MODULE 1 4.

Immunologic reactions - Examples are autoimmune

BASIC MECHANISM OF PATHOPHYSIOLOGY reactions against one’s own tissues, allergic reactions against
environmental substances, and excessive or chronic immune
responses to microbes. In all of these situations, immune
Introduction to Pathophysiology responses elicit inflammatory reactions, which are often the
cause of damage to cells and tissues.
Pathophysiology - The field of pathophysiology is devoted to 5. Genetic abnormalities - Genetic abnormalities can result in
understanding the causes of diseases and the changes in cells, pathologic changes as conspicuous as the congenital
tissues, and organs that are associated with disease and give rise to malformations associated with down syndrome or as subtle
the presenting signs and symptoms in patients. as the single amino acid substitution in hemoglobin giving
rise to sickle cell anemia. As a consequence of deficiency of
Etiology - refers to the underlying causes and modifying factors functional proteins, such as enzymes in inborn errors of
that are responsible for the initiation and progression of the metabolism, or accumulation of damaged DNA or
disease. misfolded proteins, both of which trigger cell death when
they are beyond repair.
Pathogenesis - refers to the mechanisms of development and 6. Nutritional imbalances - Protein calorie insufficiency among
progression of disease, which amount for the cellular and impoverished populations remains a major cause of cell
molecular changes that give rise to the specific functional and injury, and specific vitamin deficiencies are not uncommon
structural abnormalities that characterize any particular disease. even in developed countries with high standards of living.
Ironically, excessive dietary intake may result in obesity and
also is an important underlying factor in many diseases, such
Note Etiology refers to why disease arises and Pathogenesis
describes how a disease develops. as type 2 diabetes mellitus and atherosclerosis.
Signs are objective. Symptoms are subjective. 7. Physical agents - Trauma, extremes of temperature,
radiation, electric shock, and sudden changes in atmospheric
pressure all have wide-ranging effects on cells.
Causes Of Cell Injury 8. Aging - Cellular senescence results in a diminished ability of
cells to respond to stress and, eventually, the death of cells
and of the organism.
1. Hypoxia (oxygen deficiency) and Ischemia (reduce blood
supply) - among the most common causes of cell injury. The
most common cause of hypoxia is ischemia resulting from an Adaptation of Cell Injury
arterial obstruction, but oxygen deficiency also can result
from inadequate oxygenation of the blood, as in a variety of Cellular Adaptation - Adaptation is the cell’s reaction to
diseases affecting the lung, or from reduction in the prolonged stress and repeated injury to protect itself and prevent
oxygen-carrying capacity of the blood, as with anemia of any recurrent injuries. Adaptations are either physical or functional.
cause, and carbon monoxide (CO) poisoning.
2. Toxins - these include air pollutants, insecticides, CO, Etiologies Of Cellular Adaptation
asbestos, cigarette smoke, ethanol, and drugs. Many drugs in
1. Atrophy - A decrease in size or number of cells; atrophy is
therapeutic doses can cause cell or tissue injury in a
due to a decline in blood flow, nerve or hormone supply, or
susceptible patient or in many individuals if used excessively
nutrition.
or inappropriately. Even innocuous substances, such as
2. Hypertrophy - An increase in cell size; It is due to increased
glucose, salt, water and oxygen, can be toxic.
workload (exercise) or increased hormone supply.
3. Infectious agents - All types of disease-causing pathogens,
3. Hyperplasia - An increase in the number of cells; hyperplasia
including viruses, bacteria, fungi, and protozoans, injure
is due to chronic irritation or increased stimulation
cells.
(increased hormone levels or abnormalities).
4. Metaplasia - A change from one mature cell type to a Characteristics of Apoptosis
different mature cell type; metaplasia is a benign process and
1. The cells and cellular organelles shrink
is usually reversible (e.g., metaplasia from columnar
2. The cell membrane remains intact
epithelium to squamous epithelium).
3. Chromatin becomes condensed
5. Dysplasia - A change from a mature cell type to an immature
4. Cytoplasmic buds and apoptotic bodies form
cell type (abnormal cell differentiation); dysplasia is partially
reversible and is considered premalignant; it can have many
etiologies (e.g., viruses, smoking, chronic exposure, Inflammation
persistent metaplasia, hyperplasia); morphologically,
dysplasia results in abnormal cellular and nuclear features. Refers to both a protective response intended to eliminate the
initial cause of cell injury and the necrotic cells and tissues
Cell Injury and Death resulting from the original insult. Inflammation can be acute or
chronic.

Types Of Cell Death

Types of Inflammation
1. Reversible cell injury - Swelling of cell organelles
1. Acute inflammation - An early response to injury (within
(endoplasmic reticulum, mitochondria) and swelling of the
hours to days) that initiates vascular changes (dilatation,
entire cell. Nuclear changes such as hyperchromasia
increased permeability of the fluid), cellular changes, and
(clumping of nuclear chromatin). Other changes include
leukocyte (white blood cell) accumulation. The leukocyte
cytoplasmic densities, membrane blebbing, and detachment
response to injury starts the inflammation process when
of ribosomes.
leukocytes exit the blood vessels through margination,
2. Irreversible cell injury - Injury that leads to cell death.
rolling, adhesion, and transmigration and start chemotaxis.
- Necrosis - The death of groups of cells due to injury
The vascular and cellular changes lead to the classic clinical
(always pathologic and never physiologic and it never
signs and symptoms of acute inflammation (redness, increase
occurs in normal tissue), which results in the release of
in temperature, swelling, pain, and limited function). The
multiple cellular components that will trigger an
goal of acute inflammation is to limit injury and restore
inflammatory reaction.
tissue. The outcome of acute inflammation can be complete
- Apoptosis - The programmed death of individual cells
resolution, abscess formation, regeneration, develop scar
(not groups of cells)
formation, or chronic inflammation. Neutrophils are the
main cells in acute inflammation.
Types of Necrosis
2. Chronic inflammation - Is prolonged, active inflammation
1. Coagulation necrosis - Usually due to hypoxia, when (lasting weeks to years) associated with tissue destruction
denaturation occurs and the cells maintain their architecture and repair. Chronic inflammation is usually preceded by
for a few days (e.g., heart and myocardial infarction). acute inflammation (e.g., bacterial infections, viral
2. Liquefactive necrosis - Results in the transformation of cells infections), although there are exceptions (e.g., chronic
into thick liquid and complete loss of their structure (e.g., granulomatous inflammation [tuberculosis, sarcoidosis],
brain and bacterial infection). immune diseases). Consists of several phases, including
3. Caseous necrosis - Cells become amorphous and lose their necrosis, parenchymal damage, granulation tissue formation,
architecture (e.g., granulomatous inflammation in and fibrosis (scar formation). Lymphocytes are the main cells
tuberculosis or fungal infection). in chronic inflammation, but macrophages, plasma cells,
4. Fat necrosis - Enzymatic necrosis that is seen in fat tissue monocytes, and eosinophils also play a role.
(e.g., fat necrosis in the breast or pancreas is the most
common).
5. Fibrinoid necrosis - Deposition of fibrin in the blood vessels
(e.g., autoimmune disease).
 Terminologies Associated with the Immune System
Tissue Repair
1. Pathogen - microorganism that is able to cause disease.
Tissue repair - This process follows acute and chronic 2. Pathogenicity - microorganism that is ability to cause disease.
inflammation with the intention to restore the normal tissue 3. Virulence - the degree of pathogenicity.
structure; it requires that some of the original cells are still viable; 4. Opportunistic pathogens - bacteria which cause disease in an
the ability of these cells to replicate (mitosis) depends on the cell immunocompromised host.
type as follows: 5. Normal flora - harmless bacteria consistently associated with
the host.
Categories of cells based on their regenerative properties 6. Infection - when an organism (including Normal flora)
breaches a body surface.
1. Labile cells - (e.g., stem cells, hematopoietic cells) replicate
throughout their lives to replace lost cells.
2. Stable cells - (e.g., fibroblasts) can replicate only when Note Doesn’t necessarily lead to disease depends on:
activated to replace lost cells. • Portal of entry
3. Permanent cells - (e.g., cardiac and striated muscle cell) • Number of pathogens
cannot replicate scar tissue (fibrosis) and lost cells will be • Immune status of the host.
replaced by scar tissue.

Defenses of the Body

Granulation tissue is the main type of tissue in the process of
tissue repair, consisting of new blood vessels, fibroblasts, and
collagen; tissue repair and the formation of collagen are Defense Systems of the Body
stimulated and monitored by several genes and chemical 1. Innate response (non-specific immunity)
mediators such as platelet-derived blood factor (PDGF), tissue - Surface barriers and Internal defenses
growth factor beta (TGF-b), fibroblastic growth factor (FGF), - The body’s foot soldiers
and vascular endothelial growth factor (VEGF). - Already in place at birth
- Is always prepared
The Immune System at a Glance - Responds within minutes
- Protects the body from all foreign substances
- Are often sufficient to ward off invading pathogens
The Immune System - Is more a functional system rather than an
single-handedly
anatomical or organ-based system. Consists of a diverse array of
- Essentially, it reduces the workload of the adaptive
molecules, trillions of immune cells (especially lymphocytes).
immune system
These molecules & immune cells inhabit lymphoid tissues &
circulate in body fluids.
Note 1st Line of Defense: Surface Barriers
Functions to protect the body from ▪ Prevents Entry of Pathogen
1. Skin
1. Most infectious microorganisms - Stratified squamous epithelium
2. Cancer cells - Nonkeratinised or keratinised
3. Transplanted organs 2. Mucous membrane
4. Graft - Lysozyme: enzymes found in saliva & tears destroy
5. Any other foreign materials bacteria.
- Sticky Mucus: in digestive & respiratory tracts traps
bacteria.
Note Can act directly by cell attack - Cilia: nasal respiratory sweep bacteria into mouth
Can act indirectly by releasing antibodies chemicals & swallowed.
antibody molecules; a form of autoimmune disease. - Acid secretion: skin, vagina, stomach kills microbes.
 Note 2nd Line of Defense: Internal Defenses It has Memory: mounts a stronger attacks on previously
▪ Prevents Spread of pathogen if Surface Barriers are encountered pathogens
breached
1. Phagocytes Note The body’s 3rd line of defense
- Macrophages - large phagocytic cells 1. Humoral Immunity (Antibody Mediated immunity)
2. Granulocytes - possess cytoplasmic granules Immunity can be transferred from person to person via
- Neutrophils - they release toxic chemicals into the serum.
extracellular fluid, killing both the target and B cells (B Lymphocyte) - Make antibodies against soluble
themselves (kamikaze) antigens. Antibodies (Immunoglobulins): circulate freely in
- Eosinophils – another type of white blood cell (kill blood & lymph, Neutralizes bacteria, toxins, & viruses
parasitic worms) marked for destruction by phagocytes or compliment.
- Basophils – important in allergic reactions 2. Cellular Immunity - Immunity can be transferred from
3. Fever - When exposed to foreigners, leukocytes & person to person via blood cells. Antigen causes activation
macrophages secrete pyrogens increases the body’s of macrophages, NK-cells, T-lymphocytes & cytokines.
thermostat. Increases metabolic rate, kills microbes, speeds
up repair. Macrophages & NK-Cells – destroy intracellular pathogens.
4. Natural Killer cells - Police the body in blood & T Cells – induce apoptosis of body cells with viruses,
lymph. Can fight & kill cancer cells & virus-infected cells. intracellular bacteria, cancerous traits.
Target all cells that lack self surface receptors (non-specific). Cytokines are secreted – enhance inflammatory response
Kill by latching onto invaders and inducing apoptosis. Also and/or activate other lymphocytes/macrophages. Activated
secrete potent chemicals that promote inflammation. cells destroy infected or foreign cells.
5. Antimicrobial proteins - Either attack microbes
directly or reduce their reproductive ability (including MODULE 2
Interferons & compliment).
INTEGUMENTARY SYSTEM
6. Inflammation - In response to physical trauma, intense
heat, bad chemicals, infection. Prevents spread of damaging
events to nearby tissue. Disposes of cell debris & pathogens.
Dermatophytosis
Set stage for repair. Characterized by heat, redness, pain &
swelling
Dermatophytosis
➢ Infection of skin, hair and nails caused by a species of
2. Adaptive response (specific immunity)
dermatophyte (fungi that live within the epidermal
- Humoral immunity (antibody-mediated immunity) and
keratin and do not penetrate deeper structures).
Cellular immunity
- The body’s elite special forces – equipped with
Etiology
high-tech weapons.
➢ Different species of dermatophyte
- Adaptive response are called into action as
➢ Trichophyton, Microsporum, Pityrosporum,
reinforcements
Epidermophyton species
- Take much more time to mobilize than the innate
response
Pathophysiology
- Attack specific foreign substances (including Antigens
➢ Digestion of keratin by dermatophytes results in scaly
and abnormal body cells)
skin, broken hairs, crumbling nails.
- When few in count > cancer, AIDS, etc.
- Tremendously amplifies the inflammatory response.
Investigations
➢ To isolate, skin scrapings, hair, nail clipping should be
Note It is Specific: recognize particular pathogens/antigens analyzed by potassium hydroxide (KOH) preparation
It is Systemic: immunity isn’t restricted to initial detection
(since these fungi live as nodes, look for hyphae, and
site
mycelia).
 limbs. Peripheral enlargement of lesions. Sites:
Management trunks, limbs, face.
➢ Topicals (cream) are effective as first-line agents and oral
Etiology: T. rubrum, E. floccosum, M. cannis, T.
therapy for other agents.
Tinea cruris.
➢ Topicals may be used as first line agents for tinea Corporis
corporis/cruris and tinea pedis (interdigital type), e.g. (Ringworm) Epidemiology: Most common in farm children
clotrimazole or terbinafine cream applied two times a and those with infected pets.
day, continued until one week after complete resolution
Examination: Microscopic examinations of
of lesions. KOH preparation of scales scraped from active
➢ Oral therapy is indicated for onychomycosis, tinea margin shows hyphae. Scales may be cultured on
capitus, e.g. terbinafine (Lamisil) or itraconazole sabourad’s agar.
(Sporanox).
Management: Lamisil cream, Clotrimazole
➢ Itraconazole is a P-450 inhibitor. It alters metabolism of cream, Fluconazole tablet.
non-sedating antihistamines, cisapride, digoxin, and
HMG CoA reductase inhibitors. Differential Diagnosis: psoriasis, seborrheic
dermatitis, pityriasis rosea

Types of Dermatophytosis Definition: Scaly patch/plaque with a

well-defined, curved border and central clearing on
medial thigh. Does not involve scrotum. Pruritic,
Definition: Non-scarring alopecia with scale.
edematous, dry/macerated.
Etiology: Trichophyton tonsurans and
Etiology: T. rubrum, T. mentagrophytes,
Microsporum species.
Epidermophyton floccosum
Tinea Cruris
Epidemiology: Affects children (mainly black),
(Jock itch) Epidemiology: Most common in adult males
immunocompromised adults. Very contagious and
may be transmitted from barber hats, theatre seats,
Examination: Same as for tinea corporis.
pets.

Differential Diagnosis:Candidiasis (involvement

Signs & Symptoms: Round, scaly patches of
of scrotum and has satellite lesion). Erythrasma
alopecia. May see broken off hairs. If tissue
(coral-red fluorescence with Wood’s lamp). Also
reaction is acute, a Kerion (boggy, elevated,
mistaken as Contact dermatitis.
purulent inflamed nodule/plaque) may form - this
may be secondarily infected by bacteria and result
Tinea Capitis Definition: Pruritic scaling and/or maceration of
in scarring.
the webspaces and powdery scaling of soles.
Examination: Involves wood’s light examination
Clinical Features: White vesicles, bullae, scale
of hair: green fluorescence only for microsporum
maceration and interdigital.
infection. Culture of scales/hair shaft may be done
on Sabourad’s agar. Microscopic examination of a
Etiology: T. rubrum, T. mentagrophytes, E.
KOH preparation of scales or infected hair shafts
reveal characteristic hyphae. floccosum
Tinea Pedis
Management: griseofulvin 15-20 mg/kg/day Epidemiology: Chronic infections are common
(Athlete’s
usually 8 weeks or terbinafine (Lamisil) 250 mg od in atopics. Heat, humidity, and occlusive footwear
Foot)
usually 2-4 weeks (vary dose by weight). are predisposing factors.

Differential Diagnosis: psoriasis, seborrheic Signs & Symptoms: Acute infection - red/white
dermatitis, alopecia areata, trichotillomania. scales, vesicles, bullae, often with maceration. May
present as flare up of chronic tinea pedis.
Definition: Pleuritic, scaly, round/oval plaque Frequently become secondarily infected by
with erythematous margin and central clearing. bacteria. Chronic infection - non-pruritic, pink,
Single or multiple lesions found on the peripheral scaling keratosis on soles, and sides of foot, often
in a “moccasin” distribution. Sites: Often
 interdigital, especially in the 4th webspace. Candidiasis

Examination: Microscopic examination of a

KOH preparation of scales from roof of a vesicle Candidiasis - An infection caused by Candida species.
or powdery scaling area. Culture of scales on
sabourad’s agar.
Types of Candidiasis
Management: Lamisil cream, Clotrimazole 1. Cutaneous candidiasis - Overgrowth of Normal Commensal
cream, Fluconazole tablet.
of the mouth, vagina, or lower GIT. Only infects the outer
Differential Diagnosis: dyshidrotic dermatitis. layers of the epithelium of mucous membrane or skin.
Allergic contact dermatitis (______/heel). Atopic Caused by Candida albicans. Affects outer layers of involved
dermatitis. Erythrasma, intertrigo (interdigital). organs. Presentation: Red, macerated area, Glistening
Psoriasis (soles or ___________).
Surface, Scaling along the advancing border, The initial
Clinical Features: acute: blisters at edge of red lesion is a papule that then becomes a pustule. The
areas on hands. Chronic: single dry scaly patch. important clinical feature is the presence of ‘satellite’
Primary fungal infection of the hand is actually
pustules beyond the border of the main infection.
quite rare; usually associated with tinea pedis with
one hand and two feet affected = “1 hand 2 feet” Treatment: Topical Therapy.
Tinea
syndrome. 2. Oral candidiasis - Caused by C. albicans. Infects oral organs
Manuum
(Affects the (gums, tongue, buccal mucosa). Presentation: White Patches
Etiology: Same as in tinea pedis.
hands) easily scraped off to leave a red, raw base. Chronic red, raw
Differential Diagnosis: contact dermatitis, gums, tongue and buccal mucosa. Treatment: Topical or
atopic dermatitis, psoriasis (all three commonly Systemic Therapy
mistaken for fungal infections). Granuloma
3. Pityriasis versicolor - Caused by normal commensals
annulare (annular in shape).
Malassezia furfur (a type of yeast). Common Superficial
Definition: Crumbling, distally dystrophic nail; Fungal-Induced rash. Presentation: flaky, discolored patches
yellowish, opaque with subungual hyperkeratotic on chest & back. Small, well defined, slightly scaly patches.
debris. Toenail infections usually precede
fingernail infection.
Either Hyperpigmented or Hypopigmented.

Etiology: T. rubrum (more than 90% of all toenail

Types of Ectoparasitic
infections).
Organism: Sarcoptes scabiei (scabies mite)
Tinea Examination: KOH preparation of scales from Transmitted from animal to human.
Unguium subungual scraping shows hyphae on microscopic
(Onychomycosis) exam. Subungual scraping may be cultured on Epidemiology: Human infestations originating
Sabourad’s agar. from pigs, horses and dogs are mild and
Aka toenail
self-limiting. Scabies infestations from other
infection Management: terbinafine (Lamisil) 250 mg od (6 humans never cure without intervention.
weeks for _________, 12 weeks for toenails) or
pulse itraconazole (Sporanox) at 200mg bid x 7d, Ecology: Mites live in stratum corneum (Don’t
then 3 weeks off (2 pulses for fingernails, 3 pulses get any deeper). Eat stratum corneal
for __________). Scabies
Keratinocytes. Make “tunnels” by eating. Mating
occurs on the host’s skin. Fertilized Female Mites
Differential Diagnosis: psoriasis (pitting, may Burrow into the Stratum Corneum (1mm deep).
have psoriasis elsewhere). ________. Lichen Salivary Secretions contain Proteolytic enzymes
planus that are strong enough to Digest Keratinocytes.

