THE 63RD MEDSOC ACADEMIC AFFAIRS DIRECTORATE PRESENTS
M2 SURVIVAL GUIDE
1st EDITION, 2012
Created by
Class of 2015
Darren Chua
Kamalesh Anbalakan
Tan Jun Hao
Class of 2014
Liu Xuandao
Table of Contents
Introduction to the M2 climate .................................................................................................................................. 3
Assessment outline ..................................................................................................................................................... 3
CA1:........................................................................................................................................................................ 3
CA2:........................................................................................................................................................................ 3
Pros: ........................................................................................................................................................................ 3
How you should study ............................................................................................................................................... 4
Table: Approach to studying for M2 ...................................................................................................................... 5
Making Notes ........................................................................................................................................................... 10
CSFC......................................................................................................................................................................... 10
What is expected of us during csfc ...................................................................................................................... 10
How the exams will be carried out...................................................................................................................... 11
What kind of "outside" questions examiners ask? ............................................................................................... 11
Comments and tips .............................................................................................................................................. 11
Resources ................................................................................................................................................................. 12
Appendix: Sample CVS Patho Notes ....................................................................................................................... 13
Introduction to the M2 climate
As you move from the study of normal form and function to the abnormal counterpart, it would be easy to think M2 will be
similar to M1. But there is drastic shift from a more conceptual content to a more detail orientated content. Subjects
that will be covered will include Genetics, Immunology, Microbiology, Epidemiology, Pathology, Pharmacology, Aging,
Neuroscience and relevant PBP.
Topics like Genetics, Immunology, Microbiology and Pharmacology are very content dense and will be taught over a very
short period of time. As such, it cannot be impressed upon you enough, the importance being consistent.
Many areas of their study can be broken down and grouped to help us organize and easily recall the pathologic steps. For
example, gene products, chromosome location, and toxin names should be memorized after you are familiar with the
terminology and pathologic processes. More than likely, the mundane facts will only reside in your short-term memory and will
only frustrate you if you first attempt to memorize words and diseases you don’t understand.
Another frustrating thing is the lack of tutorial or lecture objectives. Unlike M1, where the profs tend to keep you
focused on the objectives, M2 profs do not. They spend the same amount of time on important and unimportant stuff. This is
best evidenced in Microbiology where the time spent on the most important bug will be the same meager one hour as the
rarest bug. This M2 Survival Guide hopes to be that tutorial objective that would help you remain focused and most importantly
sane.
Assessment outline
The exam format for M2 is pretty daunting, but fear not, the key is in keeping your focus right and being consistent:
CA1:

Paper 2: MEQ paper consist of 9 MEQs to be answered in 3 hours and that roughly comes to 20 minutes per question.
So unlike M1 where you only have 2 MEQs with a luxurious 30min+ to write one essay, M2 paper is a lot about
planning your time and writing a focused essay.
o What is the breakdown for MEQs?
 Note that questions will be integrated, as usual. Eg. A microbiology question can be combined with its
corresponding antibiotic, or pathology of disease.
 1 Ethics
 2Microbiology
 1 Immunology
 1 Epidemiology
 1 Medsoc
 3 Pathology/ 2Patho + 1 Pharm
Paper 1: MCQ paper consists of 120 questions.

CA2:



Paper 2: MEQ paper with 9 questions
o Breakdown?
 2 Pharm
 5-6 Patho (can be fused with PBP)
 1-2 Medsoc
Paper 1: MCQ consist of 120 questions
Paper 3: OSPE paper:
o 10 pictures will be given to you to identify and this can include microbiology and immunology not just
the patho pots.
 Many people freak out when they see CA1 microb and immune tested but it will be
Pros:

Paper 2: MEQ paper with 9 questions
o Breakdown?
 1-2 Pharm
 3-4 Patho (can be fused with PBP)
 1 Medsoc (most likely combined with patho question)
 1 Ethics
 1 Microb


 1 Immunology
Paper 1: MCQ consist of 120 questions
Paper 3: OSPE paper:
o 10 pictures will be given to you to identify and this can include microbiology and immunology not just
the patho pots.
How you should study
There is definitely A LOT to study in M2. You will invariably, at some point, get lost. You may break down and cry, go
crazy and do funny things in the library. But fortunately, with proper direction, you can avoid the need of SSRIs to keep yourself
in balance.
The important thing to realize is that in medicine, about half the diseases you study accounts for 90% of the things
you’ll see in practice. M2 is a year of abnormal structure and function, aka disease. Therefore, the way things are set up is
that you can naturally spot exam topics. If you were the examiner, would you test a student on HIV or mad cow disease?
When you actually get down to studying, it doesn’t matter if you’re aiming to
just pass, pass comfortably, or outgun the smartest of the class. The basic
principle always applies: do the basic stuff really well, then move on to the
less important stuff. The top scorers of your class are often not just people who
know the esoteric conditions in depth. They are people who have very solid
understanding of the basic principles and conditions, and are able to go into the
details of these common things. Of course, they often are also broad-based, and
scare you with their knowledge of bacteriology trivia.
Disclaimer: it is not our intention to
encourage you become a poor doctor with
a poor knowledge base. Rather, we’re
providing a means for you to refine your
focus in learning, making you a more
efficient and well-prioritized doctor.
Ultimately, it is your decision to selectively
pay less attention to some topics.
Start with this table we’ve created!
Microbiology
Lecture topic
Gram negative rods
(including fastidious)
Step 1: Know what you’re
studying!
 Especially true for microbiology – it
is very easy to get lost in details
and you forget what class of
organisms the bacteria you’re
reading falls under.
Important stuff for MEQs
Must Know
Good to Know
E. coli
Shigella
Salmonella
V. parahemolyticus
V. cholera
L. pneumophila
P. aeruginosa
V. vulnificus
H. influenzae
B. pseudomallei
H. ducreyi
B. pertussis
A. baumannii
Step 2: Study smart. Move from
left to right.

Cover the basics first. As a general rule,
whatever can come out for MEQs will
come out for MCQs, and the converse is
only occasionally true. So, ask yourself:
what’s the yield?
Advice for MCQs
Klebsiella
Proteus
Serratia
Enterobacter
Step 3:
Aeromonas
Consolidate by
Pleslomonas
practice
S. maltophilia

