podocyte foot

processes)

b./ Intracapsular (within the Bowmans capsule) pressure

increases

2./ Tubular lesion

CAUSES:

IIMMMMUUNNOOCCOOMMPPLLEEXXMMEEDDIIAATTEEDDLLEESSIIOONN

Local (in situ) immunocomplex formationEndogenous Ag: tissue Ag; e.g. BM - Goodpastures sy

Exogenous Ag: bacterial Ag:

Similar to anionic glomerular components

Circulating immunocomplex formationEndogenous Ag: - DNA and tumor

Exogenous Ag: - Staphylococcus, Streptococcus and viral

antigen

NNOONN--IIMMMMUUNNOOCCOOMMPPLLEEXX--MMEEDDIIAATTEEDDLLEESSIIOONNToxic damage of podocytes

Activation of the alternative pathway of the complement system

Necrotic lesionAs an effect of free radicals and proteolytic enzymes released from

leukocytes

Hyperfiltration injury

of intracapillary hydrostatic pressure due to resistance

(vasodilatation) of the afferent artery

Atubular glomerulusProximal tubules are sensitive to hypoxia

(ischemia or tubulointerstitial disorders)

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Short term: Hyperfiltration of the intact glomerulari are responsible for the GFR

Long term: Glomerular lesion results in:

Proteinuria

Hypertension: Due to TGF-, angiotensin II, PDGF and

endothelin

Increase of EC matrix that leads to

Glomerular hypertensionProgressive renal failure


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IIII..//GGLLOOMMEERRUULLOONNEEPPHHRRIITTIISS::MAIN POINT:

Inflammation of glomeruli: Leukocyte infiltration

Antigen - antibody complex deposition

Complement activation

Proliferation: Originating from glomerular cell matrix or leukocytesintra /endocapillary proliferation

(endothelial cells)extracapillar proliferation

(originating from Bowmanns capsule, epithelial cells and/or

monocytes)

COURSE: acute, subacute or chronic

EXTENSION: focal or diffuse

SYMPTOMS: Oliguria < 400 ml

Intracapsular pressure increases due to proliferative processes in

the Bowmans capsule. This pressure is opposite to that of the

filtration one, therefore GFR decreases.Proteinuria/albuminuria

Less than in nephrotic syndrome, because proliferation reduces

filtration surface

Hypoproteinemia

Edema Partially due to reduced onkotic pressure and

permeability increase

Hypo- or asthenuria

Reduced tubular function is the consequence of decreased renal

tubular blood supply due to glomerular damage

Hematuria (deformed/dysmorphic RBCs),

Casts: granular, hyalin and RBCHypertension

Azotemia

Renal failure


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TYPES:

Acute nephritic syndromeEndocapillary proliferative glomerulonephritis (GN)

-hemolytic Streptococcus (Type 12)Nephritis-associated streptococcal cationic protease and its zymogen

precursor (NAPR) have been identified as a glyceraldehyde-3-phosphatedehydrogenase that functions as a plasmin(ogen) receptor. This binds toplasmin and activates complement via alternate pathway. Antibody levelsto NAPR are elevated in streptococcal infections (of group A, C, and G)

Membranproliferative GN

Dense deposit disease

Rapidly progressive glomerulonephritisSemilunar-type GN

Necrotizing and semilunar-type GN

Granular immune deposit GN

Linear immune deposit GN

Asymptomatic hematuria and/or proteinuriaIgA nephropathy the most common GN

Diffuse mesangial proliferative GN

Focal proliferative and necrotizing

Thin basement membrane GN

Alport nephropathy

Chronic GN and renal failure

SLE (WHO)


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TTUUBBUULLOOIINNTTEERRSSTTIITTIIAALL DDIISSEEAASSEESS

DEFINITION: These diseases generally involve tubules and/or the interstitium of the kidney and

spare the glomeruli

TYPES:

I./ Acute:

Causes:

a./ Drugs:

NSAID, sulphonamide, diuretics,

anticonvulsives, antiepileptics,

ACE inhibitors, H2(histamine) blockers

b./ Acute infections:

Bacteria: Streptococcus, Staphylococcus, E. coliViral: Ebstein-Barr, Cytomegalo and HIV

Idiopathic

Pathological signs:

Interstitial edema

Cortical and medullary leukocyte infiltration

Focal tubular cell necrosis

Clinical picture: - A c u t e p y e l o n e p h r i t i s

Cause: Infection (hematogenous or ascending)

Signs: Shivering, high body temperature,

tachycardia

Diarrhea, nausea and vomitus

Pain (costovertebral)

Blood: Leukocytosis (shift to the left),

Increased red blood cell sedimentation rate

Bacteria (in haematogenous infections)

Urine: Bacteriuria

(105colonies/mL)

PyuriaWBC and WBC casts

Microscopic hematuria

Renal function: Intact

Blood pressure: Normal

Course: - complete recovery orlater

- chr. pyelonephritis


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II./ ChronicCauses: a./ Hereditary renal disease: polycystic kidney,

Fanconi sy. with tubular damage

b./ Toxic agents:

Exogenous toxins:- Drugs: analgesics and aspirin

- Lead- Lithium

Endogenous toxins: Uric acid gout

Hypercalcemia

Hypokalemia (polyuria, polydipsia)