Transmission: High prevalence in children

(50%) and adults (25%) in tropical remote
communities. Spread by close physical contact.
 Presentation: Itch (Exacerbated at night and
after hot showers). Chloritic, Excoriated Rash on Diagnosis:
Trunk, associated with Scaly Burrows on the Diagnosis = Conditioner + Comb Technique:
fingers and wrists. Often vesicles and pustules on o Very Practical for parents
the palms and soles and sometimes on the scalp. o Cost effective
o High Sensitivity
Clinical Diagnosis: Chronic itch with o Conditioner ‘Stuns’ the lice by suffocating
symmetrical Rash and Burrows. Simple Skin them, which prevents them from running away.
Scraping - Look for Scabies Mites:
➢ Intact larvae, nymphs or adults Management/Treatment:
➢ Unhatched or hatched eggs ➢ Conditioner & Nit Comb
➢ Molted skins of mites ➢ Physical Removal
➢ Fragments of molted skins ➢ Cut Hair
➢ Mite feces ➢ Topical Insecticidal Cream
➢ Good idea to wash pillows and hats though –
Treatment: Topical Permethrin or Oral Hat washes are not preferable
ivermectin. ➢ Treat all body hair for Pubic lice

Environmental Measures: Since mite can Reasons for Treatment Failure:

contaminate bedding, chairs, floors, and even ➢ ___________ application of the
walls, proper sanitation is essential (Usually only product
a problem with crusted scabies). Wash, exposure ➢ Lice are resistant to _________
to sun, vacuum, surface insecticide. ➢ Failure to retreat to kill nymphs
emerged from eggs
Community Prevention: Treat all close ➢ ____________.
contacts, especially in Indigenous Communities.
Simultaneous effective Treatment.
Viral
3 Types: Pediculus humanus capitis (head lice), 1. Viral warts - caused by Human papilloma virus.
P. humanus corporis (body lice), Phthirus pubis
2. Herpes simplex - caused by Herpes simplex virus.
(pubic lice).
3. Chicken pox - caused by Herpes varicella zoster virus. May
Head Lice: Pediculus Humanus Capitis lead to shingles (affects nerves)
Epidemiology: Common in Primary School
Children in the Tropics. Higher prevalence in
Aboriginal Children. Types of Viral
Diagnosis: Conditioner + Fine-Tooth Comb.
Wipe combings on white tissue to see the What is it? Benign Tumors of the skin.
presence of lice. Common in children. Infectious (Spread by
direct contact)
Body Lice: Pediculus Humanus Corporis
Live on clothes, and come to the body to feed. Organism: Typically from HPV (human
Pediculosis papilloma viruses). HPV 6 & 11 = Genital &
(Head lice) Cutaneous Warts. HPV 16 & 18 = Cervical &
Pubic Lice: Phthirus pubis
Largely sexually transmitted. Blood Feeder. Can Penile Cancer.
infect any body Hair (Pubic, Trunk, Leg, Axilla,
Beard) but rarely the head. Appearance:
Viral warts
Verrucous surface - keratotic exophytic surface.
Lifecycle: Can often see a tiny black dot in the middle
➢ Eggs laid in hair (knits) due to thrombosed capillary blood vessel.
➢ Larvae grow into adults
➢ capable of blood sucking (adults in hair) Presentation:
- Common on back of fingers, toes and knees
Transmission: Head to head contact. - Common Warts (Skin, ______, Palmar)
- Genital Warts (Cervix, Vulva, Penis)
Presentation: Scalp and neck can be Itchy. - Note: Cervical Papillomas - Can cause
Knits are noticeable on the hairs. cervical cancer.
 - Laryngeal papilloma caused by HPV. What is it? Highly transmissible disease.
Typically childhood disease (before ___ yrs).
No Reliable Treatment: One infection thought to confer __________
- 50% of childhood warts disappear within immunity.
6mths; 90% are gone in 2 years.
- Many don’t bother with treatment. Organism: Herpes varicella zoster virus
- Surgical Excision/ Chemical Treatment/ (HHV3) (AKA: Chicken Pox Virus, Varicella,
Cryotherapy/ Electrosurgery (Cauterize) Zoster)

Clinical Significance: Transmission:

- Gardasil and Cervarix - prevent Cervical - Highly Infectious
cancer. - From person to person
- Central blood vessels > Bleed profusely when - ______ Droplets
the surface is ________. - Direct contact with ___ from open sore.

Pathophysiology:
What is it? Common Mucosal Viral Infection - Incubation Period = 2 weeks
that presents with localized blistering. Can - (__________) Initial Mucosal Infection >
reside in a latent state. Viraemia > Epidermal Lesions
- May lead to Latent infection of Dorsal
2 Types: Ganglion Cells of Sensory Nerves.
HSV Type I - (_______) Reactivation of latent Varicella
Typically facial/oral infections (Cold ______ Virus in Peripheral Nerves
sores/fever blisters). Occur mainly in infants &
young kids. Signs & Symptoms:
- Itchy rash or red papules
HSV Type II - Begins on the trunk and will progress on the
Mainly Genital. Occur after puberty (often Chicken pox Face and Extremities
transmitted sexually). (Herpes varicella - May cover entire body
zoster virus) - High fever/ headache/ cold-like symptoms/
Stages of Infection: vomiting/ diarrhea.
1. Prodromal Stage Vesicle or "blister" stage
2. Ulcerate stage Diagnosis:
3. Crust stage - Clinical Diagnosis
Herpes simplex - People will not order expensive tests
(Cold Sores/Genital Presentation: - Test for Elevated VZV-Specific Antibodies
Lesions) The virus grows down the nerves and out into (IgM - Primary Infection; IgG - Second
the skin where it will be Localized Blistering. Infection)
- Neuralgia - pain in the nerves.
- Lymphadenopathy - swollen lymph nodes. Treatment:
- High Fever - Symptomatic
- Recurrences can be triggered by: minor - Usually resolve on its own.
trauma/ Other infections/ UV radiation/
Hormonal factors/ stress is common/ Complications:
Operations/ procedures on face. - Varicella during pregnancy can cause
Congenital Varicella Syndrome: Spontaneous
Treatment: Abortion (3-8% in 1st trimester) or IUGR
- Mild cases require no treatment - Skin: Cutaneous Defects, Hypopigmentation
- Sun protection to prevent - Neuro: Intrauterine Encephalitis, Brain
- Oral Antiviral Drugs (Stop the virus Damage, seizure, Developmental Delay
multiplying) - Eye: Chorioretinitis, Cataracts, Anisocoria
- Musculoskeletal System (MSK): Limb
Complications: Hypoplasia
- Encephalopathy - Systemic: cerebral cortical atrophy
- Trigeminal Neuralgia (Neurogenic Pain) - - Renal: Hydronephrosis, Hydroureter
affects the facial nerve. - GI: GORD
- CVS: Congenital Heart Defects
 - Perinatal Varicella Infection: - Epidemic in _______ __________
o ______ mortality rate of 30% - Transmitted through skin contact
- Outbreaks associated with poor hygiene/
crowded living conditions
Bacterial
Treatment:
1. Impetigo - caused by Staphylococcus aureus. May lead to - Cover Affected Areas
Glomerulonephritis. - Abstain or refrain from going to School
2. Folliculitis - caused by S. aureus. Infection of hair follicle. - Systemic or Topical Antibiotics
May produce boils/furuncles.
What is it?
3. Abscesses - caused by S. aureus. Infection of hair follicle Folliculitis:
leading to boils then abscess. - Acute pustular infection of a hair follicle
4. Cellulitis - associated with S. aureus. Underlying causes of - Commonly after Waving/Shaving

Tinea and Herpes simplex virus. Boils (Furuncles):

5. Necrotizing Fascilitis - Group A Streptococcus, S. aureus, - A deeper form of folliculitis.
Vibrio, Clostridium, Bacteroides.
Organism:
6. Gas Gangrene - caused by Clostridium perfringens. Folliculitis &
- Staphylococcus Aureus
7. Leprosy - caused by Mycobacterium leprae. Furunculosis
(Boils)
Presentation:
- Folliculitis: An Erythematous Pustule
Types of Bacterial Infection
centered on a Hair Follicle.
- Boils (Furuncles): Tender, red nodule which
What is it? Superficial bacterial Skin
enlarges & may later discharge mass
Infection. Most Common in school kids. Very
contagious (Spread by Close Contact & Poor
Treatment:
Hygiene). Usually resolves slowly.
- Treated aggressively with antibiotics and
drainage.
Organism:
- Mostly _______________ _______
Usually Staphylococcus Aureus
- Sometimes Streptococcus Pyogenes
- Begin as superficial infections of hair follicles
- Can lead to Glomerulonephritis or rheumatic
(folliculitis)
Fever if it is Strep
➢ Organisms travel down Hair Follicles
a. Staph. Aureus (bullous) Abscesses
following Disruption (Eg. After Shaving)
b. ____________ (Non-bullous)
➢ Development of boils (furuncles)
- Number of boils clustered together results in
Presentations:
Carbuncle (aka Abscess)
- Occur most commonly on face
Impetigo - Fragile vesicles rupture & crust What is it?
(School Sores) - Can be confused with HSV - Bacterial infection of the Dermis
and Sub-Cutaneous tissue
1. Nonbullous/Crusted Impetigo:
- (most common) Organism:
- Yellow crusts and erosions - Adults: 90% due to Staph. Aureus/GAS
- Itchy/Irritating (but not painful). - Most common in Children: H. influenzae b
2. Bullous impetigo: - Associated with cat/dog bite: Pasteurella
- Always due to S. Aureus Cellulitis multocida
- Mildly irritating blisters that erode rapidly
leaving a blood crust. Presentation:
3. Ulcerative ________: - Painful, raised and Edematous Erythema.
- Always due to S. pyogenes. (Most commonly on Lower Limb)
- ____ _________ in Aboriginal - Possible blistering
Communities - Lymphadenopathy & Malaise & Fever.

Very Infectious Distribution:

 - Children - Periorbital Area - Tuberculoid and lepromatous forms
- Adults - Lower leg - Mainly affect skin and nerves
Leprosy
- Mycobacterium tuberculosis infects the lungs
There’s usually an underlying cause: in the form of a pulmonary tuberculosis
- Lymphoedema
- Tinea, Herpes simplex infection,
- Chronic sinus infection Skin Manifestation of Metabolic Diseases
- Chronic dermatitis
- Poor lower leg circulation
- Untreated wounds Metabolic Disease
Jaundice - a condition in which the skin, sclera (whites of the
Treatment: Antibiotics
eyes) and mucous membranes turn yellow. Affected organ is the
What is it? Medical Emergency - Often needs liver.
Radical Debridement of Necrotic Tissue

Organisms: Inflammatory Skin Disorders

- Group A Strep (GAS)
- Staph. Aureus
- (Both cause severe, systemic toxicity) Inflammatory Disease
- Others (Vibrio, Clostridium, Bacteroides) Psoriasis - multifactorial caused by genetic and immune
Necrotizing responses.
Pathogenesis:
Fasciitis
- The Necrosis is Toxin-Mediated. YOU
CAN’T JUST TREAT WITH A. Psoriasis
ANTIBIOTICS because it is the toxins that are Etiology: Multifactorial (Genetic & Immune)
causing the Necrotizing Fasciitis.
- Not due to a Flesh Eating Bacteria
Pathogenesis: Sensitized T cells infiltrate the skin and secrete
Types: cytokines and growth factors. Therefore, continuous stimulation
Type I - Polymicrobial Infection of basal cells. Increased cell turnover. Inflammation, Vascular
Type II - Monomicrobial Infection
Proliferation Angiogenesis
Organism:
- Clostridium perfringens Morphology Gross:
- Black covered with Silvery Scales (Due to Hyperkeratosis &
Pathogenesis:
- Generally, occurs at site of trauma or recent Parakeratosis)
surgical wound - Always Bilateral
- Usually only occurs with Poor Blood Supply - Well-demarcated
(E.g. diabetic foot)
- Systemic Based
- Anaerobic conditions
- Toxins are produced that cause the Tissue
death and associated Symptoms Clinical Significance (List 3x Clinical Features):
Gas Gangrene Can cause Multi-System Disorder:
Presentation:
- Arthritis
- Inflammation at the Site of Infection
- Brownish-red and extremely painful tissue - Myopathy (Muscle pain)
swelling - Enteropathy (Stomach pain)
- Gas may be felt in the tissue when the swollen - Immunodeficiency
area is pressed
- Margins of the infected area expand rapidly
- Nail pitting
(Within a few minutes)
Auspitz Sign: Micro bleeding when crusts are removed.
Prognosis: The involved tissue is completely
destroyed (Toxin-Mediated Destruction)
B. Urticaria (Hives)
Etiology: Type I hypersensitivity reaction – Allergy (Food/ 3. Neurovascular compromise – can pull, tear,
drug/ plant/ etc) compress, rupture surrounding nerves/vessels.

Pathogenesis: Dislocations:
- Antigen is Re-Exposed to a sensitized Mast-Cell/Basophila ➢ The displacement of Joint Surfaces such that Normal
IgEBound Mast Cell Degranulates: Releasing Inflammatory Articulation no longer occurs.
mediators (Histamine) of Type-1-Hypersensitivity Reactions. ➢ When forces on joint are greater than stabilizing forces
- Perivascular inflammatory infiltrate: lymphocytes, neutrophils of Bone, such as Ligament & Muscle.
or eosinophils. ➢ Emergency Because:
1. The longer the delay before reduction, the
Clinical Significance: more difficult it becomes, as the muscle around
- Usually on the trunk and extremities. the joint contracts.
- Individual lesions are transient, usually resolved in 24 hours, 2. Delay can also result in significant joint &
but the entire episode may last for days. ligament damage. Therefore, the Impairment of
- All ages, more in ___________. them could affect their function.
3. Neurovascular compromise – can pull, tear,
compress, rupture surrounding nerves/vessels.
MODULE 3
MUSCULOSKELETAL SYSTEM Dismemberment:
➢ Loss of limb or extreme Tissue-loss resulting in
permanent functional impairment of that limb.
Bone Injuries
Factors Affecting the Degree of Urgency:
Key words + Definitions: ➢ Abnormal ABC
1. Fracture: A breaking in a Bone ➢ Bleeding
2. Compound fracture: A compound Fracture where ➢ Major Vascular Compromise
there is broken skin. ➢ Open and Closed injury
3. Dislocation (or “Luxation”): The Displacement of Joint ➢ Neurological Compromise
Surfaces with Abnormal Articulation. ➢ Pain
4. Reduction: Restoration of a fracture or dislocation to ➢ Potential loss of Function if Injury is Untreated.
the correct alignment.
5. Splint: Medical device for immobilizing limbs/spine to The Basic Priorities of MSK Care:
prevent further injury ➢ Primary Survey – “ABC” (Life before Limb)
6. Neurovascular compromise: Vessels (Nerves Damage) ➢ Physician will Identify Injury
due to injury cause functional impairments. ➢ Analgesia
7. Compartment syndrome: Bleeding and Swelling into a ➢ Splint
muscle compartment causes Compress vessels/nerves. ➢ Prevent Infection
➢ Reduction (Restoring Alignment)
What is a Musculoskeletal Emergency?
Fractures: Benefits of Reduction & Splinting:
➢ Breaks in Bone. ➢ Splinting:
➢ Emergency Because: 1. Reduces pain
1. If it’s an ‘Open Fracture’ – Risk of Infection 2. Reduce Bleeding
2. Some fractures won’t heal without treatment 3. Promote Healing
 4. Reduce risk of Further Compromise (Bone, ➢ Risk of Compartment Syndrome - Bleeding and
Neuro, Vascular, Functional) swelling into a muscle compartments causes compress
➢ Reduction: blood vessels and nerves; May lead to “______
1. Reduce pain __________”
2. Restore Function
3. Reduce risk of Further Compromise (Neuro, Note: Cushing Syndrome:
Vascular, Functional) ➢ Muscle _________/Necrosis due to Compartment
Syndrome > pain, _______, Inflammation, DIC,
FRACTURES & FRACTURE HEALING: Rhabdomyolysis > ___ __________.

Etiology: Treatment:
➢ Traumatic Injury ➢ Reduction (Either Open or Closed Reduction)
➢ Pathological Fracture – Osteolytic Bone Metastasis, or ➢ ___________ (Splint, Cast, Rod, Pins, Brace, etc.)
poor bone integrity ➢ Analgesia - Rest > Physio

Mechanisms of Fracture Healing: Morphology of Fractures (Refer to PPT)

1. 1-3 days - Hematoma & Inflammation (Blood Clot + 1. Transverse (Non-displaced and Displaced)
Fibrin Mesh) 2. Spiral
2. 1-3 weeks - Soft Callus (Deposition of Osteoid + 3. Oblique
Granulation Tissue + Fibroblasts) 4. Linear
3. 1-2 months - Hard Callus (Mineralization of Osteoid) 5. Incomplete
(Note: Visible On Xray) 6. Greenstick
4. More than 2 months - Remodeling of Woven Bone with 7. Impacted
Lamellar Bone 8. Comminuted
9. Compound
Bone Remodeling:
➢ Bone remodels in response to:
1. Calcium requirements in body
Arthritis
2. Mechanical stress
3. Physical Activity (Stress)
A. CRYSTAL ARTHROPATHIES (GOUT ARTHRITIS)
4. Nutrition
5. Vitamin D
Etiology:
6. Age
➢ Anything that causes increased Urea Production or
7. Hormones (Eg. PTH, PHRP)
decreased Urea Excretion (Eg. High Protein Diet and
Alcohol Diet) (Note: Also Secondary Causes Eg. Renal
Note Resorption – destruction of old bone matter by osteoclast Failure, Thiazides, ___________, Hemolysis, Obesity)
Apposition – deposition of new bone matter by osteoblast

Pathogenesis:
Clinical Features: ➢ Derangement in Purine Metabolism probably increase
Emergency Because: production or decrease excretion. Will build up in the
➢ Risk of Infection - If a Compound Fracture/Open blood, a condition called Hyperglycemia, and then it
Fracture. will favor the Monosodium Urate Crystal Deposition in
➢ Some require treatment to heal. Joint tissue that forms “Tophi” that causes pain.
➢ Risk of Neurovascular Compromise – can pull, tear, Unchanged lifestyle will lead to Forms “Masses”, or
compress, rupture surrounding nerves/vessels. Chronic Inflammation, or Destruction of the tissue
Morphology: Pathogenesis:
Gout: Red, Hot, Swollen Joints (Typically 1st MTP Joint & ➢ Mechanical, then Inflammatory: Cartilage Hydration
Hands) + lumps Tophi Decreases with Age. Becomes less Resistant to Friction.
Cartilage Erosion can lead to exposure of Bone.
Clinical Features: Grinding of bones can result to Mechanical Damage &
➢ Typically Males >______ Inflammation

Recurrent Severely Painf ul Episodes of Acute Arthritis: Morphology:

➢ Typically Lower Extremities First (1st MTP Joint) 1. Eburnation of Bone (Shiny, thickened, hardened bone)
➢ Can also affect Hands 2. Cartilage Degeneration
➢ May mimic Cellulitis (But will have decreased ROM; 3. Peripheral Osteophytes causing “Joint Lipping” (New
Cellulitis has normal ROM bone formation around the joint edges)
➢ Attacks last feverish
Clinical Features:
Gouty Tophi: ➢ Typically at 40 years old. Common in males.
➢ Uncontrolled uric deposition in Joints, Cartilage,
Bursae, & soft tissue) Symptoms:
➢ Common Sites: 1st MTP joint, Tendon Insertions, ➢ Large, Weight-Bearing Joints (spine, knees)
pressure Points ➢ Nodular/Bulky, Painful Joints + JointLine Tenderness
➢ Painless but decreased ROM ➢ Pain worsens with Activity & Cold Weather
➢ Pain gets better with Rest
Effects on Kidney: ➢ Joint Instability & Crepitus (due to irregular joint
➢ _____ ______ Stones surface) > decreased ROM with Muscle Wasting
➢ ______ __________ ➢ Bony ___________ (Osteophytes) > ______ –
(“Bouchard’s nodes” in PIP Joints and “Hebeden
Diagnosis: Nodes” in DIP joints, or “Bunions” in the Toes)
➢ Clinical Diagnosis
➢ _____ ______ & Microscopy (Needle-Shaped Diagnosis:
MonosodiumUrate Crystals) ➢ Normal blood chemistry
➢ Imaging – (Narrowing Joint Space, “Joint Lipping”,
Treatment: Ankylosis & Varus Deformity)
➢ Colchicine (For Acute Relief)
➢ Allopurinol (Preventative Only; Can Worsen an Acute Treatment:
Attack) ➢ SIMPLE Analgesia (Panadol Osteo)
➢ Non-steroidal anti-inflammatory drugs (NSAIDs) ➢ _______ – (Joint Replacement / Spinal Fusion)
➢ Corticosteroids - damages the stomach ➢ Maintain Physical Activity
➢ Lifestyle Change (Avoid High-Purine Foods such as
Meats, Fish, Beans, Peas, Beer)
C. RHEUMATOID ARTHRITIS (SEROPOSITIVE
B. OSTEOARTHRITIS (DEGENERATIVE ARTHRITIS):
ARTHROPATHY):
Etiology:
Etiology: ➢ Genetic Autoimmune
➢ Degenerative Wear & Tear
Pathogenesis: ➢ Endocervical/Urethral Swab or Urine PCR for
➢ Genetic (HLA-DR4 & -DR1 Genes) will produce Gonococcal specie
Rheumatoid Factor Production (AntiIgG Ab) > fall
under autoimmune disease > Macrophage - Mediated Treatment:
Local Joint Inflammation & Destruction ➢ If Gonococcal specie – Azithromycin, Ceftriaxone or
➢ Erosion of the Articular Cartilage down to the bone Doxycycline
➢ If Staph. Aureus – Ampicillin, Erythromycin or
Morphology: Vancomycin
➢ Erosion of the Articular Cartilage down to the bone. ➢ Analgesia - reduce pain and manage fever
➢ Pannus - Inflamed thickened hyperplastic synovium ➢ Arthroscopy – Aspiration & Washout (Surgical
with papillary projections (Note: Normal synovium is Debridement/Joint Replacement) (Note: DO NOT
very thin and smooth and shiny) USE Intra-Articular Steroids)
➢ Fibrous Ankylosis (can have a bone fusion)
Complications:
D. SEPTIC ARTHRITIS ➢ Vascular Necrosis of Femoral Head (if increase
Intra-Articular Pressure due to Pus)
Etiology: ➢ Cartilage & Epitaxial Destruction
➢ Joint infection ➢ Osteomyelitis (Bone Infection)
➢ Common causes – N. gonorrhoea, S. aureus, other less
common.

