Pn Pathology Notes.docx New

8/10/2019 Pn Pathology Notes.docx New

1/83


2/83

2

b. Ataxia telangiectasia

c. Down syndrome

d. Wiscott Aldrich syndrome

3. Viral infection:

a. Human T cell Leukemia Virus-1(HTLV): T cell leukemia

b. Ebstein Bar virus: lymphomac. Herpes virus-8: Kaposis sarcoma

d. Hepatitis C: lymphoma

e. HIV: B-cell and Burkitts lymphomas

f. Helecobacter pylori: lymphoma of stomach

4. Environmental agents:

a. Ionizing radiation: Leukemias

b. Drugs:

i. Phenytoin: lekemias and lymphomas

ii. Cancer chemotherapy-leukemia

c. Gluten sensitivity: intestinal lymphomad. HIV: B cell lymphomas

5. Immune deficiency:

a. Congenital or acquired immune deficiency: leukemia and lymphoma

6. Iatrogenic Factors:

a. Radiotherapy- leukemia

2. Pathogenesis:

1. Malignant transformation of a single clone of cells belonging to lymphoid or myeloid series due

to a genetic damage to DNA; this is followed by proliferation of affected clone

2. Chromosomal translocation: eg: Philedelphia Chromosome t(9;22) in CML

3. Maturation defect: i.e failure to mature beyond myeloblast or lymphoblast;4. Myelosupression: bone marrow is suppressed by the excessive cancer cells

5. Infiltration: bone marrow and liver, spleen, lymphnodes and CNS are infiltrated by leukemic

cells

Classification

Types of classification:

1. Historical classification

2. French American British classification (FAB)

3. WHO classification

I. Historical classification:


3/83

3

1. Leukemias: Acute in the sense the disease progresses rapidy and blast cells predominate in blood

smear; chronic in which disease progresses slowly and blast cells are not seen in early smears

a. Acute myeloblastic leukemia (AML)

b. Acute lymphoblastic leukemia(ALL)

c. Chronic myeloid(myelocytic) leukemia(CML)

d. Chronic lymphocytic leukemia(CLL)2. Lymphomas:

a. Hodgkin

b. Non Hodgkin

II. Present major classification:

1. Lymphoid neoplasm: arise from precursors of lymphocytes:

2. Myeloid neoplasm: arise from hematopoietic stem cells that give rise to:

3. Histiocytic neoplasms

FAB Classification:

1. WHO Classification of Lymphoid neoplasms:

1. Acute lymphoblastic leukemia, ALL

a. Precursor B cell neoplasm( blast cells):

i. Precursor B Lymphoblastic leukemia/lymphoma

b. Peripheral B cell neoplasm (mature cells):

i. Chronic lymphocytic leukemia (CLL)

ii. Follicular lymphomas

iii. Hairy cell leukemia

iv. Burkits lymphoma etc

c. Plasma cell neoplasms:

1. Plasmocytoma/Plasma cell myeloma

d. Precursor T cell neoplasm( blast cells): (Acute lymphoblastic leukemia, ALL)

i. Precursor T Lymphoblastic leukemia/lymphoma

ii. Peripheral T cell and NK cell neoplasm (mature cells):

iii. Adult T cell leukemia/lymphoma


4/83


5/83

5

i. Myeloid sarcoma

5. Acute biphenotypic leukemia

Blood and bone marrow pictures:

1. Acute lymphoblastic leukemia ALL: peak incidence at 2-5 years of age, and another peak in old age1. Blood and Peripheral smear:

a. Changes in WBC:

i. Total count may be very high 50-100x10or less than 10,000/microL

ii. Lymphoblasts:

1. Are seen in large no. (Convent party appearance)

2. The cells are round and small,

3. Cytoplasm is scanty and homogeneous;

4. Granules are absent;

5. Nucleus one or two nucleoli.

6. The cells are PAS/Sudan Black negative; acid phosphatase positive;7. Some Markers:

a. CD 19 positive in B cell type

b. CD 7 positive in T cell type

iii. RBC: normochromic and normocytic anemia

iv. Platelets: thrombocytopenia

2. Bone marrow changes in ALL:

1. Lymphoblasts:

a. Are seen in large no. Counts more than 20% (WHO) and 30% (FAB) are diagnostic of ALL

b. Lymphoblasts are large cells; contain large round or indended nucleus; stippled with

nuclear chromatin; nuclear membrane is dense; nucleoli 1-2 are seen; cytoplasm is scanty;it is basophilic and without granules;

c. Lymphoblasts are TdT and adenosine deaminase positive;

2. Erythropoietic series:reduced in no; megaloblasts and ring sideroblasts may be seen.

3. Megakaryocytes are reduced or absent.

4. Cytogenetics :

a. Aneuploidy in 75%

b. Philadelphia chromosome in 15%

5. Cell markers seen ALL:

a. Leukocyte common antigen

b. Positive sheep erythrocyte rosette test in B cell types

2. Acute Myeloblastic (myelogenous; myeloid) Leukemia (AML): median age 50 years; may

rarely occur in childhood.

1. Blood Picture:

a. Total Leukocyte count is raised; occasionally normal

b. Plenty of blast cells:

i. Blast cells are large in size

ii. Round or oval nucleus nearly filling the cell


6/83

6

iii. Abundant granular cytoplasm

iv. Auer rods are seen sometimes which are abnormal derivatives of primary

azurophilic granules

v. Nuclear chromatin is delicate

vi. Nucleoli 3-5

vii. Cytochemistry:1. Peroxidase and sudan black positive

2. Phosphatase negative

viii. Markers:

1. CD 19 negative

2. CD 7 Negative

3. CD 13 and 33 positive

c. Polymorphs and few lymphocytes are seen

d. RBC: normochromic normocytic anemia

e. Platelets: severe thrombocytopenia

2. Bone Marrow:a. Maroow is hypercellular; occasionally hypocellular

b. Myeloblasts are predominant; > 20%(WHO) or > 30% FAB is diagnostic of ALL

c. Immature granulocytes, erythroblasts, megaloblastic erythroblasts and sideroblasts are

seen

d. Plasma cells and monocytes are moderately elevated

e. Megakaryocytes are reduced or absent

f. Cytogenetics:

i. Presence of cells with aneuploidy; translocation or inversions

ii. Philadelphia chromosome in 3% cases

g. Cytochemistry:i. Myeloperoxidase, sudan black, PAS are positive in M6 cells

ii. Non specific esterase positive in M4 and M5

iii. Acid phosphatase positive in M4 and M5

h. Biochemistry:

i. Serum muramidase elevated in M4 and M5

ii. Serum uric acid elevated in general

3. Chronic lymphocytic (lymphatic)leukemia (CLL):over 50 years of age with male

preponderance; hepatosplenomegaly, lymphadenopathy and anemia

a. Blood picture:

i. Normochromic and normocytic anemia; mild reticulocytosis; 20% coombs have

positive hemolytic anemia

ii. Absolute neutrophil count is within normal range; granulocytopenia in advanced

stage

iii. Marked leukocytosis(50,000-200,000/l)

iv. 90% of leukocytes is mature small lymphocytes; degerated lymphocytes are called

smudge or basket cells

v. Platelets is normal or moderately reduced


7/83

7

b. Bone marrow:

i. Increased lymphocyte count

ii. Reduced myeloid precursors

iii. Reduced erythroid precursors

c. Other tests:

i. Lymph node: Replacement of lymphnode with diffuse small lymphocytesii. Erythrocyte rosette test: positive with mouse RBCs

iii. Markers: CD5 is positive for immunoglobulins

iv. Coombs +ve in 20%

v.

4. Chronic Myeloid (myelocytic) leukemia (CML): peak in 3-4 decades of life; juvenile form in

children; anemia, weight loss, bleeding, priapism, lymphadenopathy and splenomegaly.

a. Blood: 3 phases: chronic, accelerated and blast crisis phases

i. RBC: Normocytic normochromic anemia

ii. WBC:

1. General: Marked leukocytosis: 200 000/L; myelocites present2. Chronic Phase:

a. Myeloblast 10%

3. Accelerated phase:

a. Increasing anemia

b. Blasts 10-20%

c. Low platelet count

4. Blast crisis:

a. Blasts > 20%

iii. Platelet: normal or raised in the casesb. Bone marrow:

i. Hypercellular marrow

ii. Myeloid predominance

iii. Increased myeloid erythroid ratio

iv. Myelocytes predominance

v. Erythropoiesis: reduction in erythropoietic series

vi. Megakaryocytes: more and smaller

vii. Cytogenetics:

1. Philedelphia chromosome in 90 to 95%; it is reciprocal translocation of long

arm of 22 and long arm of chromosome 9

viii. Cytochemistry:

1. Neutrophil alkaline phosphatase is reduced; increased in leukaemoid

reaction

ix. Other findings:

1. Serum B 12 elevated

2. Serum uric acid elevated


8/83

8

S.N: Philadiphia chromosome:

The Philadelphia chromosome is made when the Abl gene on chromosome 9 is mistakenly

transferred to chromosome 22 and attaches to the Bcr gene. This creates a new fusion gene called

Bcr-Abl which leads to leukemic process.

S.N: Leukemoid reaction:

The term leukemoid reactiondescribes an elevated white blood cell count, that is a physiologic

response to stress or infection (as opposed to a primary blood malignancy, such as leukemia)

Leukemoid reaction may be myeloid (more common) or lymphoid

Causes:

1. Infections:

Staphylococcal pneumonia

Meningitis

Diphtheria

Any sepsis Endocarditis

Septic abortion

2. Toxins:

Eclampsia

Mercury poisoning

Burns

3. Malignancy:

Multiple myeloma

Myelofibrosis

Hodgkin CLL

4. Severe Hemorrhage and hemolysis

Lab:

1. Myleloid luekemoid reaction:

Leukocytosis upto 100,000/L

Blasts < 5%

Toxic granulation or Dohle bodies in Neutrophils in infections

Philadelphia chromosome negative


9/83

9

No organ infiltrations

2. Lymphoid leukemoid reaction:

Infections:

Pertusis

Infectious mononucleolus

Cytomegalo virus Chickenpox

Measles

Tuberculosis

Lab:

Leukocyte count upto 100,000/L

Mostly mature lymphocytes

Mimics CLL

Difference between leukaemoid reaction and leukemia

S.No Leukaemoid reaction Leukemia

1 The infection leading to leukemoid

reaction will be present

Splenomegaly, lymphadenopathy and bleeding

tendency are evident

2 Leukocyte count upto 100,000/L Leukocyte count often more than 100,000/L

3 Immature cells are less Immature cells are more

4 WBC may show toxic granulation due to

infection

Absent

5 Anemia is less More

6 Bone marrow: less hypercelluar More hypercellular

7 Autopsy: no organ infiltration of blasts Present in liver, spleen, CNS etc


10/83

10

2. A 35 years, old man was admitted with history of painless cervical

and axillary lymphadenopathy. He had history of loss of weight,

fever and night sweating and was found to have cutaneous anergy.

