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THE KIDNEY
Diseases of the kidney- Classification

1. CONGENITAL

PCKD- Polycystic kidney diseased.

has many types

show symptoms in the later stage of life (some may show early too)

like hypertension

usually accidentally found

2. GLOMERULAR DISEASES

primary glomerular nephritis- directly affects kidney

secondary glomerular nephritis- due to an existing pathology like DM/ due to

streptococcus infection, etc

3. TUBULAR DISEASES

ischemic effect

toxins (toxic tubular necrosis)

tubulo- interstitial diseases: acute and chronic pyelonephritis

4. VASCULAR DISEASES

blood vessels affect- hypertension

5. OBSTRUCTIVE DISEASES

nephrolithiasis

hydronephrosis

6. TUMORS

benign

malignant

THE KIDNEY 1
 GLOMERULAR DISEASES

GLOMERULONEPHRITIS
A.K.A Bright's disease

Can be primary/ secondary

Primary: acute and chronic

Secondary: Includes systemic and hereditary diseases which secondarily affect the
glomeruli- SLE, Diabetic neuropathy, amyloidosis

1. ACUTE GLOMERULONEPHRITIS

( a/ c diffuse proliferative GN, endocapillary GN)

2 Types:

a/c post- streptococcal GN - throat infection (1-2 weeks)

a/ c non streptococcal GN

→ A/ C POST STREPTOCOCCAL GN

mc form of glomerulonephritis

common in children 2- 14 years of age

sudden onset 1-2 weeks of streptococcal infection (pharyngitis/ skin- impetigo)

ETIOLOGY:

Beta hemolytic streptococci

PATHOGENESIS:

Deposition of the immune complex in the basement membrane of the glomeruli —→

inflammation (proliferative)

Proliferation of mesangial, endothelial and epithelial cells → capillary obstruction —

> decreased blood flow —> decreased GFR → oliguria

Retention of fluid —> oedema

Decrease of excretion of metabolites —> uremia/ azotemia

Damaged glomerular endothelium —> increased vascular permeability —>

proteinuria, hematuria

Stimulation of JGA —> Increased BP (only in adults, when severe)

THE KIDNEY 2
 Proteinuria, haematuria, azotemia, oedema, oliguria, hypertension— all these are mild=
Nephritic syndrome

MORPHOLOGY

Gross

Bilateral enlarged kidneys

Petechial hemorrhage of the cortex - Flea bitten appearance

Microscopic

Glomeruli: diffuse involvement; enlarged, hypercellular, proliferation of mesangial,

endothelial and occ. epithelial cells—> infiltration of neutrophils, monocytes,
deposits of fibrin

Tubules: swelling and hyaline droplets in tubular cells, lumen with red cell casts

Interstitium: edema and WBC infiltration

Electron microscopy: Deposition of immune complex on glomerular basement

membrane

Immunofluorescence- IgG and C3 (if IgA is present - Ig A nephropathy==

differentiating point b/ w the 2 conditions)

Clinical Features

2 - 14 yrs

sore throat/ skin infection = 1-2 weeks prior

Sudden onset of fever , malaise, nausea, oliguria

microscopic/ intermittent hematuria

periorbital edema

hypertension ( poor prognosis)

Lab investigations

urine micro- RBC, Red cell cast

Urine chemical - Blood, Protein

Blood- azotemia (urea, creatinine, BUN); leukocytosis, neutrophilia; Increased ASO

titre

→ A/ C NON STREPTOCOCCAL GN

Bacteria- staphylococci, pneumococci, meningococci, salmonella, pseudomonas

THE KIDNEY 3
 Virus- herpes, mumps

Parasite- plasmodium, toxoplasmosis

Prognosis is not very good

ACUTE NEPHRITIC SYNDROME

Acute onset of microscopic hematuria, mild proteinuria, edema, oliguria, hypertension

following infective illness

HEMATURIA- Slight with smoky urine ; urine microscopy shows RBCs, Red cell
casts; Chemical examination shows Hb