Osteoporosis (Porous Bones)

Pathogenesis:
➢ Routes of spread – Hematogenous (Commonest),
WHO definition: Osteoporosis - A Bone Mineral Density of
Direct from Adjacent Tissue, Iatrogenic.
х-2.5 StDs below the mean Bone Mineral Density (BMD)

Clinical Features (A Medical Emergency):

➢ (If Gonococcal infection is untreated you can have Note Osƚeopenia - A BMD of between -1.0 & -2.5 StDs below
Preceding Bacteremia with Maculopapulovesicular Skin the mean BMD
Lesions & Migrating polyarthritis. Settling into
monoarthritis – Typically Knee) Etiology (Primary & Secondary):
➢ Typically Severe Mono-Arthritis (Joint often held in
Primary:
slight flexion to decrease Pain)
A. Type 1: Post Menopausal
1. Swelling
B. Osteoporosis (Typically Vertebrae & neck of femur
2. Erythema
fracture (NOF); females only)
3. Hot
1. Decreased Estrogen will now favor the Increased
4. Decreased ROM due to Pain
Osteoclast Activity
5. Fever and Malaise
C. Type 2: Senile Osteoporosis
6. Signs of Acute Sepsis – Fever, Chills,
1. (Affects all bones, males & females) Decreased
dehydration, Lethargy
replicability or synthetic ability of the Osteoblasts >
decreased osteoblastic activity
Diagnosis:
➢ Joint Aspirate + MCS. (Crystals, Gram Stain)
Secondary:
➢ CBC (increase WBC)
➢ Endocrine disorders - Cushing syndrome increase PTH
➢ Increase ESR, CRP
hyper or hypothyroidism; DM Acromegaly, Addison’s
disease
 ➢ Pregnancy & Lactation Investigation for Underlying causes:
➢ Myeloma ➢ ESR (Exclude _______)
➢ Malnutrition/malabsorption ➢ _________ (Exclude secondary Osteoporosis)
➢ Drugs (Corticosteroids, Chemo, etc) ➢ PTH Level (Exclude Hyperparathyroidism )
➢ Alcohol ➢ _______ (Exclude Hyperthyroidism)
➢ Immobility
Treatment & Prevention:
Pathogenesis:
➢ Increase Osteoclast while decrease Osteoblast Function Pharmacological:
Imbalance ➢ Bisphosphonates (Eg. Alendronate [Fosamax],
➢ Increase Bone Resorption will produce Porous Bones Risedronate) – (Monthly Dose)
➢ Decrease Bone Mass (Bone Mineral Density) ➢ Strontium > (Stimulates CaDeposition & Inhibits Bone
_________)
Morphology: ➢ +/- Hormonal (SERMS (Eg. Raloxifene) or HRT (If
➢ Trabecula are Thinner & Fewer than Normal ____________/Post-Menopausal)
➢ OTC Supplements ʹ (Calcium & Vit D)
Clinical Features (Symptoms & Complications): ➢ Occupational (Reduce Falls Risk, ↑ Weight-Bearing
Exercise)
Symptoms:
➢ Often __________ until Fracture

Complications:
➢ Fragility fractures (Fractures from _______________ Osteomyelitis
E.g. From standing height)
1. Note: Rel-Risk DOUBLES with every 1.0 St. Etiology:
Deviation Below the Mean ➢ Bone infection = Bacterial, Viral or Fungal.
2. (Less than 30% _______ in Elderly; 40% ➢ S. aureus (Common)
Morbidity) ➢ Pseudomonas
➢ Vertebral Compression Fracture can > __________ ➢ Haemophilus influenzae
Compression, Cauda Equina Syndrome
Pathogenesis:
Investigations: ➢ Bacterial – S. aureus (Commonest), Pseudomonas
➢ (_________) (Iatrogenic), H. influenzae (Children)
➢ _____ (Dual-energy X-ray Absorptiometry)
Bone-Mineral Density Scan: Morphology:
1. ESSENTIAL: Lumbar Spine + Hip ➢ Macro: Local swelling & Redness
2. OPTIONAL: ________ ➢ Micro: Medullary Inflammation & Edema

Interpretation of T-Scores & Z-Scores: Clinical Features:

a. T-Score = Pts BMD Vs ͘Young-Normal BMD ➢ History of Infection at Another Site + Direct trauma to
- Used only for Post-Menopausal Women the Area
b. Z-Score = Pts BMD Vs ͘Age-Matched Mean BMD ➢ Local Tenderness and swelling Heat at Metaphysis and
- Used only for people less than 50yrs decrease ROM
(Premenopausal Women, Men, & ➢ (Signs of Acute Sepsis – Fever, Chills, dehydration,
Children) Lethargy)
Diagnosis:
➢ Diagnostic lab – increase ESR, WBC, CRP, Positive Morphology (Size Classification & Staining/Color):
Cultures
➢ Culture – Normal if Acute; radiolucency after 2-4 weeks Size Classifications:
➢ Onion-Skin Appearance if Chronic ➢ Microcytic: Small - Reduced MCV
➢ CT scan & MRI – Medullary Oedema, Cortical ➢ Normocytic: Normal MCV
Destruction & Articular Damage. ➢ Macrocytic: Large – Increased MCV

Treatment: Staining/Color:
➢ Long Course IV Antibiotics (4-6 weeks) - Rifampicin, ➢ Normal RBCs stain well (Normochromic)
Erythromycin, Tetracycline, Vancomycin ➢ Anemic cells stain lightly (Hypochromic)
➢ Irrigate, Debridement, Amputation
➢ Replacement of Affected area A. Anemia of Malnutrition
IRON DEFICIENCY ANEMIA (Malnutrition Anemia)

MODULE 4 Note: Most common type of Anemia

HEMATOPOIESIS SYSTEM
Etiology:
➢ Chronic blood loss > MOST common cause of Iron
Hematology Deficiency (Eg. Parasitic Worm Infestation, malignancy,
Menorrhagia, GI Ulcers)
DISORDERS OF THE RED BLOOD CELL – ANEMIA ➢ Increased Need (over demand): Pregnancy, Rapid
Growth (children)
General: ➢ Poor diet (poor absorption): Malnutrition (decrease
➢ Decrease hemoglobin concentration in blood Greens & Meat) __________, intestinal surgery, gastric
➢ May be Low Hemoglobin (Hb) or low Hematocrit atrophy.
(Packed Cell Volume).
➢ Anemia = generally ____ than 100g/L Pathogenesis:
➢ Iron is a fundamental constituent of Hemoglobin
Normal Hb Range: ➢ Therefore, iron deficiency results in decreased
➢ Normal Hb Concentration depends on age, sex, race, Hemoglobin Synthesis (and decreased RBC
gender, and the general health of the person production) of Anemia.
➢ 13 -16g/dl (male) (130-160g/L)
➢ 11.5 -16g/dl (Female) (115-160g/L) Morphology (Blood Film):
➢ Microcytic (increase Divisions of Progenitors) (decrease
Etiology: MCV)
➢ Decrease Production (Fe, Folate, B12 Deficiency ➢ Hypochromic (increase central power of RBCs)
Increase, pernicious anemia, Chronic Disease, Aplastic (decrease Hb Content)
anemia) ➢ Anisocytosis (variations in size)
➢ Blood Loss (Hemorrhage, Hookworm, Menorrhagia) ➢ Poikilocytosis (variations in shape)
➢ Destruction or Abnormality of RBCs hemolytic ➢ Some “Pencil cells”. (RBCs with one Sharp Edge)
anemia, Microangiopathy, G6PD, Sickle, Thalassemia,
Spherocytosis)
➢ Spurious (Increased Plasma Volume – Eg. Pregnancy, Clinical Features:
Fluid Overload)
Symptoms & Signs (General Anemia Symptoms): ➢ Gastric – Deficiency of stomach (Eg. Pernicious anemia
1. Fatigue, Headaches & faintness – autoimmune response to parietal cells of stomach ↓IF
2. Exertional dyspnea ↓Vitamin B12 Absorption)
3. Exertional angina ➢ Intestinal– eg. Resected Ileum/Crohn’s Disease
4. Intermittent Claudication
5. Include Exacerbations of CVS/Respiratory problems in Folate Deficiency
Elderly (Eg. Claudication & Angina) Possible causes:
➢ Malnutrition – Lack of Vitamin B12 Dietary Intake
Symptoms & Signs (General Anemia Signs): ➢ Malabsorption – eg. Coeliac Disease, Intestinal
1. Pallor (Mucosal, Facial, Palmar Crease) infection
2. Fast heart rate ➢ Exacerbation – eg. Pregnancy, Lactation, Chronic
3. Systolic Flow Murmur (Hyperdynamic Circulation) Inflammation, Cancer
4. Cardiac failure (Eg. Pedal Oedema) ➢ Excess Urinary Loss – eg. Acute Liver Disease,
Congestive Heart Disease
Signs Specific to Iron Deficiency Anemia: ➢ Other General Causes: Alcoholism (or Liver Disease)
➢ All due to cytochrome oxidase functional deficiency – Cytotoxic, Chemo Drugs, Old Age
Which requires iron to work
➢ Atrophic glossitis (Atrophy of Papillae of tongue) Pathogenesis:
➢ Angular Cheilitis/Stomatitis ➢ Vitamin B12 (Folate) are Necessary for Nuclear DNA
➢ Koilonychia (Spoon Nails) Synthesis > defective Nuclear Maturation of
➢ Brittle nails, Brittle Hair erythroblasts > reduced RBC Production

Diagnosis: Morphology (Marrow Biopsy):

➢ Blood Count & Film (Microcytic, Hypochromic, ➢ Megaloblasts in Bone Marrow (large, erythroblast with
Poikilocytosis, Anisocytosis, Pencils) Immature Nuclei)
➢ Blood Film:
Iron Studies: (decrease Ferritin; decrease iron; increase TIBC) 1. Normochromic
2. Oval Macrocytes (Large, Oval RBCs)
Treatment: Iron Supplementation 3. Hyper segmented Neutrophils (Some with
More than 6 Lobes in Nucleus)
B. Anemia of Malnutrition 4. Pancytopenia (Reduction in Number or ALL
MEGALOBLASTIC ANEMIA/VITAMIN B12 Cells – RBCs, WBCs, Platelets)
DEFICIENCY ANEMIA/PERNICIOUS ANEMIA ➢ Attempted increase of Erythropoiesis: increase
(Macrocytic Anemia) Reticulocytes - Some “Polychromatophils” (bigger,
Blueish RBCs)
Note: 2nd most common type of anemia ➢ Some Nucleated RBCs:
1. Anisocytosis (variations in size)
Etiology: 2. Poikilocytosis (variations in shape)
➢ Megaloblasts = large, Erythroblasts with Immature
Nuclei (seen in the Marrow) Clinical Features (General Anemia Symptoms & Signs):
Investigations:
Vitamin B12 Deficiency ➢ Blood Film (Oval Macrocytes, Hypersegmented
Possible causes: Normochromic, Pancytopenia)
➢ Malnutrition – Lack of Vitamin B12 Dietary Intake. ➢ CBC (↑MCV, Pancytopenia)
 ➢ Bone Marrow Biopsy (Shows Megaloblasts) – Rarely ➢ Hemosiderin (iron from Hb) in Urine
Required (Hemosiderinuria)
➢ Serum B12/Folate (decrease if B12/Folate Deficiency) ➢ LFTs – (↑Bilirubin, ↓ Haptoglobins)
➢ Blood Smear – (Broken RBCs, Reticulocytosis,
Treatment: Congenital RBC Disorders, Anemia)
➢ Oral B12 ➢ Host Test – (If Autoimmune Hemolytic Anemia)
➢ Oral Collate
➢ Corticosteroids and B12 Supplements (If Pernicious
Bleeding Disorders and Evaluation
Anemia)

Potential Causes Of Bleeding Disorders

C. Anemia of secondary to increased destruction
HEMOLYTIC ANEMIA
A. Vascular Disorders:
➢ Abnormalities in Blood Vessel Structure or Perivascular
What is it? Anemia due to Increased, Abnormal, Premature
Connective Tissue Leads to Easy bruising
RBC Destruction

B. Thrombocytopenia:
Etiology (Refer to PowerPoint):
➢ Due to decrease number of platelets
➢ Intravascular Hemolysis: Occurs within the Circulation
➢ Results from either:
➢ Extravascular Hemolysis: Occurs in the
1. Decrease Platelet Production
Reticuloendothelial System (Liver, Spleen, Bone
2. Increase Platelet Destruction
marrow)
3. Increase Platelet Consumption (in large
injuries, burn)
Pathogenesis:
➢ Increase of RBCs due to any cause results in Release of
C. Defective Platelet Function:
Free Hemoglobin in Plasma.
➢ There are enough platelets, but not working properly
➢ > Heme Molecule > Protoporphyrin & Iron
➢ May be Inherited (rare) or acquired (eg. From Aspirin
➢ > Protoporphyrin Excess Bilirubin ↑Bilirubin
and other blood thinners)
(Unconjugated) > Jaundice
➢ > Bilirubin Conjugated in Liver > Excreted in feces &
D. Von Willebrand's Deficiency (vWF):
urine
➢ Either Not enough vWF or Dysfunction of vWF
➢ vWF is necessary for platelet adhesion
Clinical Features (Symptoms):
➢ Therefore, Deficiency results in Poor platelet plug
➢ General Anemic Symptoms & Signs + Symptoms
formation
Specific to Hemolytic Anemia:
1. Jaundice (Mild & Fluctuating)
E. Coagulopathy = Defective Coagulation:
2. Splenomegaly
➢ Bleeding disorders due to deficiency in 1 or more
3. Pigment Stones (If Chronic HA)
Coagulation Factors
4. Venous Stasis and Ankle Ulcers (If sickle cell)
5. Microangiopathy, Infarction, Raynaud’s
Hereditary Coagulopathies:
syndrome
1. Hemophilia A: Factor VIII Deficiency:
➢ Most common - Sex Linked Recessive (Female Carriers;
Laboratory Evaluation:
Affected Males)
➢ Elevated Free-Hb in Blood (Hemolysis)
➢ Treatment - Recombinant clotting factors
➢ Dipstick in Urine (Hemoglobinuria) a RedBrown Urine
2. Hemophilia B: Factor IX Deficiency:
➢ AKA Christmas Disease (less common)
 ➢ Sex Linked Recessive (only affects males) 1. ADP
➢ Treatment - Recombinant clotting factors 2. Amino Acid
3. Other deficiencies (Factors V, VII, X, XI & XIII) Rare 3. Collagen
➢ Just know they exist. ➢ Measures the decrease in optical density that occurs in
solution as platelets aggregate.
Acquired Coagulopathies:
1. Vitamin K Deficiency (Factors II,VII, IX, X) 4. Tests of Coagulation-Factor Function:
➢ Dietary a) Prothrombin Time (PT):
➢ Malabsorption ➢ Time taken for plasma to clot after addition of
➢ Long-term warfarin tissue factor (Factor III)
2. Chronic Liver Disease: ➢ Measures Extrinsic Pathway + part of Common
➢ Eg. Bilirubin Obstruction: Pathway
➢ Hinders absorption of Fat-Soluble vitamins ➢ Measures factors VII, X, V, II (Prothrombin) and I
➢ Reduced synthesis of Factors II, VII, IX & X (fibrinogen)
➢ Eg. Severe Hepatocellular Damage: ➢ Normally last 12-15 sec
➢ Reduced synthesis of Factor V & Fibrinogen ➢ 15 sec and more = One/more of the above factors
3. DIC - Disseminated Intravascular Coagulation: are deficient
➢ AKA Consumptive Coagulopathy ➢ INR (International Normalized Ratio) is derived
➢ Formation of small clots inside blood vessels from PT (Universal measurement)
throughout the body b) Activated Partial Thromboplastin Time (aPTT):
➢ Leads to increase of Consumption of Platelets & ➢ Time taken for plasma to clot after addition of
Coagulation Factors. phospholipids
➢ Measures intrinsic pathway and the Common
Evaluation of Bleeding Disorders (Platelet Count) Pathway
➢ Literally the count of platelets/volume of blood ➢ Measures factors XII, XI, IX, VIII, X, V, II
➢ Normal range = 150-400x109 /L (Prothrombin) and I (fibrinogen)
➢ Excessively Low platelet count is called ➢ Normally 25-45seconds
Thrombocytopenia (bleeding disorder) ➢ 45 sec and more = One or more of the above factors
are deficient.
1. Platelet Function Tests c) Thrombin Time:
➢ Complete Blood Count (CBC) and Full Blood ➢ Measures how quickly Thrombin is being activated
Evaluation (FBE): ➢ Time taken for a clot to form, following the
1. Include platelet count & morphology. addition of animal Thrombin Measures:
2. Eg. Bleeding time 1. The conversion of fibrinogen to Fibrin
2. Any deficiency of fibrinogen
2. Bleeding Time 3. Any inhibition of thrombin
➢ Time taken for wound to clot
➢ If bleeding time is high may suggest platelet
Disorders of the White Blood Cells - Leukemia
dysfunction.
➢ If bleeding time is high, but normal platelet level may be
What Are Leukemias?
due to vWF Deficiency.
➢ Myeloproliferative & Lymphoproliferative Disorders
➢ A Type of Cancer Caused by Unregulated Proliferation
3. Platelet Aggregometry
of Abnormal ‘White Cells’ from a Mutant
➢ Measures platelet aggregation with common hemostatic
Hematopoietic Stem Cell
agonists
 ➢ Successive generations of cells from that Mutant HSC a CLASSIFICATION OF LEUKEMIA
“clonal expansion”
Type of Leukemia Distinguishing Feature
➢ Note: Disease occurs when sufficient excess in
Leukocytes. Acute Children
Lymphocytic Good prognosis
Leukemia Small Lymphoblasts, Small Cytoplasm,
Mutation – Genetic Alteration within a Single Myeloid or (ALL) No Granules/Nucleoli
Lymphoid Tissue Progenitor.
Adults
a) Chromosomal Translocation: Poor Prognosis (2 months if untreated)
Acute Myeloid
➢ Philadelphia Chromosome: #1 Cause of Gum Hypertrophy
Leukemia
“Auer rods bodies” in AML Myeloblast Cells
CHRONIC MYELOID LEUKAEMIA (AML)
Big Myeloblasts, Big Cytoplasm,
b) Chromosomal Deletion/Addition: Granules, Nucleoli
➢ Monosomy 7: #1 Cause of ACUTE MYELOID
Chronic Elderly
LEUKAEMIA Lymphocytic Commonest Leukemia Insidious Onset
c) Point Mutations Leukemia Good Survival (9yrs) but NO Cure
(CLL) “Smudge cells” on blood film
d) Gene Amplifications:
➢ Changes in Proto/Anti-Oncogenes: Adults
1. Anti-Oncogenes: Code for proteins involved in Chronic Myeloid Philadelphia Chromosomes in 80% Good
Leukemia Prognosis with Glivec (Imatinib)
cell proliferation/differentiation (CML) 3 Phases: Chronic, Accelerated, Blast
2. Abnormal Proto/Anti-Oncogenes Cancers (ie. Crisis. Marked telemetry

Leukemia)
3. Eg. A Hypermorphic Mutation in an
Note Myeloids are always in Adults; Lymphoids are extremes of
Oncogene results a hyperactive Proliferation Age
4. Eg. A Hypomorphic Mutation in a
Tumour-Suppressive Gene results a All are Good Prognosis EXCEPT AML

Hyperactive Proliferation CML = Philadelphia Chromosome & Tri-Phasic with

“Blast Crisis”
Result:
➢ Extreme numbers of White Cells in blood Altered
Hematocrit:
MODULE 5
1. Huge buffy coat (of WBCs generally abnormal)
CARDIOVASCULAR SYSTEM
2. Low Proportion of RBCs (Results in anemia)

Risk Factors: Cardiovascular

➢ Radiation Exposure – Nuclear, XRay, Microwave
➢ Previous chemotherapy – Particularly Alkylating Agents
ATHEROSCLEROSIS AND HYPERTENSION
➢ Genetic – eg. Down’s Syndrome
➢ Occupational Chemical Exposure – Benzene/Other
Arteriosclerosis - Hardening of any artery (broad term):
Aromatic Organic Solvents
➢ Viral Infection
A. Macroangiopathy = Atherosclerosis
- Hardening of Large & Medium Arteries
B. Microangiopathy = Arteriolosclerosis
- Hardening of Small Arteries
- Hyperplastic
- Hyaline
C. Arteritis - Inflammation of any artery
ATHEROSCLEROSIS 5. Lower Extremities - forming Peripheral Vascular Disease
➢ A progressive Chronic Inflammation of Arteries (PVD) (Eg. Claudication, Gangrene of legs, Arterial Leg
characterized by: Ulcers)
1. Inflammation, (macrophage engulf LDLs which
will form the Foam Cells) Investigation: Coronary Angiogram also called Cardiac
2. Fibrosis (Connective Tissue Matrix, Collagen, Catheterization
Elastin)
3. Lipid deposition (Cholesterol Esters & Cholesterol Management:
in Cells) 1. Risk Factor Modification:
- Statins
Note Athero – Fat - ACE-I/B-Blocker - (Hypertension)
Sclerosis – Hardening - Control DM
- Diet and Physical Exercise (For obese)
Etiology: - Decrease Smoking and Alcohol intake
➢ Begins with Endothelial Injury 2. Prevent Thrombosis: Aspirin/Clopidogrel
➢ BIG Inflammatory Component 3. Surgical Intervention: Balloon Angioplasty, Stent
➢ Risk Factors: Angioplasty, Bypass Surgery
a) Non Modifiable: Age (40-60), Male, Family
History, Indigenous Atherosclerosis: A General Overview
b) Modifiable: Cholesterol, Hypertension, Smoking,
Diabetes, Obesity, Metabolic Syndrome ➢ “Athero” = Gruel/Porridge (ie. The fat in the blood)
➢ “Sclerosis” = Hardening, usually a Progressive Chronic
Pathogenesis: Inflammatory Disease of the Blood Vessel Wall. Due to
1. Endothelial Injury & Inflammation Vessel Injury forming Fatty Plaque Formation wherein
- Hypertension, Smoking, Diabetes, Turbulence, Toxins, an Occlusion of Blood Vessel. Reduced blood flow to
Infection, Immune the local area. Therefore, Imbalance of Supply &
2. Endothelial Inflammation Demand of oxygen
- Macrophage & Smooth MuscleMigration ➢ Occurs Silently Over Many Decades
3. Accumulation of Lipoproteins ➢ Advanced Plaque & Plaque Thrombus:
- Fatty Streak Formation a) If Apical Cap becomes unstable will Rupture
4. Proliferation & Fibrosis Massive Thrombus (Clot)
- Conversion of Fatty Streak into a mature Atheroma b) Thrombus completely Occludes Vessel
5. Complicated plaque formation
- Thin Fibrous Cap become Rupture and then producing Characterized By Accumulation of:
Thrombus which will then lead to Acute Coronary ➢ Lipids (Cholesterol Esters & Cholesterol in Cells)
Syndrome (ACS) ➢ Fibrous Elements (Connective Tissue Matrix, Collagen,
Elastin)
Clinical Features (Complications): ➢ Local Inflammatory responses (Macrophages engulf
1. Multi-Organ Disease: Heart - forming the Ischemic Heart LDLs forming Foam Cells)
Disease (IHD)
2. Brain - forming Cerebral Infarction (Stroke) Principal cause of Heart Disease & Stroke:
3. Kidneys - forming Renal Infarction ➢ Cause of 90% Myocardial Ischemia
4. GIT - forming GI-Ischemia/Infarction ➢ Due to Occlusion of Coronary Circulation
➢ Cause 50% of deaths in Western Society
 2. Fatty Streak Formation:
Lipids: The Main Culprits
a. Fat Deposition Under the TunicaIntima Vessel-layer
b. The Typical Early Atherosclerotic Lesion.
3 Types of Lipids in Plasma:
1) Majority Are Clinically Silent
1. Cholesterol + Esters
2) Reversible If Diet Changes
2. Phospholipids
c. Yellow Color Reflects:
3. Triglycerides
1) Oxidized Lipids
2) Presence of Foam Cells
Lipid Transport:
➢ Insoluble In Water - Must be Packaged to be suspended
3. Lipid Plaque:
in plasma.
a. Fatty Streak gets more profound
➢ Fats Absorbed in GI - Packaged into Chylomicrons (in
b. ‘Foam Cells’ Unable to Digest Lipid Contents will Die
small intestine) travel to the Lymphatics circulation then
1) Extracellular Lipids
to the (Left Sub Clavian Vein) down to the Liver.
2) Cell debris
➢ Liver Repackages Chylomicron Remnants into
c. Oxidized LDLs – Attract Immune Cells, Cytokines,
Lipoproteins and back to the Circulation
Platelets, Smooth Muscle, Connective Tissue
1) Positive Feedback.
Note LDLs - Attribute to Atherosclerosis - Bad cholesterol d. Plaque Builds - becomes complicated
HDLs - Help Prevent Atherosclerosis - Good cholesterol