No hepatosplenomegaly.

a) What is your most probable diagnosis?

b) Give the classification of the condition.

c) Describe the morphology of any two types.

Lymphomas1. These are malignant neoplasm derived from lymphocytes, usually in lymph nodes but also in

other organs or in soft tissue.

Unlike the leukemia the tumor cells do not appear in the blood in detectable numbers

2. TYPES OF LYMPHOMAS:

The lymphomas are broadly grouped into two types:

A. Non-Hodgkins lymphomas (60%)

B. Hodgkins lymphoma (also known as Hodgkin's disease) (40%)

3. Cells of origin:

The non- Hodgkins lymphomas are derived from either B or T lymphocytes. The cell of origin inHodgkins lymphoma is now known to be of B-cell origin

Hodgkins disease

1. Neoplasm (lymphoma) arising from lymph node with secondary involvement of extra nodal sites

2. Age 15-35 yrs with male preponderance; another peak at 5th decade

3. Symptoms include

painless swelling of the lymph nodes in the neck, armpits, or groin

fever and chills

night sweats weight loss

loss of appetite

itchy skin

nodes are painful after alcohol consumption

4. Classifications:

1. Conventional:

a. Non Hodgkin- heterogynous group

b. Hodgkin (Reed Sternberg cell +ve)

2. Rye classification:


11/83


12/83

12

i. Lymph nodes are replaced by mixture of apparently normal cells:

lymphocytes, histiocytes, eosinophils, Neutrophils, and plasma cells

ii. Areas of fibrosis and necrosis may be seen

f. Lymphocyte depletion type:

i. Diffuse fibrotic variant: entire node is replaced by fibrous tissue appearing as

fibrillar hyaline material; few lymphocytes, atypical lymphocytes,pleomorphic RS cells are present.

ii. Reticular variant: more cellular; few lymphocytes, large no. of atypical

histiocytes and few typical RS cells are seen.

II. Nodular-lymphocyte predominant type:

I. Newly described

II. Nodular appearance

III. Small lymphocytes predominance

IV. Few RS cells

V. CD 45 positive

VI. Chronic relapsing courseVII. May transform into large B cell NHL

Non Hodgkin Lymphomas: The types of NHL represent different stages in lymphocyte differentiation

85% are of B cell origin, the rest are T cell or null cell

Classification of NHL

1. Low grade (indolent)

o Long life expectancy if left untreated

o 85-90% present at stage III or IV disease

o IncurableTypes:

1. Small lymphocytic(similar to chronic lymphocytic leukaemia)

This lymphoma is slow growing and composed of small round lymphocytes with scant

cytoplasm and very few mitoses. They almost all of B-cell origin and express pan B-cell

markers, such as CD20, as well as CD5 and CD23. In time they may transform to more

aggressive forms of large cell lymphoma

2. Follicular lymphomas-

Further subdivided on the basis of the relative numbers small cleaved and large non-

cleaved cells in the follicles, into (a) small cleaved, (b) mixed or (c) large

2. Intermediate

Diffuse lymphomas- again subdivided on the same basis as the follicular lymphomas into

(a) small cleaved cell, (b) mixed or (c) large cell

3. High grade (aggressive)

o Life expectancy in weeks if not treated

o Potentially curable

o Types:

Lymphoblastic

Burkitts lymphoma:


13/83

13

Burkitt's lymphoma (BL) (Short notes)

Is a cancer of the lymphatic system (in particular, B lymphocytes).

Highly aggressive lymphoma

Usually found in extranodal sites or presenting as an acute leukaemia.

> 90% are E-B virus positive

EBV has trophism for B cells; considered as causative factor for Burkitts lymphoma Currently Burkitt's lymphoma can be divided into three main clinical variants; By morphology, it

is almost impossible to differentiate these three clinical variants:

o The African endemic,

o The sporadic and

o The immunodeficiency-associated variants.

1. The endemic variant:

o Occurs in equatorial Africa.

o Disease characteristically involves the jaw or other facial bone

2. The sporadic type:

o Jaw is less commonly involved, comparing with the endemic variant. Ileo-cecal region isthe common site of involvement.

3. Immunodeficiency-associated Burkitt lymphoma:

o Is usually associated with HIV infection or occurs in the setting of post-transplant

patients who are taking immunosuppressive drugs.

o Actually, Burkitt lymphoma can be the initial manifestation of AIDS.

Morphology

Consists of sheets of monotonous population of medium size lymphoid cells with high

proliferative activity and apoptotic activity.

The "starry sky" appearance seen under low power is due to scattered macrophages containing

dead body of apoptotic tumour cells.

Multiple myeloma (Myeloma)

1. It is malignancy of plasma cells; monoclonal proliferation of B-cells

2. peek incidence 50-60 years; more in males

3. Aetiology:

1. Radiation


14/83

14

2. Occupational exposure to petroleum products

3. Chromosomal deletions and translocations; Abnormalities are commonly found on

chromosome 13 and chromosome 11,

4. Oncogenes: MYC and RAS

Pathogenesis:

1. Multiple myeloma cells adhere to the stromal cells in the bone marrow; inhibitosteoblastic activity.

2. Adhesion of the multiple myeloma cells stimulates production of interleukin-6, a growth

factor required for survival of the multiple myeloma cells.

3. Interleukin-6 stimulates increased osteoclastic activity

4. This results in bone lesions (lytic lesions), osteoporosis, and hypercalcemia

5. Multiple myeloma cells produce excessive monoclonal proteins - M proteins, which are

classified as heavy amino acid chains and light amino acid chains.

6. The M protein level is referred to as the M-spike in immune electrophoresis. In multiple

myeloma patients the M protein is most commonly Ig.G or IgA.

7. The light amino acid chains are of two types: kappa and lambda. Kappa is twice asprevalent as lambda. When detected in the urine the light chain fragments are called

Bence-Jones proteins. They are followed as an indicator of disease activity and

progression.

Morphology: osseous and extra osseous lesions

1. It begins in bone marrow in 95% cases

2. Multiple bones are involved- skull, spine and pelvis

3. Normal marrow is replaced by reddish grey gelatinous tissue

4. In X-ray punched out appearance is characteristic

5. bone marrow aspiration may be a dry tap; biopsy required

6. Bone marrow:1. Hyper cellular

2. >10% are myeloma cells: similar to plasma cells but vary in size; nuclus is

eccentric; unlike normal plasma cell its nuclear chromatin does not show car-

wheel pattern

3. Nucleoli are present

4. Cytoplasm is abundant with perinuclear halo; vacuolation and Russel bodies

containing antibodies

5. Variants of plasma cells:

Flame cells: red cytoplasm

Mott cells: contain grapelike cytoplasmic droplets


15/83

15

Plasma cell Myeloma cell: eccentric nucleus with halo; no cart

weel

Normal Protein electrophoresis Myeloma- M spike in Gamma region

7. Extra osseous:

1. Atypical plasma cells in blood

2. Anaemia

3. Hyperviscocity of blood

4. Nephrosis due to Bence-Jones proteinuria

5. Polyneuropathy

6. Pathologic fractures of bones

7. Systemic amyloidosis myeloma proteins

8. Hepato splenomegaly due to myeloma cells

Bence Jones Protein:

1. Multiple myeloma cells produce excessive monoclonal proteins - M proteins, which are classified

as heavy amino acid chains and light amino acid chains

2. The light amino acid chains are of two types: kappa and lambda. Kappa is twice as prevalent as

lambda. When detected in the urine the light chain fragments are called Bence-Jones proteins

3. Light chains (molecular weight 22,000 d) are polypeptides synthesized by plasma cells and

assembled with heavy chains to form the various classes of immunoglobulins, for example,

immunoglobulin G (IgG), immunoglobulin M (IgM), and immunoglobulin A (IgA).

4. Plasma cells normally produce a slight excess of light chains that are either excreted or

catabolized by the kidney

5. 1% of myeloma are nonsecretory: no Bence-Jones proteins in urine
http://www.google.co.in/imgres?imgurl=http://myelomablog.com/wp-content/uploads/2008/11/multiple-myeloma-flame-shaped-plasma-cell-100x5-website-arrow.jpg&imgrefurl=http://www.myelomablog.com/2008/11/14/predicting-early-or-late-mortality-in-multiple-myeloma/&usg=__hL94ZslSDoxy7Pk9JNT2Gv0iKVs=&h=890&w=1183&sz=78&hl=en&start=139&zoom=1&tbnid=mUqawBWwh7uQgM:&tbnh=119&tbnw=140&prev=/images?q=myeloma+cells&um=1&hl=en&sa=N&biw=1344&bih=555&rlz=1W1ADFA_en&tbs=isch:1&um=1&itbs=1&iact=hc&vpx=559&vpy=133&dur=904&hovh=195&hovw=259&tx=189&ty=124&ei=58IETYapIY22vQPe1MDNBg&oei=bcIETdXYEsaGrAfSzJyTDw&esq=16&page=7&ndsp=24&ved=1t:429,r:19,s:139http://www.google.co.in/imgres?imgurl=http://myelomablog.com/wp-content/uploads/2008/11/multiple-myeloma-flame-shaped-plasma-cell-100x5-website-arrow.jpg&imgrefurl=http://www.myelomablog.com/2008/11/14/predicting-early-or-late-mortality-in-multiple-myeloma/&usg=__hL94ZslSDoxy7Pk9JNT2Gv0iKVs=&h=890&w=1183&sz=78&hl=en&start=139&zoom=1&tbnid=mUqawBWwh7uQgM:&tbnh=119&tbnw=140&prev=/images?q=myeloma+cells&um=1&hl=en&sa=N&biw=1344&bih=555&rlz=1W1ADFA_en&tbs=isch:1&um=1&itbs=1&iact=hc&vpx=559&vpy=133&dur=904&hovh=195&hovw=259&tx=189&ty=124&ei=58IETYapIY22vQPe1MDNBg&oei=bcIETdXYEsaGrAfSzJyTDw&esq=16&page=7&ndsp=24&ved=1t:429,r:19,s:139http://www.google.co.in/imgres?imgurl=http://myelomablog.com/wp-content/uploads/2008/11/multiple-myeloma-flame-shaped-plasma-cell-100x5-website-arrow.jpg&imgrefurl=http://www.myelomablog.com/2008/11/14/predicting-early-or-late-mortality-in-multiple-myeloma/&usg=__hL94ZslSDoxy7Pk9JNT2Gv0iKVs=&h=890&w=1183&sz=78&hl=en&start=139&zoom=1&tbnid=mUqawBWwh7uQgM:&tbnh=119&tbnw=140&prev=/images?q=myeloma+cells&um=1&hl=en&sa=N&biw=1344&bih=555&rlz=1W1ADFA_en&tbs=isch:1&um=1&itbs=1&iact=hc&vpx=559&vpy=133&dur=904&hovh=195&hovw=259&tx=189&ty=124&ei=58IETYapIY22vQPe1MDNBg&oei=bcIETdXYEsaGrAfSzJyTDw&esq=16&page=7&ndsp=24&ved=1t:429,r:19,s:139http://www.google.co.in/imgres?imgurl=http://myelomablog.com/wp-content/uploads/2008/11/multiple-myeloma-flame-shaped-plasma-cell-100x5-website-arrow.jpg&imgrefurl=http://www.myelomablog.com/2008/11/14/predicting-early-or-late-mortality-in-multiple-myeloma/&usg=__hL94ZslSDoxy7Pk9JNT2Gv0iKVs=&h=890&w=1183&sz=78&hl=en&start=139&zoom=1&tbnid=mUqawBWwh7uQgM:&tbnh=119&tbnw=140&prev=/images?q=myeloma+cells&um=1&hl=en&sa=N&biw=1344&bih=555&rlz=1W1ADFA_en&tbs=isch:1&um=1&itbs=1&iact=hc&vpx=559&vpy=133&dur=904&hovh=195&hovw=259&tx=189&ty=124&ei=58IETYapIY22vQPe1MDNBg&oei=bcIETdXYEsaGrAfSzJyTDw&esq=16&page=7&ndsp=24&ved=1t:429,r:19,s:139


