Chapter 1: Cell Pathology

Define the two major types of cellular injury

• Cell injury occurs if we go too far out of homeostasis, for too long.

Reversible Cell Injury

• Only reversible if stimulus is removed, usually the injury is mild and short lived.

• Example: Hydropic changes (cell swells)

Irreversible Cell Injury

• REMINDER A REVERSIBLE CELL INJURY CAN CROSS THE POINT OF NO RETURN AND BECOME IRREVERSIBLE IF STIMULUS IS NOT REMOVED.

• Things that can cause irreversible cell injuries: high dose heavy metals, anoxia, severe or prolonged hypoxia, etc.

Describe the cellular alteration in reversible and irreversible cellular injury

Reversible

• Example: Hydrophic change (influx of water into cytoplasm)

  • No energy, no Na+/K+ ATPase activity, Na+ which is found in high levels outside of the cell SPRINTS down its concentration gradient (into the cell), water then chases the salt. Bada-bing Bada-boom cell swells

• Decreases Energy Production

  • When the cell swells, the mitochondria also swells (not a good thing for the power house)

  • The mitochondria is less efficient when it swells and must use anaerobic glycolysis which generates less ATP

    • this also increases the amount of lactic acid in a cell

• Decrease Protein Synthesis and Enzyme activity

  • Since there is more lactic acid in the cell, the pH drops.

  • The acidic levels of the cytoplasm decreases metabolism (enzymes can’t work in these conditions, they’re gerber daisies)

  • The acidic levels of the cytoplasm also starts to “beat up” the RER so protein synthesis decreases

• Increase Auto-phagocytosis (eating your own self)

  • As damage occurs from the low pH, the cell does what it normally does - destroys them in a lysosome. These destructive elements may leak into the cell and the vicious cycle continues

Irreversible

• Irreversible Injuries to the Nucleus

  • Pyknosis - condensation of chromatin

  • Karyorrhexis - nucleus fragments into smaller

  • Karyolysis - enzyme dissolved nucleus chromatin (DNA gone)

Describe the causes of cellular injury

Hypoxia and Anoxia

• Hypoxia is low O2

• Anoxia is NO O2

• Most important and common type of cell injury

  • Cells can only survive on anaerobic respiration for so long.

    • Different cells can be survive without O2 for longer periods of time (they’re less sensitive to hypoxia/anoxia)

      • Brain cells can survive for a few min

      • Heart cells for a like 1-2 hours

      • Kidney cells for a few hours

      • Connective tissue cells can even last for 24 hours after death

Toxin Cell injury

• Direct toxin: adverse response is directly caused by the substance, it doesn’t need to be “activated” by the body

  • Think heavy metals like mercury

• Indirect toxin - adverse response is due to resulting metabolites

  • CCl4 is converted by the liver to CCl3

    • CCl3 is what is toxic (its a free radical)

  • Dose-Dependent Toxicity: Some medications can also be toxic if taken in large amounts

    • Tylenol is chill unless it is taken in large doses

      • its metabolized by the liver and in high doses the end product is toxic to the liver

Microbial Pathogens

• Bacteria produce toxics that inhibit some cell functions

  • Food Poisoning: (salmonella/e.coli) unfrigerated leftover food is caused by exotoxins which are released by bacteria

    • Symptoms are a consequence of “cell poisoning”

• Virus

  • typically “kill from within” by disturbing cellular processes or integrity of cell membrane

  • Can also hijack the cells machinery by sticking their DNA into our DNA

    • Immune system will recognize the foreign viral proteins and attack the cell

Genetic and Metabolic Disturbances

• Many genetic diseases adversely affect the normal intermediate metabolism with subsequent accumulation of toxic metabolites in the cells

• Example

  • DM

    • hyperglycemia which alters the metabolism of major organs, such as the liver or kidneys

    • Also produces pathologic changes in small blood vessels which will impede mircocirculation and cause pathologic tissue changes related to chronic hypoxia

Explain cellular adaptation to injury

• Prolonged exposure of cells to adverse or exaggerated normal stimuli leads to adaptation of the cells

