Sublime White Coat

Whom am I addressing?
basically this is for 4th year GMC students … i will be specific about teachers favourite test and viva questions … but any medical student can benefit from general guidelines about the subject …

Why me?
As being topper of class and obtaining 3rd position in KMU in 4th year … i think its my responsibility and duty to share my knowledge and study techniques and tips … so that my junior students should get more benefit in less time and i believe in sharing … knowledge spreads by sharing and sharing is caring …
i stood 2nd in pathology … Farhat was 1st in pathology both theory and viva … and i stood 1st in community both theory and viva … i would also like to take his advice into this post …

Dedication:

These guidelines are dedicated to my three friends in 4th year sami, nafees and jamshed. I dedicate them these guidelines because they discuss everything with me except Study. Nowadays they take ping pong classes from me but whenever i ask about studies they are very good at changing the subject. Best Wishes to them and all the 4th year.

Requests:

I request Farhat ullah Bettani and all my classfellows specially fawad, qaiser, shoaib and imran to include their inputs into these guidelines…

WHICH BOOKS TO STUDY :

these study tips are not an alternative to your course books… so study them …
1) Robbins ( Long / medium)
2) Dr. Shahzad Iqbal Volume 1 and 2 (for certain topics that are not in robbins and given in our exams such as investigations of diseases )
3) Zahid Jan compiled papers ( these are chapter wise and gives you very good idea about important questions) and also new pattern papers

NEW UPDATE: I have uploaded Zahid Jan papers on net for important questions of both pathology and community medicine on request of Harem at comment No. 4  … Zahid jan papers can be downloaded by clicking on Zahid Jan compiled papers present above or here.

UPDATED ON 27-06-2011

Basically it does not depend upon the book … but it depends upon the reader how he studies the book …

Some students try to use harsh mohan … i have not read it … liked robbins too much … Whenever you have difficulty in choosing a book … Always read same topic from both the books and then choose the book according to that topic …

Always try to use a single book .. you will be less confused … more focussed … more quick to learn …

DOWNLOADS SECTION

1. Zahid Jan compiled papers

2. WBC Pathology Notes.pdf

3. Charts for Glomerular Diseases

BEST WEBSITE ON NET for PATHOLOGY:

http://www.pathguy.com – strongly recommended by me.

HOW TO STUDY SPECIAL PATHOLOGY:

Special pathology is like a sea … if you do not focus on topics, you will wander and be confused and at the end you will miss the important topics … and important topics are not few … there is a long list of topics and they repeat … so cover them first to be on safe side then study anything else … … your year will end but special pathology is so long it will not end …

you should do some chapters completely … like RBC, WBC, heart, Liver, Female Reproductive Tract, others are selective … buy Papers by Zahid jan … and consult from it for specific topics in lungs, male genital tract, breast, kidney etc … i will try to cover them in detail one by one…

Once you know the important questions … try to prepare them for annual exam … giving it a read is not enough… you must be clear about the headings … divide each question into headings in your mind like definition, causes, pathogenesis, classification, clinical features (less imp in patho) , morphology (most imp) macroscopic and microscopic, Diagnosis, Staging and grading in case of few tumors (not all tumors, but if for any tumor apply generalized staging and grading)

First Generalize the things , then make them specific… let me give you examples … most tumors are grey white in colour … remember only those who have specific colours … write grey white for the others … there are some general investigations which are done for all the tumors make a list of it then remember specific tumor markers and specific investigations for specific tumors… if you know the general features of benign and malignant tumors you can apply them to all the specific benign and malignant tumors … All the GIT lesions can be of three types Excavated (ulcer) , Exophytic (protruded) , or Flat … remember it generally for morphology of GIT tumors and lesions … it modifies in certain specific conditions … remember the specific conditions and it will be quite easy for you … but you may not always have the easy way sometimes you have to cram classifications and morphology … as we have done it you can also do it … so be confident

General Guidelines for Staging: REMEMBER STAGING is based on MACROSCOPIC FEATURES (GROSS FEATURES visible with naked eye)

Stage 1: it will always be limited to site of origin…

Stage 2: Spreads to adjacent areas but not upto anatomical boundary like lateral pelvic wall or diaphragm

Stage 3: Spreads upto anatomical boundary and may cross it.