PROTEINURIA- Mild= 3mg/ 24hrs

EDEMA- Mild due to Na- Water retention

OLIGURIA- Variable according to severity

HYPERTENSION- Mild, Variable according to severity

PRIMARY GLOMERULONEPHRITIS

RPGM

Minimal change GN

MGN

Focal

Focal segmental glomerulosclerosis

Rapidly progressing GN/ Cresentic GN/ extracapillary GN

proliferation of parietal epithelial cells lining the bowmwn's capsule, visceral

epithelial cells and mononuclear cells

clinically: A/c GN or ARF

eg: SLE, Goodpasture' s syndrome

THE KIDNEY 4
 Minimal change disease- Lipoid nephrosis, foot process disese,

idiopathic, drugs, HIV, Hodgekins disease

No apparent change in the glomeruli= change in the shape of epithelial cells ( foot
process flattening

clinically: nephrotic syndrome

Membranous GN/

Diffuse thickening of glomerular capillary wall. Thickened BASEMENT

MEMBRANE- duplication of GBM. c/c inflammatory cells

SLE, idiopathic

Membranoproliferative GN

increase in the cellularity of mesangium with

Focal proliferatve GN - mesangial prolif GN

Only certain glomeruli/ 1 or 2 lobules of affected glomeruli

clinically: nephrotic syndrome

SLE, PAN Ig A neuropathy

Ig A Nephropathy - Berger's disease,

c/ c Liver disease, IBD, leprosy, dermatitis

Ig A deposits in the mesangium= elevated serum levels of Ig A

THE KIDNEY 5
 clinically: nephrotic syndrome

SECONDARY GLOMERULAR DISEASE

glomerular disease secondary to certain systemic diseases/ hereditary diseases

clinical evidence of renal diseases appear long after the other manifestations have
appeared

Examples:
Lupus nephritis

SLE- (in some people kidney is 1st affected- primary; if bones 1st and then kidney-
secondary

Diabetic Nephropathy- diffuse glomerulosclerosis nodular glomerulosclerosis

hereditary nephritis- alport's syndrome, fabry's disease

NEPHROTIC SYNDROME

A group of features in different diseases characterized by massive proteinuria,

hypoalbuminemia, gross edema, hyperlipidemia, lipiduria, hypercoagulability of blood

ETIOLOGY

primary GN

systemic disease- DM, SLE, amyloidosis

Hypersensitivity reaction- drugs, bee stings

malignancy

prognancy- toxaemia

circulatory disturbance- renal vein thrombosis

hereditary disease- alports syndrome

THE KIDNEY 6
 PATHOGENESIS

Increased glomerular permeability—> excess of plasma protein filtered out exceeding

capacity of tubules for resorption—> heavy proteinuria > 3gm/ day
urinary albumin loss—> hypoalbuminemia

hypoalbuminemia—> decreased colloid osmotic pressure—> oedema

na - water retension—> oedema
heavy urinary protein loss —> massive hepatic protein synthesis —> increased
synthesis of lipoproteins—> hyperlipidemia
hyperlipidemia—> lipiduria

increased urinary loss of antithrombin, increased synthesis of coaglulants, increased

platelet aggregation—> hypercoagulability

TUBULOINTERSTITIAL DISEASE

inflammatory process that predominantly involves renal interstitial tissues primarily

It is of 2 presentations: acute and chronic pyelonephritis

A/ C PYELONEPHRITIS
a/c suppurative inflammation of kidney caused by pyogenic bacteria

ETIOLOGY

Ascending infection

UTI - cystitis, urethritis, prostatitis ( E. Coli, Klebsiella, pseudomonas)

Urethral instrumentation _ catheterization, cystoscopy

Hematogenous - septicemia

Females - shorter urethra and close proximity with rectum

In DM, pregnancy, urinary tract obstruction, debilitated patient. immunosuppressed

Neurogenic bladder dysfunction, incompetence of vesico-ureteric orifice, flaccid

bladder (spinal cord injury)

PATHOGENESIS
Infection → a/c inflammation of interstitium and destruction of tubules

MORPHOLOGY

THE KIDNEY 7
 Gross:
1/ both kidneys involved

enlarged/ swollen
C/S
small yellow white abscess mainly in cortex scattered / in 1 region

microscopic

liquefactive necrosis with abscess formation in renal parenchyma, Large number of

neutrophils in inter

CLINICAL FEATURES
Predisposing condition - urinary obstruction (BPH)
instrumentation

vesicoureteric reflex

acute onset of fever, chills, malaise, loin pain, dysuria and urgency

increased frequency of micturition

lumbar tenderness - costovertebral angle

urine turbid ( WBCs, pus cells )

LAB INV

Urine - pus cells, pus cell casts, enormous bacteria

blood - leukocytosis, neutrophilia

COMPLICATION
Papillary necrosis

pyonephrosis - multilocular ac filled with pus

perinephric abscess

THE KIDNEY 8
 C/C PYELONEPHRITIS

From repeated attacks of infection and scarring

ETIOLOGY

Reflux neuropathy - incompetence pf vesicouterine reflex, neurogenic bladder

dysfunction; flaccid bladder (spinal cord injury)
Obstructive

PATHOGENESIS
recurrent infection recurrent inf tissue destruction healing by scarring