Excellent
B. cepacia
resources for
HACEK group
MEQs, MCQs
C. granulomatosis
and OSCEs can
Brucella be found below.
Bordetella
Pasteurella
Yersinia
Francisella
Table: Approach to studying for M2
Immunology
Lecture Topic
Soluble factors
Cellular factors
Ag processing and
presentation
T cell function
Humoral immune
responses
Important stuff for MEQ
Must know
Good to know
Complements, their
Acute phase reaction
pathways and effectors
Type I IFN
All Immune cells and
Basophils are good to
their functions (Not
know, all others MUST
strictly MEQ testable,
KNOW
but knowledge here
forms much of the
grounding for essays in
pathology, microbiology
and immunology)
MHC I & II pathways
Positive and negative
selection of naïve cells
Signals I,II,III for naïve T
cell activation, including
B, T cell receptor
the cell-contact and
rearrangement
cytokine signals involved
MHC molecule structure
Types of APCs and their and principles behind it’s
main functions
polymorphic structure
Organ transplantation
Cytotoxic function
Helper function (TH1,
TH2)
Antibody isotypes and
their functions
Process of classswitching and the
molecules and cytokines
involved
Principle of humoral
immunity and
vaccination (Especially
use of conjugate
vaccines)
Advice for MCQs
Know generally what the
common cytokines do
Principle function plus
important cytokines
released by the cells.
IL-1, IL-6, TNF alpha
important, all others not
so important
Must know and good to
know will cover MCQs
well
Helper function (TH17,
Treg)
Usually will not test in
MCQ.
Somatic hypermutation &
affinity maturation
Must know and good to
know will cover MCQs
well
Molecular process of
class-switching and the
genes involved
Clinical applications:
Antibody titres
Principles of T
dependent and
independent responses
Immune response genes
Vaccines
MAIN Vaccine types
Vaccine schedules
Immune tolerance
Mechanism of central &
peripheral tolerance
NIL (ALL under “MUST
KNOW”)
TCR & BCR genes
MHC genes
Eg. New vaccine
technologies
Questions will be based on
“must know” facts.
Consequence of failure
to deliver signals 1 & 2
Autoimmunity
Principles of
autoimmune disease
(See below)
Proposed theory of
autoimmune disease
Rheumatoid Arthritis
(Will cover in bone path)
Bystander effect &
molecular mimicry
Cancer and
autoimmunity
Need to know examples of
molecular mimicry, tested
before.
Immunopathology of AI
disease (SLE MOST
IMPORTANT!)
HSC transplantation
Sources of HSC
Pathophysiology of
GvHD
Graft Vs Leukemia
effect
Time course of bone
marrow repopulation
Type of
immunosuppression to
use
Questions on
pharmacology of
immunosuppression.
Scenario based questions
on HSC transplantation
will be tested.
Knowing when to
increase alloreactive T
cells
Transplant
MOA of
immunosuppressive
therapy
Allogenic recognition
and consequence of
mismatch
Type of
immunosuppression to
use
MCQs on principles of
MHC allocompatibility will
be tested.
Immune mechanisms of
organ rejection
Hyperacute, Acute,
Chronic rejection
Immunodeficiencies
Corticosteroids
Immunosuppression
Pathology
MOA of
immunosuppressive
therapy
HIV & AIDS
Mechanism of action
Adverse effects
Drug interactions
Contraindications
Corticosteroids
Mainly MCQ->
Autoimmune
polyendocrine
SCID
X-linked
aggammaglobulinemia etc
(Not that I have seen them
test so far, but do prepare
just in case)
Nil (Must know this well)
Cyclosporin
Tacrolimus
Sirolimus
General pathology
Inflammation,
Haemodynamic
disorders
Infection, cancer, cellular
response.
Cardiovascular
Hypertension,
Valvular pathology,
Know how intermediate
molecules involved in
corticosteroid mediated
immune suppression.
AZT
Mycophenolate motefil
Polyclonal Ab
Monoclonal Ab
Fusion proteins
Must know and good to
know drugs likely to be
tested in MCQ, the above
drugs are unlikely but do
prepare for them. Need to
know adverse effects,
contraindications and
indications of each
medication.
Eg. focus on the steps of
inflammation, no need to
memorise the trivial
factors such as MMP, etc.
Pericarditis,
Atherosclerosis,
Ischemic heart disease,
Acute myocardial
infarct,
Heart failure,
Infective endocarditis
Aneurysms
Myocarditis,
Cardiomyopathy,
Vasculitis,
Congenital heart disease
Respiratory
Infections: Pneumonias,
TB pathology,
Asthma & COPD (Must
know VERY WELL) ,
Lung CA (SCLC +
NSCLC) and their
PARANEOPLASTIC
SYNDROMES
Nasopharyngeal CA
(NPC), Pulmonary HTN
& Cor Pulmonale,
Pulmonary edema,
Pulmonary embolism,
Bronchiectasis,
Pleural effusions,
Pneumothorax
Nasopharyngeal pathology
(Very unlikely to be tested
in MEQ, EXCEPT NPC),
Respiratory distress of
newborn,
ARDS,
Restrictive lung disease,
Pneumoconiosis,
Mesothelioma,
Mediastinal pathology
GIT
Gastritis (Acute +
Chronic)
Peptic ulcer disease,
Causes of upper and
lower GI bleed, Acute
appendicitis,
Diverticulosis (OSPE),
Gastric & Colorect CA
Oral cavity CA,
Esophageal CA,
Barrett esophagus
(know the metaplasia),
Intestinal obstruction,
Bowel ischemia,
Inflammatory bowel
disease (UC, crohns)
Leukoplakia
Salivary gland pathology
(IMPT in MCQs!),
Inflammatory bowel
disease, Miscellaneous CA
(GIST, Carcinoid)
Hepatobiliary, pancreas
Jaundice (ESPECIALLY
OBSTRUCTIVE),
Cirrhosis, Viral hepatitis
(HBV), Portal
hypertension,
Cholelithiasis,
cholecystitis,
HCC
Acute Renal Failure
AND Acute Kidney
injury,
Chronic Renal Failure,
End stage kidney,
Urolithiasis,
Urinary tract
obstruction,
Nephrotic & Nephritic
syndrome,
Viral hepatitis (Other
than HBV),
All Biliary pathology
(other than those stated
under must know),
Pancreatitis, Pancreatic
CA, Diabetes Mellitus
Liver vascular pathology,
Liver neoplasms EXCEPT
HCC, Pancreatic
endocrine neoplasms
Acute tubular necrosis,
Acute interstitial
nephritis, Pyelonephritis,
Glomerulopathies for
nephrotic & nephritic,
Urothelial carcinoma
Renal developmental
pathology, Polycystic
kidney disease,
Glomerulopathy for
microscopic hematuria,
Lupus nephritis, IgA
nephropathy,
Renal neoplasms except
RCC and urothelial CA,
Germ cell tumours
Fibrocystic disease,
Fibroadenoma,
Mastitis, Papilloma,
Phyllodes tumour,
Simple goitre,
Hashimoto thyroiditis,
Follicular adenoma,
Cushing’s
Hodgkin lymphoma
DeQuervain thyroiditis,
Pituitary pathology,
Anaplastic carcinoma,
Medullary carcinoma,
Lymphadenopathy,
Leukemias
Pseudogout & Gout,
Osteoporosis,
All other bone tumours
except osteosarcoma &
Urogenital + male
genital
Renal cell carcinoma,
Breast
Endocrine
Lymphoreticular
Bones and joints
Male: Prostatic CA, BPH
Diagnostic triad, Breast
malignancies (Esp DCIS
and invasive lobular CA)
Multinodular goitre,
Grave’s disease,
Follicular & Papillary
CA,
Know principles of
diagnosing lymphomas
(pathologically) ,
Non-hodgkin lymphoma
(DLBCL, Follicular
lymphoma, MALT
lymphoma, Burkitt)
Osteoarthritis &
Rheumatoid Arthritis,
Nervous system
Osteosarcoma,
Chondrosarcoma
Raised ICP,
Cerebrovascular
accidents,
Intracranial
hemorrhage,
Hypertensive
encephalopathy,
Osteomalacia,
Osteomyelitis
Hydrocephalus, Cerebral
herniation,
CNS tumours: Gliomas &
Medulloblastoma
chondrosarcoma
Infection: Abscesses,
Viral encephalitis
Neural tube defects
Microbiology
Introduction to
microbes
How microbes cause
disease
How microbes spread
Infection control
Antibiotic resistance
General and diagnostic
bacteriology
Gram positive cocci
Gram negative cocci
Gram negative rods
(including fastidious)
Gram positive rods
Comparison between
endotoxin and exotoxin
Different types of
spread- Direct, indirect,
vector, droplet, fecaloral & airborne
Nil
Different mechanisms
employed by bacteria to
bring about resistance
How to collect CSF,
urine and faecal matter
S. pneumoniae
S. aureus
S. saprophyticus
N. meningitidis
N. gonorrheae
E. coli
Salmonella
V. cholera
P. aeruginosa
H. influenzae
L. pneumophila
Alcoholic encephalopathy
Nil
Nil
Nil
Nil
Nil
Nil
Nil
This topic is probably
tested as one question in
MCQ paper and it is
normally straight forward
Specific details on Lab
methods of accessing
resistance
Nil
Nil
S. pyogenes
Coagulase – Staph
M. catarrhalis
Shigella
V. parahemolyticus
V. vulnificus
B. pseudomallei
H. ducreyi
B. pertussis
A. baumannii
B. anthracis
B. cereus
Anaerobes
All Corynebacterium
All Clostridia
L. monocytogenes
All Clostridia
Chlamydia, mycoplasma,
rickettsia
C. trachomatis
M. pneumoniae
Spiral bacteria + “nontrue spirals”
T. pallidum
C. jejuni
H. pylori
M. tuberculosis
Ch. Psittaci
Ch. Pneumoniae
M. hominis
U. urealyticum
M. genitalium
Mycobacteria
Infection: Fungal, Syphillis,
Parasitic, Prion
Forebrain abnormalities
Infection: Meningitis, TB
Alzheimer disease
Parkinson disease
Nil
CNS tumours
A. israelii
F. necrophorum
M. leprae
S. agalactiae
Group D strep
Viridians strep
Klebsiella
Proteus
Serratia
Enterobacter
Aeromonas
Pleslomonas
S. maltophilia
B. cepacia
HACEK group
C. granulomatosis
Brucella
Bordetella
Pasteurella
Yersinia
Francisella
N. asteroides
Lactobacilli
E. rhusopathiae
F. nucleatum
Anaerobe lecture
Ch. Psittaci
Ch. Pneumoniae
M. hominis
U. urealyticum
M. genitalium
Bejel, Pinta, Yaws
Borrelia
Leptospirosis
Atypical mycobacterium
Fungi
Introduction to virology
Respiratory viruses
Candida
Aspergillus
Dermatophytes
Cryptococci
All other fungi
Influenza A viruses
Influenza B viruses
Parainfluenza
RSV
Rhinovirus
Adenovirus
Coronavirus
Metapneumovirus
Dengue
Know everything about
dengue
Hepatitis
Enteroviruses
HBV, HCV
Poliovirus (Esp
immunologic basis of
polio vaccines)
Herpes
Coxsackie A, B
EV 71
HHV 1-5
MMR
Prions, rabies,
parvovirus, poxvirus
Gastroenteritis virus
HIV
Protozoa
HAV
HHV 8 (Pathophy of
Kaposi sarcoma in cancer
biology)
Measles, Mumps, Rubella
(on top of this you need
to know about the
vaccine)
Parvovirus B19
Rotavirus
Hospital acquired
infections
Phamacology
Neuroscience
Patient
Based
Programme
Need to know
everything
Need to know bare
minimum
Please treat this
seriously, many
questions may appear in
both MEQ and MCQ
HHV 6-8
Smallpox
Molluscum contagiosum
Rabies
JC virus
Prion disease
Norwalk virus
Astrovirus
Adenovirus
Know everything,
methods of diagnosis,
window period, phases
of infection, AIDS
defining illnesses,
prognostic factors
Plasmodium
Toxoplasma
Helminths
Laboratory diagnoses
Hantavirus
Alpha virus
JE virus
HDV, HEV
Need to know the
various lab tests
available and the specific
ones used in diagnosis
of certain infections!
This will be mentioned
in greater detail in the
notes!
Know about MRSA,
Enterobacteria,
Pseudomonads and
what conditions
predispose a patient to
HAI.
Nematodes
Cestodes
Trematodes
May come out for MCQ,
of particular importance is
Syphillis, Chlamydia,
Gonococci and S. pyogenes
-
-
Note:
For the section on pathology and microbiology, any question on any condition/infection may come out as a MCQ. The
conditions stated under the MCQ advice column are usually not tested as an MEQ and will thus more likely appear in the
MCQs. That does not mean however that one does not prepare for the common conditions as likely questions in an MCQ,
YOU MUST KNOW all conditions under the “must know” and “good to know” column as they will VERY LIKELY come
out the MCQs too!
The OSCEs
In this section of the examinations, a series of 10 questions are given. You are given 6 minutes per question, and
you are to answer a series of short questions, with reference to a picture(s).
Many different types of questions exist, and below
are some of the common type of OSCEs
- X-ray
- Photograph of site of lesion
- Photograph of a patient (General appearance)
- Histology slide
- Bacteria culture
- Pathology pots (Gross specimen)
A sample OSCE question
- Describe the gross appearance
- What is the differential diagnosis
- What signs and symptoms can you expect from
the patient
- Complications of the disease
To do well in OSCEs, you have to be prepared for anything. By anything, it means even PBP lecture notes. One
would also have to be well-versed in not only theory, but how the pathology/ microbiology/ etc slides look like as
well. It is definitely one of the more difficult areas of the final exams to prepare for.
Making Notes
With all the truckloads of information they dump on you in M2, there is a more pressing need for notes to
retain all that information! Notes-making is an important and helpful asset.
Certain skills are required to make good notes. You have to understand the information thoroughly, pick
out the important bits, and synthesize easy-to-recall bullet points. Mnemonics help greatly, especially for
microbiology and pharmacology! Here’s a link that demonstrates how to create mnemonics.
http://eastasiastudent.net/study/make-mnemonics/
Finally, if you can’t make your own notes for one reason or other, be sure to seek out seniors’ notes. But always
use them with caution! Remember, if you can’t understand or easily recall what the guy says, whoever’s notes they
are, they are not helpful to your learning.
Check out the Appendix for a sample set of notes contributed by Kamalesh!
CSFC
What is expected of us during csfc
1. Being able to perform all physical examination with steps as given in the mini-CEX
2. Being able to take a full history, or parts of the history of the patient
3. Basic knowledge about the concepts utilized in physical examination and history taking (elaborated below)
How the exams will be carried out
Basically, the CSFC exams have 6 stations.
The breakdown is as follows (for 2011/2012):
a. 2 stations for history taking
b. 3 stations for physical examinations
c. 1 station for clinical skills (Examples includes: BP measurement, AMT, Basic ADL, IADL etc)
How the stations will run
The stations are in a round-robin fashion, each lasting 9 minutes. Meaning, the entire exams will last for exactly 54 minutes
and you’re done. The breakdown for 9 minutes is as follows:
Time allocated
Task
Remarks
1 minute
Sitting outside the consultation
room to read a short description of
what you’re about to encounter
inside the room
Example: Mr Tan is a 54 year
old gentleman complaining of
epigastric pain for 4 days. Perform
an abdominal examination on him.
Example: Take a social and past
medical history from Mr Tan.
*Note that history taking
usually only requires certain parts of
the history
8 minutes
Entering the room and actually
performing the task as explained by
the piece of paper outside the room
Many seniors will advise leaving
a little time (ideally 2 minutes) to
allow for questions by the examiner.
Hence, the task should ideally be
completed in 6 minutes.
What kind of "outside" questions examiners ask?
As mentioned, if there is spare time, the examiners will try to throw a few theory questions at you.
Below is a list of examples
1. What are the signs of heart failure?
2. Explain the grading system when measuring power during a neurological examination? What do you think the power
grade of the patient is?
Just a passing comment:
With basic inference skills you will realize that tutorials during CSFC, while still highly important, and not really necessary (when you’re
practical about examinations). And also, reading textbooks and memorizing signs and symptoms are not nearly as important as perfecting
the steps of all examinations.
Comments and tips
Many will be highly confused and frustrated by CSFC as the aims are not that clearly stated, and you will come to realize
that the introduction lecture for CSFC is pretty useless. So here are some tips compiled by various seniors, hopefully it will
answer some of the common questions.
1.
2.
Focus on the medical physical examinations first. Every year, invariably there are no surgery physical exams. Things like
breast exam, arterial, venous and hernia should be at the bottom of your priority list. However, some basic knowledge
of approach to surgical problems is expected in the history taking stations.
During history taking, it is not necessary to ask EVERY SINGLE question in the mini-CEX. If you read carefully, the
question paper outside the consultation room (where you are supposed to understand the task in 1 minute) will state
that you are supposed to ask questions where relevant. So questions like religion, hobbies, pets, sexual orientation are
highly controversial and should only be asked when you have a reason backing it. For instance, pets when the patients
have fever, sexual history when patient have UTI, religion I don’t know why maybe when patient is about to die.
3.
Physical examination: Yes you are required to finish the ENTIRE procedure in the 8 minutes in the room. However,
often the examiner will ask you to skip some steps. For example, upper limb examination they might ask you to skip
fine touch and move on to pain (same actions anyway). But I suggest you should practise with the time limit in mind.
4.
History taking is super difficult to keep within time limit. So practise with time limit in mind! Try not to take half an
hour history from patients (which will happen more often than not, trust me)
5.
As some doctors might teach you guys to do running commentary (especially for GS surgeons), it is not necessary
unless the examiners ask you to. Usually they will ask you to even before you start, so just look out for it.
6.
REMEMBER TO WASH YOUR HANDS. The handwash green thing will be placed inconveniently (super far away,
cannot find, hide behind the examiner etc). But against all odds, find the bottle and squirt many times to wash your
hands.
Resources
You will be receiving a folder entitled “M2 Acad Survival Pack of Awesomeness”, either from your seniors directly or from
Dropbox shared by your class rep. This is like the Yunnan CD of M2. Inside this folder there is a wealth of information and
notes by various seniors. Below is a list of resources that are more popular, but remember 2 golden rules:
1. You will only be tested stuff that came out (albeit vaguely) in lectures
2. Notes that don’t help you remember stuff are as good as a pile of words
Pathology
 Hwee’s Patho
Microbiology
 Hwee’s microB, Wenchong’s microB
Pharmacology
 Wenchong’s Pharmacology Tables, Tan Seng Kiong’s tables
OSCEs
 Ching Hui’s Patho OSCEs
TYS MEQ Answers
 Liang En’s Answers
Exam Papers Database
 Access via http://libportal.nus.edu.sg/frontend/index
 Guide available at http://medacad.wikispaces.com/Pros+Exam+Papers
As for the rest of the subjects, rarely you will find someone using senior’s notes as lectures notes are sufficient. Hwee’s
notes tends to be info bomb, but has everything under the sun.
d.
Appendix: Sample CVS Patho Notes
e.
f.
Pathology:
Pathology is a high-volume topic that progresses and builds on complex concepts.
However, many areas of this study can be broken down and grouped to help us organize
and easily recall the pathologic steps. For example, gene products, chromosome location,
and toxin names should be memorized after you are familiar with the terminology and
pathologic processes. More than likely, the mundane facts will only reside in your shortterm memory and will only frustrate you if you first attempt to memorize words and
diseases you don’t understand.
So what do I mean by framework?
1. Normal anatomy & physiology,
2. Epidemiology,
3. Pathogenesis (macro and micro),
4. Management & treatment.
When making your notes, it’s advisable to organize the information this way.
Pathology Profs are weird people; their notes are ridiculously short with hardly any
information or organization. I like to think of their notes as a contents page of what you
need to study. 90% of Robbins is only applicable to pathologist, so please don’t read the
entire book, you are wasting your time.
g.
Valves
a.