4. Complicated Plaques:
What Is The Process? a. ‘Cap’ forms on plaque will become more Unstable. May
rupture and become a Thrombus then form Occlusion
1. Vessel Injury – Endothelial Damage: b. Clinical Manifestations (Different Types of
Complicated Plaques):
1) Hypertension – High Pressure can split 1) Plaque Rupture - Thrombosis (Responsible for
arteries (Particularly where they branch) 90+ % of MI’s)
2) Smoking – Toxins from cigarettes.
3) Toxins/Poisons
2) Narrowing - Vessel Rigidity & Fragility
Risk Factors 4) Virus 3) Hemorrhage Into Plaque - narrow of Lumen
5) Bacteria
4) Fragmentation of Plaque - Distal Emboli
6) Immune reaction
7) Diabetes 5) Weakening of Vessel Wall - Aneurysms

1) Increased Vessel Permeability – Become

Leaky
2) Platelet - maintain vascular integrity
3) Monocytes Adhere - Transform to
Hypertension
Endothelium
Macrophages
Damage Becomes 4) Blood LDLs Enters and Bind to their
Activated Apolipoprotein ‘Receptors’ and will be What is it? Consistent Systolic of +140mmHg AND/OR
Activated & Oxidized Consistent Diastolic of +90mmHg
5) Oxidized LDL Presence Causes
Inflammation
Etiologies & Types:
1) Oxidized LDLs – Attract Immune Cells,
➢ 95% = Primary Idiopathic Hypertension:
Cytokines, Platelets, Smooth Muscle,
Local Connective Tissue a. Idiopathic Likely (not curable)
Inflammation 2) Macrophage Engulf Oxidized LDL > b. Risk factors for HT:
Transform to Lipid-Leiden Foam Cells
3) Plaque Building slow Begins
▪ GENETICS/Family history
▪ High cholesterol /Salt Diet
▪ Diabetes/Obesity
▪ Smoking/Alcohol
 ▪ Stress ▪ Vision Disturbances (Papilledema, Retinal
▪ Age Bleed)
c. Subtypes: ▪ Headache, Drowsiness, Confusion
▪ Isolated Diastolic Hypertension (Typically ▪ Nausea, Vomiting
Older Men) - high levels e. Management:
▪ Isolated Systolic Hypertension (Eg. ▪ Smoothly Reduce BP over 24 to 36 hours to
>160/<90) - normal levels <150 / 90
• In Young Adults - Due to Overactive
Sympathetic nerve system lead to increase Note Malignant Hypertension is rare, but can arise in HT of any
Cardiac Output etiology.
• In Older Adults - Due to decrease Arterial
Excessive reduction may cause Coronary, Cerebral, Renal
Compliance (Calcification/Fibrosis)
Ischemia

➢ 5% = Secondary Hypertension
a. Cardio - Coarctation, Hypervolemia, Rigid Aorta Clinical Features (Symptoms & Signs):
b. Renal – Acute Glomerulonephritis, CKD,
Polycystic disease, Renal Artery Stenosis Symptoms:
c. Endocrine - Hyperadrenalism, Acromegaly, ➢ Typically Asymptomatic (Unless Malignant, Headache,
Hypothyroidism, Hyperthyroidism, Phaeo, Dizziness, N/V, Visual Changes)
Cushing Syndrome
d. Neurologic - Psychogenic, Raised ICP, Sleep Signs:
Apnea, Acute Stress ➢ Signs of primary causes - Eg. Thyroid, Cushing
e. Pre-Eclampsia: (10% of pregnancies) - Placental syndrome, Acromegaly, Polycythemia, CKD, Pregnancy
Ischemia then Placental vasoactive mediators to ➢ Abdomen: Renal or Adrenal Masses (for possible
increase Maternal BP in effort to increase placental causes), or for abdominal aortic aneurysm (AAA)
perfusion ➢ Renal Bruit: (Renal Artery Stenosis)

➢ Accelerated Malignant Hypertension: Complications of Hypertension:

a. Rapid inc in BP (more than 200/120mmHg) ➢ Major Precursor For:
Sufficient to cause Vascular Damage: a. Coronary Artery Disease or Ischemic Heart Disease
▪ Retinopathy (Papilledema, Bulging Discs) b. Hypertensive Heart Disease (Heart Failure,
▪ Brain (Mental Status Changes) Hypertrophic Cardiomyopathy)
▪ Renal (Creatinine Rise) c. Stroke
▪ Rapid Organ Failure d. Aortic Dissection
b. Pathophysiology Not well Understood e. Renal Failure
c. Common Causes: f. Peripheral Vascular Diseases (PVD)
▪ Cessation of Antihypertensive (Rebound g. Microangiopathy/Arteriolosclerosis (Small Vessel
Hypertension) Diseases)
▪ Sympathetic Hyperactivity - stress ➢ Relationship between Degree of Hypertension &
▪ Stimulants (Cocaine/Amphetamines) Degree of Complications.
▪ Glomerulonephritis (Nephritic Syndrome) ➢ Heart:
▪ Head Trauma (increase ICP) a. Increase Afterload - Left Ventricle - pump blood to
▪ Tumors (Eg. Thyroid, Phaeo, Adrenal) the aorta. Eventually Diastolic Failure
▪ Pre-Eclampsia b. Increase workload lead to increase Oxygen Demand
d. Symptoms Include: will be Exacerbated Coronary Ischemia
➢ Lungs:
 a. Pulmonary Congestion, Pulmonary edema & Right Congestion. Hence, Shortness of Breath
Ventricular-Hypertrophy
➢ Cerebrovascular: SVT or VT or VF (due to Re-Entrant
Ventricular Arrhythmias
Focus & Altered Conduction Patterns)
a. Intracerebral Hemorrhage (Rupture of
Artery/Arterioles in brain)
➢ Aorta/Peripheral Vascular: Angina Pectoris
a. Mechanical Arterial Damage (eg. Aneurysms,
Dissecting, Atherosclerosis)
Etiology:
➢ Kidneys:
➢ Decrease Myocardial Perfusion (relative to demand) due
a. Nephrosclerosis (hardening of kidney glomerulus)
to Coronary Insufficiency.
lead to Renal Failure

Causes:
Ischemic Heart Disease ➢ Atherosclerosis, Vasospasm, Embolism, Ascending
Aortic Dissection
Ischemia Vs. Hypoxia Vs. Infarction: ➢ Exacerbated by Ventricular-Hypertrophy, Tachycardia,
➢ Ischemia: A Flow Limitation, Typically due to Hypoxia, Coronary Arteritis (e.g. in SLE)
Coronary Artery Stenosis (Narrowing)
➢ Hypoxia: An oxygen limitation, Typically due to Pathogenesis:
High-Altitude, Respiratory deficiency, etc. ➢ A late sign of Coronary Atheroma Symptoms Imply
➢ Infraction: Irreversible Cell DEATH, Typically due to about 70% Occlusion!
sustained Ischemia ➢ Insufficient Coronary Perfusion Relative to Myocardial
Demand
Regional Vs. Global Myocardial Ischemia:
A. Regional Ischemia: - Due to: Stable Atherosclerotic Coronary
➢ Local Atherosclerosis/Thrombosis and Ischemia Obstruction (No Plaque Disruption)
Stable Angina
- Presentation: Chest pain on Physical Exertion,
Confined to Specific Region of Heart. which fades quickly with Rest (minutes)
B. Global Ischemia (Rare):
- Due to: Coronary vasospasm (May not be
➢ Severe Hypotension/Aortic Aneurysm lead to sudden Variant/Prinzmetal Atheroma)
deficiency of blood going to the heart Angina - Presentation: Angina Unrelated to Activity
(Ie. At Rest)

What Happens During Myocardial Ischemia? - Due to: Unstable Atherosclerotic Plaque (with
or without Plaque Disruption & Thrombus)
Unstable Angina - Presentation: Prolonged Angina at Rest
Initially Subendocardial Ischemia/ “Preinfarction Angina” (Either New Onset, increase Severity, increase
Infarction (ST-Depression & T-Wave Frequency)
Myocardial Damage Inversion) > Progresses to - Red Flag that MI may be Imminent
Transmural-Ischemia/Infarction
- Due to: Ischemia masked by neuropathy (eg.
(ST-Elevation & Pathological Q-Waves).
Diabetes, decrease B12, etc.)
Silent Ischemia
- Presentation: Painless, but may have Nausea,
Metabolic Changes - Increase lactate; (Anaerobic Metabolism) Vomiting, Diaphoresis, and Abnormal ECG
(Aerobic to Anaerobic) decrease pH

Nociceptor (pain receptor) Activation > Clinical Features of Angina Pectoris

Pain
Angina Pain

Global Autonomic Tachycardia, Sweating, Nausea Common Presentation:

Symptoms
➢ Less than 15mins of Crushing, Central, Retrosternal
Pulmonary Congestion Left Ventricle - Failure Æ Pulmonary Chest Pain that are Radiating to Arms, Neck or jaw
 ➢ Stable: On exertion, Prinzmetal: Rest, Unstable: Etiology: 3 Factors
Worsening, Prolonged, at Rest 1. Environmental Factor - Group-A-Beta-Hemolytic Strep
➢ Dyspnea - difficulty in breathing (Pulmonary (Pyogenes) Pharyngitis
Congestion) 2. Genetic Susceptibility (3% of Population) - HLA DR-2
➢ Fear of Impending Doom & DR-3 Positive
3. Autoimmunity - Antibodies (Antigenic Mimicry)
Management/Treatment - GABH-Strep there is a Production of Anti-MProtein
Antibodies that will Cross React with Cardiac
Prevention, Smoking, Hypertension, Hyperlipidaemia, Diabetes, Connective Tissue.
Management of Obesity, Etc.
CV Risk Factors
Pathogenesis (Mitral Stenosis):
1. Anti-Anginal Therapy: 1. GABH Strep pharyngitis (In HLA-DR2/3-Positive
a) Nitrates (GTN) - Coronary ______ > increase Person)
Cardiac Perfusion
b) B-Blockers (metoclon) – To decrease Workload 2. 2 weeks Later, Immune Response to GABHStrep will
Medical Therapy
of the Heart cause Rheumatic Fever and then Carditis
c) Ca-Channel Blockers (Diltiazem/Verapamil) To
(__________)
decrease Afterload
Note: 2 weeks Delay due to Lymphocyte Activation
2. Antiplatelet Therapy: 3. Subsequent GABH-Strep Infections > Secondary
a) Aspirin or Clopidogrel (STRONGER) Immune response: Recurrent Rh-Fever
3. Lipid-Lowering Therapy:
a) Atorvastatin or Simvastatin > Cumulative Valve Damage (Fibrosis) > Rheumatic
Heart Disease
1. PCI - (Percutaneous Coronary Intervention)
a) Coronary Angioplasty: Balloon
Dilation/Stenting of Coronary Arteries via Clinical Features & Diagnosis
Revascularization
Femoral Artery
(Definitive) Acute Rheumatic Fever:
2. CABG - (Coronary Artery Bypass Grafting):
a) Harvested Vein (Saphenous/Wrist) Æ Bypasses
the collateral circulation Jones Criteria Rules - Must Have:
a. Evidence of Previous GABH-Strep (Strep. Pyogenes)
culture resulted to a positive growth of
Group-A-Beta-Hemolytic Strep
Rheumatic Fever and Rheumatic Heart Disease
b. 2x Major Criteria OR 1 Major + 2 Minor

Background:
Evidence of Previous Strep Infection:
➢ Rheumatic Fever (RF) = Delayed Autoimmune
a. Antistreptolysin-O Titre
Complication of a GROUP A BETA HEMOLYTIC
b. Anti-DNase B Antibodies
STREPTOCOCCI Tonsillo Pharyngitis.
c. Positive Throat Swab Culture
➢ Acute rheumatic fever or Carditis - Acute Phase of
Rheumatic Fever
Major Criteria
➢ Chronic Rheumatic Heart Disease (RHD) - Typically
a. Joint Involvement - Migratory Polyarthritis Not
producing Mitral Stenosis
necessarily arthralgia
b. Carditis - Including Pericarditis - Friction Rub, Quiet
Rheumatic Fever (RF) & Rheumatoid Arthritis (RA)
Heart Sounds, Tachycardia
are 2 different diseases
c. Nodules - Subcutaneous, painless, on extensor surfaces
➢ RF - Licks joints but bites heart (Temporary Arthritis,
d. Erythema Marginatum - Non-Pruritic, Tinea-like Rings
but Permanent Valvular Damage)
on trunks & limbs
➢ RA - Licks heart but bites joints (Mild Myocarditis, but
e. Sydenham’s Chorea - Rapid, Involuntary Movements
Permanent Severe Arthritis)
Minor Criteria c. Tension pneumothorax
a. Fever
b. Arthralgia Compensatory Mechanisms
c. Elevated ESR ➢ “Cardiac Reserve” = Maximal % that CO can Increase
d. Prolonged PR Segment Above Normal (Typically 300-400%)
➢ (IMMEDIATE) increase Sympathetic Tone:
Chronic Rheumatic Heart Disease ▪ Barrier receptors will increase Sympathetic nervous
➢ Cardiac murmur (Typically Left Heart) system which increases Heart rate & Contractility.
➢ Mitral Stenosis (with or without Regurg) Therefore, increase Cardiac Output
➢ Aortic Stenosis (with or without Regurg) ➢ (DELAYED) Renal (Kidney):
➢ Mitral Stenosis: ▪ Angiotensin-II is a General vasoconstrictor that
a. Mitral Facie - Malar, Butterfly Rash over Cheeks & increase blood pressure
Nose ▪ Antidiuretic hormone (ADH) - decrease Urine
b. Mid-Diastolic Rumbling Murmur - Loudest at Output result to increase Blood Volume and increase
Apex on Expiration & transmitted on Axilla blood pressure
c. Pulmonary Congestion & CCF - RVHypertrophy, ▪ EPO - hematopoiesis will increase Blood Volume
Exertional Dyspnea and increase blood pressure
➢ Atrial Fibrillation - From Atrial Stretch due to Mitral
Stenosis 3 Stages of Shock
➢ Risk of Infective Endocarditis 1. Non progressive Stage (Less than 15% (less than 750ml) Blood
Loss):
➢ Stable & reversible
Shock
➢ Signs of Compensated Hypovolemia:
▪ Tachycardia
➢ Inadequate Perfusion of Vital Organs (Heart, Brain, ▪ Oliguria (Low Urine Production)
Kidneys) 2. Progressive Stage (15-40% (2,000ml) Blood Loss):
➢ Unstable, Decompensating, Reversible
Etiology ➢ Signs of Decompensation:
1. Hypervolemic Shock ▪ Hypotension
➢ Severe Dehydration - (Eg. Sweating, Vomiting, Diarrhea, ▪ Delayed CRT (decrease Peripheral Perfusion)
DKA & Diuresis, Seeping Burns) ▪ Tachycardia
➢ Severe Blood Loss/Hemorrhage ▪ Organ failure (Anuria, Confusion/ALOC, Heart
➢ Anything that decrease blood volume Failure, Tachypnoea, Acidosis)
2. Cardiologenic Shock ➢ But Still Reversible with Treatment:
➢ Second to Heart Failure - (Eg. Acute MI, Valvular, ▪ Reverse causative agent + Volume Replacement;
Cardiomyopathy, Myocarditis) Otherwise Fatal if Untreated
3. Distributive Shock 3. Irreversible Stage (more than 40% (more than2000mL) Blood
a. Septic Shock - Extracellular Fluid Shift then leads to Loss):
Hypotension results to Shock ➢ Unstable, Irrecoverable Organ Failure.
b. Anaphylactic Shock - Extracellular Fluid Shift in ➢ Patient WILL Die - Treatment will delay death, but NO
Systemic edema & Hypotension treatment will save Patient’s life.
c. Neurogenic Shock - Sudden loss of Vasomotor Tone ➢ Symptoms:
will have a Massive Veno Dilation ▪ Anuria
4. Obstructive Shock ▪ Acidosis
a. Massive pulmonary embolism (PE) ▪ Coma
b. Cardiac tamponade
 ▪ Multi organ failure (Renal, Cardiac, Pulmonary, cough and bronchial hyperreactivity can be prolonged
CNS) in some cases of viral infection.
➢ In individuals who do not smoke, chronic cough is
MODULE 6 commonly caused by:
RESPIRATORY SYSTEM 1. Postnasal drainage syndrome
2. Non-asthmatic eosinophilic
3. Bronchitis
Clinical Manifestations of Pulmonary Diseases 4. Asthma
5. Gastroesophageal reflux disease.
COUGH ➢ In persons who smoke:
1. Chronic bronchitis - most common cause of
What is it? chronic cough,
➢ Cough is a protective that helps clear the airways by an ➢ Lung cancer to be considered
explosive expiration. Inhaled particles, accumulated ➢ ACE inhibitors
mucus, inflammation, or the presence of a foreign body
initiates the cough reflex by stimulating the irritant in DYSPNEA
the airway.
➢ There are few such receptors in the most distal bronchi What is it?
and the alveoli; thus it is possible for significant amounts ➢ Dyspnea is defined as a subjective experience of
of secretions to accumulate in the distal respiratory tree breathing discomfort that is comprised of qualitatively
without cough being initiated. distinct sensations that vary in density
➢ The cough reflex consists: ➢ Multiple factors:
1. Inhalation 1. Physiological
2. Closure of the glottis and vocal cords 2. Psychological
3. Contraction of the expiratory muscles 3. Social
4. Reopening of the glottis, and then forceful 4. Environmental
expiration that removes the offending matter. ➢ It is often described as breathlessness, air hunger,
➢ Cough occurs frequently in healthy individuals; shortness of breath, labored breathing, and
however, those with an inability to cough effectively are preoccupation with breathing.
at greater risk for pneumonia. ➢ Pulmonary diseases, or many other conditions such as
pain, heart disease, trauma, and anxiety.
a. Acute cough ➢ The signs of dyspnea
➢ Resolves within 2-3 weeks of the onset of illness or 1. Flaring of the nostrils
resolves with treatment of the underlying condition. 2. Use of accessory muscles of respiration
➢ Result of 3. Retraction (Pulling back) of the intercostal
1. Upper respiratory tract infections spaces.
2. Allergic rhinitis 4. Retractions of tissue between the ribs
3. Acute bronchitis (intercostal retractions) – lung parenchyma in
4. Pneumonia origin (more commonly in children).
5. Congestive heart failure
6. Pulmonary embolus or aspiration HYPOXIA, HYPOXEMIA

b. Chronic cough Hypoxemia

➢ Persisted for more than 3 weeks, although 7-8 weeks ➢ Reduced oxygenation of arterial blood (reduced Pao2)
may be a more appropriate timeframe because acute ➢ Respiratory alterations
 HEMOPTYSIS
Hypoxia
➢ Reduced oxygenation of cells in tissues ➢ Hemoptysis is the expectoration of blood or bloody
➢ May be caused by alterations of other systems as well. secretions.
➢ Confused with hematemesis, which is the vomiting of
Note Although hypoxemia can lead to tissue hypoxia, tissue blood.
hypoxia can result from other abnormalities unrelated to ➢ Blood produced with coughing is usually bright red, has
alterations of pulmonary function, such as low cardiac an Alkaline pH, and is mixed with frothy sputum.
output or cyanide poisoning. Hypoxemia results from
➢ Blood that is vomited is dark, has an acidic pH, and is
problems with one or more of the major mechanisms of
oxygenation mixed with food particles.
➢ Indicates infection or inflammation that damages the
bronchi (bronchitis, bronchiectasis) or the lung
1. Oxygen delivered to the alveoli
parenchyma (pneumonia, tuberculosis, lung abscess)
a. Oxygen content of the inspired air (Fio2)
➢ Other causes include cancer and pulmonary infarction.
b. Ventilation of the alveoli
➢ The amount and duration of bleeding provide
2. Diffusion of oxygen from the alveoli into the blood
important clues about its source.
a. Balance between alveolar ventilation and perfusion
➢ Bronchoscopy, combined with chest computed
b. Diffusion of oxygen across the alveolar capillary
tomography (CT), is used to confirm the site of
barrier
bleeding.
3. Perfusion of pulmonary capillaries