Malignant tumor

c./ Recurrence of acute infections

Pathologic signs:

Interstitial - nephritis

- fibrosis

Propagation ofmononuclear cells

Tubular damage: - atrophy- dilatation

- thickening of basement membrane

Clinical picture: - C h r o n i c p y e l o n e p h r i t i s

Cause: Acute pyelonephritis or

Chronic beginning of a bacterial infection

Signs: Fatigue, anemia,

nausea,vomiting

Blood: leukocytosis is absent

Increased red blood cell sedimentation rate

normal Se creatinineUrine: proteinuria (tubular)a significant fraction of

the protein is low molecular weight

microscopic hematuria

WBC in urine, with leukocyte casts

Urine might be sterile, as well

(bacteria cannot be detected)

pyuria

Renal function: tubular dysfunction

specific gravity of the urine is reduced

Blood pressure:highretinal vessel alterations


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PREDISPOSING FACTORS FOR NEPHROLITHIASIS:

1./ Organic core formation:fibrin, mucopolysaccharides, bacteria and inflammatory cells (WBCs)

2./ Concentration of stone forming substance exceeds solubility in the urine:urates, phosphates and oxalates

3./ Obstruction of urinary outflow:congenital disorders, tumors and pregnancy

4./ Alterations in the urine:concentrated due to insufficient fluid intake

pH acidic

basic (due to genitourinary infection)

decreased inhibitory factor for nephrolithiasis:

Mg, pirophosphate, citrate and peptides

5./ Other risk factors:

genetic, climatic, dietary, mineral content of water, exercise and age


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CLINICAL SIGNS OF STONES:

pain, spasm

vomitus

anuria

paralytic ileushematuria

COMPLICATIONS OF STONES:

Urine stagnation: Urinary tract infection

Decrease of filtration and anuria

Tubule damage

RREENNAALL FFAAIILLUURREE

DEFINITION: Kidneys fail to adequately function:Urine is not formed - anuria

Do not detoxicate - azothemia

TYPES:

ACUTE RENAL FAILURECHARACTERISTICS: Sudden decrease of glomerular filtration (in hours)

50% decrease of creatinine clearance

Anuria occur

Increase of Se creatinine is 44 micromol/L (50% increase)

Sudden deterioration of renal function that requires dialysis

CAUSES:

I./ Prerenal:

1./ Condition with hypovolemia (exiccosis):

External loss (intestinal tract, kidney and skin)

Internal loss (into interstitium, abdominal cavity and intestines)

2./ Conditions with decreased cardiac output :

Myocardium disorders: MI

Pericardial tamponade, fibrosis

Vitiums

ArrhythmiasPulmonal hypertonia

3./ Disturbed renal filtration:

Renal vessel constriction: A and NA effect and

Hypercalcemia

In hepatorenal syndrome:

renal perfusion due to abdominal

vessel dilatation

Hyperviscosity syndrome: Macroglobulinemia

Myeloma

Polycystic kidney


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II./Renal:

1./ Renovascular occlusion:

a./ renal artery occlusion:

atherosclerosis, thrombosis, embolia and vasculitis

b./ renal vein occlusion:thrombosis and external occlusion

2./ Glomerular and microvessel disorders:

glomerulonephritis

vasculitis

microangiopathy:

hemolytic uremic syndrome /HUS,

thrombotic thrombocytopenic purpura /TTP,

disseminated intravascular coagulation /DIC)

toxemic pregnancy

malign hypertension

3./ Acute tubular necrosis

a./ toxic:endogenous -myoglobin - rhabdomyolisis

hemoglobin - hemolysis

urea - cell lysis

these substances are filtrated via glomeruli,

precipitated in the tubules and

cause epithelial cell degradation

exogenous toxins: ethylene glycol

chemotherapy medicines

antibiotics (aminoglycosides)radiological contrast media


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III./Neuromuscular signs:

Dementia due to aluminium intoxication

Decreased concentrating ability

Muscle spasm (restless leg)

Peripheral neuropathy, due to elevation of remnant nitrogen

Enecephalopathy,Cerebral hemorrhage,

Cerebral edema,

Sensory and motory nervous system disorders

IV./ Cardiovascular system: hypertension,

heart failure,

pericarditis,

rhythmic disorders

V./ Pulmonary disorders: pleuritis,

dyspnoe

VI./ Gastrointestinal signs: Nausea, vomitus, hiccupAnorexia

Gastrointestinal hemorrhage

Uremic halitus

Uremic ulcus: due to defense

Helicobacter pylori infection

VII./Endocrine system: Secondary hyperparathyroidism

Hyperglycemia

Amenorrhea

Oligospermia, decreased testosterone

Decreased growthVIII./ Skin:

Anemic skin

Yellow deposits due to urochrom

Purpuras due to thrombocyte function disorders

Pruritus due to increase of pathological metabolic substances

IX./Metabolic changes: Hypothermia due to decreased metabolism

Hypertrigliceridemia

Metabolic acidosis

Hypo- or hypernatremia and hypo- or hyperkalemia

might occur as wellGlucose intolerance

kidney pathophysiology

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