Stage 4: Distant Metastasis

General Guidelines for Grading: REMEMBER GRADING is based on MICROSCOPIC FEATURES (visible with microscope)

Grade 1: Well Differenciated

Grade 2: Moderately Differenciated

Grade 3: Poorly Differenciated

UPDATED ON 23/06/2011

CHAPTERS:

RBC:

V.imp Level 1 Most Important both paper and viva point of view …

NORMAL ADULT REFERENCE RANGES;

Remember normal Adult reference ranges, DON’T forget to REMEMBER the UNITS.

Tip: Remember normal ranges of kumar, it will help you both in medicine and pathology.

MCV (mean corpuscular volume) = 80 – 96 fL

Anemia with less than 80 MCV is Microcytic Anemia.

Anemia with more than 96 MCV is Macrocytic Anemia.

Anemia with 80 – 96 MCV is Normocytic Anemia.

Remember Normal values and ranges of Hb, RBC, WBC, ESR, Retic Count and platelets. Normal range of Platelets is 150,000 – 400,000 / micro Litre. But Generally thrombocytopenia is considered when the level falls below 100,000 / micro Litre.( NOT BELOW 150). (viva Q)

In All HYPOCHROMIC Anemias MCH ( Mean corpuscular Hemoglobin) level is decreased.

In All HYPOCHROMIC Anemias MCHC ( Mean Corpuscular Hemoglobin Concentration) level is decreased except HEREDITARY SPHEROCYTOSIS (HS) and SICKLE CELL ANEMIA (SCA), in these diseases MCHC is raised. (Viva question).

Chrome stands for colour and colour of RBC is due to Hemoglobin, so it stands for the amount of hemoglobin. HYPERCHROMIC (more Hb) HYPOCHROMIC (less Hb) NORMOCHROMIC (normal Hb). All types of Anemias can occur.

I m discussing now HYPOCHROMIC ANEMIAS.

MCH is MASS of Hb per given red cell. It’s mass, hence its unit is pico gram.

MCHC is CONCENTRATION of Hb per VOLUME of packed cells. Its mass per Volume hence its unit is gm/dl. It’s a ratio between mass and volume.

i have made a video in order to explain the difference between MCH and MCHC … and the link is given below …

In All HYPOCHROMIC Anemias, MASS or content of Hb is DECREASED and volume is less decreased, except in Hereditary Spherocytosis and Sickle Cell Anemia, in which both MASS and VOLUME are decreased. Comparatively VOLUME is more decreased. So in HS and SCA, MCHC is INCREASED (because it is inversely proportional to volume). Volume is decreased due to dehydration of RBCs.

ESR depends upon level of fibrinogen and immunoglobulin. They are present in plasma and depend on level of plasma. Hence in Anemia less RBCs more plasma more fibrinogen and Immunoglobulin so more or increased ESR. In polycythemia more RBCs less plasma less ESR

RDW ( Red Cell Distribution Width ) is raised in Iron deficiency anemia but constant in thalassemia. Thalassemia all RBCs are of same size. In Iron deficiency Anemia RBCs are of different sizes (Anisocytosis). So in Iron deficiency Anemia, RDW is increased.

ANEMIA;

Definition of Anemia; Remember Dr. Ameen Jan’s Definition. Its Asked in Viva. Anemia is present when there is decreased level of Hb below the reference level for age and sex of individual. (Also it is in Kumar)

Classification of anemia very imp.