16/83

16

6. Kappa light chains usually exist as monomers (22,000 d) and are therefore small enough to be

filtered through the glomerulus, but they may exist as dimers. Lambda light chains usually exist

as dimers (44,000 d) and, therefore, are less likely to be filtered and appear in urine.

7. Light-chain proteins appear in urine in high concentration either when the production of light-

chain proteins is markedly increased or when the ability of the proximal tubules to reabsorb all

the filtered protein is exceeded.8. Since mostly excreted in urine they are not present in detectable amount in blood except in

renal failure.

9. They on heating precipitate at 40-60 C and redissolve at higher temperature

10. Causes:

1. Multiple myeloma

2. Plasmacytoma

3. Waldenstrom macroglobulinemia

11. Tests:

1. 5 ml of urine is mixed with 2-3 drops of acetic acid and heated in a water bath; at 40-60C

there will be cloudiness and precipitation; on further heating over 70C the precipitatedissolves and reappear when cooling below 60 C

2. Serum electrophoresis demonstrates M-band

Multiple myeloma affecting kidney:

1. Tumour invasion: ureteric obstruction and renal hypertension

2. Hypercalcemia

3. Hyperurecemia

4. Amyloidosis

5. BJ proteinuria

6. Glomerular disease

Myeloma kidney (cast nephropathy)1. Myueloma kidney is one of the several renal dysfunctions due to light chain proteinuria

2. Light chains bind with Tamm-Horsfall mucoprotein, which is secreted by tubular cells in

ascending loop of Henle, forming casts

3. Light chains can precipitate in the tubules, leading to obstructing, dense, intratubular casts in

the distal and collecting tubules that may initiate a giant cell reaction

4. Multinucleated giant cells surround the casts which produces nephropathy

5. Light chain proteins also have direct toxic effect on renal epithelial cells

6. It may also be deposited in basement membrane to produce glomerulopathy

LABORATORY INVESTIGATION OF SUSPECTED MYELOMA1. Diagnostic triad:

1. myeloma cells >10% in bone marrow

2. Lytic lesions in bones

3. M proteins in serum and urine

2. Serum proteins:

1. Rise in total serum proteins due to paraproteinemia (M proteins or abnormal

immunoglobulin e.g. Bence Jones proteins)

2. Normal IgG, IgA, IgM and albumin levels are low


17/83

17

3. Serum electrophoresis:

1. Spike produced by M proteins; in the region of IgG in 50%; IgA in 25%

2. Another 20 have only light chains in serum

3. No M-bands in non secretary myeloma(1%)

4. Serum viscocity: Hyperviscocity in myeloma

The normal reference range is 1.4-1.8 Centipoises ; >5 in myeloma Rouleaux formation is often present with increased serum viscosity.

5. Hypercalcemia

6. Hyperurecemia

3. Urine: Bence Jones proteins are present in urine; >6 gms/dL4. Bone marrow:

1. Hyper cellular

2. >10% are myeloma cells: similar to plasma cells but vary in size; nuclus is

eccentric; unlike normal plasma cell its nuclear chromatin does not show car-

wheel pattern

3. Nucleoli are present4. Cytoplasm is abundant with perinuclear halo; vacuolation and Russel bodies

which contain antibodies

5. Variants of plasma cells:

Flame cells: red cytoplasm

Mott cells: contain grapelike cytoplasmic droplets

1. Polycystic kidney disease: PKD(short notes)

1. Renal parenchyma is converted into cysts of varying sizes

2. Two types:

1. Adult type: autosomal dominant (ADPKD)

2. Infantile type: autosomal recessive (ARPKD)

3. Adult type:

1. Incidence 1 in 400 to 1000
http://www.google.co.in/imgres?imgurl=http://wwww.ivoryresearch.com/images/raymond-harlow-fig2.jpg&imgrefurl=http://wwww.ivoryresearch.com/raymond-harlow.php&usg=__H08aIFTbYtih7YIJyAqCLRHJybU=&h=211&w=450&sz=29&hl=en&start=21&zoom=1&tbnid=CmiEPBkHnygJeM:&tbnh=86&tbnw=184&prev=/images?q=paraproteins+in+myeloma&um=1&hl=en&sa=N&biw=1344&bih=555&rlz=1W1ADFA_en&tbs=isch:1&um=1&itbs=1&iact=hc&vpx=693&vpy=229&dur=15740&hovh=154&hovw=328&tx=134&ty=109&ei=3PIITY-kFo28vgOJ55H_Dw&oei=t_IITdCSCpCqrAfaw6zXDg&esq=7&page=2&ndsp=21&ved=1t:429,r:11,s:21http://www.google.co.in/imgres?imgurl=http://wwww.ivoryresearch.com/images/raymond-harlow-fig2.jpg&imgrefurl=http://wwww.ivoryresearch.com/raymond-harlow.php&usg=__H08aIFTbYtih7YIJyAqCLRHJybU=&h=211&w=450&sz=29&hl=en&start=21&zoom=1&tbnid=CmiEPBkHnygJeM:&tbnh=86&tbnw=184&prev=/images?q=paraproteins+in+myeloma&um=1&hl=en&sa=N&biw=1344&bih=555&rlz=1W1ADFA_en&tbs=isch:1&um=1&itbs=1&iact=hc&vpx=693&vpy=229&dur=15740&hovh=154&hovw=328&tx=134&ty=109&ei=3PIITY-kFo28vgOJ55H_Dw&oei=t_IITdCSCpCqrAfaw6zXDg&esq=7&page=2&ndsp=21&ved=1t:429,r:11,s:21


18/83

18

2. PKD gene is located is in chromosome 16 and rarely in 4

3. Bilateral and diffuse

4. Symptoms appear in 30-50 years of age

5. Morphology:

1. Bilaterally enlarged; lobulated; may weigh up to 4 kg

2. Cut surface show cysts in different size; contain straw yellow to reddish brownmaterial

3. Renal pelvis is distorted by cysts; do not communicate with each other( contrast

to hydronephrosis)

6. Histology:

1. Cysts are parts of nephrons

2. Epithelial lining of cysts are that tubules

3. Parts of glomerulus could be recognized among the cysts

4. Intervening normal renal parenchyma may be seen

5. Acquired inflammation due to pyelonephritis, nephrosclerosis etc may be seen

7. Clinical:

1. Manifest in 30-50 years of age

2. Presents as hematuria and renal pain

3. Hypertension is common

4. Associated cystic changes in liver, panctreas and spleen etc may be present

5. Berry aneurysm of circle of Willis present in 15%

6. Acquired infections may further damage the kidney

2. Infantile type:

1. Autosomal recessive

2. 1 in 20,000 incidence

3. Mutation in chromosome 6-6p-21

4. Bilateral

5. Manifest at birth and renal failure in early childhood

6. Morphology:

1. Bilateral enlargement

2. Smooth surface and shape not distorted

3. Cut surface: small cysts extend radially to cortex; mostly normal parenchyma; pelvis and

ureters normal
http://www.google.co.in/imgres?imgurl=http://kidney.niddk.nih.gov/kudiseases/pubs/polycystic/images/PolycysticKidney.jpg&imgrefurl=http://kidney.niddk.nih.gov/kudiseases/pubs/polycystic/&usg=__uyEK96Pe50n9CtUgXGvHvkjsdrQ=&h=211&w=211&sz=18&hl=en&start=0&zoom=1&tbnid=EVPlCzRu6zwqCM:&tbnh=118&tbnw=118&prev=/images?q=polycystic+kidney+disease&hl=en&sa=G&biw=1344&bih=555&gbv=2&tbs=isch:1&itbs=1&iact=hc&vpx=624&vpy=115&dur=2652&hovh=168&hovw=168&tx=59&ty=126&ei=G-sMTYm8NM6rrAeKj8zDCw&oei=G-sMTYm8NM6rrAeKj8zDCw&esq=1&page=1&ndsp=22&ved=1t:429,r:3,s:0http://www.google.co.in/imgres?imgurl=http://kidney.niddk.nih.gov/kudiseases/pubs/polycystic/images/PolycysticKidney.jpg&imgrefurl=http://kidney.niddk.nih.gov/kudiseases/pubs/polycystic/&usg=__uyEK96Pe50n9CtUgXGvHvkjsdrQ=&h=211&w=211&sz=18&hl=en&start=0&zoom=1&tbnid=EVPlCzRu6zwqCM:&tbnh=118&tbnw=118&prev=/images?q=polycystic+kidney+disease&hl=en&sa=G&biw=1344&bih=555&gbv=2&tbs=isch:1&itbs=1&iact=hc&vpx=624&vpy=115&dur=2652&hovh=168&hovw=168&tx=59&ty=126&ei=G-sMTYm8NM6rrAeKj8zDCw&oei=G-sMTYm8NM6rrAeKj8zDCw&esq=1&page=1&ndsp=22&ved=1t:429,r:3,s:0


19/83

19

7. Histology:

1. Total no of nephrons are normal

2. Sponge like cysts develop from collecting tubules and show cylindrical and secular

dilatation lined by cuboidal or columnar epithelium

3. Many glomeruli undergo cystic dilatation

8. Clinical:

1. Gross enlargement may interfere normal delivery

2. Renal failure occurs early

3. Associated cystic disease in liver may lead to congenital fibrosis, portal hypertension

and splenomegaly

4. Severely affected infants are often born with pulmonary hypoplasia and suffer from

respiratory compromise

Glomerulonephritis
http://radiographics.rsna.org/content/20/3/837/F4.large.jpghttp://radiographics.rsna.org/content/20/3/837/F4.large.jpghttp://radiographics.rsna.org/content/20/3/837/F4.large.jpghttp://radiographics.rsna.org/content/20/3/837/F4.large.jpghttp://radiographics.rsna.org/content/20/3/837/F4.large.jpg


20/83

20

Glomerulonephritis (Bright disease; nephritic syndrome)

1. Definition:Renal diseases in which an immunologic mechanism triggers inflammation and proliferation of

glomerular tissue that can result in damage to the basement membrane, mesangium, or

capillary endothelium.