Atrophy: cell/tissue/organ/entire body gets small or reduced number of cells/tissue/organ/entire body

• Physiologic atrophy occurs with age and involves the entire body basically

• Pathologic atrophy typically occurs as a result inadequate nutrition, oxygen supply, or hormonal stimulation

  • General body wasting from cancer/malnutrition

• Damaged or old organelles are taken up by autophagosomes and degraded

  • Undigested residues can be seen in the cytoplams as lipofuscin which is what makes the cadavers brownish

  • Extra proteins released from damaged organelles are mark for disruption by ubiquitin a scavenger protein

Hypertrophy and Hyperplasia

• Hypertrophy: an increase in the size of tissue or organs caused by enlargement of individual cells

• Hyperplasia: an increase in size of tissue or organs caused by a an increase in the number of cells

• Hypertrophy and hyperplasia are besties, they usually go everywhere together

  • Hypertrophy occurs by itself only in the heart because these cells cannot divide (AKA Pure hypertrophy)

• Hypertrophy with hyperplasia occurs in lots of conditions like when the bladder wall thickens when obstructed by BPH or in uterine smooth muscle cells in pregnancy

• Physiologic Hypertrophy: skeletal muscles get swoll when you work out

• Pathological Hypertrophy: heart muscle in CHF

• Pure hyperplasia typically results from hormonal stimulation

  • Endometrial hyperplasia with estrogen (may progress to neoplasm)

  • BPH

• In chronic injury, hyperplasia may also occur (like you wear high heels everyday)

  • Hyperplastic lesions (like polyps) may have no obvious cause (idiopathic) and are probably some early neoplasms

Metaplasia (Metamorphosis)

• Changing from one cell type to another

• In smoking, the ciliated columnar bronchial epithelium into squamous epithelium

• Can be reversible - like if you stop smoking - but if stimulus remains it progress to dysplasia (disorderly arrangement of cells) which may progress to neoplasm.

Intracellular Accumulations

• Intracellular accumulation may result from an overload of various metabolites or exogenous materials

• exogenous examples

  • Example: Anthracosis (Coal Lung)

    • Coal particles get stuck in the lungs

• Endogenous Examples:

  • Hemosiderosis: an accumulations of blood-derived brown pigment (hemosiderin) which is usually derived from hemolyzed RBCs.

    • Its just the aggregation of ferritin

    • Prussian Blue Stain

    • Can occur in the livers of people who get lots of blood transfusions and in those with hemolytic anemia

    • Can also result as a genetic disorder where you cannot absorb iron in food

  • Lipid Accumulation

    • Can occur in the liver (like fatty liver cirrhosis) from deposit of triglycerides

Define the two types of cellular death

• Reminder: necrosis and apoptosis happen to cells in LIVING individuals

  • If the person is dead, then it is known as autolysis

Necrosis: exogenously induced cell death

• tends to be messier (cell swells and ruptures, membrane is destroyed)

  • when the cell explodes it will affect multiple cells

• used in immune functions

• vital processes of the cell are inhibited

• Ends with phagocytosis of NEUTROPHILS (polymorphonuclear)

Apoptosis: endogenously programmed cell death (may also be exogenous)

• This process is energy dependent and vital processes maintained

  • AKA active cell death

• tends to be cleaner and only affect one cell

• The cell membrane is fully intact but, the insides are fragmented (apoptotic bodies)

• Ends with phagocytosis of macrophages

• suicide genes

• Physiological: In fetal development the cells that make of the webbing of the fingers die or clonal deletion in the immune system or cells that are just not needed anymore

• Pathological: Cells with DNA damage/ER stress or infections

  • Lack of apoptosis is also a problem, like if the fetus’ finger webs don’t die we get syndactyly or in some cancers (like follicular lymphoma (NHL)) cells forget to die

Describe the various types of necrosis

• Secondary liquefaction necrosis AKA Wet gangrene may happen after coagulative necrosis

  • the dead tissue gets infected by the bacteria, you get inflammation and it smells like death

  • Very common in the feet of DM patients

• If necrotic tissue dries out like The Mummy (with academy award winning Brendon Fraiser) its Dry gangrene