The average weight of a heart is approximately 250 to 300gm in females and 300 to
350gm in males
The usual thickness of the free wall of the right ventricle is 0.3 – 0.5 cm, and that of
the left ventricle is 1.3 – 1.5 cm
Greater heart weight or ventricular thickness indicates hypertrophy, and an enlarged
chamber size implies dilation. An increase in cardiac weight or size is termed
cardiomegaly.
Myocardium
a.
b.
c.
Four cardiac valves: tricuspid, pulmonary, mitral and aortic
Anatomy of the Heart
a.
Cardiovascular pathology:
Cardiac Structure

Atrial myocytes are generally smaller and arranged more haphazardly than their
ventricular counterparts
Some atrial cells have electron-dense granules in the cytoplasm known as specific
atrial granules which are storage sits for atrial natriuretic peptide
Intercalated discs link individual cells and contain specialized junctions that permit
both mechanical and electrical (ionic) coupling
Abnormalities in spatial distribution of gap junctions and their respective proteins in
ischemic and myocardial heart disease may contribute to electromechanical
dysfunction (arrhythmia) and heart failure
b.
c.
Composed of a collection of specialized muscle cells called cardiac myocytes
Contractile unit is the sarcomere, an orderly arrangement of thick filaments
composed of myosin, thin filaments containing actin, and regulatory proteins such as
troponin and tropomysin
Strings of sarcomeres in series is responsible for the striated appearance
d.
The heart has three surfaces: sternocostal (anterior), diaphragmatic (inferior) and a
base (posterior) and it also has an apex that is directed downward, forward, and to
the left
i.
Sternocostal surface is formed by the right atrium and right ventricle and
these are separated by a vertical atrioventricular groove
 The right ventricle is separated from the left ventricle via the
interventricular groove
ii.
Diaphragmatic surface is formed mainly by the right and left ventricles
separated by the posterior interventricular groove
iii.
The base of the heart is formed mainly by the left atrium, into which open
the four pulmonary veins open
iv.
Apex of the heart is formed by the left ventricle and is directed downward,
forward, and to the left. It lies at the level of the 5 th intercostal space 9cm
from the midline
The walls of the heart is formed by the myocardium, epicardium and the
endocardium
i.
The junction between the right atrium and the right auricle is a vertical
groove is the sulcus terminalis which on the inside forms a ridge, the crista
terminalis
 Posterior to the ridge is smooth and anterior to the ridge is
trabeculated by musculi pectinati
Openings into the right atrium:
i.
Superior vena cava opens into the upper aspect and inferior vena cava opens
into the lower part of the right atrium
ii.
Coronary sinus which drains most of the blood from the wall, opens into the
right atrium
iii.
The right atrioventricular orifice lies anterior to the inferior vena cava
opening.
Foetal remnants
i.
ii.
e.
f.
g.
h.
i.
Fossa ovalis which is the remnant of the foramen ovale
Anulus ovalis is the upper part of the fossa ovalis
Right ventricle:
i.
Approaching the pulmonary orifice it becomes funnel-shaped conduit which
is called infundibulum
ii.
It has raised ridges called trabeculae carneae which is further subdivided into
papillary muscles, moderator band and the muscular ridges
iii.
The papillary muscles are connected to the fibrous chords called chordate
tendineae and the moderator band connects the right branch of the
atrioventricular bundle from the septa to the anterior wall
Left atrium:
i.
The left atrium is behind the right atrium and form the greater part of the
base and it separated from the pericardium from the oesophagus
ii.
The pulmonary veins open through the posterior wall
Left ventricle
i.
The interventricular blood pressure is 6 times higher than inside the right
ventricle and hence it’s about 3 times thicker
ii.
Contains trabeculae carneae but no moderator band
iii.
The part of the ventricle that opens into the aortic orifice is called the aortic
vestibule
Conduction of the heart:
i.
Sinuatrial node to the atrioventricular node to the atrioventricular bundle
then the left and right bundle branches and the subendocardial plexus of
purkinje fibres
Arterial supply of the heart is supplied by the right and left coronary arteries which
arise from the ascending aorta
i.
The coronary arteries and their branches lie within the
subepicardial connective tissue
ii.
The right coronary artery goes forward between the pulmonary trunk and
the right auricle and it then descends almost vertically in the right
atrioventricular groove and passes posteriorly at the inferior border of the
heart to anastomose with the left coronary artery
 It has the anterior ventricular branches, normally 2-3, and the
largest is the marginal branch that runs along the lower margin of
the coastal surface to the apex
 It has posterior ventricular branches
 Posterior interventricular descending artery
 Atrial branches
iii.
The left coronary artery which is larger supplies a major part of the heart
and it passes forward between the pulmonary trunk and left auricle
 Anterior interventricular descending branch towards the apex of
the heart
Circumflex artery of similar size winds around the left margin of the
heart in the atrioventricular groove. A left marginal artery supplies
the left margin of the left ventricle
Areas of auscultation:
i.
The tricuspid valve is best heard over the right half of the lower end of the
body of the sternum
ii.
The mitral valve is best heard over the apex beat
iii.
The pulmonary valve is best heard over the medial end of the 2 nd intercostal
space
iv.
The aortic valve is best heard over the medial end of the second right
intercostal space

j.
Heart Failure


A clinical condition where the heart is unable to meet the bodies
metabolic demands although the venous filling pressure is normal or
raised
i.
Decreased cardiac output is forward failure and venous congestion is
backward failure
Clinical picture to assess venous filling pressure:
i.
The term "central venous pressure" (CVP) describes the pressure in
the thoracic vena cava near the right atrium (therefore CVP and right
atrial pressure are essentially the same)
ii.
A decrease in cardiac output either due to decreased heart rate or loss
of inotropy (e.g., in ventricular failure) results in blood backing up into
the venous circulation (increased venous volume) as less blood is
pumped into the arterial circulation. The resultant increase in thoracic
blood volume increases CVP
iii.
The upward deflections are the "a" (atrial contraction), "c" (ventricular
contraction and resulting bulging of tricuspid into the right atrium during
isovolumetric systole) and "v" = atrial venous filling
Types of cardiac failure: Acute cardiac failure vs. Chronic cardiac failure
a.
b.
Acute: sudden onset, no time for compensatory mechanisms leading to circulatory
collapse known as cardiogenic shock
i.
E.g. acute infarction
Chronic cardiac failure: Gradual severity of disease with compensatory mechanism