2. Classification:

1. Primary:

1. Acute:

1. Post streptococcal

2. Non streptococcal

2. Rapidly progressive

3. Minimal change disease4. Membranous

5. Membrano proliferative

6. Focal proliferative

7. Focal segmental glomerulosclerosis

8. IgA nephropathy

9. Chronic GN

2. Secondary:

1. SLE

2. Diabetic nephropathy

3. Amyloid nephropathy4. Polyarteritis nodosa

5. Wageners granulomatosis

6. Goodpasture syndrome

7. Henoch-Schonlein purpura

8. Systemic infection: Bacterial endocarditis; Falciform malaria etc

9. Idiopathic mixed cryoglobulinemia

3. Hereditary nephritis:

1. Alports syndrome

2. Fabrys disease

3. Nail-patella syndrome

3. Etiopathogenesis of post streptococcal glomerulonephritis (PSGN):

1. Glomeruli consists of: endothelium, epithelium,mesangium and basement membrane(GBM)

2. Acute glomerulonephritis follows infection with certain strains of group A beta-hemolytic

streptococci (GABS). The ones that produce a clear zone of hemolysis around the colony are

called beta hemolytic streptococci;

3. GABS contain M, T and R proteins. Of these, the M protein is the nephritogenic antigen. It is

located in the bacterial cell wall

4. Among the M types, commonly identified nephritogenic strains are 12,4,1


21/83

21

5. It follows mostly skin infection but can also occur after throat infection with nephritogenic

strains

6. Evidence:

1. Low serum complement (C3) levels in the acute phase

2. High serum levels of antibodies to streptococcal antigens

3. Electron microscopy reveals lumpy-bumpy deposits on glomerular membrane and inmesangium

7. Immune-mediated renal injury is a result of renal deposition of circulating immune complexes or

due to their in-situ formation or both

8. Glomerular inflammation follows which leads to complement (C3) activation by classic or more

probably alternate pathway

9. The immune complexes are deposited in the glomerulus produce structural and functional

changes by destruction of basement membrane and accumulation of inflammatory cells

Pathology:

1. Morphology:

1. Kidneys enlarge symmetrically2. Petichial hemorrhages on the cortical surface give flea-bitten appearance

2. Light microscopy:

1. Glomeruli:

Enlarged and hypercellular glomeruli

Proliferation of mesangial, endothelial and occasionally epithelial cells

Infiltration of polymorphs and sometimes monocytes

2. Tubule:

Deposition of fibrin in tubular lumen and mesangium

RBCs in tubular lumen

3. Interstitium: Edema and leukocytic infiltration in renal interstitium

4. Vessels:

No changes in blood vessels

3. Clinical:

1. Age incidence is 5-12 years

2. Symptoms develop 1-2 week following streptococcal infection

3. Oliguria and smoky urine

4. Edema is the most frequent manifesting symptom

5. Gross hematuria occurs at onset6. Hypertension is the third cardinal feature

7. Salt and water retention

8. Complications:

1. CCF

2. Hypertensive encephalopathy

3. Acute renal failure

4. Progressive glomerulonephritis

9. Prognosis:


22/83


23/83

23

3. Classification of types of glomerular disease:

1. Antibody mediated: Three forms of antibody mediated injuries:

1. In situ immune complex deposition:

1. Fixed or in situ : Intrinsic glomerular antigens

2. Planted: Antigens planted within the glomerulus

2. Circulating antigen antibody complexes:1. Endogenous:

a. DNA, tumor antigens

2. Exogenous:

Infectious products

3. Cytotoxic antibodies

2. Cell mediated

3. Alternate complement pathway

Normal Post streptococcal

Membranous


24/83

24

4. In situ Immune complex disease

1. Fixed or in situ immune complex: Anti GBM antibody inducednephritis: two

experimental models:

i. Masugi model;

a. Antibodies are formed against antigens which are normal components of

GBMb. Diffuse linear pattern of immune complex deposition along GBM

c. 5% of Nephritis belong to this model

d. Eg: Good pasture syndrome

ii. Heymann model:

a. Antibodies react with antigens in the basal surface of visceral epithelial cells

b. This is followed by complement activation

c. Immune complexes are formed and deposited along the sub epithelial

aspect of basement membrane in a granular pattern

d. Eg: membranous glomerulonephritis

2. Planted antigen antibody complex:i. Bacterial, viral and parasitic products and other such antigens may get deposited in

glomerulus

ii. Antibodies bind to these antigens and induce complement activation leading to

immune complex formation and glomerular inflammation.

iii. Eg. Post streptococcal GN

3. Circulating antigen antibody complexes:

i. Endogenous: eg: SLE

i. Antigen from host tissue form antibody complexes and then get trapped in

glomeruli

ii. Complements are activatediii. Glomerular injury occurs

iv. Eg: nephritis in SLE

ii. Exogenous:

i. Antigens are formed against infections like streptococci, Hepatitis B,

Treponema, Plasmodium etc

ii. Trapped in glomeruli followed by inflammation

iii. Eg: Nephritis associated with streptococci, Hepatitis B, Treponema,

Plasmodium etc

4. Cytotoxic antibodies:

i. Glomerular cells themselves may act as antigens

ii. Antibodies develop and immune complexes are formed

iii. Injury is caused by cytotoxic mechanism

5. Cell mediated injury:

iv. T cells get sensitized and together with activated macrophages can cause

glomerular injury

v. Cytokines and other mediators from T cells are responsible for this cytotoxic injury

vi. Example: pauci-immune glomerulonephritis

6. Alternate complement pathway:


25/83

25

1. The normal complement system consists of the classic and alternative pathways. The

classic pathway is activated by the interaction of C1 with an antigen-antibody complex.

This interaction results in the formation of C4b2a, which is the classic pathway C3b

convertase. The alternative pathway utilizes C3 and factors B and D to form the

alternative pathway convertase C3b,Bb.

2. Mainly Complement- 3 contributes to this type of injury3. Immune complexes are found in the mesangium and subendothelial spaces, and they

trigger complement activation and the release of cytokines and chemokines. The release

of inflammatory mediators causes an influx of inflammatory cells and leads to mesangial

and endothelial cell proliferation.

4. Example : Memranoproliferative glomerulonephritis

7. Mediators of glomerular injury:

5. Cells:

1. Neutrophils and monocytes: release proteases which cause GBM degradation;

2. Macrophages and T lymphocytes and NK cells: produce variety of lymphokines

and other mediators3. Platelets: release eicosanoids and growth factors

4. Mesangial cells: release cytokines, chemokines, eicosanoids and growth factors

etc

6. Soluble mediators:

1. Formation of C5b-C9 causes cell lysis

2. Interleukin-1 and TNF produce leukocyte adhesion and other effects

3. Fibrin leaks into Bowmans space and induce crescent formation

4. Plasminogen activator inhibitors induce thrombosis and fibrosis

8. Glomerular localization of antigen antibody complexes:

1. Immune complexes get deposited in mesangium, subenotheilal space, sub epithelial space2. The deposits may be granular or diffuse linear pattern

3. Localization depends on molecular charge:

1. anionic : sub endothelial

2. cationic: sub epithelial

3. neutral: mesangium

9. The injury process due to antigen antibody complexes:

1. There are histologic and functional changes

2. Histologic:

1. Histologic changes may be diffuse, global or segmental or masangial

2. Leukocytic infiltration at the site and hypercellularity3. Proliferation of measangial and epithelial cells

4. Formation of crescent

5. Basement membrane thickening

6. Hyalinization and sclerosis

10 . Functional changes:

1. Proteinuria

2. Hematuria

3. Renal failure


26/83

26

Short notes:

Synonym: rapidly progressive glomerulonephritis:1. Definition:

1. A syndrome of severe glomerular injury

2. Does not denote any specific etiology

3. Rapid and progressive loss of renal function

4. Classic histology is presence of crescents in most glomeruli;

2. Classification:

1. Group I:

1. Anti GBM antibody induced glomerulonephritis

2. Linear deposits of Ig.G and C3 in GBM

3. In some similar lesions in lungs (Good pasture syndrome)

2. Group II:

1. Immune complex mediated disease

2. Granular pattern of immune complex deposits

3. Eg. Post infectious, SLE, IgA, Henoch-Schonlein nephropathies

3. Group III:

1. Pauci immune type

2. No immune complex or anti GBM antibody deposits

3. Antineutrophil cytoplsamic or perinuclear antibodies are present in serum

4. Mostly idiopathic

5. Probably a manifestation of small vessel vasculitis limited to glomerulus

3. Pathology:

1. Kidneys are enlarged, pale with petichiae

2. Crescents are present in Bowman capsule; they are formed by proliferation of parietal

cells, monocytes, macrophages, Neutrophils and lymphocytes in a fibrin meshwork;

3. Rupure of GBM and passage of proteins, inflammatory cells into Bowmans space which

form crescents.

4. Clinical:

1. Hematuria

2. Hypertension and edema

3. Hemoptysis in Good-pasture syndrome

4. Presence of serum anti-GBM, antinuclear, ANCA antibodies depending on the type


27/83

27

5. Plasma exchange, steroids, cytotoxic agents may help in recovery.

1. Definition: It is a membranous glomerulopathy with diffuse thickening of glomerular capillary

wall, immune complex deposits along the sub epithelial side of GBM

1. Massive proteinuria >3.5 gm/day

2. Hypoalbuminemia < 3 gm/dL

3. Edema

4. Hyperlipidemia and lipiduria

2. Age: 6-8 years

3. Etiology and Classification:1. Idiopathic

2. Drug induced: gold, NSAID

3. Malignancy: Hodgkin, Ca Lung, colon and melanoma

4. SLE

5. Infections: Hepatitis B,C, syphilis, malaria etc

6. Autoimmune : thyroiditis

4. Pathogenesis:

1. Immune complex mediated

2. Idiopathic form: the in situ antigenis an unidentified antigen due to a genetic

susceptibility3. C5b-C9 complex induce mesangial and epithelial cells to liberate proteases and oxidants

which cause capillary wall injury and increased protein leakage.