Remember both the classifications … According to Cause (blood loss, inc. destruction, dec. production) According to Morphology (Microcytic, Macrocytic, Normocytic)

Hemolysis is of three types …

1) Intra Vascular hemolysis ( inside the blood vessels can be due to trauma or toxins etc. )

2) Extra Vascular hemolysis ( At Spleen and Liver due to phagocytosis by Macrophages over there because of tight spaces and less deformability of RBCs ) RBC size 8 mm while splenic spaces are 3 mm wide … due to remarkable variabilitiy in shape … RBCs can pass through it … but when RBC lose membrane they lose this variability and they repture … so they are phagocytosed by macrophages over there. Liver macrophages are called Kupffer Cells…

3) Ineffective Erythropoises ( hemolysis of precursor red cells at bone marrow )

Remember JAUNDICE is HYPERBILIRUNINEMIA not hemoglobinemia.

RBCs only contain enzymes and no organelles like Mitochondria… and they get energy by anaerobic respiration (does not require oxygen) … one of the enzymes of RBCs, required for anaerobic respiration is lactate dehydrogenase … whenever there is hemolysis … repturing of rbcs its contents like lactate dehydrogenase will be released … in all types of hemolysis … hence raised lactate dehydrogenase is a marker of hemolysis but it is non-specific … is also present in many cells …

why does RBC get energy by anaerobic respiration ? this is nature’s perfect design … if RBC were able to get energy by aerobic respiration they would have utilized the oxygen they were carrying … so RBC carries oxygen but cannot utilize it hence it is a good carrier …

Vit B12 deficiency can be due to many causes like
1) Decreased Intake (inadequate diet, vegetarian {Vit B12 has animal sources only}]

2) Impaired Absorption
( a. Intrinsic Factor deficiency – problem lies at stomach… pernicious anemia (autoimmune gastritis), Gastrectomy (removal of stomach)
b. ileitis (problem at ileum )
c. bacterial overgrowth (small intestine)
d. malabsorption states (small intestine) etc )

3) increased demand
pregnancy, hyperthyroidism, chronic infection, cancer etc

Vitamin B12 deficiency has many causes, one of its cause is pernicious anemia. When autoimmune gastritis causes vitamin b12 deficiency, it is called pernicious anemia. it is common in western world so it is stressed in western books. in our setup dietary deficiency is more common.

REMEMBER the absorption sites…
Iron at Duodenum
Folic Acid at Jejunum
Vitamin B12 at Ileum

so whenever their is Malabsorption state (eg. celiac disease, spru ) in small intestine, there will be three types of Anemias…
Iron Deficiency Anemia ( Microcytic Hypochromic )
Folic Acid Deficiency Anemia (Macrocytic)
Vitamin B12 Deficiency Anemia (Macrocytic)

and Blood Film will have Dimorphic Picture (Two types of RBCs)
1) Microcytic
2) Macrocytic

TO BE CONTINUED … LAST UPDATED ON 27-06-2011

WBC:

It is one of most important chapters… I tried to read it a little differently which made it easier to understand … I will tell you how did I read it …

First of all you should have some core knowledge … you should know and understand some basic terms. Hematopoietic system has two cellular components …

1. Myeloid Series (it includes RBCs, platelets, Granulocytes and Monocytes) (simply All Blood Cells except Lymphocytes)
2. Lymphoid Series (it includes T and B Lymphocytes i.e. Agranulocytes )

We have differentiated them like that because they arise from different progenitor cells. Myeloid Series Cells arise from Common Myeloid Progenitor while Lymphoid Series Cells arise from Common Lymphoid Progenitor, you don’t believe me see for yourself :p open robbins and see the differentiation of blood cells (p591). Look at the picture. Identify the position of Stem Cell (it is a pluripotent cell), Multipotent Progenitor Cells , and MYELOBLAST ( a unipotent progenitor… note that it differentiates into neutrophil … I personally think its name should have been neutrophiloblast but it is not… it is named differently to confuse you basically it is a neutrophiloblast )

Remember a Pluripotent Stem Cell can differentiate into cell of ANY germ layer. Here Haematopoitic Stem Cell is a pluripotent Stem Cell, it can differentiate into both Myeloid and Lymphoid Series Cells. A defect in Pluripotent stem cell can affect both myeloid and lymphoid series.