  • Usually due to a lack of blood-flow like frost bite

• Necrotic tissue attracts calcium salts and often calcifies (duh)

  • This is dystrophic calcification

• Fun fact: maggots are used to treat patients with necrosis that aren’t candidates for surgery because maggots only eat necrotic tissue

• Gas gangrene is a medical emergency that usually results in deep trauma wounds (combat injuries/surgical settings)

  • Bacteria gets in there, releases toxins, blood flow is disrupted

  • you get bubbles and crepitus (snap, crackle, pop)

  • Smells like death

  • Blisters usually drain

Coagulative Necrosis

• most common form of necrosis

• Marked by rapid inactivation of cytoplasmic enzymes so lysis is inhibit and tissues maintain their form and consistency

• Proteins are denature and it “gunks" up the works

• Very common in solid organs (heart, liver, kidneys)

Liquefactive Necrosis

• Marked by rapid liquefaction by enzymes that results in abscess or pus formation

  • Pus tends to be full of dead and dying leukocytes and debris

• Most often in soft/fatty tissue (like the brain)

Caseous Necrosis

• Typically found in TB patients or fungal infections

• The love child between liquefactive and coagulative

• Tissue is “cheesy” because it is destroyed from the inside out

Enzymatic Fat Necrosis

• Special type of liquefactive that is caused by lipolytic enzymes

• Marked by chalky white/yellow deposits (soap scatter)

  • its literally soap, the enzymes melt the fat and it binds to calcium (you’ve seen fight club you know how this works)

• usually seen in fatty tissues like pancreas and breast

  • In pancreatitis, this can be seen on CT and is know as stratification

Chapter 2: Inflammation

List the signs of Inflammation

• First described by our Roman homie Celsus

Calor

• Heat

Rubor

• Redness

Tumor

• Swelling

Dolor

• pain

Loss of Function

• the latin name is functio laesa if you wanna be fancy

Explain the inflammatory process

Circulatory Changes

• Changes in blood flow are the bodies 1st response to injury (vascular spasm or vasoconstriction)

  • Vasoconstriction only last for a few seconds

• Next we get vasodilation, the capillaries are quickly filled with blood

  • hydrostatic pressure increases, filtration increases, we get light swelling

  • More blood in the capillaries also causes the red appearance

  • Since injured tissues need more blood, we get active hyperemia

    • We know what it is but the patho book describes it as an influx of blood into inflamed areas

Vascular Changes

• Most of the changes have to do with

  • increase hydrostatic pressure

  • slowing down of circulation

  • adhesion of leukocytes and platelets

  • Release of soluble mediators from WBCs, platelets, and endothelial cells

Humeral Response

• The release and action of soluble mediators produced by inglammatory cells and various organs in responds to injury (see chemical mediators)

Cellular Response

• Blood flow in the capillaries is slow (greater cross section area) this leads to redistribution of RBCs and WBCs

  • RBCs form stacks (rouleaux) which impede circulation and lead to turbulent flow

  • WBCs undergo Margination (pushed to the walls of the capillaries)

    • pavementing is them attaching to the walls

    • As leukocytes activate, the develop long protrusions which allow for them to stick better to the endothelial walls

      • in neutrophils the adhesion molecules are selectin and integrin

        • these molecules are only found on ACTIVE leukocytes

        • the molecules themselves are activated by cytokines (IL or TNF which are found in high concentration at sites of inflammation)

• Increase permeability of vasculature last for a little while, more and more fluid leaks into the interstitial space aka Transudation

  • Pure fluid is transudate

  • As cells start to migrate into the interstitial space, we get exudate (exudate = presence of cells) which is more protein rich

    • Usually the cells in exudate are PMNs (polymophonuclear nuetrophils)

• Inflammation begins when PMNs get into the tissue (Here’s the order of actions)

  1. adhesion to endothelial cells

  2. insertion of cytoplasmic pseudopods between the junctions of endothelial cells.