4. No circulating immune complex

5. In secondary forms specific antigens could be identified

5. Pathology:

1. Kidneys are enlarged and pale

2. Glomeruli:

1. Diffuse thickening of capillary wall

2. Thickening of GBM

3. No cellular proliferation3. Tubule:

1. Normal

4. Interstitium:

1. Fine Fibrosis and scanty inflammatory cells

5. Vessels:

1. Hypertensive changes in late stage

6. Electron microscopy:

1. Immune complex deposits in subepithelial location


28/83

28

2. GBM appear as spikes between deposits

7. Immunoflorescence:

1. Granular deposits of immune complex (IgG+C)

6. Complications:

1. Hypertension

2. End stage renal disease and renal failure3. Azotemia

4. Renal vein thrombosis

1. In 1919, Good pasture described a syndrome characterized by hemoptysis, alveolar hemorrhage

and necrosis, and proliferative glomerulonephritis in a patient during an influenza epidemic.

Autopsy revealed that the patient had a vasculitis

2. Definition:

Is a triad of diffuse pulmonary hemorrhage (as seen in the images below),

glomerulonephritis, and circulating anti glomerular basement membrane (anti-GBM)

antibodies.

3. It is a type I of crescentric glomerulonephritis

4. It is a immune complex disease due to anti GBM antibodies which also cross react with

pulmonary alveolar basement membrane producing both pulmonary and renal lesions

5. The antigen called Goodpasture antigen is a component of alpha 3 chain of collagen type IV

6. Pathology:

a. Kidneys are enlarged, pale with petichiae

b. Crescents are present in Bowman capsule; they are formed by proliferation of parietal

cells, monocytes, macrophages, Neutrophils and lymphocytes in a fibrin meshwork;

c. Rupture of GBM and passage of proteins, inflammatory cells into Bowmans space

which form crescents.

d. Diffuse linear pattern of immune complex deposition along GBM

1. It is a tubulo interstitial diseasae resulting from repeated attacks of inflammation and scarring.

2. Etiopathogenesis: two typesa. Reflux nephropathy

b. Obstructive pyelonephritis

3. Reflux nephropathy:

a. Congenital absence or shortening of intravesical portion of ureter leading to reflux

during micturition as the valvular mechanism is lost

b. Urine reflux into ureter and pelvis

c. One or both kidneys are damaged with scarring

d. Urinary infection is also common


29/83

29

4. Obstructive pyelonephritis:

a. Obstruction can occur at variable levels( eg. Pelvi ureteric junction or posterior urethral

valve or renal calculi)

b. Unilateral or bilateral

c. Infections superimpose obstruction

d. Inflammations lead to chronic pyelonephritis5. Morphology:

a. Gross:

i. Kidneys are irregularly scarred

ii. Small and contracted

iii. Capsule is adherent with scars

iv. If bilateral the involvement is asymmetrical as opposed to chronic

glomerulonephritis which is symmetrical

v. The diseased cortex is dilated, blunted, and deformed.

vi. The overlying cortex is represented by scar which show U shaped depressions

on the cortical surfacevii. Pelvis is dilated

b. Microscopic:

i. Interstitium:

1. Chronic inflammation is seen

2. Varying degrees of inflammation in the cortex and medulla

3. Neutrophilic infiltrations

4. Pus casts in the tubules

5. Xanthogranulomatous pyelonephritis occurs in proteus infections

6. Fibrotic changes in cortex, medulla and calyx

7.ii. Tubules:

1. Tubules show atrophy, hypertrophy and dilatations

2. Dilated tubules are filled with colloid casts (throidization)

iii. Glomerulus:

1. Periglomerular fibrosis may be present

2. Focal segmental glomerulosclerosis may be seen

iv. Blood vessels:

1. Show obliterative endarteritis

2. Secondary changes may occur due to hypertension

v. Pelvi calyceal system:1. Pelis and calyx are dilated

2. Walls show chronic inflammation with lymphoid follicles

3. Epithelium undergoes squamous metaplasia


30/83

30

Short notes:

1. Definition: it is an acute suppurative inflammation of the kidney caused by pyogenic bacteria

2. Etiopathogenesis:

a. Mostly ascending infection from lower UTI with E.coli (90%), Enterobacter, Klebsiella,

Psuedomonas and Proteus

b. Haematogenous from sites of infection

3. Ascending infection:

Female:

i. Fecal contamination of urethral orifice in female

ii. Short urethra

iii. Bacterial adherence to mucosa due to hormonal influence

iv. Prostatic secretion is antibacterial and is lacking in female

v. Urethral trauma during sexual intercourse (honeymoon pyelitis)

vi. Aggravating factors:

1. Diabetes

2. Pregnancy

3. Urinary obstruction due to calculi etc

4. Bladder catheterization

vii. In bladder they produce asymptomatic bacteria; on ascending up to renal cortex

pyelonephritis is produced;

viii. Reflux mechanism is not involved as in chronic pyelonephritis

4. Haematogenous infection:a. Infants

b. Malignancy with immunoincompetence

5. Morphology:

a. Gross:

i. Enlarged and swollen kidneys; bulge on section

ii. Cut surface show small pockets of pus with hemorrhagic rim mainly in cortex

b. Microscopy:

i. Acute inflammation of interstitium with large no of polys
http://www.google.co.in/imgres?imgurl=http://www.mdconsult.com/books/bbmapAsset?appID=MDC&isbn=978-1-4377-0792-2&eid=4-u1.0-B978-1-4377-0792-2..50025-0..gr32..t&assetType=thumb&imgrefurl=http://www.mdconsult.com/books/page.do?eid=4-u1.0-B978-1-4377-0792-2..50025-0--cesec91&isbn=978-1-4377-0792-2&type=bookPage&from=content&usg=__anxdA2ofUT2nzRBA9teGyYEccJ4=&h=80&w=51&sz=4&hl=en&start=202&zoom=1&tbnid=z5MN5YR4fs85wM:&tbnh=80&tbnw=51&prev=/images?q=chronic+pyelonephritis&hl=en&sa=G&biw=1362&bih=555&gbv=2&tbs=isch:1&itbs=1&iact=hc&vpx=1159&vpy=205&dur=2418&hovh=80&hovw=51&tx=108&ty=27&ei=AQIYTZ33HITmvQPL-4GNDg&oei=xf4XTYz0EsatrAfM48y7Cw&esq=11&page=10&ndsp=26&ved=1t:429,r:17,s:202http://www.google.co.in/imgres?imgurl=http://www.edrep.org/media/textbook/reflux.gif&imgrefurl=http://www.edrep.org/pages/textbook/reflux.php&usg=__zuwxaSX4Lg6EiIu-8awiL2rYI3o=&h=348&w=630&sz=14&hl=en&start=0&zoom=1&tbnid=FzlRkHT-zt79iM:&tbnh=90&tbnw=163&prev=/images?q=chronic+pyelonephritis&hl=en&sa=G&biw=1362&bih=555&gbv=2&tbs=isch:1&itbs=1&iact=hc&vpx=806&vpy=119&dur=7878&hovh=167&hovw=302&tx=165&ty=91&ei=xf4XTYz0EsatrAfM48y7Cw&oei=xf4XTYz0EsatrAfM48y7Cw&esq=1&page=1&ndsp=22&ved=1t:429,r:5,s:0http://www.google.co.in/imgres?imgurl=http://www.mdconsult.com/books/bbmapAsset?appID=MDC&isbn=978-1-4377-0792-2&eid=4-u1.0-B978-1-4377-0792-2..50025-0..gr32..t&assetType=thumb&imgrefurl=http://www.mdconsult.com/books/page.do?eid=4-u1.0-B978-1-4377-0792-2..50025-0--cesec91&isbn=978-1-4377-0792-2&type=bookPage&from=content&usg=__anxdA2ofUT2nzRBA9teGyYEccJ4=&h=80&w=51&sz=4&hl=en&start=202&zoom=1&tbnid=z5MN5YR4fs85wM:&tbnh=80&tbnw=51&prev=/images?q=chronic+pyelonephritis&hl=en&sa=G&biw=1362&bih=555&gbv=2&tbs=isch:1&itbs=1&iact=hc&vpx=1159&vpy=205&dur=2418&hovh=80&hovw=51&tx=108&ty=27&ei=AQIYTZ33HITmvQPL-4GNDg&oei=xf4XTYz0EsatrAfM48y7Cw&esq=11&page=10&ndsp=26&ved=1t:429,r:17,s:202http://www.google.co.in/imgres?imgurl=http://www.edrep.org/media/textbook/reflux.gif&imgrefurl=http://www.edrep.org/pages/textbook/reflux.php&usg=__zuwxaSX4Lg6EiIu-8awiL2rYI3o=&h=348&w=630&sz=14&hl=en&start=0&zoom=1&tbnid=FzlRkHT-zt79iM:&tbnh=90&tbnw=163&prev=/images?q=chronic+pyelonephritis&hl=en&sa=G&biw=1362&bih=555&gbv=2&tbs=isch:1&itbs=1&iact=hc&vpx=806&vpy=119&dur=7878&hovh=167&hovw=302&tx=165&ty=91&ei=xf4XTYz0EsatrAfM48y7Cw&oei=xf4XTYz0EsatrAfM48y7Cw&esq=1&page=1&ndsp=22&ved=1t:429,r:5,s:0http://www.google.co.in/imgres?imgurl=http://www.mdconsult.com/books/bbmapAsset?appID=MDC&isbn=978-1-4377-0792-2&eid=4-u1.0-B978-1-4377-0792-2..50025-0..gr32..t&assetType=thumb&imgrefurl=http://www.mdconsult.com/books/page.do?eid=4-u1.0-B978-1-4377-0792-2..50025-0--cesec91&isbn=978-1-4377-0792-2&type=bookPage&from=content&usg=__anxdA2ofUT2nzRBA9teGyYEccJ4=&h=80&w=51&sz=4&hl=en&start=202&zoom=1&tbnid=z5MN5YR4fs85wM:&tbnh=80&tbnw=51&prev=/images?q=chronic+pyelonephritis&hl=en&sa=G&biw=1362&bih=555&gbv=2&tbs=isch:1&itbs=1&iact=hc&vpx=1159&vpy=205&dur=2418&hovh=80&hovw=51&tx=108&ty=27&ei=AQIYTZ33HITmvQPL-4GNDg&oei=xf4XTYz0EsatrAfM48y7Cw&esq=11&page=10&ndsp=26&ved=1t:429,r:17,s:202http://www.google.co.in/imgres?imgurl=http://www.edrep.org/media/textbook/reflux.gif&imgrefurl=http://www.edrep.org/pages/textbook/reflux.php&usg=__zuwxaSX4Lg6EiIu-8awiL2rYI3o=&h=348&w=630&sz=14&hl=en&start=0&zoom=1&tbnid=FzlRkHT-zt79iM:&tbnh=90&tbnw=163&prev=/images?q=chronic+pyelonephritis&hl=en&sa=G&biw=1362&bih=555&gbv=2&tbs=isch:1&itbs=1&iact=hc&vpx=806&vpy=119&dur=7878&hovh=167&hovw=302&tx=165&ty=91&ei=xf4XTYz0EsatrAfM48y7Cw&oei=xf4XTYz0EsatrAfM48y7Cw&esq=1&page=1&ndsp=22&ved=1t:429,r:5,s:0


31/83

31

ii. Destruction of tubules

iii. Abscess in renal parenchyma

iv. Glomerulus and renal vessels not much affected due to their resistance to

infection

6. Clinical:

a. Acute onset of chills with feverb. Loin pain

c. Dysuria

d. Frequency of micturition

7. Lab: Urine

a. Bacturia

b. Pus cells

c. Pus cell casts

8. Complications:

a. Papillary necrosis

b. Pyonephrosis(bag of pus in kidney)c. Perinephric abscess(due to local spread)

Short notes:

1. Urinary castsare cylindrical structures produced by thekidney and present in theurine in

certain disease states.