CLUBBING
CYANOSIS

➢ Clubbing is the selective bulbous enlargement of the

➢ Cyanosis is a bluish of the skin and mucous membranes
end (distal segment) of a digit (finger or toe)
caused by increasing amounts of desaturated or reduced
➢ Its severity can be graded from 1 to 5 based on the extent
hemoglobin (which is bluish) in the blood.
of nail bed hypertrophy and the amount of changes in
➢ It generally develops when 5g of hemoglobin is
the nails themselves or as early, moderate or severe.
desaturated, regardless of hemoglobin concentration.
➢ It is usually painless.
➢ Commonly associated with diseases that cause chronic
a. Peripheral cyanosis
hypoxemia
➢ Slow blood circulation in fingers and toes
1. Bronchiectasis
➢ Most often caused by poor circulation resulting from
2. Cystic fibrosis
intense peripheral vasoconstriction, such as that
3. Pulmonary fibrosis
observed in persons who have Raynaud disease, are in
4. Lung abscess
cold environments, or are severely stressed.
5. Congenital heart disease.
➢ Best observed in the nail beds.
6. Lung cancer - even without hypoxemia because
of the effects of inflammatory cytokines and
b. Central cyanosis
growth factors (hypertrophic osteoarthropathy)
➢ Caused by decreased arterial oxygenation (low Pao2)
from pulmonary diseases or pulmonary or cardiac
right-to-left shunts.
➢ Best detected in buccal mucous membranes and lips.
 ➢ Most common cause of pneumonia in children is the
Infections of the Lungs
Respiratory Syncytial Virus (RSV)

Pneumonia
Pathogenesis
Definition: infection of the pulmonary parenchyma
➢ Transmission: airborne spread and droplet transmission
➢ Incubation Period: 1-4 days before signs and symptoms
Normal lung defenses
appear
• Cough reflex closure of the glottis
➢ Contagious: 1day Before Symptoms Onset, and the next
• Tracheobronchial mucociliary transport
7days.
• Type II dust cell
➢ Viral-Induced Epithelial Dysfunction & Destruction
• Inflammatory immune system response

Clinical Features
Risk factors impairing lung defenses
➢ Symptoms: Chills, Fatigue, Cough, Myalgias,
• Smoking, toxic inhalation, aspiration, mechanical
Arthralgias, Headache
obstruction, ETT/NTT intubation, respiratory therapy,
➢ Signs: High Fever (less than 40C); But Chest Clear
pulmonary edema, hypoxemia, acidosis
(Unless 2o Bacterial Pneumonia)
immunosuppression, uremia, DM, malnutrition, elderly
➢ Complications: Secondary Bacterial Pneumonia, Otitis
age, decreased LOC
Media

Pathogenesis
Diagnosis
• Aspiration of upper airway organisms: S. pneumoniae, S.
➢ Clinical Diagnosis (Signs & Symptoms)
pyogenes, Mycoplasma, H. influenzae, M. catarrhalis
➢ Note: Chest X ray (CXR) is usually Normal.
• Inhalation of infectious aerosols: Mycoplasma, H.
influenza, Legionella, Histoplasma, C. psittaci, Q fever
Treatment and Prevention
• Other: hematogenous (S. aureus, Fusobacterium), direct
➢ Primarily Supportive Treatment: Bed Rest, Fluid,
trauma (blood)
Paracetamol/Analgesics, Antitussives, Decongestant
➢ Antivirals (Effective 48 hours of onset): Oseltamivir
Clinical presentation
(Tamiflu TM) and Zanamivir (Relenza TM) will
• Typical and Atypical pneumonia syndromes but in real
Reduce the symptoms in less than 24 hours
life it's often difficult to differentiate between the two
➢ Vaccine: Flu vaccine is recommended Annually or yearly
• Elderly often present atypically; altered LOC is
for Everyone
sometimes the only sign
• Epidemiology affects clinical presentation and treatment
PCV13 PPSV23

General Pneumonia Triad (Diagnosis): 1. Helps protect against 13 different 1. Helps protect against 23 different
- Fever strains of pneumococcal bacteria strains of pneumococcal bacteria
2. Usually given 4 separate times to 2. Generally given once to anyone
- Tachycardia children under two over 64
- Tachypnea (with or without shortness of breath) 3. Generally given only once to 3. Given to anyone over 19 who
adults older than 24 or 19 if they regularly smokes nicotine
have an immune condition products like cigarettes
VIRAL PNEUMONIA
Note: PCV13 comes first before the PPSV23

Seasonal Flu (INFLUENZA A & B)

Note Flu vaccine is reformulated each year to
Etiology include current serotypes
➢ Influenza virus A & B for adults (less than 10% of
pneumonia among adults)
BACTERIAL PNEUMONIA Treatment
➢ Penicillin or vancomycin (if penicillin allergic) usually
Streptococcus pneumoniae for 7-10 days and drain any empyema
➢ Most common bacterial pneumonia
➢ At risk: secondary complication to a viral Respiratory Mycoplasma pneumoniae
Tract Infection (RTI) ➢ Most common atypical pneumonia; "walking
pneumonia"
Clinical presentation ➢ At risk: young adults (especially 5-15 years old)
➢ Abrupt onset with fever, pleurisy, and "rusty" sputum; ➢ Incubation: 12-14 days (insidious onset)
watch for meningeal involvement
Clinical presentation
CXR ➢ Constitutional illness with fever, persistent hacking
➢ Classically causes a lobar consolidation Sputum cough, with or without scant sputum, chills uncommon
➢ PMNs and gram-positive oval-shaped diplococci ➢ Extrapulmonary features: headache, diarrhea,
non-exudative pharyngitis, skin, arthralgia, myalgia,
Labs hemolytic crises, bullous myringitis, CNS (e.g. myelitis,
➢ Leukocytosis (10,000 is common, but may be Guillain-Barré syndrome, meningoencephalitis)
leukopenic on admission)
CXR
Treatment ➢ Classically worse than clinical presentation; usually
➢ Penicillin (erythromycin if penicillin allergic; bilateral, patchy air-space diseases
vancomycin, ceftriaxone or cefotaxime if resistant)
usually for 7-10 days Sputum
➢ More mononuclear cells and fewer PMNs than bacterial
Prevention: Pneumovax (give once only) pneumonia, but mycoplasma not visualized

Staphylococcus Aureus Labs

➢ Sudden onset bronchopneumonia ➢ Complement fixation shows significant titre rise in up to
➢ At risk: secondary complication of influenza infection or 80% anti-I (IgM) increased in 50%, cold agglutinins,
in hospitalized patient with underlying disease, severe WBC not significantly increased (PMNs slightly
diabetes, drug abusers, immuno compromise elevated)

Clinical presentation Treatment

➢ High fever, chills, progressive difficulty in breathing ➢ Macrolide, newer generation quinolones, doxycycline
➢ Cyanosis, cough, pleuritic pain usually 10-14 days
➢ Quite toxic-appearing
Klebsiella pneumoniae
Complications ➢ At risk: alcoholics
➢ Cavitation (necrotizing pneumonia), pneumothorax,
empyema, pneumatoceles in children Clinical presentation
➢ Explosive onset of fever, prostration; similar to
Sputum pneumococcus; bloody sputum (redcurrant jelly)
➢ PMNs and gram-positive diplococci in clusters, chains,
and pairs Complications
➢ Rapid cavitation, abscess, high mortality
CXR ➢ Lesions usually heal and fibrose in the
➢ Classically lobar consolidation with bulging fissure immunocompetent
➢ Secondary/post-primary TB: reactivation of dormant
Sputum organisms and proliferation in aging or
➢ Large gram-negative encapsulated rods immunocompromised patients

Treatment Clinical presentation

➢ Cephalosporin and aminoglycoside; adequate drainage ➢ Usually asymptomatic but may have fever, lassitude,
of empyema (can cause extensive scarring) erythema nodosum, cough, sputum
➢ Post-primary TB: reactivation of dormant organisms in
Pneumocystis carinii immunocompromised patients
➢ At risk: patients on immunosuppressed (e.g. transplant ➢ Early systemic symptoms: fever, sweats, anorexia, weight
recipients) or chemotherapy, AIDS when CD4 count loss
less than 200 ➢ Late localizing symptoms: dyspnea, pleuritic chest pain,
cough, purulent sputum, hemoptysis
Clinical presentation ➢ Miliary TB (post-primary dissemination of multiple tiny
➢ Atypical, concurrent opportunistic infections granulomas in immunocompromised patients): fever,
anemia, splenomegaly, meningitis
CXR ➢ Primary TB: nonspecific lower lobe calcified infiltrates,
➢ Diffuse interstitial infiltration, often isolated to upper hilar and paratracheal node enlargement, pleural
lobes effusion
➢ Post-primary TB: cavitation in apical regions segment of
Labs upper lobe and/or superior segment of the lower lobes
➢ Giemsa stain; lower yield in patients on prophylaxis; with or without calcification
diagnosis may require BAL ortransbronchial biopsy ➢ Miliary TB: Uniformly, very fine nodules (like seeds)
throughout
Treatment
➢ TMP-SMX, pentamidine, TMP-dapsone, Investigation
Tindamax-primaquine, atovaquone; add corticosteroids ➢ Culture of involved sites and identification of acid-fast
if PaO2 is less than 70 mm Hg or AaDO2 is more than bacilli (Ziehl-Nielsen stain)
35 mm Hg ➢ Mantoux Skin Test
➢ CXR
Prevention
➢ In AIDS, after an episode of PCP or when CD4 count FUNGAL PNEUMONIA
is less than 200 use TMP-SMX, TMP dapsone
PRIMARY PATHOGENIC FUNGI
Pulmonary Tuberculosis
Etiology
Pathogenesis ➢ Histoplasma capsulatum, Coccidioides immitis, vaseline
➢ Inhalation of aerosolized droplets from close contacts dermatitidis
➢ Primary TB: development of glomerulus reactions in
the lungs, with or without local spread to lymph nodes Pathogenesis
and hematogenous to distant organs (GI TB, e.g. ➢ Primary granulomatous lung infection
kidneys, bone) ➢ Systemic hematogenous dissemination
 ➢ Fungus is usually destroyed if patient Endobronchial Testing For Aspergillosis
immunocompetent ➢ At risk: chronic lung disease
➢ Persists as chronic systemic granulomatous infection in ➢ Chronic cough and hemoptysis
immunocompromised
Treatment: Amphotericin B, surgical resection of aspergilloma
Clinical presentation
➢ Usually asymptomatic or mild respiratory illness Cryptococcosis
➢ Acute pneumonia that resolves with granuloma
formation and calcification Etiology
➢ Chronic cavitary pneumonia clinically and ➢ Cryptococcus neoformans
radiologically like TB or cancer
➢ Disseminated disease: meninges, brain, bone, liver, Clinical presentation
spleen, kidney, joints ➢ Acute: usually resolves spontaneously in the
immunocompetent
Diagnosis: Tissue biopsy for staining and culture ➢ Chronic: intense pulmonary granulomatous reaction
with hematogenous spread to brain causing fatal
Treatment: Antifungal, itraconazole meningoencephalitis if not treated;
immunocompromised patients at risk

OPPORTUNISTIC FUNGI Treatment: Amphotericin B with or without flucytosine

Aspergillosis Candidiasis

Etiology Etiology
➢ Mostly Aspergillus fumigatus - Candida albicans

Clinical Presentation Clinical presentation

➢ Allergic bronchopulmonary aspergillosis (see ➢ Fever, septicemia
Pulmonary Infiltrates with Eosinophilia) ➢ Usually hematogenous spread to lungs
➢ Aspergilloma (fungus ball) ➢ CXR: diffuse, vaguely nodular infiltrate visible only
when numerous abscesses are present
Noninvasive ball of hyphae colonizes a preexisting
lung cavity Treatment: Amphotericin B and flucytosine
➢ Ranges from asymptomatic to massive hemoptysis
1. CXR - round opacity surrounded by a thin
Chronic Obstructive Pulmonary Disease (COPD)
lucent rim of air, often in upper lobes (air
crescent sign)
COPD
➢ HEAVILY ASSOCIATED WITH SMOKING
Invasive
➢ Characterized by progressive development of airflow
➢ At risk: immunosuppressed, especially neutropenics
limitation that is irreversible or minimally reversible
➢ Severe symptoms with fever, cough, dyspnea, pleuritic
➢ Includes chronic bronchitis and emphysema; usually
pain, tends to cavitate
coexist to variable degrees in most patients - five
1. CXR: local or diffuse infiltrates with or
pathophysiological processes associated with COPD
without pulmonary infarction
1. Inflammatory narrowing of respiratory and membranous ➢ Obstruction due to narrowing of the airway lumen by
bronchioles mucosal thickening and excess mucus
2. Proteolytic digestion of connective tissue framework of the ➢ Usually due to smoking but air pollution increasingly
lung resulting in decreased parenchymal tethering of airways important
3. Loss of alveolar surface area and capillary bed ➢ Exacerbation due to respiratory tract infections
4. Lung hyperinflation caused by loss of lung elastic recoil (typically viral), air pollution, bronchospasm, mucus
5. Increase pulmonary vascular resistance caused by clogging, and CHF
vasoconstriction and loss of capillary bed ➢ Some have features of asthma and chronic bronchitis
(asthmatic bronchitis)
Risk Factors
➢ Smoking is the most important risk factor.
Airway Hypersensitivity
➢ Minor risk factors include:
1. Environmental factors: air pollution, occupational
ASTHMA
exposure, IV drug abuse or talcosis
What is Asthma? A chronic Inflammatory Disorder of the
2. Treatable factors: low BMI, α-1-antitrypsin deficiency,
Airways it is Episodic, reversible Constriction.
bronchial hyperactivity
➢ Demographic factors: Age, family history, male sex,
Etiology
history of childhood respiratory infections and
Types:
socio-economis status
1. Atopic (allergic) Asthma (Type 1 Hypersensitivity
Reaction - IgE.)
a. Emphysema
2. Non atopic Asthma (Viral-Induced/DrugInduced (Eg.
Aspirin)/Occupational)
Pathologic definition
Environmental Triggers
➢ Dilatation and destruction of air spaces distal to the
➢ Dust, Pollen, Dander, Mould, Smoke, Pollution,
terminal bronchiole without obvious fibrosis
Perfume, Cold Air
➢ Decreased elastic recoil of lung parenchyma causes
Genetic Factor – (Family history is Common)
decreased expiratory driving pressure, airway collapse,
and air trapping
Pathophysiology
➢ 2 types
Type 1 Hypersensitivity Reaction:
1. Centriacinar (respiratory bronchioles
➢ Rapid Immune Reaction to a Previously Sensitized
predominantly affected)
Antigen causes Mast-Cell, Basophil Degranulation.
▪ typical form seen in smokers
Then Release inflammatory Mediators which causes
▪ primarily affects upper zones
Asthma
2. Panacinar (respiratory bronchioles, alveolar
ducts, and alveolar sacs affected)
i. Early Phase:
▪ responsible for less than 1% of emphysema
➢ Vasodilation & increase Permeability (bronchial edema)
cases
➢ Smooth muscle (Bronchoconstriction)
▪ primarily affects lower lobes
➢ Epithelial Damage causes decreased Mucociliary
Function then results in Mucus Accumulation.
b. Chronic Bronchitis
➢ A clinical diagnosis
ii. Late Phase:
➢ Immune-Mediated Epithelial Damage
Definition
➢ Decrease Mucociliary Function and Accumulation of
➢ Chronic cough and sputum production on most days
mucus
for at least 3 consecutive months in 2 successive years
 Ethanol An example of toxin
Clinical Features
Atrophy A decrease in size or number of cells
➢ Asymptomatic between ‘attacks’ – (But may have
allergic rhinitis, Hives or Eczema) A process with the intention to restore normal
Tissue Repair
➢ ‘Attacks’ of Severe difficulty in breathing & Wheezing - tissue structure

Often Triggered by Allergen (Pollens, Dust, Dander) A white blood cell that targets and kill parasitic
Eosinophils
worms

Complications Macrophages Large Phagocytic Cells

➢ Status asthmaticus: Acute Asthma
Pathogenicity The ability of a microorganism to cause disease
➢ Unresponsive to Bronchodilators or Corticosteroids
(fatal) Kill by latching onto invaders and inducing
Natural Killer Cells
apoptosis

Diagnosis Virulence It is the degree of pathogenicity

Phthirus pubis Known as Pubic Lice

Clinical Features
➢ Dyspnea, Chest pain, Cough HSV type I
A type of HSV that occurs mainly in infants and
kids
➢ Difficulty breathing or Wheezing
➢ Fast heartbeat, Hyperinflation, Increase Respiratory A yellow breakdown product of normal heme
Bilirubin
Effort catabolism

Gas gangrene Caused by Clostridium perfringens

Management
Gallstones Most common causes of obstructive jaundice
➢ Prevention:
1. Mild Asthma: Inhaled corticosteroid Impetigo Known a School Sores

(Budesonide or Fluticasone) Or Inhaled Urticaria Results from Food, drug, plant allergy
Antimuscarinic (Ipratropium Bromide) – If
Stercobilin A product that is excreted in the feces
ICS-Intolerant.
2. Moderate Asthma: LABA + Inhaled Human papilloma
Causative agent of Viral Warts
Corticosteroid Combinations Symbicort virus (HPV)

[Budesonide + formoterol] or Seretide Inflammatory mediator of Type 1 hypersensitivity

Histamine
[Fluticasone + Salmeterol] reactions

3. Severe Asthma: Oral Leukotriene Inhibitors Condition in which the skin, sclera and mucous
Jaundice
(Singulair) membranes turn yellow

Viral warts Benign tumors of the skin

Innate Immune
Also known as non-specific Immune system A type of jaundice that involves increased rate RBC
system Pre-hepatic jaundice
breakdown
A change from a mature cell type to an immature
Dysplasia A group of parasites that causes obstructive
cell type or abnormal cell differentiation Liver Flukes
jaundice
Pathogen Microorganism that is able to cause a disease
M.leprae Causative agent of Leprosy
Irreversible Cell
Necrosis that leads to cell death Hematogenous Most common route of septic arthritis
Injury

Permanent Cell A type of cell that cannot replicate when damage Rheumatoid Causes Macrophage - Mediated Local Joint
Arthritis Inflammation & Destruction
A type of cell that replicate only when activated to
Stable Cells Osteopenia BMD value of -1.0
replace lost cells

Ischemia The most common cause of hypoxia Fragility Fractures Fractures from minimal Trauma
Compound Fracture An open fracture where there is broken skin Cough A reflex that clears airways

Dislocation or Displacement of Joint Surfaces with Abnormal Characterized by progressive development of

COPD
Luxation Articulation airflow limitation

Vancomycin Treatment for osteomyelitis Aspergilloma Known as fungus ball

Osteoarthritis A type of arthritis due to degenerative wear & tear Hypoxia Oxygen levels are decreased in cells of tissues

Splint Use to immobilize movements of the limbs Hematemesis Vomiting of Blood

Rheumatoid A type of arthritis due to a genetic or autoimmune Which of the following is not a Bleeding Disorder?
Arthritis origin
1. AML
Extravascular A type hemolysis that occurs in the Spleen 1&4 2. Vitamin K deficiency
3. VWf deficiency
Monosomy 7 Most common cause of Acute Myeloid Leukemia 4. DIC
5. Hemophilia B
A type of Cancer from a Mutant Hematopoietic
Leukemia
Stem Cell Which of the following is incorrectly paired?