MORPHOLOGY
Gross

1/ both kidneys
small and contracted kidney ( uneven)

surface is scarred with U shaped depression

capsule adhered at scars

THE KIDNEY 9
 dilated pelvis

Microscopic
chronic inflammatory cell infiltration

interstitial fibrosis
dilatation and contraction of tubules
wall of the pelvis shows fibrosis

CLINIAL FEATURES
insidious onset
hypertension

CRF features
sometimes features of a/c pyelonephritis

LAB INVESTIGATION

Urine

chemical - albuminuria
culture - bacterium

IV pyelography

USG - Asymmetrically contracted

COMPLICATION

Glomerulosclerosis

Amyloidosis

NEPHROLITHIASIS
Formation of urinary calculi at any level of urinary tract
calcium - mc - calcium oxalate

ETIOLOGY

THE KIDNEY 10
 Hypercalcemia and hyper calciuria - hyperthyroidism; defect in bowel/ kidney ; idiopathic

PATHOGENESIS
Imbalance b/ w degree of supersaturation of ions forming stones and conc. of inhibitors
in urine
Alkaline urine. Decreased urinary volume and increased excretion of oxalate and uric
acid may contribute

MORPHOLOGY
Multiple, amll, ovoid, granular rough surface (mulberry stone) dark brown color (dueto
blood deposit)

calcium phosphate
PATHOGENESIS
Infection induces (secondary stone) - UTI with urea splitting organisms that produces
ureas and ammoniacal urine ( proteus, klebsiella)

MORPHOLOGY

Yellow, white/ grey

Solitary smooth, soft, friable, irregular in shape
(stag horn stone - large solitary stone taking the shape of renal pelvis)

uric acid stone

hyperuricemia and hyperuricosuria ( gout, myeloproliferative disorders - leukemia,

uricosuric drugs)
acidic urine and low urinary volume helps

PATHOGENESIS
Solubility of uric acid in urine decreases in acidic urine → ppt of uric acid stone

MORPHOLOGY
Smooth, yellowish - brown, hard, faceted and multiple
C/S - wavy concentric marking
NOT VISIBLE ON X Ray- Radiolucent

CYSTINE STONE

THE KIDNEY 11
 Genetic defect in the transport of cysteine and other amino acid across renal tubules →
cysteinuria

Small round, smooth, mulptiple, yellowish and waxy

When exposed outside changes to green
Not radio opaque. If sulphuis present it becomes radio opaque

XANTHHINE STONE
Inherited abnormality of enzyme metabolism
Smooth, round and brick red
C/S - Lamellar appearance

RENAL FAILURE
Syndrome characterized by renal dysfunction with oliguria/ anuria, increase in metabolic
waste pdcts in blood and development of uremia

ETIOLOGY

Glomerular diseases

Tubular diseases

Interstitial diseases

Vascular diseases

Obstructive diseases

CLASSIFICATION

Acute

Chronic

ARF
Characterised by rapid loss of renal function with sudden rise in metabolic waste
products in blood and oliguria

ETIOPATHOGENESIS

1. Pre- renal causes - decreases in RBF

hypotension/ hypovolemia - severe hemorrhage, burns

THE KIDNEY 12
 Renal hypoperfusion- fluid loss, CFC, circulatory insufficiency, renal arterial
obstruction, vascular diseases

PATHOGENESIS
Renal tissue is not injured
decreased RBF → decresed GFR → oliguria, azotemia, fluid retention, oedema (PRE-
RENAL SYNDROME)

2. Intra - renal cause - intrinsic damage to the kidneys -

Glomerular disease, a/c tubular necrosis due to ischemia/ toxins, tubulointerstitial

disease

PATHOGENESIS
→ Syndrome of a/ c nephritis: Associated with a/ c post streptococcal GN and RPGN
decrease in GFR and increased Na, water retention

Mild proteinuria, haematuria, edema, mild hypertension

→ Tubular pathology
Oliguric phase: urine less than 400mL/ day
Accumulation of waste products of protein metabolism - Azotemia, metabolic acidosis,
hyperkalemia, hypernatremia, hypervolaemia