2. They form in thedistal convoluted tubule andcollecting ducts ofnephrons,then dislodge and

pass into the urine, where they can be detected bymicroscopy.

3. They form via precipitation ofTamm-Horsfallmucoprotein which is secreted byrenal tubulecells, and sometimes also byalbumin in conditions ofproteinuria.

4. Cast formation is pronounced in environments favoring protein denaturation and precipitation

(low flow, concentrated salts, lowpH). Tamm-Horsfall protein is particularly susceptible to

precipitation in these conditions.

5. The Tamm-Horsfall protein is a glycoprotein isolated from normal urine by Tamm and Horsfall in

the early fifties. This protein is excreted by the thick ascending branch of the loop of Henle and

the first part of the distal tubules. Normal daily excreted quantity ranges from 25 to 50 mg.

This protein is the major fraction of the uromucoprotein.

6. Casts are elements of the urinary sediment, formed by the polymerisation of the Tamm-Horsfall

fibrils, taking the shape of the site of its formation (casting). Casts are formed, after the loop, inthe late section of the distal tubules and the early section of the collecting tubes. The formation

site is the nephron's section where the dilution is maximal.7. As mentioned earlier, fibril's formation is inhibited by a low ionic strenght, and the precipitation

is promoted by the addition of albumin.8. Types of casts:

1. Hyaline casts

a. The most common type of cast, hyaline casts are solidifiedTamm-Horsfall mucoprotein

secreted from the tubular epithelial cells of individual nephrons.
http://en.wikipedia.org/wiki/Kidneyhttp://en.wikipedia.org/wiki/Urinehttp://en.wikipedia.org/wiki/Distal_convoluted_tubulehttp://en.wikipedia.org/wiki/Collecting_ducthttp://en.wikipedia.org/wiki/Nephronhttp://en.wikipedia.org/wiki/Microscopyhttp://en.wikipedia.org/wiki/Tamm-Horsfall_proteinhttp://en.wikipedia.org/wiki/Mucoproteinhttp://en.wikipedia.org/wiki/Renal_tubulehttp://en.wikipedia.org/wiki/Albuminhttp://en.wikipedia.org/wiki/Proteinuriahttp://en.wikipedia.org/wiki/PHhttp://en.wikipedia.org/wiki/Tamm-Horsfall_proteinhttp://en.wikipedia.org/wiki/Tamm-Horsfall_proteinhttp://en.wikipedia.org/wiki/PHhttp://en.wikipedia.org/wiki/Proteinuriahttp://en.wikipedia.org/wiki/Albuminhttp://en.wikipedia.org/wiki/Renal_tubulehttp://en.wikipedia.org/wiki/Mucoproteinhttp://en.wikipedia.org/wiki/Tamm-Horsfall_proteinhttp://en.wikipedia.org/wiki/Microscopyhttp://en.wikipedia.org/wiki/Nephronhttp://en.wikipedia.org/wiki/Collecting_ducthttp://en.wikipedia.org/wiki/Distal_convoluted_tubulehttp://en.wikipedia.org/wiki/Urinehttp://en.wikipedia.org/wiki/Kidney


32/83


33/83

33

Legend: A: Hyaline cast; B: Fatty cast; C: Hyaline to finely granular cast; D: Cellular cast;

E: Cellular to coarsely granular cast; F: Coarsely granular cast; G: Finely granular cast; H:

Granular to waxy cast, I: Waxy cast.

Short notes:

Synonym:

Chronic glomerulonephritis:


34/83

34

End stage renal disease:

1. Chronic glomerulonephritisrepresents the end-stage of all glomerulonephritis with

unfavorable evolution. This general (glomerular, vascular and interstitial) affection constitutes

the "end stage kidney". In most cases, it is associated with systemic hypertension.

2. Causes:There are a number of different forms of glomerulonephritis, including:

1. acute glomerulonephritis,2. membranoproliferative glomerulonephritis,3. rapidly progressive glomerulonephritis,4. idiopathic membranous glomerulonephritis, and

5. IgA nephropathy, any of which can progress to chronic glomerulonephritis.6. Systemic hypertension

3. Morphology:1. Gross: Kidneys are symmetrically contracted,and have diffusely granular cortical

surfaces.

2. C.S: the cortex is thinned; peripelvic fat is increased;

3. Microscopic:i. Glomeruli: reduced in no.; mostly converted into hyalinized tufts

ii. Tubules: atrophy of tubules; tubular cells show hyaline deposits

iii. Interstitium: show fine fibrosis and chronic inflammatory cells

iv. Vessels: in hypertension, the vessels show arteriolar sclerosis

4. Patients on dialysis: show acquired cystic disease, adenomas, calcification of tufts.

Short notes:

1. Definition: destruction of tubular epithelial cells leading to acute renal failure.

2. Commonest cause of renal failure3. Pathogenesis: two types:

1. Ischemic; & Toxic

2. Tubular epithelium is highly susceptible for ischemic or toxic agents

3. Arteriolar vasoconstriction and toxins produce necrosis of tubules and the debris causes

obstruction to urinary outflow

4. Increased intratubular pressure produce damage to basement membrane and rupture of

tubules

5. Leakage of fluid from tubules produce interstitial edema

6. This further compress tubules and arterioles leading on to a vicious cycle.

7. The events end up in acute renal failure reduced GFR and olguria4. Ischemic ATN: synonyms: lower nephron nephrosis; shock kidney

1. More common- 80%

2. Due to hypotension from:

1. Burns

2. Hemorrhage

3. Crush injuries

4. Mismatched blood transfusion

5. Black water fever


35/83

35

3. Morphology:

1. Gross: kidneys are enlarged and swollen

2. C.S: pale cortex and dark medulla

3. Microscopy:

a. Glomeruli are not affected

b. Interstitium show edemac. Tubules:

Dilatation

Focal necrosis

Flattened epithelium

Lumen contains eosinophilic hyaline and hemoglobin casts

Disruption of tubular basement membrane

4. Prognosis: depends on underlying cause; usually worse

5. Toxic ATN: upper nephron nephrosis

1. Etiology:

1. Poisons: Mercuric chloride, carbon tetrachloride, mushroom poison, insecticides2. Heavy metals: lead, mercury, arsenic, phosphorus and gold

3. Drugs: sulfonamides, gentamycin, halothane, salicylates

4. Radiographic contrasts

2. Morphology:

1. Gross: kidneys are enlarged and swollen

2. C.S: pale cortex and dark medulla

3. Microscopy:

a. Glomeruli are not affected

b. Interstitium show edema

c. Tubules: Diffuse and not focal involvement

Proximal tubules are necrotic and desquamated and calcified

Tubular basement membrane is intact

Flat and thin epithelial regeneration may be seen

4. Prognosis:

5. Relatively good

Short notes:

Nephrolithiasis or urolithiasis1. Incidence 2%; 20-30 years of age;

2. Types:

1. Calcium stones:

1. 75% commoner

2. Calium oxalate, phosphate or mixed

3. Etiology:

a. Mostly idiopathic

b. Hyperparathyroidism


36/83

36

c. Renal hypercalciuria

4. Pathogenesis:

a. Imbalance between calcium ions and factors inhibiting precipitation

b. An epithelial debris forms a nidus around which Ca is deposited

5. Morphology:

a. Stones are small, ovoid, hard, granular rough surface2. Mixed stones:

1. M,ade of magnesium ammonium- calcium phosphate called struvite stones

2. Etiology: fallow infection like proteus( not with E.coli)

3. Morphology:

a. Yellow-white

b. Soft and friable

c. Irregular

d. Stag horn stone: the stone takes the shape of renal pelvis

3. Uric acid:

1. Radiolucent2. Formed in Gout and Leukemias due to hyperuricosuria

3. Salicylates and probenacid also produce uricosuria

4. Acidc pH and low urinary volume are favourable for the stone formation

5. Stones are yellow brown , multiple and smooth and hard, C.S show lamination

4. Cystine stones:

1. Associated with cystinuria

2. Exces cystine in urine form crystals and then stones

3. Stones are small, rounded, smooth and multiple; yellow and waxy.

5. Others: Xanthine stones occur in hereditary xanthinuria

S.N:

1. Leading cause of renal morbidity

2. 40% of diabetics develop end stage kidney disease

3. Diabetes affects:

a. Glomerulus:

i. Non nephrotic proteinuria

ii. Nephrotic syndrome

iii. Chronic renal failure

b. Renal arterioles:i. Hyalinizing arteriolar sclerosis

4. Proteinuria:12-22 years after diabetes; initially microalbuminemia occurs followed by nephrotic

type proteinuria;

5. Pathogenesis:

a. It is described as diabetic microangiopathy

b. Glycosylation end products leads to thickening of GBM and increased mesangial matrix

c. Hemodynamic changes i.e increased GFR, increased glomerular capillary pressure,

glomerular hypertrophy lead to glomerulosclerosis


37/83

37

d. Sequence of changes:

Hyperglycemiaglomerular hyperperfusionrenal hyperperfusiondeposition of

protein in measngium glomerulosclerosisrenal failure

6. Morphology:

a. GBM: increased thickening is the basic pathology

b. Measngium: proliferation of mesangial cells and increase in mesangial matrixc. Diffuse Glomerulosclerosis:

i. Capsular cap: eosinophilic hyaline thickening of the parietal layer Bowmans

capsule

ii. Fibrin cap: eosinophilic material on the walls of lobular capillary vessels

d. Nodular Glomerulosclerosis:

i. Occurs in juvenile diabetes

ii. Nodular lesions appear in glomeruli which contain lipid and fibrin

iii. Nodules compress glomerular capillaries which ultimately lead to contracted

kidney

e. Vascular lesions:i. Atherosclerosis of renal arteries

ii. Arterioscelrosis of afferent and efferent arterioles

iii. They produc renal ischemia

f. Pyelonephritis:

i. Bacterial infections lead to papillary necrosis leading to pyelonephritis (acute

and chronic)

g. Tubular lesions:

i. Glycogen deposits in the epithelial cells of proximal convoluted tubules

ii. They are called Armanni-Ebstein lesions

S.N: Analgesic nephropathy.