Prothrombin Time A test that measures factor VII 1. Von Willebrand's Deficiency - Poor platelet Plug
formation
A test that measure conversion of Fibrinogen to 2&4
Thrombin Time 2. Coagulopathy - Deficiency to platelet functions
Fibrin 3. Christmas Disease - Deficiency with Factor IX
4. Vitamin K Deficiency - Factor II, VIII, IX, X
AML A type of leukemia associated with Auer Rods 5. Hemophilia A - Factor VIII Deficiency

Prothrombin Time A test that measures the extrinsic pathway Which of the following can cause secondary
osteoporosis?
Formation of small clots inside blood vessels
DIC
throughout the body 1. Prolonged used of corticosteroid
1,3,5
2. Osteoarthritis
Thrombin Time Measures how quickly Thrombin is being activated 3. Renal disease due to alcohol
4. Osteomyelitis
Anemia due to abnormal increase in RBC 5. Malabsorption syndrome
Hemolytic Anemia
destruction
All of the following are treatments for Gouty
Extreme Tissue-loss resulting in permanent Arthritis Except?
Dismemberment
functional impairment of that limb
1. Life Style Change
Gouty Arthritis Caused by decrease urea excretion in the body 4&5
2. Colchicine
3. Allopurinol
A type of arthritis due to decrease estrogen and
Osteoporosis 4. Joint Replacement
increase osteoclast activity
5. Azithromycin

Restoration of a fracture or dislocation to the

Reduction Arrange the following steps of bone repair process
correct alignment
1. formation of a hard callus
Compartment 4-2-1-3
A syndrome that compresses vessels and nerves 2. the formation of soft callus
Syndrome
3. remodeling and addition of bone
4. the formation of hematoma at the break
A classification of emphysema that affects the lower
Panacinar
lobes of the lungs
Which of the following is/are risk factor of
osteoporosis?
Klebsiella
Associated with bloody sputum
pneumoniae
1. Obesity
2&4
2. Age
Hemoptysis Coughing of Blood
3. Sports
4. Hormonal Problems
Mycoplasma
Most common cause atypical pneumonia 5. Smoking
pneumoniae

1&5 Which of the following is not a secondary cause of

Hypoxemia Oxygen levels are decreased in arterial blood
 osteoporosis? is/are incorrectly stated, except:

1. Decrease Osteoblastic activity I. Hyperplasia - increase size of cells - increase in

2. Addison's Disease size of the organ
3. Cushing syndrome II. Atrophy - decrease or shrinkage in cellular size
4. Corticosteroids III. Metaplasia - irreversible replacement of one
5. Postmenopausal mature cell type
IV. Dysplasia - abnormal changes in cell size, shape
Which of the following is an incorrect match? and organization of mature cells
V. Hypertrophy - increase in size of cells leading to
● Simple Fracture - occurs inside and no bone an increase in the size of the organ
separation
● Compound - separates two fragments of bone Immunological diseases is a disease created by
● You Answered insufficient nutrient resources of the body.
Greenstick Fracture
● Comminuted Fracture - bone fracture was Both statements are
exposed outside the body through an open false Pathogenesis is the study of structural alterations in
wound cells, tissues and organs that helps to identify the
● Greenstick Fracture - occurs in the concave side cause of disease.
of the bone
● None of these The following is/are correctly stated about the
cellular adaptation, except:
All of the following are causes are of Pre-hepatic
jaundice except? I. Metaplasia involves replacing of one cell type by
another and is considered irreversible.
C. Hepatitis A. G6PD II. Dysplasia results in cells of varying size, shape
B. Malaria and appearance which may be irreversible if
C. Hepatitis offending agent is removed
I, II & V Only
D. Malaria III. Atrophy will result in a decrease in cell size or
shrinkage of cells and is often considered as
The following diseases are associated with adaptive and reversible
Kids/neonates except? IV. Hyperplasia results in an increase number of
cells which leads to an increase in size of the organ
None of the above A. Viral Warts V. Hypertrophy results in an increase in individual
B. Head Lice cell size of cells and causes an organ to metastasize
C. HSV type I in other areas of the body
D. Obstructive Jaundice
The following cellular adaptation is/are incorrectly
Which of the following is not a product of heme stated, except:
anabolism?
I. Dysplasia refers to any unusual changes in the
None of the above A. Bilirubin size, shape and organization of immature cells.
B. Urobilinogen II. Physiologic hypertrophy is a result caused by an
C. Stercobilin increased demand, stimulation by hormones and
D. Unconjugated bilirubin II, III, & V Only growth factors.
III. Hypertrophy is due to an increase in cellular
Which of the following may cause a Type I size thus increasing the size of the organ.
hypersensitivity? IV. Metaplasia is the replacement of one mature
cell type by another which is considered as
A. Food irreversible.
D. All of the above
B. Plant V. Disuse atrophy usually occurs in an individual
C. Drug who were immobilized for a longer period of time.
D. All of the above
E. None of the above Which of the following statement is/are incorrectly
stated:
Which of the following is not associated with
genitalia or sexual transmission? I. Ischemic injury is often caused by an acute
narrowing of arteries and complete blockage of
D. HSV type I A. Cutaneous Candiasis I, II, & V Only blood clots.
B. Pubic Lice II. Basal Cell carcinoma is characterized by an
C. HPV 6 uncontrolled growth of a pigment producing cells
D. HSV type I in the epidermis.
III. Caseous necrosis is usually a combination of
II, IV & V Only The following are the cellular adaptation which coagulative and liquefactive necrosis.
IV. Risk factors such as stress causes an increase in
body production of corticosteroids thus decreases
the body's immune function
V. Irritant contact dermatitis is considered a
specific inflammatory dermatitis caused by an
activation of the innate immune system.
MODULE 7 Note Viral Hepatitis:
THE DIGESTIVE SYSTEM 1) Hepatitis A & Hepatitis E = Acute
2) Hepatitis B & Hepatitis D = Acute & Chronic
3) Hepatitis C = Chronic

Hepatobiliary Tree Disorders HEPATITIS A VIRUS (Acute)

Hepatitis - liver inflammation Etiology

➢ Hepatitis A Virus (Most Common Viral Hepatitis
Etiology Worldwide)
- viral infection
- toxins Pathogenesis
- drugs ➢ Fecal-Oral Transmission
- other (immune mediated) ➢ 2-6 weeks Incubation
➢ Virus is Directly Cytopathic to the Liver - But Does
NOT lead to Cirrhosis
Viral Hepatitis
ACUTE VIRAL HEPATITIS
Clinical Features
➢ Acute Symptoms ONLY; No Chronic
Definition
➢ Viremia > Fever, Malaise, Anorexia, Nausea, Arthralgia
➢ Viral hepatitis lasting for less than 6 months

Signs
Clinical Features
➢ Jaundice (After 1-2 weeks) Due to Intrahepatic
➢ Most are subclinical
Cholestasis
➢ Prodrome (flu-like illness) may precede jaundice by 1-2
1) Increase Conjugated Bilirubin
weeks
▪ Pale Stools
➢ Nausea, vomiting, anorexia, taste/smell disturbance
▪ Dark Urine
(aversion to cigarettes) headaches, fatigue, malaise,
➢ With or without Hepatomegaly, Splenomegaly, Tender
myalgias
Lymphadenopathy
➢ Low-grade fever may be present arthralgia and urticaria
➢ Rarely - Hepatic Encephalopathy & Death
(especially hepatitis B)
➢ Clinical jaundice (icteric) phase (50% of cases) lasting
Investigations
days to weeks
➢ Liver Function Tests (LFTs) - Everything Raised
1) Pale stools and dark urine 1-5 days prior to
➢ Hepatitis A Serology
icteric phase
➢ Hepatitis A PCR
2) Hepatomegaly plus RUQ pain
3) Splenomegaly and cervical lymphadenopathy
Prognosis
(10-20% of cases)
➢ Usually Self-Limiting with Supportive Treatment Only
➢ Hepatic enzymes
1) Hepatocellular necrosis which causes increased
HEPATITIS E VIRUS (Acute)
AST, ALT > 10-20X normal
➢ Very Similar to Hepatitis A; But HIGH MORTALITY
2) ALP and bilirubin minimally increased
in PREGNANCY (20% > DIC in 3rd Trimester)
3) WBC normal or slightly decreased initially

Etiology
➢ Hepatitis E Virus (A Herpes virus)
Pathogenesis Hepatitis B serology
➢ Virus is Directly Cytopathic to the Liver ➢ HBsAg: surface antigen
➢ HBeAg: e antigen (a component of HBV core); marker
Clinical Features of viral replication
➢ Fecal-Oral Transmission (Include Vectors: Dogs, Pigs, ➢ HBcAg: core antigen (cannot be measured in serum)
Rodents) ➢ Both HBsAg and HBeAg are present during acute
hepatitis B
Clinical Picture - Same as Hepatitis A ➢ Anti-HBs follows HBsAg clearance and confers
long-term immunity
Investigations ➢ Anti-HBe and anti-HBc appear during the acute and
➢ Liver Function Tests (LFTs) - Everything Raised chronic phases of the illness but do not provide
➢ Hepatitis E Serology immunity
➢ Hepatitis E PCR ➢ Anti-HBe indicates low infectivity

Prognosis Prevention
➢ 1-2% Mortality (From Fulminant Hepatic Failure) ➢ HBV vaccine = recombinant HBsAg
➢ 20% Mortality in Pregnancy (From DIC in 3rd ➢ Seroconversion rates about 94% after 3 injections
Trimester) ➢ Hepatitis B immune globulin (HBIG) = anti-HBs
1) For needle stick, sexual contact, and neonates born
to mothers with acute or chronic infection
ACUTE AND CHRONIC VIRAL HEPATITIS

HEPATITIS C VIRUS (HCV)

HEPATITIS B VIRUS (HBV)
➢ Transmission is chiefly parenteral
➢ Transmission via parenteral route or equivalent
1) Transfusions (HCV is the most common cause of
➢ Vertical transmission
post-transfusion hepatitis)
1) Occurs during 3rd trimester or early post-partum
2) IV drugs use
2) HBsAg +ve, HBeAg +ve mothers 90% of infants
3) Sexual transmission occurs but risk is less than with
infected
HBV
3) HBsAg +ve, anti-HBe +ve mothers 10-15%
4) 40% of cases have no risk factors
infected
➢ Clinical incubation period 5-10 weeks
4) Give HBIG and full HBV vaccination to newborns
➢ AST and ALT levels fluctuate (unlike Hep A or B)
of HBsAg +ve mothers (90% effective)
➢ More than half progress to chronic liver disease
➢ Incubation period 6 weeks to 6 months
➢ Serology
➢ Infectivity: during HBsAg positivity
1) HCV RNA (detected by PCR assay)
➢ High-risk groups
2) Anti-HCV
1) Neonates of carriers (vertical transmission)
3) Develops in 6-8 weeks in 85% of patients
2) Partners of acutely and chronically infected
4) Persists in chronic infection and does not confer
individuals, with male homosexuals at particular
immunity
risk
3) IV drug users
Prevention: no accepted vaccine for HCV
4) Hospital employees
5) Patients from endemic country
HEPATITIS D (HDV) 2) Next 24-48 hrs.: hepatic necrosis resulting in
➢ Infectious only in the presence of HBV because HBV increased aminotransferases, jaundice, possibly
surface antigens are required for replication hepatic encephalopathy, acute renal failure, death
➢ 2 patterns of transmission 3) After 48 hrs: continue hepatic necrosis/resolution
1) Nonparenteral transmission by close personal 4) Note: potential delay in presentation in
contact in endemic areas (Mediterranean) sustained-release products
2) Transmission by blood products in non-endemic ➢ Blood levels of acetaminophen correlate with the
areas (IV drugs, blood transfusions) severity of hepatic injury
➢ Predisposes to severe or fulminant course ➢ Therapy:
➢ Serology: HBsAg, anti-HDV IgM or anti-HDV IgG 1) Gastric lavage/emesis (if less than 2 hrs after
ingestion)
Types of infection 2) Oral charcoal
1) Coinfection: simultaneous HBV and HDV infection 3) N-acetylcysteine PO/IV within 8-10 hours of
2) Superinfection: appears as clinical exacerbation in a ingestion, most effective for up to 72 hours
chronic HBV patient (promotes hepatic glutathione synthesis)

Prevention: HBV vaccine II. Chlorpromazine

➢ Cholestasis in 1% after 4 weeks; often with fever, rash,
HEPATITIS E VIRUS (HEV) jaundice, pruritus and eosinophilia
➢ Fecal-oral transmission occurring in epidemics in Asia,
Africa, Central America III. INH
➢ Most have mild disease, but in 3rd trimester of ➢ 20% develop elevated transaminases but less than 1%
pregnancy 10-20% have fulminant liver failure develop clinically significant disease
➢ Serology: anti-HEV ➢ Susceptibility to injury increases with age

Prevention: no vaccine available IV. Methotrexate

➢ May rarely cause cirrhosis, especially in the presence of
obesity, diabetes, alcoholism
Drug induced liver disease or Drug induced hepatitis
➢ Scarring develops without symptoms or changes in liver
enzymes, therefore biopsy may be needed in long-term
Specific Drugs
treatment
I. Acetaminophen
➢ Metabolized by hepatic cytochrome P450 System
V. Amiodarone
➢ Can cause fulminant hepatic failure (transaminases >
➢ Can cause same histology and clinical outcome as
1,000 U/L)
alcoholic hepatitis
➢ Requires 10-15g in normals, 4-6g in
alcoholics/anticonvulsant users
CHOLELITHIASIS
➢ Mechanism:
1) High acetaminophen dose saturates
Pathogenesis
glucuronidation and sulfation elimination
➢ Imbalance of cholesterol and its solubilizing agents, bile
pathways, therefore a reactive metabolite is formed
salts and lecithin concentrations
which covalently binds to hepatocyte membrane
➢ If hepatic cholesterol secretion is excessive then bile salts
➢ Presentation:
and lecithin are overloaded, supersaturated cholesterol
1) First 24 hrs.: nausea and vomiting usually within
precipitates and can form gallstones
4-12 hours
Types of Stones ➢ No cholelithiasis in 20% (acalculous)
➢ Cholesterol (80%) = mixed (more than 70% cholesterol
by weight), radiolucent Signs and Symptoms
➢ Risk factors ➢ Often have history of biliary colic
1) Female, fat, fertile, forties ➢ Severe constant epigastric or RUQ pain
2) North American First Nations peoples have highest ➢ Anorexia, nausea and vomiting are common
incidence ➢ Systemic signs – low grade fever (more than 38.5°C);
3) Diabetes mellitus (DM), pancreatitis tachycardia
4) Malabsorption, terminal ileal resection or disease ➢ Focal peritoneal findings
(e.g. inflammatory bowel diseases 1) Murphy's sign (sudden cessation of inspiration
➢ Pigment stones (20%), may be radio-opaque with deep RUQ palpation)
1) Smooth green/black to brown - composed of ➢ Palpable gallbladder in one third of patients
unconjugated bilirubin, calcium, bile acids
2) Black pigment stones - associated with cirrhosis, Differential Diagnosis
chronic hemolytic states ➢ Perforated or penetrating peptic ulcer, MI, pancreatitis,
3) Calcium bilirubinate stones - associated with bile hiatus hernia, right lower lobe pneumonia, appendicitis,
stasis, biliary strictures, dilatation and biliary hepatitis, herpes zoster
infection (Clonorchis sinensis)
Diagnostic Investigation
Natural History ➢ Elevated WBC, left shift
➢ 80% are asymptomatic ➢ Mildly elevated bilirubin, ALP
➢ 18% develop symptoms over 15 years ➢ Sometimes slight elevation AST, ALT
➢ Ultrasound shows distended, edematous gallbladder,
Clinical Presentation (in severity of increasing pericholecystic fluid, large stone stuck in gallbladder
order) neck, sonographic Murphy's sign (maximum tenderness
➢ Asymptomatic stones elicited by probe over site of gallbladder)
1) Most asymptomatic gallstones DO NOT require
treatment
2) Consider operating if calcified porcelain
gallbladder, sickle cell disease (15-20% associated
DISORDERS OF THE STOMACH
cancer), DM, history of biliary pancreatitis
➢ Biliary colic
GASTRITIS
➢ Cholecystitis - acute and chronic
➢ Inflammation of the Stomach Lining
➢ Complications of cholecystitis
➢ Choledocholithiasis (CBD stones)
Etiology & Pathogenesis
➢ Cholangitis
➢ Acute:
➢ Biliary induced pancreatitis
1) 15% Alcohol
➢ Biliary induced ileus
2) NSAIDs > Inhibits COX > decrease Prosƚaglandin
> Hyperacidity > Inflammation
CHOLECYSTITIS
3) Severe Burns > decrease Plasma Volume >
ACUTE CHOLECYSTITIS
Sloughing of Stomach Mucosa
➢ Chronic:
Mechanism
1) 80% Bacterial - Helicobacter Pylori (Most
➢ Inflammation of gallbladder resulting from sustained
Common)
obstruction of cystic duct by gallstone (80%)
 ➢ Atrophic: ➢ Nausea & Vomiting
1) Autoimmune ʹPernicious Anemia (Antibodies ➢ Anorexia & Weight Loss
against Parietal Cell & IF > B12 Deficient) ➢ Hematemesis/Melena
➢ (Perforation > Acute Peritonitis)
Clinical Features
➢ Symptoms: Investigation
1) Abdo Pain, Dyspepsia, Bloating, Nausea, Vomiting, ➢ Clinical History
with or without Hematemesis (if PUD), with or ➢ Endoscopy + Biopsy (Ulcer H. Pylori Gastric Cancer?)
without Anemia (If Pernicious B12 Deficiency) ➢ C13 Urea Breath Test - (H. Pylori The Best
NON-Invasive Diagnosis)
Investigations ➢ Serology (IgG) - (H. pylori)
➢ C13 Urea Breath Test - (H.Pylori) ➢ H. Pylori Fecal Antigen Test - (H.pylori)
➢ Serology (IgG) - (H.Pylori)
➢ H.pylori Fecal Antigen Test - (H.Pylori) Treatment
➢ Endoscopy + Gastric Biopsy - (H.Pylori Microscopy + ➢ Conservative - Avoid Precipitating Factors
Gastric Cancer) (Alcohol/NSAIDs)
➢ Antacids
Treatment ➢ PPIs - (Omeprazole) or H2-Antagonists - (Ranitidine)
➢ Conservative ➢ H. Pylori Triple Eradication Therapy (Clarithromycin
1) Avoid Precipitating Factors (Alcohol/NSAIDs) + Amoxicillin with or without Metronidazole)
2) Antacids ➢ Emergency Surgery (If Hematemesis, Rupture,
3) PPIs - (Omeprazole) or H2-Antagonists - Peritonitis, Cancer
(Ranitidine)
4) H.Pylori Triple Eradication Therapy - Complications
(Clarythromycin + Amoxicillin with or without ➢ GI Bleeding > Anemia
Metronidazole) ➢ Perforation > Hemorrhage/Shock, Peritonitis, or Into
5) If Pernicious ʹ (B12 Injections) Pancreatitis
➢ Pyloric Stenosis (Scarring) > Gastric Outlet
PEPTIC ULCER DISEASE Obstruction > Vomiting
➢ GASTRIC CANCER (Note: H. Pylori > 6x Risk of
Etiology (Either) Cancer)
➢ Increase Attack (Hyperacidity, Zollinger Ellison
Syndrome)
DISORDER OF THE PANCREAS
➢ Decrease Defense (H.Pylori, Stress, Drugs [NSAIDs &
Corticosteroids], Smoking)
ACUTE PANCREATITIS

Morphology
Etiology
➢ Small, Single, Round, Punched out Ulcer
➢ 50% - Gallstones (Cholelithiasis) > Ampulla/Common
➢ 90% in Duodenum or Lesser-Curve of Stomach
Bile Duct Obstruction
➢ Healing Peptic Ulcers have Radiating Mucosal Folds
➢ 40% - Alcohol Abuse
due to scar contraction.
➢ 10% Infections/Metabolic (increase Ca in
hyperparathyroidism) DKA, Uremia Pregnancy,
Clinical Features
Trauma, Ischemia, Duodenal, Ulcer, Scorpion Venom,
➢ Burning Epigastric Pain; (Most Severe when Hungry.
Drugs, Unidentified
Relieved by Food)
 DISORDERS OF THE INTESTINES
Pathogenesis
➢ Autodigestion of Pancreas > Reversible Inflammation >
GASTROENTERITIS
with or without Necrosis
Bacterial Gastroenteritis & Food Poisoning
➢ Can lead to Systemic Inflammatory Response
Syndrome
1. TOXIGENIC DIARRHEA (FOOD POISONING)
1) Shock
2) Acute Renal Failure
Etiology
3) Acute Respiratory Distress Syndrome
➢ Staph Aureus (Poor Food Handling)
➢ Bacillus Cereus (Mostly found in cereal
Clinical Features
➢ An Acute Medical Emergency:
Symptoms
➢ Signs/Symptoms:
➢ Onset Within 4hrs - Vomiting, Stomach Cramps,
1) Epigastric/Abdominal Pain
Diarrhea
2) Precipitated by Large Meal or Alcohol
3) Peritonitis - (Guarding + Rigidity)
Pathogenesis
4) Vomiting
➢ Toxigenic Diarrhea
5) If Hemorrhage > Hypotension & Shock > Grey
➢ Note: Some toxins are Heat Stable
Turner’s and Cullen sign
➢ Local Complications:
Diagnosis
1) Pancreatic Abscess/Infection
➢ History + Clinical Course
2) Pseudocysts
➢ Retrospective Epidemiology > Find Common
3) Duodenal Obstruction
Denominator (Who ate what??)
➢ Systemic Complications:
➢ Stool OCP if worried.
1) Jaundice
2) DIC (Diss.Iv.Coag)
Treatment
3) ARDS (Respiratory Distress)
➢ Supportive Treatment - (Fluid & Electrolyte
4) Acute Renal Failure
Replacement)
➢ Anti-Diarrheal Controversial > Symptomatic but
Diagnosis
decreases toxin expulsion
➢ Rule out Other Causes of Acute Abdomen
1) Appendix, Diverticulitis, Peptic Ulcer,
2. ESCHERICHIA COLI – (TRAVELERS DIARRHEA)
Cholecystitis, Ischemia Bowel, Bowel Obstruction
➢ Increase Serum Amylase (Within 24hrs)
➢ ETEC: (Enterotoxigenic E. coli)
➢ Increase Serum Lipase (After 72hrs/3days)
1) Produces Toxins:
➢ CBC - Neutrophil Leukocytosis
2) Travelers Diarrhea
➢ Increase Alkaline Phosphatase; If Biliary Stasis
➢ EIEC: (Enteroinvasive E. coli)
➢ Increase Bilirubin
1) Active Intestinal Invasion/Destruction
➢ (ERCP/MRCP if Indicated)
2) Travellers Dysentery
➢ NOT Biopsy HAZARDOUS
➢ EPEC: (Enteropathogenic E. coli)
1) Sporadic disease in babies and children
Prognosis
➢ EHEC: (Entero-Hemorrhagic E. coli)
➢ 80% - Self-Limiting with Supportive Treatment
1) The Serious One:
➢ 20% - Life Threatening & one or More-Organ Failure
(Requires ICU)
 2) Produce Verotoxin > Destroys Platelets & RBCs > Pathogenesis
HEMOLYTIC-UREMIC SYNDROME > ➢ Destruction of Enterocytes > Gastroenteritis
Kidney Failure, Bleeding, Dysentery ➢ Produces ͚Toxic Rotavirus Protein- NSP4 > Induces
Chloride Secretion > Inhibits Water Absorption in gut
3. SALMONELLA; TYPHOID
Clinical Features
Etiology ➢ Timeframe:
➢ Salmonella typhi 1) Incubation Period = 2 days
2) Duration of Symptoms = 6 days
Pathogenesis 3) Still infective for = 2 days after symptoms subside
➢ Dysentery ➢ Any kid with vomiting/diarrhea should stay home for
➢ Can cause Septicemia more than 1 week to minimize transmission
➢ Also, Fever, rose spots, delirium, perforation of bowel
Symptoms
Management ➢ Vomiting (projectile)
➢ Ceftriaxone with or without Ciprofloxacin ➢ Diarrhea
➢ Flu-Like Illness - (Fever, Irritability, Poor Feeding,
4. LISTERIOSIS (LISTERIA) Myalgia)