Clinical: This results from a decline in stroke volume that is due to systolic
dysfunction, diastolic dysfunction, or a combination of the two.
i.
Systolic dysfunction results from a loss of intrinsic inotropy
(contractility), most likely due to iterations in signal transduction
mechanisms responsible for regulating inotropy. Systolic dysfunction can

also result from the loss of viable, contracting muscle as occurs
following acute myocardial infarction.
ii.
Diastolic dysfunction refers to the diastolic properties of the ventricle
and occurs when the ventricle becomes less compliant (i.e., "stiffer"),
which impairs ventricular filling
Adaptive compensation during heart failure:
i.
Increased heart rate via baroreceptor reflex
 Baroreceptors are fast mechanism mediated via the pressure
sensors within the walls of the carotid sinus. Sympathetic via
norepinephrine will act of β2 adrenergic receptors
ii.
Increased in myocardial contractility
iii.
Myocardial hypertrophy
iv.
Frank-starling mechanism:
 The volume of blood ejected by the ventricle depends on the
volume present in the ventricle at the end of diastole. **cardiac
output is equal to venous return
Left-sided Heart Failure
a.
b.
Cardiac hypertrophy
a.
b.
c.
Pressure load causes ventricular hypertrophy and volume load causes ventricular
hypertrophy and dilation
Cellular changes:
i.
Increased protein synthesis, increased number of sarcomeres & mitochondria
ii.
Altered gene expression via induction of foetal gene programme such as
conversion to the β-isoform of myosin heavy chain from the α-isoform AND
abnormal protein presence
iii.
Reduced adrenergic drive
iv.
Decreased calcium availability and impaired mitochondrial function
v.
Microcirculatory spasm and myocardial apoptosis
Once adaptive mechanisms are exceeded then it’s going to cause myocardial fibrosis
and inadequate vasculature
Causes of heart failure
a.
b.
c.
Hypertension (afterload),
Valvular disease is any disease process involving one or more of the valves of the
heart (the aortic and mitral valves on the left and the pulmonary and tricuspid valves
on the right)
Infarction
 Sequence of events subsequent to the above conditions:
i.
Results in increased cardiac work, which leads to increased wall stress
 This should lead to an adaptive measure of hypertrophy
ii.
Eventually this leads to increased volume leading to dilation and finally
failure
a.
Causes of left ventricular failure:
i.
Volume overload: Mitral valve or aortic valvular disease and in high-output
states such as anaemia
ii.
Pressure overload: Systemic hypertension
iii.
Loss of Muscle: infarction
iv.
Loss of contractility: poisons and myocardial infections
v.
Restricted filling: pericardial effusion
Effects of left heart failure:
i.
Forward failure leads to hypotension and poor tissue perfusion, this leads
to reduced oxygenation and the availability of metabolic substrates
 Kidney: activation of RAAS and reduced excretion of nitrogenous
products
 Brain cerebral hypoxia
ii.
Backward failure leads to left atrium dilation and pulmonary
hypertension, this leads to pulmonary oedema
Right-sided Heart Failure
Causes of right ventricular failure:
i.
Left sided failure can eventually lead to right-sided failure due to
increased pulmonary pressure and this leads to a condition called
congestive heart failure where both sides are failing (Common)
ii.
Pure right-sided failure
 Right heart valvular disease
 Cor pulmonale which occurs due to pulmonary hypertension
1. Chronic parenchymal lung disease such as emphysema and
2. primary pulmonary hypertension
3. Recurrent pulmonary thromboemboli
4. Chronic sleep apnoea
a. Sleep apnoea is a sleep disorder characterized
by abnormal pauses in breathing or instances of
abnormally low breathing, during sleep
Causes of Cor Pulmonale
a.
b.
glycosaminoglycans, hyaluronic acid, and other
mucopolysaccharides) in subcutaneous tissue
Congenital Heart Disease (CHD)
During conditions of hypoxia such as in high altitude there
is going to be increased RBCs due to erythropoietin
release from the kidney
i.
Polycythaemia causes an increase in viscosity
and according to poiseuille hagen equation
leading to pulmonary hypertension
ii.
Low Po2 itself can cause hypoxic
vasoconstriction of pulmonary vasculature
leading to increased pulmonary pressure
Acidosis and hypercapnia
i.
Hypercapnia is a condition where there is too
much carbon dioxide in the blood this can be
caused by sleep apnoea leading to respiratory
acidosis
 This again leads to narrowing of the
pulmonary vascular bed
 Definition: A structural abnormality of
heart/vessels present from birth
i.
Incidence: 1% of live births
Types of Congenital Heart Disease
a.
Left to right shunt: oxygenated blood is
mixing with deoxygenated blood
i. Typically acyanotic at onset, but may
become cyanotic with eventual pulmonary
hypertension or shunt reversal
 Atrial septal defect
 Ventricle septal defect
 Patent ductus arteriosus
b.
Right to left shunt
c.
Obstructive CHD
Effects of Heart Failure
a.
b.
c.
d.
Congestive hepatosplenomegaly
Congestive splenomegaly
Effusion in body cavity
Peripheral subcutaneous oedema
Pathogenesis of oedema in Cardiac
failure


Peripheral pitting oedema is the more
common type, results from water
retention, which is seen in conditions
such as heart failure
Non-pitting oedema is observed when
the indentation does not persist. It is
associated with such conditions as
lymphedema, lipoedema and myxedema
o Lymphedema is due to lymphatic
blockage
o Myxedema) describes a specific
form of cutaneous and dermal
oedema secondary to increased
deposition of connective tissue
components (like
Left to Right Shunts

Left to right shunt:
i.
Blood in the inferior vena cava and superior vena cava have a 75% saturation
of haemoglobin while those in the left heart are
almost 100% saturated
 Hence the shunt leads to
“step-up” saturation occurs on the right side
ii. At the bifurcation of the pulmonary
trunk there is a connection to the aorta called
the ductus arteriosus
 In foetal life, the lungs are not
working, and the pulmonary arterioles are
constricted due to hypoxia and the blood from
the right ventricle will be diverted via the PDA
to the aorta
 At birth, the increased oxygen
will lead to dilation of pulmonary vessels and
lead to reduced resistance and blood will then
start to flow towards the pulmonary vasculature
 Increased oxygen tension will
lead to PGE2 decrease that leads to spasm of
PDA
iii.
a.
Atrial septum has in foetal life contains the foramen ovale which allows blood
from the right side of the heart to the left side of the heart, this is closed off at
birth to form the foetal remnant fossa ovalis
ASD:
i.
ii.
iii.
iv.
b. VSD:
i.
ii.
c.
iii.
PDA
i.
Abnormal, fixed opening in the atrial septum due to incomplete tissue
formation
Despite right sided volume overload, ASD is usually well totally and
asymptomatic until adulthood
Ejection systolic murmur (due to excessive flow through the pulmonary
valve) + permanent splitting of S2
Right bundle brunch block due to stretching of the RV due to dilation
Incomplete closure of the ventricular septum (mostly in the membranous
portion, minority of muscular part)
Functional consequence depend on size of VSD
 If small, asymptomatic until adulthood
 If large, cause right ventricular hypertrophy & pulmonary
hypertension virtually from birth, which may progress to
irreversible pulmonary vascular disease and shunt reversal
(Eisenmenger syndrome)
Clinical: Pan-systolic murmur
Depending on diameter of PDA may result in progressive obstruction
changes in pulmonary vasculature (due to pulmonary volume overload)
ii.
Clinical: continuous, harsh murmur
Right to Left Shunts