Diuretic phase: Increased volume of urne

Healing of tubules
Sp gravity of urine: low/ fixed

Recover phase: tubular cells regenerate. Tubular function restored

Severe cases no recovery

3. Post renal cause - urinary obstruction

mass within on the wall or outside the urinary tract - renal calculi. BPH, neoplasms

Tubular insufficiency

PROGNOSIS
ARF is short lived

THE KIDNEY 13
 HEMODIALYSIS is required in:

uremic encephalopathy

fluid overload

severe hyperkalemia

severe acidosis

CRF
Syndrome characterised by progressive and irreversible deterioration of renal function,
due to slow destruction of renal parenchyma, eventually terminating in death when
sufficient number of nephrons are dmaged

Azotemia

Acidosis

Uremic syndrome

ETIOLOGY

1. Glomerular pathology - primary; systemic disease - SLE, DM

2. Tubulointerstitial pathology - infections (chronic pyelonephritis); toxic (analgesic);

obstructive; vascular (nephrosclerosis

3. congenital diseases

4. amyloidosis

DECREASED RENAL RESERVE

Marginal damage to parenchyma

GFR - 50% of normal

BUN, creatinine normal except in acute episodes

Asymptomatic except during stress

RENAL INSUFFICIENCY

75% functional renal parenchyma is lost

GFR 25% of normal

BUN, creatinine elevated

RENAL FAILURE

THE KIDNEY 14
 90% of functional parenchyma is lost

GFR 10% normal

Tubular cells nonfunctional

No regulation of Na - H2o —> edema, metaboli acidosis, hyperkalemia

signs of uremia

END STAGE KIDNEY (C/ C KIDNEY DISEASE)

GFR less than 5% of normal

Uremic syndrome with primary(renal) and secondary systemic(extra renal)

symptoms

Clinical manifestations

Primary uremic - renal

secondary uremic - extra renal

Primary uremic - renal

Azotemia

Metabolic acidosis- excess H+ ions, low HCO3- level acid base balance is lost →
Kussmaul breathing

Na - water imbalance → fluid retention → edema

Hyperuricemia, hyperkalemia, hypercalcemia

secondary uremic - extra renal

Manifestations due to acid - base and fluid - electrolyte imbalance and toxic effects of
metabolic waste products

CVS: Na - water imbalance → fluid retention → hypervolemia → circulatory

overload → CCF ; Hyperkalemia → cardiac arrythmia, weaknes, nausea, intestinal
colic, diarrhea, muscular irritability, flaccid paralysis

Hyperuricemia → Gout

Respratory system → Hypervolaemia → pulmonary congestion ; pulmonary edema

→ dyspnea

Uremic pnemonitis → butterfly bt wing opacity pattern of edema and congestion in chest
radiograph

THE KIDNEY 15
 GIT - Azotemia → muscular ulceration → bleeding; Azotemia → GIT irritation →
Hiccup, nausea, vomiting

Anemia - decreased production of erythropoetin; GIT bleeding, Normocytic

normochromic

CNS - Headache, lassitude, weakness, muscle twitching, convulsions or coma

Skeletal system (Renal osteodystrophy) → decreased activity of kidney →

deficiency of Vit D → decreased Ca absorption → inadequate deposit of Ca in bones
→ Osteomalacia

Osteitis fibrosa - elevated PTH → resorption of Ca from bones and tubular

resorption → hypercalcemia and deposition in joints and soft tissues

Urine - Pyuria. haematuria, proteinuria, casts (cells discarded from nephrons that
take the shape of tubules)

Integumentary system - deposit of urinary pigment - urochrome → in skin shallow

yellow color

Uremic frost - white crystals on skin → urea in sweat remains as powder on evaporation
of perspiration
Pruritis, purpura

VASCULAR DISEASES

Primary Rebal Vascular lesion - Diseases which disturb renal vascular system
Secondary Vascular lesions - Diseases which disturb the control of RBF like systemic
and local hemodynamic and hormonal

HYPERTENSION - 10M
Elevation in the SBP and DBP above normal

Normal - 120/ 80
Persistent elevation of SBP > 130mm Hg and DBP > 80 mm Hg
STAGE 1 -

THE KIDNEY 16
 SBP : 130 - 139 mm Hg

DBP: 80 - 89 mm Hg

STAGE 2
SBP > 140 mm Hg
DBP > 90 mm Hg

CLASSIFICATION
ETIOLOGICAL CLASSIFICATION
PRIMARY/ ESSENTIAL HYPERTENSION

Genetic

Racial and environmental factors

Other risk factors

SECONDARY HYPERTENSION
Due to diseases of kidney, endocrines, some other organ

Renal - vascular/ Parenchymal disease

Endocrine - Adrenocortical, hypo/ hyperthyroidism, oral contraceptives

Neurogenic - Psychogenic, polyneuritis

Cardiovascular - coarctation of aorta , Polyarthritis nodosa

Miscellaneous - Increased vascular volume (polycythemia) Medications

(Glucocorticoids)