Etiology Diagnosis
➢ Listeria Monocytogenes – (G-Pos) ➢ Clinical Diagnosis of Gastroenteritis
➢ (Soft Cheeses & Cold Deli Meats) ➢ Definitive Diagnosis via Stool Sample
1) Enzyme Immunoassay
Risk to Pregnant Women & Immunocompromised 2) RT-PCR

5. CHOLERA Management
➢ Supportive Mx
Etiology ➢ FLUID REPLACEMENT!
➢ Vibrio Cholerae ➢ Quarantine (Especially for Immunocompromised or
Chemo Pts)
Symptoms
➢ Profuse Rice-Water Stools o CONSTIPATION
The passage of infrequent or hard stools with straining (less than
Management 50 ml per day)
➢ Fluid Replacement o Prognosis: Self-Limiting
➢ Note: DYSENTERIC ORGANISMS: Salmonella, Etiology
Shigella, Entamoeba Histolytica ➢ In the absence of other clinical problems, most
commonly due to lack of fiber in the diet, change of
VIRAL diet, or poorly understood gut motility problems
➢ Organic causes include:
Etiology 1) Medication side effects (antidepressants, codeine)
➢ 80% Norovirus (Adult Diarrhea) 2) Left sided colon cancer (consider in older patients)
➢ Rotavirus (Kid Diarrhea <3 y/o); usually from Day Care 3) Metabolic
Centers ▪ DM
➢ Fecal-Oral Transmission ▪ Hyperthyroidism
 ▪ Hypercalcemia GIARDIA
4) Collagen vascular diseases
▪ Scleroderma Pathogenesis
▪ Amyloidosis ➢ Not Toxigenic; Rather, it covers the brush border >
5) Neurological Malabsorption
▪ intestinal pseudo-obstruction
▪ Parkinson’s disease Diagnosis
▪ Multiple sclerosis ➢ Cysts in Stools

Investigations Complications
➢ Swallow radio opaque markers to quantitate colonic ➢ Chronic Infection
transit time (normal: 70 hours) ➢ Malabsorption
1) Malnutrition
Treatment: (in increasing order of potency) 2) Fatty Stools
➢ Surface acting (soften and lubricate)
o Docusate salts and mineral oils Treatment
➢ Bulk forming ➢ Metronidazole
o Bran, psyllium seeds
➢ Osmotic agents CRYPTOSPORIDIUM
o Lactulose, sorbitol, magnesium citrate, magnesium
sulfate, magnesium hydroxide, sodium phosphate Transmission
➢ Cathartics ➢ Ingestion of oocysts (Contaminated Drinking Water or
o Castor oil, senna (watch out for melanosis coli) Public Pools)
➢ Can survive Chlorination

PARASITIC GUT INFECTIONS

Pathogenesis is mostly unknown
➢ Possibly induces inflammatory response > Disrupts
PARASITIC GUT INFECTIONS (Protozoa & Helminths)
absorptive surface
➢ Damages Villi > Crypt Cells Replicate faster to replace
Transmission
them > Immature cells in the villus > Poor absorption.
➢ Fecal-Oral - (Ingestion of Dormant Cysts in
Contaminated Food and Water)
Treatment
➢ Nitazoxanide (Normally Self-Limiting if
Diagnosis
Immunocompetent)
➢ Stool Samples (Looking for cysts) under Direct
Microscopy
Long term Effects
➢ Antigen Testing
➢ AIDS PATIENTS DO NOT RECOVER > Chronic
Infection
Prevention
➢ Boiling Water to Eliminate Cysts
Diagnosis
➢ Good Hygiene
➢ Cysts in Stools
➢ Avoiding Fecal Contact
ENTAMOEBA HISTOLYTICA (The Amoebic Dysentery)

Transmission
➢ Ingestion of oocysts (Fecal Oral)

Pathogenesis
➢ Intestinal Invasions, Ulcerations, Dysentery (Bloody
Diarrhea)

Diagnosis
➢ Cysts in Stools

Management
➢ Metronidazole

HELMINTHIC INFECTIONS
➢ Clinically significant helminths are soil transmitted

1) Infection via swallowing infected eggs

a. Ascaris lumbricoides (roundworm)
b. Trichuris trichiura (whipworm)
2) 2. Infection via Active skin penetration
a. Strongyloides stercoralis (threadworm)
b. Ancylostoma duodenale (hookworm)

Management
➢ Albendazole
 PATHOPHYSIOLOGY

Clinical Features:
MODULE 8 OUTLINE - Usually, Unilateral o Painful Hematuria ʹ
Macro/Micro
I. Lithiasis - Writhing in pain͕ pacing about and unable
a. Nephrolithiasis to lie still͟
b. Urolithiasis - Hydronephrosis > Stretching of Renal
II. Common infections of the Renal System Capsule > Flank Pain & Tenderness.
a. Pyelonephritis o Stone in Ureteropelvic Junction >
b. Cystitis Deep flank pain. No radiation.
c. Gonococcal and Non-Gonococcal Distension of the Renal Capsule.
Urethritis o Stone in Ureter > Intense, Colicky
III. Glomerular Diseases Pain (Loin > Inguinal Region >
a. Nephritic Syndrome Testes/Vulva) + N/V.
b. Nephrotic Syndrome o Stone in Ureterovesical Junction >
IV. Renal Failure Dysuria, Frequency, + Tip of penis
a. Acute pain
b. Chronic Complications:
- Hydronephrosis
LITHIASIS - Post-Renal Failure
NEPHROLITHIASIS & UROLITHIASIS - Infection >ʹ (UTI/Pyelonephritis/Perinephric
Abscess)
Etiology: Investigations:
- Hypercalcemia (Eg. Inc intake, or Hyper- - Abdo USS – (Confirm Stone)
PTH) > Calcium Stones 80% - Abdo XR – (Confirm Calcium Vs Radio-
- Chronic UTI > Triple Phosphate /Struvite/ Lucent Stone)
“Staghorn” Stones 15% - UECs – inc. Calcium or inc. Urea
- Uremia > Urate Stones (+ Gout) Management:
- Conservative – (Daily Na-Bicarbonate
Pathogenesis: Tablets to Alkalize Urine > Dissolve Urate
- Hypercalcemia > Calcium in Urine Stones)
Precipitates out of Solution > Calcium - (ESWL) Extracorporeal Shock-Wave
Stones 80% Lithotripsy - (For Calcium Stones)
- Chronic UTI > Gram-Neg Rods (Proteus, - Surgical – (For All Stones Not Amenable to
Pseudomonas & Klebsiella - NOT E. coli) > the above)
Triple Phosphate/Struvite/ “Staghorn” Location of Stones
Stones 15% a. calyx
- May cause > Urinary Obstruction > - may cause flank discomfort, recurrent
Hydronephrosis > Stretching of Renal infection or persistent hematuria
Capsule > Pain) - may remain asymptomatic for years and
not require treatment
Morphology: b. pelvis
a. Calcium Stones 80% - tend to cause UPJ obstruction renal pelvis
- Small, hard Stones (1-3mm); and one or more calyces
- Stones have sharp edges c. staghorn calculi
- Radio-Opaque - often associated with infection
b. Triple Phosphate/Struvite/ “Staghorn” Stones - infection will not resolve until stone
15% cleared
- Large Stones (Molds to Renal - may obstruct renal drainage
Pelvis/Calyces) ʹ Hence Staghorn͘͟ d. ureter
- Chronic Irritation of Epithelium surrounding - 5 mm diameter will pass spontaneously in
Stone > Squamous Metaplasia 75% of patients the three narrowest
passage points for upper tract stones
include: UPJ, pelvic brim, UVJ

[MODULE 8 – RENAL] Handout Prepared by: Michael Angelo Sumugat RMT, MD 1

 PATHOPHYSIOLOGY

Stone Pathogenesis 3. Uric Acid Stones

Factors promoting stone formation - Account for 10% of all stones
- stasis (hydronephrosis, congenital - Description and diagnosis
abnormality) o orange colored gravel, needle
- medullary sponge kidney • infection shaped crystals
(struvite stones) o radiolucent on x-ray
- hypercalciuria o filling defect on IVP
- increased oxalate o Radiopaque on CT scan
- increased uric acid o Visualized with ultrasound
Loss of inhibitory factors Etiology
- magnesium (forms soluble complex with o hyperuricosuria (urine pH < 5.5)
oxalate) o secondary to increased uric acid
- citrate (forms soluble complex with production, or drugs (ASA and
calcium) probenecid)
- pyrophosphate o hyperuricemia
- glycoprotein o gout
o myeloproliferative disease
STONE TYPES o cytotoxic drugs
1. Calcium Stones o defect in tubular NH3 synthesis
- Account for 80 - 85% of all stones (ammonia trap for H+)
- Ca2+ oxalate most common, followed by o dehydration, IBD, colostomy and
Ca2+ phosphate description ileostomy
- grey or brown due to hemosiderin from Treatment
bleeding o increase fluid intake
- radiopaque o NaHCO3 (maintain urinary pH no
2. Struvite Stones less than 6.5)
- Female patients affected twice as often as o allopurinol
male patients o avoid high protein/purine diet
- Etiology and pathogenesis
o account for 10% of all stones 4. Cystine Stones
o contribute to formation of staghorn - Autosomal recessive defect in small bowel
calculi mucosal absorption and renal tubular
o consist of triple phosphate (calcium, absorption of dibasic amino acids
magnesium, ammonium) - Seen in children and young adults
o due to infection with urea splitting - Aggressive stone disease
organisms NH2CONH2 + H2O ––> - Description
2NH3 + CO2 o hexagonal on urinalysis
o NH4 alkalinizes urine, thus o yellow, hard
decreasing solubility o radiopaque (ground glass)
- Common organisms o staghorn or multiple
o Proteus o decreased reabsorption of “COLA”
o Klebsiella o cystine (insoluble in urine);
o Pseudomonas ornithine, lysine, arginine (soluble in
o Providencia urine)
o S. aureus
o not E. coli Diagnosis
o amino acid chromatography of urine
Treatment ––> see COLA in urine
- Complete stone clearance o serum cystine
(ESWL/percutaneous nephrolithotomy) o Na+ nitroprusside test
- Acidify urine, dissolve microscopic
fragments
- Antibiotics for 6 weeks
- Follow up urine cultures
[MODULE 8 – RENAL] Handout Prepared by: Michael Angelo Sumugat RMT, MD 2
 PATHOPHYSIOLOGY

Clinical Presentation
Treatment - Rapid onset (hours to a day)
o greatly increase water intake ––> 3- - Lethargic and unwell, fever, tachycardia,
4 L urine/day shaking, chills, nausea and vomiting,
o HCO3– myalgias
o decrease dietary protein ––> - Marked CVA or flank tenderness; possible
methionine abdominal pain on deep palpation
o penicillamine chelators ––> 2 g daily, - Symptoms of lower UTI may be absent
soluble complex formed; use (urgency, frequency, dysuria)
cautiously - May have symptoms of Gram-negative
o a-mercaptopropionylglycine (MPG) – sepsis
–> similar action to penicillamine, Laboratory Investigations
less toxic - Urine dipstick: +ve for leukocytes and
o captopril (binds cystine) nitrites, possible hematuria
o Irrigating solutions: N-acetylcysteine - Microscopy: > 5 WBC/HPF in unspun urine
(binds cystine), Tromethamine-E or > 10 WBC/HPF in spun urine, bacteria
- Gram stain: Gram negative rods, Gram
III. COMMON INFECTIONS OF THE URINARY positive cocci
SYSTEM - Culture: > 105 colony forming units
(CFU)/mL in clean catch midstream urine or
a. Pyelonephritis > 102 CFU/mL in suprapubic aspirate or
catheterized specimen
1. Acute Pyelonephritis - CBC and differential: leukocytosis, high %
- Infection of the renal parenchyma with local neutrophils, left-shift (increase in band cells
and systemic manifestations of infection - immature neutrophils)
- may be classified as uncomplicated or - Blood cultures: may be positive in 20% of
complicated cases, especially in S. aureus infection
o uncomplicated: in the absence of - Consider investigation of complicated
conditions predisposing to anatomic pyelonephritis:
or functional impairment of urine o if fever, pain, leukocytosis not
flow resolving with treatment within 72
o complicated: occurring in the setting hr, if male patient, or if there is
of renal or ureteric stones, history of urinary tract abnormalities
strictures, prostatic obstruction (abdo/pelvis U/S, CT for renal
(hypertrophy or malignancy), abscess, spiral CT for stones,
vesicoureteric reflux, neurogenic cystoscopy)
bladder, catheters, DM, sickle-cell Treatment
hemoglobinopathies, polycystic - Uncomplicated pyelonephritis with mild
kidney disease, immunosuppression, symptoms
and post-renal transplant o 14-day course of TMP/SMX or
Etiology fluoroquinolone or third generation
- Usually ascending microorganisms, most cephalosporin
often bacteria o Start with IV for several days and
- in females with uncomplicated then switch to PO (can then be
pyelonephritis usually E. coli treated as outpatient)
- causative microorganisms are usually E. coli, - Patient more than mildly symptomatic or
Klebsiella, Proteus, Serratia, Pseudomonas, complicated pyelonephritis in the setting of
Enterococcus, and S. aureus stone obstruction is a urologic emergency
- If S. aureus is found, suspect bacteremic (placing patient at risk of kidney loss or
spread from a distant focus (e.g. septic septic shock)
emboli in infective endocarditis) and o start broad spectrum IV antibiotics
suspect (possible multiple intra-renal micro until cultures return (imipenem or
abscesses or perinephric abscess) meropenem or piperacillin
/tazobactam or ampicillin plus
gentamicin) and treat 2-3 weeks
[MODULE 8 – RENAL] Handout Prepared by: Michael Angelo Sumugat RMT, MD 3
 PATHOPHYSIOLOGY

o follow-up cultures 2-4 weeks after 1. MCD (Minimal Change Disease) / Foot Process
stopping treatment Disease/ Nil Disease)
- If no improvement in 48-72 hr, need to - MCD = THE Childhood cause of Nephrotic
continue on IV antibiotics, assess for Syndrome (1-8yrs)
complicated pyelonephritis or possible renal Etiology:
or perinephric abscess - Post-Infective (URTI)
Clinical Features:
Prognosis - Eg. 2yo Boy with sudden onset Polyuria,
- Treated acute pyelonephritis rarely Oedema & Proteinuria following URTI.
progresses to chronic renal disease - Children (1-8yrs)
- Recurrent infections often constitute - Prognosis - Spontaneous Remission <70% of
relapse rather then re-infection patients; Some may progress to FSGS

2. Chronic Pyelonephritis 2. MGN (Membranous Glomerulonephrosis):

- MGN = >50% of Adult Nephrotic Syndrome:
- A form of chronic tubulointerstitial nephritis
of bacterial origin Etiology
- Cortical scarring, tubulointerstitial damage, - Autoimmune - Ag:Ab Complex Deposition
and calyceal deformities seen Clinical Features:
- May be active (persistent infection) or - Eg. 35y female, Tired for years, Worsened
inactive (persistent focal sterile scars post- for two months. She has noted swelling of
infection) her legs and puffiness around eyelids
- Histologically indistinguishable from many (Periorbital edema - A classic sign of
other forms of TIN (severe vesicoureteral nephrotic syndrome).
reflux, hypertensive disease, analgesic - Adults - 40-60yrs
nephropathy) - Nephrotic Syndrome - Polyuria, +++
- Active chronic pyelonephritis may respond Proteinuria, edema.
to antibiotics - Prognosis - Good, but Occasionally
- Need to rule out TB progresses to ESRD

III. GOMERULAR DISEASES 3. FSGS (Focal Segmental Glomerulosclerosis):

a. NEPHROTIC SYNDROMES - <35% of Adult Nephrotic Syndrome

(Incomplete Glomerular-Membrane Damage) - Vey similar to MCD but in adults

Clinical Features Etiology: Same as MCD

- Normal GFR - Often a recent history of an URTI
- +++Polyuria Clinical Features:
- ++++ Proteinuria (>3000mg/day: Nephrotic) - Eg., 49 y/o Nephrotic Syndrome, non
o > Granular (Protein) Casts. responsive
o > Edema (Especially Periorbital) - Nephrotic Syndrom - +++ Selective
o > Hypercoagulability (Loss of Proteinuria
Antithrombin-III in Urine) - Prognosis – Poor: 30% Remission; 50% CKD
o > Immunocompromise state (Loss of and 20% RPGN
Ig in Urine)
o Hyperlipidemia (Attempted Hepatic b. NEPHRITIC SYNDROMES
Compensation for dec. Plasma (Complete Glomerular-Membrane Damage)
Osmolarity)
- Serum Creatinine Mildly Elevated Clinical Features of Nephritic Syndrome:
o (Dehydrated due to Polyuria; But - Dec GFR
Edematous due to Proteinuria) - Oliguria
o > Renal Hypertension
(Hypoperfusion of JG Cells due to
dec GFR)

[MODULE 8 – RENAL] Handout Prepared by: Michael Angelo Sumugat RMT, MD 4

 PATHOPHYSIOLOGY

o > Fluid Overload Edema: (dec Plasma Pathogenesis:

Osmolality & Na + H2O Retention) - Rapidly Progressing Glomerulonephritis >
- Microalbuminuria Renal Failure within Weeks.
- ++++ Hematuria Clinical Features:
o > RBC (Cellular) Casts. - Nephritic Syndrome - Oliguria, Painless
o > Anemia Hematuria, Non-Selective Proteinuria,
- Inc. Creatinine Oedema, Hypertension
Prognosis:
Fluid Overloaded due to Oliguria; And Edematous - Poor: Quickly progresses to ESRF
due to Fluid Overload)
IV. RENAL FAILURES
1. PSGN (Post-Strep Glomerulonephritis)
a. Acute Renal Failures
- PSGN = THE Childhood cause of Nephritic
Syndrome (3-15yrs) Acute Renal Failure - General Information:
- Eg. 8-year-old girl with fever, oliguria, Etiology:
smoke colored urine & hypertension - Rapid loss of kidney function͟
following upper respiratory tract infection.
Etiology: 1. Pre-Renal Renal Failure:
- Post-Infective (GABH-Streptococcal - Before the Blood Reaches the Kidney (Ie.
Pharyngitis) Ag:Ab Complex Deposition Dec. Glomerular Perfusion)
Clinical Features: o Hypovolemia (Eg. Blood Loss)
- Nephritic Syndrome - Oliguria, Painless o Decreased cardiac output (Eg. Heart
Hematuria, Non-Selective Proteinuria, Failure)
Edema, Hypertension o Renal artery obstruction (Eg.
Prognosis: Embolism)
- Good Prognosis in Children (But progressive 2. Intra-Renal Renal Failure - The kidney itself is
in adults) damaged
- Acute glomerular nephritis
2. IgA Nephropathy (Berger’s Disease) - Tubular diseases e.g., acute tubular necrosis
- IgA-Nephropathy = THE Adult (15-30yrs) - Interstitial diseases e.g., auto immune
Cause of Nephritic Syndrome disorders such as SLE
- Eg. 18y male Recurrent, Episodic Painless - Vascular diseases e.g., polyarteritis nodosa
+++Hematuria, 3-6 days, usually following
URTI. 3. Post-Renal Renal Failure
Etiology: - Due to outflow obstruction from the
- Autoimmune - Ag:IgA Complex Deposition kidneys
in Glomerulus o Cancer - Bladder / Prostate /
Clinical Features: Ureteric / Cervical
- Nephritic Syndrome - Oliguria, Painless o Blood clot
Hematuria, Non-Selective Proteinuria, o Calculi (Kidney stones - Bilateral)
edema, Hypertension o Accidental surgical ligation
- High Serum IgA Clinical Features:
- Uremia - (Fatigue, Malaise, Anorexia,
Prognosis: Headache, Nausea, Vomiting)
- 30% > Slowly Progressive - Hyperkalemia > Brady-Arrhythmias \
- 10% > Renal Failure - Fluid Retention > Oedema (Peripheral &
Pulmonary)
3. RPGN (Rapidly Progressive Glomerulonephritis): o RARELY, Hypertension & Cardiac
- RPGN = NOT a Separate Disease; ANY Tamponade.
Glomerulonephritis can > RPGN - Hematuria - Painless (Cancer) or Painful
Etiology: (Stones/LUTS)
- Progression of any Glomerulonephritis - Flank pain (in specific conditions -
(Autoimmune) Particularly Inflammatory or Ischemic)