Typically cyanotic clubbing of toes and fingers (connective tissue
deposition under the nail bed) and erythrocytosis/polycythaemia
a. Tetralogy of Fallot: Most common cyanotic CHD
i.
Characterized by: ventricular septal defect, aorta that overrides the
VSD, pulmonary stenosis (just before the valves in the infundibulum) and
right ventricular hypertrophy
 Overriding aorta overrides the septa defect so it can take
blood from both ventricle
ii.
Heart is enlarged and boat shaped
iii.
Normally right ventricular heart failure is not very common
iv.
Patient likes to assume a squatting position so as to compress the
femoral artery so as to increase pressure in the aorta so the blood will
flow through the stenosed pulmonary trunk
v.
Increased risk of hypoxic spells that can lead to syncope or fallot’s spells
 Especially during exercise where the systemic blood pressure
falls
b. Transposition of the Great Arteries:
i.
Ventriculoarterial discordance: aorta originates from the RV and
pulmonary trunk from the LV
ii.
Due to abnormal formation of truncal septa
iii.
Right ventricular hypertrophy and left ventricular atrophy
iv.
Without surgical repair, patients die within first few months of life
c. Tricuspid Atresia
i.
Complete occlusion of the tricuspid valve orifice due to unequal division
of the atrioventricular canal
ii.
Concomitant ASD & VSD allows maintenance of pulmonary & systemic
circulation
iii.
High mortality within the first weeks or months of life
d. Persistent Truncus Arteriosus
i.
Single great artery receiving blood from both ventricles due to a failure
of separation of truncus arteriosus into aorta & pulmonary trunk
Obstructive Congenital Anomalies
a.
b.
Coarctation of Aorta
i.
A narrowing or constriction of the aorta which usually occur distal to
the branches of the arch of the aorta
ii.
Results in hypertension of the upper extremities and hypotension in the
lower extremities (weak pulses, intermittent claudication, and coldness
iii.
LV hypertrophy (due to pressure overload)
iv.
Radiographically, notching of the undersurfaces of the ribs evident (due
to dilation of intercostal arteries involved in anastomosis to bypass
coarctation
Pulmonary Stenosis & Atresia
i.
c.
May occur in isolation or as part of a more complex anomaly (e.g.
Tetralogy of Fallot
ii.
RV hypertrophy due to pressure
overload
Aortic Stenosis & Atresia
i.
LV hypertrophy due to pressure
overload
b.
Embolism
c.
Ostial Stenosis in syphilitic aortitis
i.
Ostial stenosis: narrowing of the
mouths of the coronary arteries as a result of
syphilitic aortitis or atherosclerosis
ii.
Begins as inflammation of the
adventitia, including the vessels that supply the
aorta itself with blood, the vasa vasorum. As it
worsens, the vasa vasorum show hyperplastic
thickening of their walls that restricts blood flow
and causes ischemia of the outer two-thirds of the
aortic wall
d.
Dissecting aneurysms
e.
Direct Trauma
f.
Arteritis
g.
Anomalous origin of left coronary artery
h.
Hypoxaemia – anaemia, carbon dioxide
poisoning and hypotensive crises
CHD complications
 Heart failure
 Shunt Reversal
 Infective endocarditis
Other clinical factors
 Is a patient with anaemia or
polycythaemia more likely to develop
cyanosis?
i.
When amount of deoxygenated
Hb is more than 5g/dl then
cyanosis
ii.
Dusky bluish red colouration
Pathogenesis
a.
In the X-ray: there will be a boot-shaped
heart in tetralogy of fallot due to displacement of
left ventricle due to right sided hypertrophy and
pulmonary artery hypoplasticity.
Pink tetralogy of fallot has mild stenosis of the pulmonary artery hence there is still a
left to right stunt.
Ischemic Heart Disease

Spectrum of disorders due to imbalance between myocardial metabolic demands
and coronary blood flow
i.
Insufficient coronary perfusion relative to myocardial demand
 Main cause is atheroma of coronary arteries (90-95%)
 Chronic progressive coronary atherosclerotic stenosis
 Acute plague change
 Thrombosis (less common)
 Vasospasm (less common)
 LV is more prone to ischemia as it has more work and greater
number of vessels
Aetiology of Ischemic Heart Disease
a.
MOST IMPT Atherosclerosis
b.
c.
Reduced coronary blood flow:
i.
Growing atherosclerotic plague
occluding lumen progressively or acute plague
changes like rupture/fissure, erosion and ulceration
that can lead to the formation of a thrombus
ii.
Requires 75% occlusion of lumen at least for symptomatic ischemia
precipitated by exercise
iii.
Requires about 90% occlusion for inadequate coronary perfusion even at
rest
iv.
Degree of occlusion does not parallel the severity or nature of the
myocardial lesion
Increased myocardial demand
i.
Exercise, infection, pregnancy, hyperthyroidism and myocardial
hypertrophy
Availability of oxygen in blood
i.
Anaemia, CO poisoning, pulmonary disease, left to right shunts
Clinical Features
a.
b.
Angina: Painful attacks of substernal or precordial chest discomfort that is described
as constricting, choking, squeezing. It is caused by transient myocardial ischemia that
falls short of inducing necrosis
Chronic:
i.
Stable angina




ii.
c.
Episodic chest pain due to increased demand via increased myocardial
work in the presence of impaired blood flow (exercise or emotional
excitement)
Fixed atheromatous lesion/chronic progressive stenosis atherosclerosis
with 75% or more narrowing
Modifiable with drugs (nitroglycerin)
Anastamotic vessels can permit collateral blood flow
Cardiac failure
Acute:
i.
Unstable angina : also known as preinfarction angina
 Occurring at rest and not linked to demand
 Progressive in frequency and severity often of prolonged
duration
 Usually due to an acute plague change with superimposed
thrombosis & possible embolization and/or vasospasm
 Most common acute coronary syndrome:
ulceration (25%) and Plague fissuring with
thrombus in lumen and/or bleeding in plague
(75%)
 Acute coronary insufficiency with possible arrhythmias and
infarction (5-8% 6 month mortality
 Anginas do not produce elevation of serum cardiac
troponin or creatine kinase
ii.
Myocardial infarction (heart attack)
iii.
Sudden cardiac death
Myocardial infarction: Ischemic necrosis of cardiac muscle
due to impaired blood supply
a.
b.
Regional myocardial infarction (90%)
i.
Thrombus on complicated atheroma
ii.
Full thickness (regional transmural MI)
iii.
Partial thickness (regional subendocardial MI)
Circumferential subendocardial infarction (10%)
i.
General hypoperfusion caused by hypotension ( in an
already occluded vessel)
Pathogenesis of Myocardial Infarction
a.
Coronary artery occlusion by acute plague event (90%):
i.
Acute plague event (fissuring, ulceration and
haemorrhaging)
Thrombogenic plague contents or subendothelial basement
membrane leading to throbus formation
 Also, platelet & injured endothelial cell-derived mediators induce
local vasospasm
Coronary artery occlusion in the absence of coronary vascular pathology (10%)
i.
Vasospasm: in association with
other causes of platelet aggregation or cocaine abuse
ii.
Emboli: from atrial fibrillation, leftsided mural thrombus, vegetation or infective
endocarditis
iii.
Others: vasculitis, shock, vascular
dissection, amyloidosis and sickle cell disease
c.
Transmural infarct - involving the entire
thickness of the left ventricular wall from
endocardium to epicardium

b.
Response to Myocardial Infarction
a.
Early ischemia is reversible but severe
ischemia for more than 20-30min leads to irreversible
damage
b.
Permanent damage when perfusion is
severely reduced for extended interval of 2-4 hours
c.
Look at Hwee’s
Factors that affect Acute Myocardial
Infarction
1.
Location, severity, rate of development of
coronary obstruction
2.
Size of tissue perfused by obstructed vessel
3.
Duration of occlusion
4.
Metabolic need of myocardium
5.
Extent of collateral vessels
6.
Severity of arterial spasm
7.
Heart rate, rhythm and blood oxygenation
Interventions: Thrombolysis (streptokinase),
Angioplasty, Coronary artery bypass graft (CABG)
surgery.
**Possible reperfusion injury
Valvular Heart Disease

Stenosis: Failure of valve to open completely (systolic murmurs)

Insufficiency/Regurgitation/incompetence: Failure of valve to close
completely

Or Both
ii.
Causes of Valvular Stenosis &/or Insufficiency: Left side is more
commonly injured

Congenital abnormalities

Degeneration with age :
i.
Degenerative calcification occurs with wear and tear of
valves
ii.
Leading to dystrophic calcification with accumulation of
calcium salts on valves

Leading to aortic stenosis

Degeneration of collagen support tissue of valve:
i.
Myxomatous degeneration which usually occurs in young
females.

Due to degeneration of collagen
support of valves (fibrosa layer) and thickening of valves by
thickening of spongiosa layer by deposition of myxomatous
material

Valves become floppy and prolapsed
ii.
Marfan syndrome

Dilation of valve ring:
i.
Aneurysms secondarily dilating the heart valves
ii.
Syphyilitic aortitis
iii.
RESULTING in aortic insufficiency and mitral
insufficiency

Post inflammatory scarring:
i.
Rheumatic heart disease: S.pyogenes infection in
children due to cross reacting antibodies formed against streptococcal M
proteins 5,14,18 and 24
 Leading to fibrosis and scarring, fusion and calcification of
ALL the valves
 Causing stenosis and regurgitation
Infective endocarditis
 Infection of the heart valves leading to inflammatory scarring and
distortion
 All valves affects
Mechanism: collagen is exposed with thrombus formation
(vegetation) & scarring with physical distortion leading to
mechanical and functional abnormalities
Destruction due to necrotising inflammation
Abnormalities of tensor apparatus:
i.
Papillary muscle rupture after post-myocardial infarction
ii.
Chordae tendineae rupture in myxomatous degeneration
iii.
Common cause of mitral insufficiency
Carcinoid syndrome:
i.
Caused by carcinoid tumours elaborating vasoactive substances like
serotonin, kallikrein, bradykinin, histamine and prostaglandins
ii.
Causes firm plague like endocardial fibrous thickenings alongside systemic
symptoms like flushing of skin, cramps , nausea and vomiting
iii.
Typically affects right heart as vasoactive substances are inactivated in their
passage through the lungs by enzymes (e.g. monoamine oxidase)
iv.
Affects tricuspid and pulmonary valves
iii.



What are the common causes of valvular heart diseases?


Aortic Stenosis


Rheumatic heart disease was the most common pre-antibiotics but now it is calcific
aortic stenosis and mitral valve prolapsed
Mitral valve prolapsed: can occur in young people especially women





Young adults; women with family history
Myxoid degeneration of valve leaflets; floppy valves
Mitral valve commonly involved
Rupture of chordae tendineae
Causes regurgitation


Atrial fibrillation and eventual LV failure
Severe pulmonary congestion and oedema
Affects the RV eventually
What is Stenosis?