CLINICAL CLASSIFICATION

Benign HP - Moderate elevation of BP that is insidious

Malignant HP - Sudden increase of SBP > 200mm Hg and DBP > 140mm Hg in a
known vase of HP/ normal individual (develop papilloedema, retinal hemorrhage ,
encephalopathy → if not treated - life expectancy < 2yrs

GENETIC HP
Familial aggregation, occurence in identical twins, identification of HP susceptibility
gene (angiotensinogen gene)

RACIAL HP

Higher incidence in african americans than whites

THE KIDNEY 17
 ENVIRONMENTAL FACTORS

Salt intake, obesity, alcohol intake, cigarette smoking, lifestyle, stress

OTHER RISKS
Atherosclerosis, DM, hyperlipedimia

It is usually dependant by interaction of the above factors

Hence, it is polygenic and hetergenous disorder due to combined effect of mutation at

several gene loci and ,multiple mechanisms

Factors HP depends on:

COP - BV,which is dependant on : Na, Cardiac factor (HR, contractility)

Peripheral resistance determined by: lumen size which depens on: thickness of
wall, effect of neural(alpha - adrenergic - contraction and of beta adrenergic -
vasodilatation) and hormonal (angiotensin 2, catecholamines, thrombaxane, lactic
acid) influence

Kidney: controls PR (RAAS), Na homeostasis, GFR, produce vasodepressor

PATHOGENESIS
Changes that alter relationship b/ w BV and total PR → HP
Depends on the above factors and etiology

Genetic + environmental factor

Defect in renal Na homeostasis

Inadequate Na excretion → Na- water retention → Increased plasma volume →
increased COP → HP

Functional vasoconstriction
Increased vascular reactivity → PR → HP

Defect in vascular SM growth

Increased vascular wall thickness → lumen is narrow→ PR → HP

SECONDARY HP

Renal HP

THE KIDNEY 18
 Renal vascular - occlusion of major renal artery, pre - eclamsia, eclampsia, PAN,
fibromuscular dysplasia of renal artery

Renal Parenchymal - GN, pyelonephritis, diabetic nephropathy, amyloidosis, PCKD,

tumors (renin producing)

Pathogenesis

Derangement in renal handling of Na and fluids → fluid volume expansion

Alternation in renal secretion of vasoactive material → systemic/ local change in

arteriolar tone

Renovascular occlusion/ parenchymal inflammmation and fibrosis → decreased

renal perfusion → activation of RAAS → increases the circulating Angiotensin II →
elevation of arterial pressure (by diresct vasoconstriction/ stimulating aldosterone)

Endocrine HP
Adrenal - Adrwnal cortical abnormalities, primary aldosteronism, cushing's syndrome,
pheochromocytoma

Pathogenesis

3. Oral contraceptives

THE KIDNEY 19
 4. Coarctation of aorta

EFFECTS OF HP
BLOOD VESSELS - Hpertensive arteiosclerosis
HEART - Hypertensive heart disease (IHD, LVF, Heart failure)
CNS - Occipital headaches (early), dizziness, ligth headedness. vertigo, tinnitus,
dimmed vision/ syncope

Serious

SPONTANEOUS INTRACEREBRAL HEMORRHAGE

Micro aneurysms in cerebral artery ruptures
At basal ganglia, pons, cerebellar cortex - sudden headache with loss of consciousness
Signs depending on the site
Death due to hemorrhage into ventricles
Haematoma → resolution → apoplectic cyst with loss of function

RETINAL
Narrowing of BV, hemorrhages, exudate and papilloedema → Scotoma, blurred vision,
blindness

THE KIDNEY 20
 Hpertensive retinopathy

Renal benign nephrosclerosis - bilateral involvement; reduced size and weight; firm and
shrunken; capsule adherent; granular surface with V shaped scarring
C/S - Narrow cortex
Microscopic
Vascular changes - Hyaline arteiosclerosis; Intimal thickening with proliferation of SM

Parenchymal changes - Atrophy of parenchyma; glomerular shrinkage, fibrosis,

tubular atrophy

THE KIDNEY 21