Remember a Multipotent Stem cell can differentiate into a number of CLOSELY RELATED CELLS. Here Myeloid and Lymphoid progenitor cells are multipotent cells. A defect in Myeloid progenitor cell can only affect Myeloid Series Cells only. A defect in Lymphoid progenitor cell can affect T and B lymphocytes only. It will affect either one of the series not both the series.

MYELOID NEOPLASM:

After reading first few pages from long robbins, which has the above basic concept go to Myeloid Neoplasms (P620 LR 8^th edition). (don’t read disorders of wbc now). Why? Because the above basic concept is used in Myeloid Neoplasms.  They will become easier if you read them now.

Interestingly Myeloid Neoplasms can overlap one another … making it confusing … but if you try to remember the DIAGNOSTIC FEATURES you will always be able to label them correctly.

The pathogenesis of All Myeloid neoplasms is summarized in the first few paragraphs. Basically there is a transformation (defect) in one cell of bone marrow. The effect of that transformation depends upon two things.

1. Position of Transformed cell ( whether it is higher (pluripotent) or lower (Multipotent or unipotent) in the chain of blood cells formation)
2. Effect on differentiation of transformed cell ( whether it is inhibited or stimulated or stopped or defective ie which type of cells the transformed progenitor cell is going to form)

Now, you can appreciate the importance of position of Transformed (or defected) cell, if you have initial concept of Pluripotent and Multipotent stem cells. The above two point pathogenesis can be applied on any Myeloid neoplasms with little differences.

Myeloid Neoplasms can be of three types

1. Acute Myeloid Leukemias (AML)
2. Myelodysplastic Syndrome (MDS)
3. Myeloproliferative Disorders ( it includes Chronic Myeloid Leukemia(CML), polycythemia vera (PV), essential thrombocytosis(ET), primary myelofibrosis (PMF) )

Almost All are Multipotent stem cell disorders except Chronic Myeloid leukemia (CML), which is a Pluripotent Stem cell Disorder.

So All Myeloid Neoplasms can differentiate into one another, while CML being pluripotent not only differentiates into myeloid neoplasms but also into Lymphoid neoplasms.

Now lets make myeloid neoplasms simple.

AML is a MULTIPOTENT stem cell disorder (position of transformed cell) in which there is maturation ARREST (arrest means stoppage) ( it is effect on differentiation of transformed cell), which leads to accumulation of immature cells in the bone marrow ( its very logical that when differentiation(division) will stop, the progenitors cells (the dividing immature cells) will accumulate ).

Hence the diagnosis is simple as well, if you find at least 20% MYELOID BLASTS ( the dividing immature progenitor cells)(they can be any blast cells like myeloblast (blast cell of neutrophil), monoblast ( blast cell of monocyte) or any other myeloid series blast cell) in the BONE MARROW, label it as AML.

MDS is a MULTIPOTENT stem cell disorder (position of transformed cell) in which there is maturation DEFECT ( defective maturation means dysplastic differentiation ) ( it is effect on differentiation of transformed cell), which leads to dysplastic (abnormal) myeloid lineages in bone marrow.

Hence if you find bone marrow dysplasia of myeloid series cells, label it as MDS. As it is multipotent stem cell disorder, it can also transform to any myeloid neoplasm such as AML. If in MDS, the Myeloid blast cells equals to 20% or more it will be transformed to AML.

In all Myeloproliferative disorders, there is NO defective differentiation but the differentiation is STIMULATED (INCREASED), so normal mature blood cells are formed in increased amounts.

Myeloproliferative disorders have certain common features and same pathogenesis.