Calcific aortic stenosis
Rheumatic heart disease
Infective endocarditis
Congenital bicuspid valve
 Two of the aortic valvular leaflets fuse during development resulting
in a valve that is bicuspid instead of the normal tricuspid
configuration
Effects:
i.
LV hypertrophy and failure
ii.
Predisposition to myocardial ischemia (due to hypertrophied
myocardium)
iii.
Sudden death
Backflow of blood through the valve in the fully closed position or failure of valve to
close completely
i.
Allowing the blood flow in the wrong direction across the valve
May be due to pathology of the:
i.
Valve cusps
ii.
Valve ring
iii.
Chordae Tendinae
iv.
Papillary muscles
Mitral Insufficiency

Narrowing of the valvular aperture at the fully open position or failure of the valve to
open completely
Prevents the forward flow of blood and is usually due to pathology of the valve cusps
Mitral Valve Stenosis
Causes:
i.
ii.
iii.
iv.
What is Regurgitation or insufficiency?
Consequences of the Prolapse



Causes: RHD, post-inflammatory disease
i.
Effects: elevated LA pressure leading to hypertrophy and eventual dilation
ii.
Atrial fibrillation which can lead to stasis which can cause mural thrombosis
in LA
iii.
Pulmonary hypertension and pulmonary oedema leading to dyspnoea due to
reduced diffusion
iv.
Eventually leading to RV hypertrophy and failure

Causes:
i.
ii.
iii.
iv.
Effects:
Floppy valve syndrome
RHD
Papillary ischemia
Dilation of valve ring: heart failure, marfan’s syndrome
i.
ii.
iii.
Atrial fibrillation
LV failure
If acute mitral valve incompetence, severe pulmonary congestion
and oedema

Aortic Insufficiency


Causes
i.
ii.
iii.
iv.
Effects
i.
ii.
Dilation of ascending aorta (hypertension and aging)
RHD
Infective endocarditis
Dilation of Valve ring (cardiac syphilis)
LF hypertrophy and eventual failure
Predisposed to myocardial ischemia
Pulmonary and Tricuspid Valves




Right side of the heart valve disease is uncommon
RHD
Intravenous drug abuse leading to right-sided infective endocarditis
Carcinoid syndrome

Pathogenesis:
i.
Derangement of
blood flow: leading to
areas of high
pressure and low
pressure
 Jet streams with
formation of eddy
current, leading
to pockets of low
pressure
ii.
Formation of sterile
platelet fibrin
deposits
iii.
Seeding by bloodborne organism and
clumping of bacteria
due to agglutinating antibodies
Morphology:
i.
Gross: Large bulky friable bacteria-laden vegetation on the heart valves
ii.
Histology: Vegetation comprises of tangled mass of fibrin, organisms
(visualised in gram stain) & inflammatory cells
iii.
Local effects is more likely with virulent strains
Infective endocarditis
Cardiomyopathy


Usually a clinical or sub-clinical illness caused by microbial infection of the cardiac
valves or endocardium
i.
Incidence 150-175 cases a year in Singapore
 Native Valve
i.
Underlying abnormalities: e.g. RHD
ii.
Normal valve: e.g. IV drug abuses
 Prosthetic valve: no endothelium to prevent adhesion of platelets
 Infection of abnormal valves:
i.
Organisms of low virulence derived from the normal commensals of skin,
gut, respiratory tract and genitourinary tract are able to infected a valve that
is predisposed like in RHD
ii.
Bacteria become enmeshed in platelet aggregates on the surface of the
abnormal endocardium
iii.
Clinically: subacute bacterial endocarditis
Infection of normal valves:
i.
Virulent pathogenic organism directly invade the valve and cause rapid
destruction
ii.
This organisms are normally introduced during surgery (open heart),
indwelling vascular catheters and mainline drug addiction



Heart disease resulting from an abnormality in the myocardium’
i.
Primary CMP: disease is confined to the heart
 Inherited CMP due to gene mutation (Duchenne’s muscular
dystrophy)
 Idiopathic CMP
ii.
Secondary CMP: Myocardial involvement is component of systemic disease
(diabetes, thyroid disease, amyloidosis and hemochromatosis),
inflammatory/infections (chaga’s disease, myocarditis) and Toxic/metabolic
(alcohol, cocaine, chemotherapy)
Complications that arise:
i.
Heart failure
ii.
Sudden death
iii.
Arrhythmias
iv.
Stroke
Dilated (congestive) CMP:
i.
Characterized by progressive cardiac dilatation and systolic dysfunction
 Causes


 Genetics (Duchenne’s)
 Alcohol
 Myocarditis
 Drugs
 Idiopathic
 Effects

progressive heart failure
 Mitral regurgitation (secondary mitral insufficiency)
 Mural thrombus formation & embolization
 Mimics: ischemic, valvular, congenital and hypertensive heart
diseases
Hypertrophic Cardiomyopathy
i.
Characterized by myocardial hypertrophy, poorly compliant left ventricular
myocardium leading to a diastolic dysfunction (impaired diastolic filling), & in
about 1/3 of the cases, intermittent ventricular outflow obstruction due to
enlarged ventricular septum
ii.
Causes
 Genetics: those coding for sarcomeric proteins
 Alcohol
 Storage diseases
iii.
Effects:
 Left atrial dilation and mural thrombus formation
 Pulmonary venous hypertension and exertional dyspnoea
 Ventricular arrhythmias
 Sudden death (one of the common cause of sudden death in young
athletes
iv.
Mimics: hypertensive heart disease, aortic stenosis
Restrictive Cardiomyopathy
i.
Characterized by a primary decrease in ventricular compliance, resulting in
diastolic dysfunction
 Causes:
 Endomyocardial fibrosis- fibrosis of ventricular
endocardium and subendocardium that extends from the
apex upward, often involving tricuspid and mitral valves
 Endocardial fibroelastosis: (fibroelastic thickening of the
mural endocardium with or without valvular involvement
o Left-sided predominance , histologically increased
collagen and elastic tissue
Pericardial Diseases
What is the pericardium?

It is made of two layers a visceral pericardium which is reflected onto the heart
and together with the underlying fibrous layer is called the epicardium & there is
a parietal pericardium which is a fibrous layer separated from the visceral
pericardium via a thin layer of fluid (serous 30-50ml)
i.
Mesothelial lining
Pericardial diseases are secondary diseases




Primary pericarditis which is the inflammation of the pericardium is almost always
due to viral infection
It can be classified as
i.
Acute
ii.
Chronic
iii.
May result in pericardial effusion with or with cardiac tamponade
Aetiology:
i.
Myocardial infarction
ii.
Viral pericarditis
iii.
Postoperative pericarditis
iv.
Bacterial pericarditis
 TB
v.
Malignant pericarditis
vi.
Uremic pericarditis
vii.
Immune pericarditis
Types of pericarditis
i.
Serous pericarditis: Non-inflammatory, viral infections (Coxsackie B,
EBV) or immune causes
ii.
Fibrinous pericarditis: myocardial infarction, rheumatic fever
iii.
Suppurative pericarditis: due to pyogenic bacteria
iv.
Haemorrhagic pericarditis: Direct spread or metastatic malignant
neoplasms
v.
Caseous pericarditis: TB
What is pericardial effusion?
 If there is more than 50ml of fluid
i.
The fluid can be serous exudates (congestive heart disease) or
hemopericardium (without inflammation) or inflammatory exudates
mixed with blood it is called haemorrhagic pericarditis (fulminant)
 Causes of hemopericardium: Trauma and MI
ii.
MI induced hemopericardium: infiltration of macrophages and
neutrophils in the removal of necrotic tissue and the enzymes cause the
softening of the area and can lead to perforation leading to heavy
bleeding
 Leading to cardiac tamponade affects diastole leading to
progressively rising JVP and falling BP


iii.
iv.
v.
On auscultation leads to muffled distant sound
Electrical alternants (varying voltages) due to variation
in heart position
 Normally occurs at 3 day due to the softening by inflammatory
cells
Lesion/dissection of the Aorta:
 Leading to bleeding into the pericardium
Traumatic perforation:
 Car accidents where rib fracture leading to perforation
Infective endocarditis:
 Acute virulent organism leading to abscess formation that leads
to rupture of ring abscess
Uremic pericarditis
Uremic pericarditis is thought to result from inflammation of the visceral and parietal
layers of the pericardium by metabolic toxins that accumulate in the body owing to kidney
failure.
Myocarditis: Inflammation that directly leads to damage to myocardium
and not inflammation leading to injury to myocardium
 Causes:
i.
Viral
 Viral: Coxsackieviruses A & B, CMV, enteroviruses, influenza, HIV
and parvovirus
 Bacterial: Chlamydial psittaci, Rickettsia, Corynebacterium
diphtheria
 Fungal- candida
 Protozoa, helminth
 How do viruses cause destruction of myocytes?
o Infection leads to lymphocytic killing or molecular
mimicry
ii.
Immune mediated:
 Post viral
 Post streptococcal (rheumatic fever)
 SLE
 Drug hypersensitivity
iii.
Others:
 Sarcoidosis
 Gross appearance:
i.
Enlarged heart, dilated cardiac chambers, flabby myocardium,
mottled appearance
ii.
Histology: Variable according to specific causative agents, evidence
of fibrosis in healing but may also be completely healed
 Mononuclear cellular infiltration




Necrosis & oedema
Polymorphs and micro-abscess
Parasites (lava and cyst)
Granulomatous
Structure of Blood Vessels



h.
i.
j.

To withstand pulsatile flow and higher blood pressures, arterial walls are generally
thicker than the walls of veins. Arterial wall thickness gradually diminishes as the
vessels become smaller, but the ratio of wall thickness to lumen diameter becomes
greater.
Basic constituents of the walls of blood vessels are endothelial cells, smooth muscle
cells and extracellular matrix, including elastin collagen, and glycosaminoglycans.
Three concentric layers:
The tunica intima – delimits the vessel wall towards the lumen of the vessel and
comprises its endothelial lining (typically simple, squamous) and associated connective
tissue. Beneath the connective tissue, we find the internal elastic lamina, which
delimits the tunica intima from the tunica media
The tunica media – is formed by a layer of circumferential smooth muscle and
variable amounts of connective tissue. A second layer of elastic fibres, the external
elastic lamina, is located beneath the smooth muscle. It delimits the tunica media from
the tunica adventitia
The tunica adventitia – connective tissue layer
Three types of arteries:
a. Large or elastic arteries – includes the aorta, its largest branches and pulmonary
arteries
b. Medium or muscular arteries comprising other branches of the aorta (eg.
coronary and renal arteries)
c. Small arteries – less than approximately 2mm in diameter, arterioles (20 to 100
μm in diameter)
Hypertension
Systemic Arterial Hypertension