1. Analgesic nephropathyis injury to thekidney caused byanalgesic medications such asaspirin,

phenacetin,and NSAID. The term usually refers to damage induced by excessive use of

combinations of these medications, especially combinations that include phenacetin2. There is a predominant involvement of tubules and interstitium3. Pathology:

a. Acute or chronic

b. There is Interstitial edema with leukocytic infiltration

c. Focal tubular necrosis

d. In chronic form there will be fibrosis and tubular atrophy

S.N: Haemolytic uremic syndrome.(Thrombotic micro angiopathy)

1. It belongs to group called thrombotic microangiopathy

2. There is thrombosis in the capillaries and arterioles through the body

3. Triad:

a. Microangiopathic hemolytic anemia

b. Thrombocytopenia

c. Renal failure
http://en.wikipedia.org/wiki/Kidneyhttp://en.wikipedia.org/wiki/Analgesichttp://en.wikipedia.org/wiki/Aspirinhttp://en.wikipedia.org/wiki/Phenacetinhttp://en.wikipedia.org/wiki/Phenacetinhttp://en.wikipedia.org/wiki/Aspirinhttp://en.wikipedia.org/wiki/Analgesichttp://en.wikipedia.org/wiki/Kidney


38/83

38

4. Classification:

a. Childhood HUS:

i. Due to bacterial dysentery and its toxic effect on capillary endothelium

b. Adult HUS:

i. Infection

ii. Antiphospholipid antibodiesiii. Pregnancy complication

iv. Oral contraceptive

v. Radiation

vi. Immunosupressive drugs

5. Pathogenesis:

a. Classic Childhood HUS:

i. Follows E.coli and shigella infection

ii. Toxin acts on endothelium of microvascular system:

1. Endothelial lysis

2. Leukocyte adhesion3. Increased thrombosis

4. Vasoconstriction

6. Morphology:

1. Diffuse cotrtical necrosis

2. Endothelial and sub endothelial swelling swelling in glomeruli

3. Measngiolysis

4. Thrombus occlusion of afferent arterioles

Pathology: short notes

1. Definition: the rate of sedimentation of red blood cells per hour

2. Estimation:

a. Wintrobes and Landsbergs method: ESR is measured on undiluted blood in a haematocrit

tube

b. Westerngrens method: measured on venous blood diluted with 1 volume of 3.8% sodium

citrate and 4 volume of blood

c.

Modified methods:

i. Zeta sedimentation ratio

ii. Micro ESR method

3. Normal ESR:

a. Westerngrens method: 10mm/hour for men; 20 mm/hour women; ESR increases normally

with age

4. Factors influencing ESR:

a. Specific gravity of plasma

b. Rouleaux formation of RBCs


39/83

39

c. No of red cells

d. Plasma viscosity

e. Prior IV fluids

5. Roleaux formation depends on:

a. Fibrinogen

b. Alpha 2 globulin and gamma gloubulinc. Glycoprotein

6. Conditions of elevated ESR:

a. Infections: TB, Kala Azar,most chronic infections

b. Inflammation: Rheumatoid arthritis, Rheumatic fever, other connective tissue disorders

c. Neoplasm: Multiple myeloma, lymphoma, paraproteinemias

d. Miscellaneous: aplastic anemia, autoimmune disorders, anemia

7. Conditions of low ESR:

a. Ploycythemia

b. Sickle cell anemia

1. Turner syndrome:

1. Pathophysiology:

a. It is a monsomy (45, X0) due to loss of one X chromosome in paternal meiotic division

b. Turner syndrome is also caused by the absence of one set of genes from the short arm

of one X chromosome

c. In addition to monosomy X, a similar clinical picture is found with a individuals with X0-

XX mosaic karyotypes.

2. The frequency is approximately 1 in 2000 live-born female infants . As many as 15% of

spontaneous abortions have a 45,X karyotype.

3. Features:

a. Short stature

b. A high arched palate suggests the diagnosis. Patients may have dental crowding or

malocclusion.

c. Ovarian failure

d. Lymphedema may be present at any age

4. Turner syndrome may be prenatally diagnosed by amniocentesis or chorionic villous sampling.

2. Down syndrome:

1. In 1866, Down described clinical characteristics of the syndrome that now bears his name.

2. It is caused by trisomy in chromosome 21

3. The frequency is about 1 case in 800 live births.

4. Causes of trisomy:

a. Non dysjunctionof one chromosome during maternal meiosis to form egg

b. Mother is a translocationcarrier in which translocation of long arm occurs between 14

and 21 chromosomes; she remains normal due to balanced translocation and the

offspring inherits the trisomy syndrome

c. Advanced maternal age is the important factor for trisomy 21


40/83

40

5. Features:

a. Mangoloid slant of palpebral fissure

b. Simian crease in palms

c. Sandle cleft between 1&2 toes

d. CHD often endocardial cushion defect

e. Proneness for leukemiaf. Association: deafness and hypothyroidism

g. Accident proneness

h. Love for music and cooperation with mother in household work are interesting faetures

6. Prognsosis:

a. Mostly aborted

b. Dath from 1 year to 50 years

Kleinfelters syndrome:

1. It is a trisomy affecting sex chromosomes; It is defined classically by a 47,XXY karyotype with

variants that demonstrate additional X and Y chromosomes.2. Affected person is a genotypically a male with abnormal feautures

3. 80% are have 47 xxy while others are mosaics

4. Approximately 1 in 500-1,000 males is born with an extra sex chromosome

5. The 47,XXY karyotype of Klinefelter syndrome spontaneously arises when paired X

chromosomes fail to separate (nondisjunction in stage I or II of meiosis, during oogenesis or

spermatogenesis). Maternal and paternal meiotic nondisjunction each account for

approximately 50% of Klinefelter syndrome cases

6. Infertility, tyeasticular dysgenesis and gynecomastia are the 2 most common symptoms that

lead to diagnosis in patients with Klinefelter syndrome.

7. Other symptoms include fatigue, weakness, erectile dysfunction, osteoporosis, languageimpairment, academic difficulty, subnormal libido, poor self-esteem, and behavioral problems.

Von Willebrand disease:

1. Hereditary coagulation disorder due to qualitative and quantitative defect in von Willebrand

factor which is Factor VIII and vWF complex

2. vWF gene is located in Chromosome 12 while factor VIII gene is in X chromosome

3. vWF is synthesised in endothelial cells, megakaryocytes and platelets while Factor VIII is

synthesised in Liver

4. vWF facilitates adhesion of platelets; Factor VIII activates Factor X in coagulation cascade

5. vWF and Factor VIII circulate and function as single unit for clotting mechanism: factor X

actvation and platelet adhesion;

6. Clinical types:

a. Type I: common variety; 50% vWF activity; synthesis of vWF is normal but release is

inhibited

b. Type II: less common; normal vWF but functionally defective

c. Type III: rare form; most severe; vWF is absent.

7. Manifestations:

a. Spontaneous bleeding from mucous membranes


41/83


42/83


43/83

43

6.Pancreatitis

7.Sickle cell anemia

8.Fat or oil introduced in the body

c. Pathogenesis: Theories:

1.Mechanical: Mechanical injury to fat tissues and entering venous circulation

2.Emulsion instability: Aggregation of plasma lipids due to disturbances inemulcification

3.Intravascular coagulation: In stress some factor actvates DIVC and aggregation of

fat emboli

4.Toxic injury: free fatty acids injure capillaries and lead to pulmonary edema

3. Amniotic fluid embolism:

a. Pathogenesis:

1.Mechanism not clear

2.May enter through tears in the myometrium and endocervix

3.Omniotic fluid may eneter uterine sinusoids during vigorous contractions

b. Morphology:1.Haemorrhages and oedema in lungs; amniotic fluid traces in pulmonary

43microcirculation

2.Changes of ARDS

3.Dilatation of Rt heart

c. Causes of death:

1.Hypoxia

2.Anaphylaxis

3.DIC

4.Haemorrhage due to thrombocytopenia

1. Autosomal recessive lipid storage disorder characterized by accumulation of sphingomyelin and

cholesterol due to deficiency of sphincomyelinase.

2. Type A: more common; infancy; hepeato splenomegaly; lymphadenopathy, mental retardation;

cherry red spot in macula of retina

3. TypeB: later childhood; progressive hepato splenomegaly; cirrhosis; lung infiltration

4. Microscopy:

a. Lysosomal deposits of sphingomyelin and cholesterol

b. The pathologic hallmark in Niemann-Pick disease types A and B is characteristic lipid-laden

foam cell, often termed the Niemann-Pick cell, on bone marrow examination.c. These cells, which can be readily distinguished from Gaucher cells by histologic and

histochemical characteristics, are histologically similar to cells found Wolman disease,

cholesterol ester storage disease, lipoprotein lipase deficiency, and, in some patients, GM1

gangliosidosis type 2.

Myelodysplastic syndrome:


44/83

44

1. Definition: group of haematopoietic clonal stem cell disorders having .All are characterized by a

hypercellular or hypocellular marrow with impaired morphology and maturation (dysmyelopoiesis) and

peripheral blood cytopenias, resulting from ineffective blood cell production.

2. All 3 cell lineages in myeloid hematopoiesis can be involved, including erythrocytic, granulocytic, andmegakaryocytic cell lines.