Pathogenesis is such as an enzyme (tyrosine kinase) gets mutated and activated. This mutated active enzyme causes proliferation and survival of bone marrow progenitor cells without need of growth factors. So increased number of mature blood cells are formed independent of growth factors.

CML is a pluripotent stem cell disorder characterized by Philadelphia chromosome (diagnostic feature). CML being pluripotent not only transforms into myeloid neoplasms (eg AML) but also into Lymphoid neoplasms (eg ALL).

In PV there is panmyelosis ( increased in production of all the myeloid cells but it is the increase in RBCs that causes all the clinical symptoms. Like all the Myeloprofilerative disorders the increase in RBC is independent of growth factor ( in this case which is erythropoietin). So in PV, there is increase in RBC level with LOW erythropoietin (diagnostic features).  ( remember in Secondary Polycythemia erythropoietin level is high)

ET is characterized by thrombopoietin independent thrombocytosis.

PMF is characterized by obliterative marrow fibrosis (most imp), dysplastic megakaryocytes, leukoerythroblastosis and teardrop shaped red cells.

Study upto here. Now go to heading neoplastic proliferation of White blood cells and read lymphoid neoplasms as well.

Important Lymphoid neoplasms are Hodgkin Lymphoma, Burkitt’s Lymphoma and Multiple Myeloma. Read all of them but remember these three.

Before reading them you should have a clear concept of difference between Lymphoma and Leukemia. (V imp VIVA question)

There are three main differences.

1. Lymphoma is neoplastic proliferation of LYMPHOID series cells in lymph node

While Leukemia is neoplastic proliferation of HSC in bonemarrow (ie both lymphoid and myeloid series)

1. Lymphoma present as discrete LYMPHOID MASSES

While Leukemia does not.

1. Lymphoma mainly arise in LYMPHOID TISSUE such as lymph node but it can arise in any organ

While Leukemia arise in BONE MARROW or BLOOD only.

Now Classification of leukemia:

Leukemia

• a)      Acute Leukemia

i)  AML
ii) ALL

• b)       Chronic Leukemia

i) Chronic Myeloproliferative Disorders

ii) Chronic Lymphoproliferative Disorders

Chronic Myeloproliferative disorders are CML, PV, PMF, ET.

Chronic Lymphoproliferative disorders are Hairy Cell leukemia, Chronic Lymphocytic leukemia (CLL), plasma cell leukemia.

Remember LEUKEMIA contains BOTH MYELOID and LYMPHOID neoplasms.

Now about WHO Classification of Lymphoid Neoplasms:

Try to remember it in the end of chapter… if you have given a read to chapter you will atleast remember the names of most of neoplasms…  it has five subclasses… if you look closely basically they are three in no.

1-      Precursor and peripheral B cell neoplasms

2-      Precursor and peripheral T cell neoplasms

3-      Hodgkin’s Lymphoma

All the precursor neoplasms have one subtype that is ALL.

Myeloid Neoplasms can be classified as;

1. AML

2. MDS

3. Myeloproliferative disorders ( CML, PV, PMF, ET )

Other Important viva questions are the following:

Difference between hodgkin and non hodgkin’s lymphomas,

Enumerate all Hodgkin’s lymphomas

What is RS cell and what are its types.

Diagnostic Findings of the above mentioned leukemias and lymphomas.

All the above questions are answered in my notes and they can be downloaded from downloads section or here.

At the end give a read to spleen and disorders of white cells like leukopenia and leukocytosis … sometimes asked in viva … ( i was asked in my stage viva about causes of neutropenia …)

Remember Splenomegally is just enlargement of spleen while Hypersplenism is enlargement of spleen along with pancytopenia.

Remember when the immature cells in bone marrow do not come to peripheral blood, it is called aleukemic leukemia or subleukemic leukemia. And when they come to peripheral blood, it is called leukoerythroblastic leukemia.

Dont forget to download the notes of WBC from downloads section or here .