When there is a sustained blood pressure of 140/90 mm Hg or above
a. It must not be a transient value as blood pressure can rise due to coffee drinking
and even white coat hypertension
b. Hence blood pressure must be monitored over a period of time and can even do
it ambulatory
c. A sustained blood pressure increases the risk of atherosclerosis
Causes of hypertension
a.
b.
c.
Primary or essential hypertension (90-95%) (non-curable)
i.
Idiopathic, multifactorial and complex disorder
 Genetic mutations in RAAS system
 Vasoconstrictive influences
 Environmental factors such as stress, obesity and physical inactivity
Secondary hypertension (5-10%) (need to treat underlying condition so
possibly curable)
i.
Due to Renal dysfunction
 Such as renal artery stenosis via atheromatous plaque
ii.
Endocrine - hypercortisolism or pheochromocytoma
 Pheochromocytoma - increase in nor-epinephrine and epinephrine
 Hypercortisolism - enhancement of epinephrine's vasoconstrictive
effect via up-regulation of α1 receptors
iii.
Neurological - increased intracranial pressure
iv.
Aortic - coarctation, atherosclerotic rigidity or aorta
v.
Labile - psychogenic, stress related
Malignant or accelerated hypertension
i.
5% of hypertensive patients with systolic pressure above 200mm Hg and
diastolic pressure above 120 mm Hg
ii.
Can lead to rapid renal failure, retinal haemorrhage/exudates and
papilledema (may not always lead to)
d.
Natriuretic factors secreted by atrial and ventricular myocardium in response to
volume expansion results in increased sodium excretion and diuresis
Arteriolosclerosis: generic term reflecting arterial wall thickening and loss of elasticity
and it affects small arteries and arterioles
a. There is hyaline arteriolosclerosis and hyperplastic arteriolosclerosis
b. Hyaline: shows homogenous, pink hyaline thickening with associated luminal
narrowing
i.
These changes stem from plasma leakage across injured endothelial cells, and
increased smooth muscle cell matrix synthesis due to hemodynamic stress
ii.
Nephrosclerosis due to chronic hypertension, the arteriolar narrowing of hyaline
arteriosclerosis causes diffuse impairment of renal blood supply and causes
glomerular scarring
c. Hyperplastic: This occurs in severe hypertension; vessels exhibit “onion-skin lesion”,
characterized by concentric laminated thickening of the walls and luminal narrowing
i.
The laminations consist of smooth muscle cells with thickened, reduplicated
basement membranes; in malignant hypertension they are accompanied by
fibrinoid deposits and vessel wall necrosis (necrotizing arteriolitis)
Symptoms

Most of the time, hypertension is a silent killer and symptoms appear when there is
end-organ damage
i.
Blood vessels – Arteriosclerosis, accelerated atherosclerosis and aortic
aneurysm
ii.
Heart – Hypertensive heart disease with ventricular hypertrophy
iii.
Kidney – Nephrosclerosis
iv.
CNS – Cerebral haemorrhage, thrombosis and hypertensive encephalopathy
v.
Eye – Hypertensive retinopathy
Hypertensive Heart Disease
a.
Regulation of normal blood pressure: SV X HR X TPR
a.
b.
c.
Cardiac output is affected by blood volume and sodium homeostasis
Peripheral vascular resistance is determined mainly at the level of arterioles and is
affected by neural and hormonal factors
i.
Humoral vasoconstrictors: Angiotensin II, catecholamines and endothelin
ii.
Vasodilators: kinins, prostaglandins and NO
iii.
Autoregulation, whereby blood flow induces vasoconstriction to protect
against tissue hyperperfusion
RAAS system
b.
c.
Hypertrophy of the left ventricle as an adaptive response to pressure overload
i.
Increased thickness leads to stiffness imparts a stiffness which impairs
diastolic filling and this leads to dilation
ii.
Eventual Left Ventricular failure
Stages of hypertension:
i.
Stage 1: systolic pressure is between 140 to 159 AND diastolic is between
90-99
 Needs to be treated with drugs
ii.
Stage 2: more than 160 systolic and diastolic above 99
Systemic blood pressure is the pressure just distal to the LV and just proximal to the
arterioles
i.
Cardiac Output affects systolic and Total Peripheral Resistance affects
the diastolic blood pressure
ii.
d.
e.
f.
g.
During diastole it’s the elastic recoil that pushing the blood through and the
LV no longer influences the pressure as the valve is closed. Hence the
degree of dilatation of the arteriole will determine the amount of blood
present in the artery and hence the diastolic blood pressure
 Different parts of the body, due to differential activity, there is
changes in arteriolar constriction. Hence, we must consider total
resistance
Hence, a disease or drug that only increases or decreases systolic pressure is
increasing cardiac output AND a drug that only changes the diastolic pressure only
affects the TPR via the arteriolar contraction
All factors that increase blood volume will result in increased EDV via frank-starling
mechanism in heart leading to systolic hypertension
i.
Sodium retention leads to increase in volume and enhance via increased
venous return
 Hyperaldosteronism
ii.
Natriuretic – cause vasodilation and hence reduce venous return and also
act on the kidney to cause natriuresis
iii.
Treatment: diuretic drugs
All factors that increase Stroke Volume (increased contractility) and Heart Rate
(positive inotropic effect) will cause increase in systolic hypertension
iv.
White coat hypertension
v.
Treatment: Beta blockers
All factors that affect TPR:
vi.
Humoral factors: we are constantly producing a balance of vasoconstrictors
and vasodilators
 Angiotensin II & catecholamine (dopamine, nor-epinephrine and
epinephrine) & thromboxane A2
 NO & Prostaglandins & Kinins
vii.
Neural factors
 Adrenergic nerve endings- α1 (constriction) and β2 (dilatation)
 Muscular arteries have more β2 while renal artery is the
other way round
Physiology

Decreased perfusion to kidney > leads to reduced glomerular filtration > leading to
increased reabsorption in the proximal tubule > lesser NaCl for reabsorption in the
distal tubule sensed by macula densa > leading to increased renin secretion > acts on
the liver protein angiotensinogen to produce Angiotensin I > in pulmonary circulation
the endothelial cells contain ACE which converts it to Angiotensin II
i.
Angiotensin II can act as venous contractor (increase venous return hence
increases CO) and arterial constriction ( TPR )
ii.
It acts on the zona glomerulosa and activate the release of aldosterone
Pathological derangements

Anyone who has problem with sodium and water retention will initially face systolic
blood pressure elevation and over time the arteriole will try to protect from
hyperperfusion of organs leading to arteriolar contraction and reactive hypertrophy
and hyperplasia of smooth muscle and connective tissue, hence diastolic blood
pressure elevation too Hyper-reactivity of arteriole leads to increase in diastolic
pressure, and eventually, since the heart needs to compress against a higher
resistance, there can be increased systolic pressure as well.
Short explanation for some common causes:


Renin producing tumours
Renal artery stenosis (especially in smokers above 50, atherosclerosis) or
fibromuscular dysplasia
Conditions that affect the kidney as a whole, polycystic kidney disease,
glomerular nephritis will have less sodium filtration hence accumulation of blood
volume hence increase in systolic blood pressure
Oestrogens or oral contraceptive or pregnancy can cause hypertension via
increased production of angiotensinogen
Conn’s syndrome leading to increased aldosterone production leading to increase
in salt and water reabsorption with hypo rennin
i.
If renin and aldosterone is increased then it’s a kidney problem
Congenital renal hyperplasia due to mutation in 11β-hydroxylase and 17αhydroxylase leading to increased aldosterone production
Liddle syndrome- condition in which the principle cells increase sodium
reabsorption





Abnormality of vessels


Hardening and thickening of the arteries with loss of elasticity
Three General Patterns, with differing clinical and pathological consequences:
a. MÖnckeberg medial sclerosis: in the medium sized arteries like radial or
ulnar arteries where there is patchy calcification in the tunica media of arteries
but it does not affect the lumen size. Age-related and it is a media related
calcification
i.
Not dangerous
b. Atherosclerosis: disease of the intima, with fibro-fatty plaques
i.
Affects the elastic arteries and the medium sized muscular arteries
 Elastic arteries include the aortic arteries, aorta, carotid
arteries and iliac arteries
 Medium sized muscular arteries are like coronary arteries,
circle of willis artery
ii.
c.
Within the intima there is the formation of the plaque that can cause
obstruction to the lumen and also degeneration of the media leading to
aneurysms
iii.
Commonly affected vessels: abdominal aortic (AAA), coronary arteries,
followed by popliteal artery and carotid artery and lastly circle of willis &
other medium size arteries
Arteriolosclerosis: affects smaller arterioles
i.
Hyaline arteriolosclerosis & hyperplastic arteriolosclerosis
 Hyaline due to accumulation of different plasma protein
accumulation
 Aging and chronic hypertension
 Hyperplastic arteriosclerosis
 When diastolic pressure is higher than 120mm Hg and
with retinal haemorrhages with or without papilladema
 Concentric rings of onion of smooth muscles
 Necrotic changes
Atherosclerosis
Epidemiology-Risk Factors
a.
b.
c.
d.

a.
Non-modifiable (Constitutional) risk factor: Age, male gender, family history
and genetics
Modifiable risk factors: Hyperlipidaemia, hypertension, diabetes and cigarette
smoking
New-kid on the block- CRP, an inflammatory component which is measured as it is
believed a chronic inflammatory disease
Additional Risk factors: inflammation, hyperhomocystinemia, metabolic syndrome,
lipoprotein A, lack of exercise, obesity, type A personality and factors affecting
haemostasis
Pathogenesis of Atherosclerosis
Atheroma formation in the intimal layer due to chronic injury that leads to chronic
inflammation
What are the causes of the chronic injury to endothelium?
i.
Hemodynamic stresses (hypertension)
 Posterior wall of abdominal aorta especially between the renal
artery to the bifurcation is most affected by the hemodynamic
stress
 At the mouth of branching arteries like that of renal artery and
other branching points are more affected by hemodynamic stress
ii.
Hyperlipidaemia (high LDL or high lipoprotein A or less HDL)
LDL is responsible for transporting cholesterol to the peripheral
tissue, hence it is the supplier
 Familial hypercholesterolemia, in which the receptor on
the liver for LDL is defective so feedback is lost
 Hypothyroidism or alcoholism
 HDL responsible for removal of cholesterol from the peripheral
tissue to the liver to be secreted in the bile
 Moderate alcohol intake can increase HDL
 Obesity and smoking reduces HDL level
o Obesity increase triglycerides, increases BP and
DM
o Smoking itself leads to toxin in the smoke that can
lead to injury to the endothelium
 The cholesterol accumulation damages the endothelial cells making
it more permeable allowing lipid accumulation
 In the presence of high LDL there is increased reactive
oxygen species from the endothelial cell leading to
inactivation of NO which can increase platelet activity
 LDL can also get oxidised to oxidised LDL
 Treatment: Statins which are HmgCoA reductase inhibitor
iii.
Homocysteine levels
 High levels leads to endothelial damage leading to
Atherosclerosis
iv.
Microbial factors:
 Endotoxin causes damage to endothelial
 Chlamydia pneumonia possible causative organism
 Viral-CMV
v.
Immune reaction
 Increase in CRP due to IL-6 and TNFα can lead to atherosclerosis
What happens to endothelium?
i.
More permeable & increased adhesion molecule with reduced NO secretion
 Becomes thrombogenic and increased infiltration of monocytes &
lymphocytes due to adhesion molecules like VCAM-1
 Increased permeability leads to influx of lipid and LDL into the
intimal layer
 The monocytes & T- lymphocytes enter the intima leading to
conversion into macrophages, and the cross talk between the
macrophages and lymphocytes lead to release of cytokines of
inflammation like TNF and IL-1 which results in even greater
activation of endothelial cells
ii.
Platelets aggregation which further activates PDGF, FGF