3. FAB classification:

a. Refractory anemia: Anemia without blasts in blood; marrow shows 15% ringed sideroblasts

c. Refractory anemia with excess blasts:

d. Chronic myelomonocytic leukemia

e. Refractory anemia with excess blasts in transformation

4. Etiology;:

a. Idiopathic

b. Radiation exposure

c. Benzene carcinogen

d. Secondary MDS follow cancer therapy

e. Fanconi anemia

5. Pathophysiology: Chromosomal defects: trisomies, translocations and deletions are seen; Mutationin N-RAS oncogene

6. Age: 6thdecade; male preponderance;

7. Clinical: Anemia, fever, wt loss, splenomegaly in 20%

8. Lab:

a. Blood: cytopenia of 2 or more cell lines-pancytopenia

b. Macrocytic or dimorphic anemia

c. Hyposegmented and hypogranular Neutrophils

d. Myeloblasts may be seen

e. Thrombocytopenia and large platelets

9. Marrow:

a. Hypo or hyper cellular

b. Ring sideroblasts

c. Hyposegmented and hypogranular myeloid precursors

d. Reduced magakaryocytes

Disseminated Intravascular Coagulation (DIC) (consumptive coagulopathy)

1. Thrombohaemorrhagic disorder occurring as a secondary complication of a systemic disease

2. Causes:

a. Massive tissue injury:

i. abruption placentae

ii. amniotic fluid embolism

iii. Retained dead foetus

iv. Crush injuries

v. Surgery

vi. Malignancy

b. Infections:

i. Endotoxicemia

ii. Gram negative sepsis


45/83

45

iii. Viral infections

iv. Malaria

v. Aspergellosis

c. Epithelial damage:

i. Aortic aneurysm

ii. Haemolytic uremic syndromeiii. Burns

iv. Acute glomerulonephritis

d. Miscelaneous:

i. Snake venom

ii. Shock

iii. Intravascular haemolysis

iv. Heat stroke

3. Pathogenesis:

a. Activation of coagulation by releasing tissue factors following tissue injury

b. Endothelial damage in microcirculation followed by platelet adhesionc. Consumption of coagulation factors during extensive coagulation

d. Fibrinolysis - a secondary event

4. Clinical:

a. Organ (kidney, brain etc) damage due thrombotic ischemia

b. Haemolytic anemia

c. Thrombotic manifestations

5. Lab:

a. Platelet count is low

b. Smear : schistocytes and fragmented red cells

c. Prolonged prothrombin, thrombin and partial thromboplastin timesd. Low plasma fibrinogen

e. Fibrin degradation products are elevated

1. Fibronectin is adhesive Glycoprotein called CAM or cell adhesion molecules, one of the components

of extra cellular matrix (ECM)

2. They are located in cell membrane where they function as receptors for hemotypic and heterotypic

interaction between cells


46/83

46

3. Fibronectin is a large protein that binds to many molecules like collagen, fibrin, proteoglycons and

cell surface receptors.

4. 2 typpes: tissue fibronectin formed by fibroblasts and plasma fibronectins synthesised in liver

5. Tissue fibronectins forms fibrils that helps in wound healing

6. Plasma Fibronectin binds to fibrin forms a provisional clot that fills a gap created by a wound

7. Tissue fibronectins are responsible for the primitive matrix found in fetus8. Fetal fibronectin is detectable in vaginal secretions of pregnant women and its estimation helps in

detecting preterm delivery; From weeks 22 to 35 in your pregnancy, there should be very little fFN

detectable.

1. A lab test for the diagnosis of SLE

2. Principle:

a. antinuclear antibodies (ANA) cannot penetrate the intact cells and need to be exposed for

ANA to bind.

b. ANA and cell nucleus binding form a mass called LE Body.c. Phagocytic leukocyte engulfs LE body and becomes an LE cell

d. Formation of LE cell can be demonstrated in vitro as follows:

e. Blood sample is traumatised to liberate leukocyte nucleus which get exposed to ANA in the

same sample; LE body is formed and leukocyte phagocytes it to form LE cell

3. LE Cell: LE body is engulfed by a neutrophil and occupies the cell space pushing the nucleus to the

margin as a rim. This cell is called LE cell and if it hapeens with monocyte it is called a Tart cell.

4. LE cell is positive in 70% of SLE and also rheumatoid arthritis, lupoid hjepatitis, penicillin sensitivity

etc

Free radicals:

1. Cells generate energy by reducing molecular oxygen to water. During this process small quantities of partially

reduced reactive oxygen forms are produced as an unavoidable by product of mitochondrial respiration

2. Free radicals are called reactive oxygen species

3. Free radicals can damage lipids, proteins and nucleic acids.

4. Cells radical scavenging system and imbalance between radical production and scavenging would result in

oxidfative stress

5. Production:

a. Ultra violet and Xrays hydrolyse water induce O and OH free radicals

b. Ccl4 can generate ccl3

c. In cellular respiration the following radicals are produced:


47/83

47

i. Superoxide

ii. Hydrogen peroxide

iii. Hydroxyl ion

iv. Nitric oxide

d. In inflammation polymorph produce superoxide ions

e. Intrcellular oxidase enzymes like xanthine oxidase also produce superoxide radicals

f. Intracellular iron and copper catalyse free radical formation as in Fenton reactiong. Nitric oxide is a free radical generated by endothelial cells, macrophages, neurons etc

6. Effects of free radicals:

a. Cell membrane damage by peroxidation membrane lipid

b. Free radicals promote oxidation of amino acid side chains leading to protein fragmentation

c. They react with DNA and produce breaks leading to cell aging and malignant transformation

7. Scavenging free radicals:

a. Spontaneous decay into stable ions

b. Vit.A, E, C and glutathione are antoxidants that block or inactivate free radicals

c. Metallo proteins like transferring, ferritin, lactoferrin and ceruloplasmin bind iron and copper

preventing them from catalyzing the formation of free radicals

d. Catalase, superoxide dismutase, glutathione peroxidise are enzymes that break down hydrogen

peroxide and superoxide radicals

1. The Rye classification of Hodgkins Disease was developed at the International Symposium in Rye,

NY in 1965(4).

2. Rye classification divides Hodgkin disease as follows:

a. Lymphocyte predominance- best prognosis

b. Nodular sclerosis- good pronsis

c. Mixed cellularity-fair prognosis

d. Lymphocyte depletion- poor prognosis

3. Value:

a. It is widely used because of its simplicity, and its clinical and prognostic value

b. It provides prognostically useful histologcal features which help in determining therapy

1. Mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular

hemoglobin concentration (MCHC) were first introduced by Wintrobe in 1929 to define the size

(MCV) and hemoglobin content (MCH, MCHC) of red blood cells. Termed red cell indices, these

values are useful in elucidating the etiology of anemias. Red cell indices can be calculated if the

values of hemoglobin, hematocrit (packed cell volume), and red blood cell count are known.

2. Variation in the size of red cells (anisocytosis) can be quantified and expressed as red cell

distribution width (RDW) or as red cell morphology index.

3. MCV defines the size of the red blood cells and is expressed as femtoliters (1015; fl) or as cubic

microns (m3).

4. MCH quantifies the amount of hemoglobin per red blood cell.


48/83

48

5. MCHC indicates the amount of hemoglobin per unit volume. In contrast to MCH, MCHC

correlates the hemoglobin content with the volume of the cell. It is expressed as g/dl of red

blood cells or as a percentage value.

6. RDW represents the coefficient of variation of the red blood cell volume distribution (size) and

is expressed as a percentage.

7. Red cell indices MCV, MCH and MCHC are calculated from hemoglobin, hematocrit, and red

blood cell count as follows:

a. MCV = PCV in L / L of blood

RBC count / L of Blood

b. MCH = ____Hb / L__________

RBC count / L of Blood

c. MCHC = _____Hb / dL______

PCV in L / L of blood

d. RDW = ( standard deviation of MCV mean MCV) 100

8. Normal values:

1. Hb%: Male: 13.8 to 17.2 gm/dL; Female: 12.1 to 15.1 gm/dL

2. RBC Count: Male: 4.7 to 6.1 million cells/mcL; Female: 4.2 to 5.4 million cells/mcL

3. MCV: 80 to 100 femtoliter(fl)

4. MCH: 27 to 31 picograms/cell

5. MCHC: 32 to 36 grams/dl

6. packed cell volume(PCV): 48% for men and 38% for women.

7. RDW : The normal value for RDW is 13 1.5%.

Automatic tissue processor:

1. It is tool for studying histopathology specimens

2. It has 12 1 separate stages completing the process in 18 hours

3. Steps:

a. 10 % formalin fixation

b. Ascending grades of alcohol to dehydration

c. Xylene/ toluene/ chloroform for clearing

d. Paraffin impregnation

4. The tissue blocks are sectioned using microtome and studied under microscope after staining

HenochSchonlein purpura.

1. A self limiting hypersensitivity vasculitis in children and young adults

2. Circulating immune complexes are deposited in vessel walls containing Ig A, C3 and fibrin

3. In some cases presecence of properdin suggests activation of alternate pathway

4. Causes

a. The etiology of Henoch-Schnlein purpura is unknown.

b. About 50% of patients have a precedingupper respiratory illness (URI).
http://emedicine.medscape.com/article/302460-overviewhttp://emedicine.medscape.com/article/302460-overview


49/83

49

c. Multiple infectious agents as well as drugs, foods, and insect bites may trigger Henoch-

Schnlein purpura.

d. Antistreptolysin O titers are raised in 20-50% of patients.

5. The most common symptoms of Henoch-Schnlein purpura include the following:

a. Rash (95-100%), especially involving the legs, may not be present on initial presentation

b. Subcutaneous edema (20-50%)

c. Abdominal pain and vomiting (85%)

d. Joint pain (60-80%), especially involving the knees and ankles

e. Scrotal edema (2-35%)

f. Bloody stools

6. Lab:

a. Urinalysis: Hematuria and/or proteinuria are present in 10-20% of patients.

b. Platelet count and coagulation studies: Platelet count is usually in the reference range but

may be elevated; the platelet count should not be low in Henoch-Schnlein purpura. A

normal platelet count rules outidiopathic thrombocytopenic purpura (ITP). A normal

platelet count and normal coagulation studies (ie, PT, aPTT, fibrin split products)rule out

thrombotic thrombocytopenic purpura (TTP).

F.N.A.C.

1. Fine needle aspiration cytology is a minimal invasive diagnostic cytology2. Almost all organs are accessible for this study3. It is used for diagnosis of palpable lesions:

a. Breast massb. Lymph nodesc. Thyroid tissued. Salivary tumourse. Abdominal massf. Testis

g. Prostateh. Bone and jointsi. Orbit

4. Advantages:a. Quick and less painfulb. No hospitalization, anaesthesia are requiredc. Multiple attempts are possibled. Cost effective

5. Procedure :a. Large bore needle with syringeb. Skin cleaned and mass fixed by fingersc. Sample tissue is aspiratedd. Aspirate is spread on a glass slidee. After air drying it is fixed with ethanolf. Stained by Papanicolaou or H&E stain

6. Uses:
http://emedicine.medscape.com/article/779545-overviewhttp://emedicine.medscape.com/article/779969-overviewhttp://emedicine.medscape.com/article/779969-overviewhttp://emedicine.medscape.com/article/779545-overview


50/83

50

a. HPEb. Microbiological examc. Flow cytometryd. Immunocytology

7. Side effects:

a. Hematomab. Infection

c. Pneumothorax

d. Tumour dissemination

Virchows triad:

1. The pathogenesis of thrombus depends on 3 factors called Virchows triad:

a. Endothelial injury

b. Stasis or turbulent blood flow

c. Hypercoagulability2. Endothelial injury:

a. Intact epithelium has:

i. Thrombus inhibitory factor

ii. Heparin like substance

iii. Thrombomodulin

iv. Platelet inhibitors

v. Tissue plasminogen activator

b. Prothrombotic factors:

i. Thromboplastin

ii. Von Willebrand factoriii. Inhibitor of plasminogen activator

c. Endoth

Documents

Pn Pathology Notes.docx New