KIDNEY:

if you do it properly … it is the most easiest chapter of pathology … if not , it will become your headache … lets make it simple …

You must have some core knowledge before starting this chapter …

Kidney diseases can be divided into 4 types depending upon anatomic components of kidney …(in other words it is classification of kidney diseases)
1. Glomerular diseases
2. Tubular diseases
3. Interstitial diseases
4. Blood Vessels diseases

Now we move towards clinical manifestations of renal diseases… its most imp part of this chapter … if you can grab this concept, this whole chapter will become easy to you …

you should know the difference between azotemia and uremia … (imp for viva)

Remember

1) Azotemia is BIOCHEMICAL ABNORMALITY only, characterized by elevation of Blood Urea Nitrogen and Creatinine levels.
2) In Azotemia, failure of renal excretory function occurs only.
3) In Azotemia, there are no secondary involvements.

Azotemia can be due to pre-renal, renal and post-renal causes.

Remember

1) Uremia is BIOCHEMICAL ABNORMALITY plus it has CLINICAL SIGN and SYMPTOMS. ( in other words when azotemic patients develop sign n symptoms, he is called uremic)
2) In Uremia, failure of renal excretory function occurs along with ENDOCRINE and METABOLIC Abnormalities.
3) In Uremia, there are secondary involvements of GIT, peripheral nerves and Heart.

Remember NePhROtic Syndrome is characterized by

1. PROteinuria > 3.5gm/day (NePhROtic has PRO in it) (it will lead to)
2. HYPOalbuminemia (this will decrease oncotic pressure and it will lead to)
3. severe Edema
4. Hyperlipidema (this will lead to)
5. Lipiduria

so all the examples of nephrotic syndrome will have the above features…

Remember Nephritic Syndrome is characterized by

1. Hematuria
2. Proteinuria (but proteinuria is more pronounced in nePhROtic syndrome)
3. Hypertension

APGN (Acute Proliferative Glomerulonephritis) and RPGN (Rapidly Progressive Glomerulonephritis) are the examples of Nephritic syndrome, almost all other glomerular diseases are examples of Nephrotic syndrome …
Now you can write about clinical features of glomerular diseases on the basis of nephritic and nephrotic syndrome…

Acute Renal Failure is characterized by oliguria/anuria plus azotemia.
Chronic Renal Failure is characterized by prolonged sign and symptoms of uremia.

Remember the classification of Glomerular Diseases, its important.

You should know about the histological alterations which will help you in remembering the morphology…
4 basic histological alterations are;
1. Hypercellularity (due to 1. cellular proliferation, 2. leukocyte infiltration, 3. Crescent Formation … basically it is the morphology of APGN … remember it from the word Proliferative in APGN)
2. BM Thickening
3. Hyalinosis
4. Sclerosis

Remember Diffuse means all Glomeruli involvement while Focal means only proportion of glomeruli are involved.
Remember Global means involvement of entire single glomerulus while Segmental means part of each glomerulus is involved.

In APGN, there is Diffuse and Global Hypercellularity …

Above is the core knowledge … now you can start remembering the diseases ..

You should remember the Glomerular diseases under the following headings like light microscopic picture, electron microscopic picture and Immunoflourescence…
Charts of Glomerular diseases made by Bilal bhai our senior and topper can be downloaded from the following address … i have added some info into it… Flow Chart of mechanism of Glomerular Diseases made by me can be downloaded along with it …

Charts for Glomerular Diseases
Other imp questions of this chapter are; Acute Tubular Necrosis, Pyelonephritis (Acute and Chronic), Urinary Tract Obstruction, Urolithiasis, and Tumors of Kidney… for details of imp questions see papers …

LAST UPDATED ON 07-11-2011

COMMENTS and QUESTIONS are welcomed: But be patient for the ANSWERS . if there were NO COMMENTS and QUESTIONS the post will stop here… it wont continue… everyone needs a little bit of encouragement

AND if you find any MISTAKES please let me know … i will be really glad …