b.
iii.
c.
Smooth muscle proliferation and
infiltration into the intima and ECM
production
 Promoted by PDGF, FGF and
TGF-α. ECM is synthesize by the
smooth muscle cell via collagen
synthesis and hence leading to
fibrosis which stabilizes the
plaques
Formation of foam cells through the
phagocytosis of LDL by macrophages via
scavenger receptors
i.
Oxidised LDL are better taken up by
macrophages and smooth muscles also
take up the lipids
ii.
The macrophages eventually die via
necrosis and their cellular content is
released leading to lipid core
iii.
Growth factors that are just under the
endothelium and platelet aggregation side
will activate more smooth muscle
proliferation and fibrosis leading to the
fibrous cap and on the medial side is the
presence of the lipid core.
 This is called an atheroma
i.
Rupture, ulceration or erosion of the
intimal surface over the plaque leading to thrombosis
which can partially or completely occlude the vessel
ii.
Haemorrhage into a plaque Rupture of
the overlying fibrous cap, or of the thin walled area of
neovascularisation at the shoulder of the plaque causing
an intra-plaque hematoma
iii.
Atheroembolism: discharge into the
blood stream
iv.
Aneurysm: Atherosclerosis induced
pressure or ischemic atrophy of the underlying media,
with loss of elastic tissue, causes weakness resulting in
aneurysmal dilation and potential rupture
Histological features of an atheroma
Presence of cholesterol clefts & lipid material and a
fibrous cap with a darker pink stained collagen
Morphology
a.
b.
c.
Early: fatty streaks
i.
Earliest lesion, prior to smooth muscle cell
proliferation and ECM synthesis
ii.
Contains foamy macrophages
iii.
Not significantly raised of 1cm or more in length
iv.
Can be seen in all children older than 10 years old, not all will become
advanced lesion
Established: Atheromatous plaque
i.
Established lesions, after smooth muscle cell proliferation and ECM synthesis
ii.
Contains 3 components: Cells such as macrophages, smooth muscle cells
and T cells, ECM & intracellular and extracellular lipids
iii.
Structurally, made up of a superficial fibrous cap of smooth muscle cells and
collagen and a soft necrotic core deep to it (cholesterol crystals and
cholesterol esters, cellular debris and foam cells)
iv.
Raised lesion, protrudes into the lumen and can lead to patchy lesions with
thrombus formations over the ulcerated areas
Complications
a.
Vulnerable or unstable plaques
a.
Composition of a plaque is dynamic
b.
Most clinically dangerous plaques are unstable
plaques
i.
May vary in size but are often the
smaller plaques
ii.
Relatively large lipid core and a thin
fibrous cap

Due to increased matrix
metalloproteinases (MMP) by macrophages that degrade
collagen and ECM

Decreased tissue inhibitors of
MMPs (TIMP) by endothelial cells, macrophages and smooth muscle
cells
 Extrinsic factors: Blood pressure and platelet reactivity
iii.
More likely to fissure, rupture, ulcerate and plaque haemorrhage to form a
suddenly large occlusive thrombus
Stable plaques
The larger and often more occlusive plaques may be paradoxically more stable
i.
Smaller lipid core and more fibrous tissue
Consequences of Atherosclerotic Disease
a.
Plaque Complications
i.
Calcification
ii.
Ulceration
iii.
Thrombosis
b.
c.
iv.
Haemorrhage
v.
Aneurysmal dilation
Chronic atherosclerotic stenosis
i.
Gradual process of vessel luminal occlusion by growing plaque which
compromises blood flow with resultant ischemic injury
ii.
Critical stenosis is point at which chronic occlusion significantly limits flow,
and demand starts exceeding supply
iii.
Ischemic manifestation: stable angina, chronic ischemic heart disease,
bowel ischemia, ischemic encephalopathy, intermittent claudication
Acute Plaque Change
i.
Rupture/ fissuring (exposed thrombogenic plaque constituents, discharges
atherosclerotic debris into bloodstream to produce atheroembolism
ii.
Erosion/ulceration exposes thrombogenic subendothelial basement
membrane
iii.
Haemorrhage into plaque (expands plaque volume and may secondarily
promote plaque rupture
iv.
Acute manifestations: myocardial infarction, cerebral infarction, aortic
aneurysm and peripheral vascular disease
 Atherosclerosis-induced pressure or ischemic atrophy of the
underlying media with loss of elastic tissue weakens the vessel wall
Vasculitis

Inflammation of the blood vessel wall
i.
Almost always immune mediated but there can be the rare infectious
vasculitis (direct invasion of the vascular wall by the infectious pathogen
Non-infectious vasculitis
a.
Immune mediated
i.
Immune complex deposition: type III hypersensitivity
 SLE and polyarteritis nodosa
 Drug hypersensitivity vasculitis
 Viral infection vasculitis
ii.
Antineutrophilic cytoplasmic antibodies (ANCA)
 ANCA-activated neutrophils degranulate, releasing ROS
 Anti-myeloperoxidase (MPO-ANCA/p-ANCA)
o Microscopic polyangiitis (affects the glomeruli and
pulmonary vessels, Churg-Strauss Syndrome
(associated with asthma and lung infiltration)
 Anti-proteinase-3 (PR3-ANCA/c-ANCA)
o Wegener granulomatosis
 Triad of acute necrotizing granulomas of
URT &/or LRT, necrotizing
granulomatous vasculitis in the lung and
glomerulonephritis
iii.
Anti-endothelial cell antibodies: type II hypersensitivity
 Like in Kawasaki disease
 Acute febrile self-limiting disease of infancy leads to
predilectation for coronary artery and can cause acute
myocardial infarction
b.
c.
Giant cell arteritis: granulomatous vasculitis amongst elderly
i.
Affects elderly and the arteries of head (temporal, ophthalmic and vertebral)
Polyarteritis nodosa: Necrotizing vasculitis that affects the renal and visceral arteries
but spares the lungs
i.
Associated with chronic HBV infection
Effects of vasculitis: Clinical manifestation may be extremely varied
 Thrombosis
 Haemorrhage
Infectious Vasculitis
a.
b.

Causes: cardiovascular syphilis
i.
Tertiary syphilis
ii.
Often affects the root of the aorta and causes vasculitis affecting vasa vasorum
obliterating them
Effects:
i.
Aortitis (scarring), coronary ostial occlusion, aneurysm of thoracic aorta and
aortic incompetence
e.
f.
g.
Complication of Aneurysms
a.
b.
c.
d.
a.
Aneurysms
b.
Localized abnormal dilatation of a vessel (or heart)
i.
True aneurysms involve an intact attenuated vessel or heart wall & may take
on saccular (focal outward bulge) or fusiform (circumferential dilatation) shape
ii.
False aneurysms form in the case of a defect in the vessel wall leading to an
extravascular hematoma bound by extravascular connective tissue which
communicates with intravascular space
c.
Weakening of the vessel wall (cystic medial necrosis)
Loss of elasticity and contractility due to a deficiency of the media
Poor quality of vascular wall connective tissue
Collagen degradation by local inflammation
Aetiology
a.
b.
c.
d.
Atherosclerosis
Syphilis
Cystic medial necrosis
Polyarteritis nodosa
Pressure on surrounding structures (leading to compression of blood vessels)
Thrombosis and embolism
Occlusion of blood vessels
Rupture with haemorrhages
Types of Aneurysms
Pathogenesis
a.
b.
c.
d.
Trauma (pulsating haematoma, arteriovenous fistula)
Congenital defect (berry aneurysms)
Infections (mycotic aneurysms)
i.
Embolization of a septic emboli (typically from infective endocarditis)
ii.
Extension of adjacent suppurative process
iii.
Circulating organism directly infecting arterial wall (e.g. bacteraemia from
salmonella gastroenteritis)
d.
Abdominal aortic aneurysms
i.
Associated with atherosclerosis
ii.
Thrombus
iii.
Rupture (hemoperitonium)
iv.
Mass and local pressure effect
Thoracic aortic aneurysm
i.
Associated with hypertension
ii.
Local pressure effects
iii.
Aortic valve insufficiency
iv.
Rupture
Berry aneurysms
i.
Small berry like saccular aneurysm at the circle of willis
ii.
Rupture leads to subarachnoid haemorrhages and can be noticed in the CSF
iii.
2% of population
iv.
90% of the time is due to anterior circulation, with multiple aneurysms in 2030% of cases
v.
Aetiology:
 Unknown congenital, genetic factors
 Developmental deficiency/weakness of media

Predisposing factors
 Hypertension, cigarette smoking and atherosclerosis
Dissecting Aneurysm
i.
Blood splaying apart laminar planes of the media to form a blood filled channel
within the vessel wall
ii.
It occurs in three groups of people
 Hypertensive patients typically males between the ages of 40-60
Connective tissue abnormalities like Marfan Syndrome (younger
patients)
 Iatrogenic (catheterization, surgery)
It can also occur in idiopathic medial degeneration (cystic medial necrosis)
 Focal degeneration of elastic tissue and muscle
 Cystic spaces filled with mucopolysaccharide
Pathogenesis:
 Initiating event: intimal tear or rupture of vasa vasorum
 Haemorrhage occurs in between the middle and outer third of media
 May dissect retrograde towards the heart or distally
 May rupture internally (through a second intimal tear forming a double
barrelled aorta) or externally (bleeding into thoracic/abdominal cavities
or into pericardial sac
Clinical manifestations:
 Death due to rupture into pericardial, pleural or peritoneal cavities
 Retrograde dissection; aortic valve insufficiency
 Cardiac tamponade
 Myocardial infarction
 Extension into aorta branches; vascular obstruction and ischemic
consequences
Patient will present with sudden onset of excruciating pain, usually beginning in
anterior chest (may be confused with angina), radiating to the back between
the scapulae, moves downwards as the dissection progresses

iii.
iv.
v.
vi.