[MODULE 8 – RENAL] Handout Prepared by: Michael Angelo Sumugat RMT, MD 5

 PATHOPHYSIOLOGY

4 Stages of Chronic Renal Failure Urine Protein:Creatinine Ratio - Is there

Stage 1 = > 90 ml/min GFR (Normal) plus Proteinuria?
other signs of renal disease
Interpretation:
Stage 2 = 90-60 ml/min GFR - Daily Creatinine Excretion is Constant : inc
P: CR = Inc Protein in Urine = Proteinuria
Stage 3 = 60-30 ml/min GFR
30-300mg = Microalbuminuria
Stage 4 = 30-15 ml/min GFR >300mg = Macroalbuminuria/Proteinuria͘͟
>3000mg = Nephrotic Syndrome
Stage 5 = <15 ml/min GFR
b. Chronic Renal Failure
Clinical Complications of Renal Disease
- General Effects/Problems Encountered in - Many etiologies: continuum of progressive
Renal Failure: (Recall the functions of the nephron loss and declining renal function
kidney and then infer what happens when - Asymptomatic until severe insufficiency
they are eliminated!) develops
o Acid Base Balance (Renal Failure > - Regional variation in leading causes
Met. Acidosis) worldwide
o Electrolyte Balance (Renal Failure > o In North America: diabetes (> 30%),
Na+ & K+ Retention) hypertensive renal disease (23%),
o Fluid Balance (Renal Failure > Fluid chronic GN (10%) (e.g. IgA
Overload) nephropathy), polycystic kidney
o Dec Erythropoiesis (Renal Failure > disease (5%)
Anemia) - Frequently patients present at end-stage
o Renin Angiotensin System > Renal with small, contracted kidneys, unknown
Hypertension etiology
o Calcium Metabolism (Renal Failure >
Osteoporosis & secondary Hyper- Classification
Parathyroidism) - glomerular: primary or secondary
o Uremia glomerulonephritis
o Dec Urine Output - tubulointerstitial disease (e.g., autoimmune
o Dec Toxin Excretion (Renal Failure > interstitial nephritis)
Accumulation of Urea & Creatinine) - vascular (e.g., DM, HTN)
- hereditary (e.g. autosomal dominant
Investigations: polycystic kidney disease, Alport’s)
- Blood Urea: Creatinine Ratio -
Distinguishing Between Intra/Pre/Post- INDICATIONS FOR DIALYSIS IN CRF
Renal Failure: - Maybe same as ARF
- more commonly = “dwindles”
Dec U:Cr = Intra Renal o anorexia, nausea, vomiting, severe
(Infection/toxin/Ischemia/Hypoxia/) fatigue, pruritus, muscle cramps
PATHOLOGIC KIDNEY!! o dialyze when creatinine clearance <
10% of normal (< 10 mL/min)
However, if: - diabetics less tolerant of uremia, dialyze
when creatinine clearance < 15% of normal
Inc U:Cr = EITHER Pre Renal ( Hypotension/ (< 15 mL/min)
Dehydration /Normal Kidney) - Prognosis: all with progressive renal failure
OR progress to dialysis/transplant
Post Renal (BPH/Bladder Stone/Normal Kidney)

******** END OF MODULE 8 ********

[MODULE 8 – RENAL] Handout Prepared by: Michael Angelo Sumugat RMT, MD 6

 PATHOPHYSIOLOGY

Invasion Via Peripheral Nerves:

MODULE 9 OUTLINE - Rabies and other Lyssaviruses may invade
Muscle Cells @ The Bite Site > Move up the
I. CNS infections Nerves to the Dorsal Root Ganglia > Spinal
a. Meningitis Cord > Brain
i. Bacterial - Herpesviruses may migrate up the nerves
ii. Fungal using normal retrograde transport
iii. Viral mechanisms
iv. Neonatal
v. Tuberculous The Blood Brain Barrier in Pharmacokinetics:
b. Encephalitis - The BBB Blocks access of certain chemicals
i. Poliovirus encephalitis to the CNS.
ii. Rabies encephalitis - Antimicrobial Drugs MUST be able to cross
c. Brain abscess the BBB in order to fight CNS Infection.
II. Drug associated
a. Alcohol intoxication Definitions:
III. Degenerative diseases 1. Viral Meningitis:
a. Alzheimer’s dementia - Inflammation of the Meninges of the brain
b. Senile (Age – related) dementia due to viral etiology.
IV. Cerebrovascular accident (stroke) - (Eg. By Herpes Simplex Virus)

CNS INFECTIONS 2. Bacterial Meningitis:

- Inflammation of the Meninges of the Brain
due to Bacterial Etiology.
- The blood brain barrier restricts the entry of - (Typically: Neisseria Meningitidis,
pathogens into the brain and meninges: Streptococcus Pneumoniae, Hemophilus
o Hematogenous spread of organisms Influenzae)
requires spread through at least 2
layers to infect the brain. 3. Encephalitis:
- Inflammation of the Brain
- (Typically due to Viruses – eg. Herpes
Simplex)

4. Meningoencephalitis:
- Inflammation of the Brain & the Meninges

5. Myelitis:
Mechanisms of Entry into the CNS: - Inflammation of the Spinal Cord > Disrupts
• Hematogenous Spread (Bloodborne Invasion) CNS functions liking the brain & limbs.
into the CNS: - (Eg. Poliovirus (Poliomyelitis))
– Growing across:
• Microbes can grow in the endothelial cells 6. Encephalomyelitis:
and then into the astrocytes or choroid - Inflammation of the Brain and Spinal Cord
plexus - Typically Immune-mediated following a viral
– Passive: infection.
• Transported across in intracellular vacuoles - (Eg. Acute Disseminated Encephalomyelitis
– Carried in infected cells: – Following Influenza, enterovirus, measles,
• Infected inflammatory cells can migrate into mumps, rubella, varicella zoster, etc.)
the brain and meninges, lyse and release
the organism or the organisms may pass 7. Brain Abscesses:
from cell to cell - Encapsulated Pus or Free-Pus in the Brain
(Eg. Infection of brain or meninges after an Acute Focal Purulent Infection.
by enteric viruses e.g. polio): - (Focal Infections include: Otitis
Media/Sinusitis)

[MODULE 8 – NEUROLOGY] Handout Prepared by: Michael Angelo Sumugat RMT, MD 1

 PATHOPHYSIOLOGY

A. MENINGITIS Meningitidis Changes the Immunogenicity of its

Capsule.
Presentation: Meningism: • Immune System has to Start Again
- *Neck Stiffness • N. Meningitidis Prevails.
- *Photophobia
- *Headache 2. Hemophilus Influenza:
- (Fever/Malaise) - Gram Negative Cocco-bacilli
- Usually in Children / Babies
Meningitis - CSF Examination: - Toxin production > Tissue damage
• Three Successive Samples are Taken: - Vaccine Available (Hib Vaccine)
- To Eliminate Contamination
- By the 3rd Sample, there should be NO 3. Streptococcus Pneumoniae:
Contamination - Gram Positive Cocci
- RBC indicates contamination - Predisposed Adults
- Neonates
Sample 1: Used for Serology
- Serology Other Etiologies:
- or PCR 1. Neonatal Meningitis:
- Escherichia coli
Sample 2: Used for Biochemistry - Group B Streptococci
- Glucose - (High Mortality Rates (35% of cases))
- Protein
- Antigen Agglutination 2. Tuberculous Meningitis:
- Mycobacterium tuberculosis:
Sample 3: Used for Bacteriology – Most Precious - Acid fast bacilli (Stains with Ziehl Neelsen
- Gram stain stain)
- Culture - Patients Typically have a Focus of Infection
Elsewhere
a. Septic/Bacterial Meningitis: • :. Most of cases are associated with Miliary
- More Severe than Viral (disseminated) Tuberculosis
- Less Common than Viral
• Pathogenesis: Features Suggestive of etiology

The 3 Common Bacterial Implicated in Bacterial 1. Rash - erythematous, petechial / purpuric.

Meningitis: a. Suggests meningococcus (rarely
Pneumococcus or Hemophilus influenzae
1. Neisseria Meningitis: type b)
- Gram Negative Diplococci
- Usually in Stressed/Crowded
- Severe toxin sequalae > Tissue damage
- Vaccine only for Serotypes A & C (Not B –
Which is the most common)

UPDATE! Serogroup B vaccine only became

available in the US in 2014 and very few have
received it.

- Serotype B Capsule molecules mimic Neural

Tissue > Vaccine Cross Reacts)
- Capsule Switching:
• By the time the immune system has
mounted an Adaptive Immune Response, N.
Meningitidis Changes the Immunogenicity
of its Capsule.
[MODULE 8 – NEUROLOGY] Handout Prepared by: Michael Angelo Sumugat RMT, MD 2
 PATHOPHYSIOLOGY

2. RATHER, It aims to Eliminate

Nasopharyngeal Carriage > Prevent
2. CSF rhinorrhea or otorrhea - basal skull fracture: subsequent transmission.
a. Pneumococcus, H. influenzae, Hemolytic 3. Offered to Household, child care
Strep. and CLOSE CONTACTS.
b. (CSF Rhinorrhea refers to the drainage of 4. No evidence for salivary spread.
Cerebrospinal Fluid through the nose. It is a
sign of Basal Skull Fracture.)
b. Fungal Meningitis:
3. Prominence of seizures or focal signs early: - Mainly Cryptococcus Neoformans
a. Consider Listeria monocytogenes, Herpes - Typically in Immunosuppressed
simplex. - Can be treated with antifungal drugs

Etiology suggested by age group c. Viral Meningitis:

- Less Severe than Bacterial
- More Common than bacterial

• Presentation:
- Usually are milder disease than bacterial
meningitis
- Headache, fever and general illness but less
neck stiffness
- Generally Complete Recovery

• Examination of CSF:
- The CSF is clear and free of bacteria
- CSF Contains Mainly Lymphocytes

• Viruses Implicated in Viral Meningitis:

a. Herpes Simplex
- Uncommon; may follow congenital
infection with HSV2
Meningitis Management: b. Mumps
- A quite common complication
1. Early Antibiotic Therapy is Essential for Good c. Poliovirus, coxsackievirus, echovirus
Outcome!!! - Commonly seen especially due to
a. Even if they are Pre-Diagnosis. echoviruses
2. Always Do Blood Cultures!! d. Enterovirus 71
3. Antibiotics must be: - May follow hand foot and mouth disease
a. Effective Against Likely Pathogens e. Japanese encephalitis
b. Able to cross an Inflamed Blood Brain - India, Southeast Asia, Japan
Barrier f. Eastern and Western equine encephalitis
c. Given Parenterally and in high dose. - Eastern and Western USA
4. Corticosteroids (Dexamethasone) are given prior g. HIV
to antibiotics > ↓CNS Inflammation: - May occur early after infection
a. > Improves Neurological Outcome in all
cases of suspected bacterial meningitis. B. ENCEPHALITIS
5. Prophylactic Measures in close contacts:
a. Meningitis Prophylaxis: Rifampicin, - Encephalitis – Infection of the Brain:
Ceftriaxone or Ciprofloxacin: - Encephalitis Is Usually Caused By Viruses:
1. Prophylaxis with the above
antibiotics WILL NOT abort infection a. Herpes Simplex Virus
in those already infected. - The infection progresses back to the
temporal lobe of the brain
[MODULE 8 – NEUROLOGY] Handout Prepared by: Michael Angelo Sumugat RMT, MD 3
 PATHOPHYSIOLOGY

- 70% mortality rate in untreated patients - Have little cross-reaction :. Vaccination

- Treatment with Acyclovir > ↓Mortality rate must contain ALL 3 Serotypes for Full
- (Including Varicella Zoster, & Immunity.
Cytomegalovirus) - (Serotype 1 causes most of the problems –
- VZV: Encephalitis generally occurs as a Ie. Paralysis)
sequel to reactivation • The major lesion results in a flaccid paralysis
- CMV: Either during primary infection (in • Transmission:
utero) or reactivation due to - Fecal Oral
immunodeficiency (HIV) - Respiratory

b. Poliovirus • Pathogenesis:
c. Rabies - Poliovirus Acquired fecal-Orally or
Respiratory Route.
- Other causes of encephalitis can include: - Virus Replicates in Lymphoid Tissue in the
Parasites such as Toxoplasma gondii and Pharynx and Gut.
Plasmodium falciparum - Viremia follows > Extension to the Nervous
- Fungi such as Cryptococcus neoformans System
- Bacteria such as Treponema pallidum - Lytic Infection of Neurons > Paralysis
- Anterior Horns of Spinal Cord are Most
Pathogenesis Affected.
- Characteristically there are signs of cerebral
dysfunction: • Clinical features:
• Abnormal Behavior - The incubation period = 7 to 14 days
• Seizures - A minor illness with malaise, fever and a
• Altered Consciousness sore throat may occur
• Nausea/Vomiting and fever - Paralysis may extend from a single muscle
to virtually every skeletal muscle
a. Poliovirus: - There may be involvement of respiratory
muscles > Lifelong Assisted Ventilation
Prevention:
- Vaccination Available b. Rabies Encephalitis:
Live Attenuated (Oral Polio Vaccine):
• Advantages: Organism:
- Easy Administration - Given Orally - Rhabdovirus (A Bat Virus)
- Cheap Transmission:
- Induces intestinal local immunity - by the bite of an infected animal
- More Robust Immune Response - The virus is present in the saliva of the
• Disadvantage: infected animal (Dogs, foxes and other wild
- Rarely causes paralysis (1 in 2.5million) species)

Inactivated Polio Vaccine (IPV): C. BRAIN ABSCESS

• Advantages:
- Carries NO risk of Vaccine-Associated Polio -Encapsulated or free-pus in the substance
Paralysis of the brain after an acute focal purulent
- Very Robust Immune Response infection is known as a brain abscess.
- Sites of Focal Infection that could lead to
• Disadvantage: brain abscesses:
- Difficult Administration - Has to be injected o Otitis Media
- Confers little Mucosal Immunity in the o Sinusitis
Intestinal Tract. o Penetrating trauma
- 5 Times more expensive than OPV. o Hematogenous dissemination
- Given the Possible Sites of Entry, Which
• 3x Serological Types: Organisms are Most Likely to be Involved?
- PV1, PV2, PV3. o Otitis Media – Strep Pneumoniae
o Sinusitis – Strep Pneumoniae
[MODULE 8 – NEUROLOGY] Handout Prepared by: Michael Angelo Sumugat RMT, MD 4
 PATHOPHYSIOLOGY

o Penetrating Trauma – Probably DEGENERATIVE DISEASES

Staph Aureus
Global Degeneration Dementias
Diagnosis: - (Age-Related (Senile)
- Blood culture should be performed, but - Alzheimer’s
often is not diagnostic - Lewy-Body
- CT or MRI are Essential for Diagnosis. - Fronto-Temporal/Pick’s
- Lumbar Puncture is Contraindicated (Due to
↑ICP) Dementia:
- Inflammatory Markers WBC, CRP & ESR are - Acquired Global Impairment of Intellect, but with
raised. no ALOC.

DRUG – ASSOCIATED DISEASES Epidemiology:

o 5% of >55yrs are demented
A. ALCOHOL INTOXICATION o 20% of >80yrs are demented
o Prevalence Doubles every 5yrs Beyond Age:60.
WERNICKES-KORSAKOFF SYNDROME o 50% of dementia pts have clinically significant
(Alcoholic Encephalopathy) behavioral/psychological symptoms.

Etiology: Common Symptoms: (In order of prevalence):

- Alcohol Abuse > Vit B1[Thiamine] Deficiency o Early - Cognitive:
**Memory loss
Pathology: o Later - Non Cognitive:
- Alcohol Abuse > Vit B1[Thiamine] Deficiency - Apathy/Depression
- Vit B1[Thiamine] is a cofactor for Glucose - Delusions (False Beliefs)
Metabolism :. Deficiency > Neuronal ATP > - Anxiety
Neuronal Atrophy (Particularly Cortex & - Agitation/Aggression
Mamillary Bodies) - Hallucinations
- (Vit B1[Thiamine] Deficiency) > Ataxia
Types of Primary Dementias:
Morphology: o Age-Related (Senile) Dementia
- Cortical Atrophy o Alzheimer’s Disease
- Mamillary Body Atrophy & Hemorrhages o Lewy-Body Dementia
- Cerebellar Atrophy o Fronto-Temporal Dementia/Pick’s Disease

Clinical Features: Clinical Diagnosis:

- Cortical Atrophy > Impaired Memory - Timeline of Symptom Progression (Memory
(Anterograde & Retrograde) + Loss > Agitation/Aggression, Wandering,
Confabulation Apathy)
- Mamillary Body Damage > Vision Changes, - Impact on ADLs (Especially Medications &
Nystagmus, Unequal Pupils Cerebellar Financials)
Atrophy > Ataxia - MMSE (Mini-Mental State Examination)

Treatment: A. AGE-RELATED (SENILE) DEMENTIA:

- Supplemental Thiamine + B12
- (NB: B12 to prevent subacute degeneration Etiology: Old Age
of the cord) Pathogenesis
- Old-Age > Neuronal Atrophy (Particularly
Prognosis: Cortex & Hippocampus) > Progressive
By the time Amnesia & Psychosis are apparent, Neuronal Loss with Time >
complete recovery is unlikely. o Decreased brain mass and
decreased dendritic branches
o Neurons are replaced by glial cells

[MODULE 8 – NEUROLOGY] Handout Prepared by: Michael Angelo Sumugat RMT, MD 5

 PATHOPHYSIOLOGY

Treatment:
Morphology: - Acetylcholine-Esterase Inhibitors
Macro: Prognosis:
- Cortical atrophy - Mean Survival = 7yrs from Onset.
- Enlarging ventricles (Compensatory - Death Typically From Aspiration Pneumonia
hydrocephalus) or Other Infections.
- Thickening of Leptomeninges (Pia Mater &
Arachnoid Mater) (The “Thin” Meninges)
STROKE
Clinical Features:
- Dementia: All Spheres of Intellect affected - A clinical syndrome characterized by sudden
onset of a focal neurological deficit
presumed to be on a vascular basis; avoid
B. ALZHEIMERS DISEASE ‘CVA’ (‘confused vascular assessment’)
- Most common cause of dementia
CLASSIFICATION
Etiology
- Exact etiology Unknown Ischemic Stroke (80%)
- Genetic & Environmental Components
- (Inevitable in Down-Syndromes) ❏ Ischemic stroke results from focal ischemia
leading to cerebral infarction. Mechanisms include
Pathogenesis: embolism from heart or proximal arteries, small
- Excess β-Amyloid Protein Formation (A vessel thrombosis, or hemodynamic from a drop in
Degradation product of Amyloid Precursors) the local perfusion pressure. Global ischemia (e.g.
o β-Amyloid Protein Deposition from cardiac arrest or hypotension) causes a
around Neurons > Neuritic Plaques diffuse encephalopathy.
o β-Amyloid Protein Deposition in ❏ Ischemic strokes vary according to their size,
Blood Vessels > Amyloid Angiopathy anatomical location in the brain, and temporal
pattern
Clinical Features:
- May be as young as 50yrs old Hemorrhagic Stroke (20%)
- SLOW Insidious Onset (Years) (Cf. Lewy- ❏ Abrupt onset with focal neurological deficits,
Body Dementia) due to spontaneous (non-traumatic) bleeding into
- Early Signs: (Neuronal Atrophy Starts in the the brain
Hippocampus) ❏ Includes ICH and SAH
o Memory Loss is :. the First Sign
❏ Subdural and extradural hemorrhages are not
- Progressive Signs: (Neuronal Atrophy
usually classified as strokes as they are associated
Progresses to the Cortex)
with trauma
o Mild Cortical Atrophy:
§ Increased Memory Loss ❏ Hemorrhage into an area of cerebral infarction
§ Confusion, Apathy, Anxiety (commonly following cardiogenic embolism) is a
§ Difficulty Handling Money hemorrhagic infarct which should be considered an
o Moderate Cortical Atrophy: ischemic stroke complicated by secondary
§ Difficulty Recognizing People hemorrhage; not a hemorrhagic stroke
§ Difficulty with Language
§ Wandering & Disorientation STROKE TERMINOLOGY
o Late Signs: (Extreme Global Cortical
Atrophy) Transient Ischemic Attack (TIA)
§ Seizures, Incontinence ❏ Stroke syndrome with neurological symptoms
§ Groaning/Moaning/Grunting lasting from a few minutes to as much as 24 hours,
followed by complete functional recovery
Amaurosis Fugax, Transient Monocular Blindness
(TMB)
❏ Due to episodic retinal ischemia, usually
associated with ipsilateral carotid artery stenosis or
[MODULE 8 – NEUROLOGY] Handout Prepared by: Michael Angelo Sumugat RMT, MD 6
 PATHOPHYSIOLOGY

❏ valvular vegetations (infection, tumour)

embolism of the retinal arteries resulting in a
sudden, and frequently complete, transient loss of ❏ treatment
vision in one eye • risk of embolization can be decreased
with anticoagulation (heparin and warfarin)
Reversible Ischemic Neurological Deficit • increase risk of hemorrhagic infarction
(RIND)/Minor Stroke implying that it is imperative to exclude the
❏ Neurological abnormalities similar to acute presence of bleeding prior to starting
completed stroke, but the deficit disappears after anticoagulants (i.e. do CT scan at 48 hours
24 - 36 hours, leaving few or no detectable post-bleed)
neurological sequelae (a better term is minor • if moderate sized infarct, delay
stroke) anticoagulation 5-14 days

Completed Stroke (CS) Risk Factors for Stroke

❏ Stroke syndrome with a persisting neurological ❏ hypertension (HTN)
deficit suggesting cerebral infarction; the ensuing ❏ smoking
neurological defect can last days, weeks, or ❏ myocardial infarction (MI)
permanently; even after maximal recovery, at least ❏ atrial fibrillation (A fib)
minimal neurological difficulties often remain
❏ diabetes mellitus (DM)
Progressing Stroke (Stroke In Evolution) ❏ alcohol abuse
❏ Neurological deficits begin in a focal or restricted ❏ homocysteinemia
distribution but over the ensuing hours spread ❏ obesity
gradually in a pattern reflecting involvement of ❏ severe carotid stenosis
more and more of the particular vascular territory ❏ parental stroke (family history)

WHAT IS THE PATHOGENESIS?

******** END OF MODULE 9 ********
Atherosclerotic Plaque
❏ inadequate perfusion of brain due to
• an embolus from an atherosclerotic plaque in a
large vessel (artery to artery embolus) (most
common)
• a large vessel thrombosis with low distal flow

❏ risk factors
• hypertension (HTN)
• diabetes mellitus (DM)
• cigarette smoking
• high cholesterol

❏ treatment
• control atherosclerotic risk factors
• carotid endarterectomy in selected patients (see
below)
• antiplatelet agents: aspirin, ticlopidine,
clopidogrel, aggrenox (dipyridamole and ASA)

Cardiogenic Origin
❏ an embolus of clot
• risk factors: A fib (commonest cause), LV
aneurysm, LV dysfunction, increased age, mitral
annulus calcification
❏ air emboli - during surgery or diving
[MODULE 8 – NEUROLOGY] Handout Prepared by: Michael Angelo Sumugat RMT, MD 7