  3. passage through basement membrane

  4. amoeboid movement away from vessel toward inflammatory site (Chemotaxis)

     • chemoattractants mediate chemotaxis and are at the highest concentration at the site of inflammation

• RBCs do NOT usually migrate into the tissue but if the space is big enough and they leak through then its call diapedesis

• When PMNs get to the inflammatory site, phagocytosis commences

  • mediated by opsonins (from complement or antibodies)

  • Bacteria or whatever is engulfed and is then killed by bactericidal substances like hydrogen peroxide or free radials

    • the killing occurs when lysosomes fuse with the phagocytic vacuole

  • PMNs usually die in the process of fighting the bacteria (fallen soldiers), this is what is found in pus

    • inflammation dominated by pus = purulent inflammation

Discuss the cells involved in the inflammation

PMNs (Neutrophils)

• must abundant WBC (60%-70%)

• segmented nucleus with granules in the cytoplasm

• Most important features

  • mobility

    • first to show up to the inflammation party

  • Phagocytosis

  • Bactericidal activity

    • granules contain hydrogen peroxide and free radicals that will beat up the bacteria

  • Cytokine production

    • secrete more inflammatory mediators like IL-1 which is an endogenous pyrogen (causes fevers)

Eosinophils

• Make up 2-3% of circulating WBCs

• Usually show up a few days after the neutrophils (slower motility)

• Still mobile, phagocytic, and bactericidal

• Interact with basophils and are prominent in type 1 hypersensitivity reactions

• Parasitic infections

• long living so may be seen in chronic inflammation

Basophils

• Make up less than 1% of circulating WBCs

• Most prominent in type 1 hypersensitivity reactions

• Precursors of mast cells which are tissue-based basophils

Macrophages

• tissue based derived from blood monocytes

• Appear at inflammation sites 3-4 days

• Phagocytes and active in bacterial killing, but their not as efficient as PMNs

• Produce cytokines that activate healer cells like myofibroblast, angioblast, fibroblast

Platelets

• fragments of the cytoplasm released from megakaryocytes

• No nucleus but they do have granules that contain various chemicals like (histamine, cytokines, coagulation proteins, growth factors (PDGF))

  • granules are released when platelets make contact with the extracellular membrane

  • PDGF promotes proliferation of connective tissue cells

Other

• Lymphocytes and plasma cells are components of chronic inflammation

• Fibroblast and angioblast participate in chronic inflammation and in healing

Describe the chemical mediators involved in inflammation

• Chemical mediators of the vascular changes can be put into 2 categories

  • Plasma Derived which circulate in an inactive form and must be activated

  • Cell-derived which are stored in granules of platelets or leukocytes, however they may be made on demand (De novo)

    • Histamine is preformed which is why it works fast

    • Prostaglandins have to be made from arachidonic acid which takes time

• Mediators are multifunctional and had numerous effects on blood vessels but just think vasodilation, constriction, vascular permeability, activation of immune cells, chemotaxis, etc.

• Typically biogenic amines, proteins, or lipids

Histamine

• Bioamine stored in granules of platelets, basophils, and mast cells

• Acts on endothelial cells of the venules

  • increase vascular permeability

  • increase filtration → edema

• Inactivated by hisaminase pretty quickly so it is called an immediate transient reaction

Bradykinin

• Kinda like histamine but acts slower

• Activated in the plasma by the enzyme kallikrein which is activated by coagulation factor XII (AKA Hageman’s factor)

  • Hageman’s factor activates both complement, clotting, fibrinolysis, and chemotaxis

• Incites pain (the dolor of inflammation)

Complement proteins

• A Cascade in which the proteins are numbered C1-C9 and there are 3 ways to activate the cascade which all end with the MAC (membrane attack complex)

  • The MAC is an enzymatically active complex that bores holes into cell membrane

  • The cleaved activated complements C3a and C3b are active components as well

    • C3b acts as a an opsonin

    • C3a acts as an anaphyloxins which cause vasodilation, increase vascular permeability, and promote chemotaxis

• The complement proteins are constantly floating around and are activated under the right conditions

• Classical pathway

  • Typically activated by an antigen-antibody complex (can also be activated by C1)

    • Madi’s extra information for completion: macrophages make contact with a bug and produce interleukin 6, this acts on the liver to produce C-reactive protein (a pentamer). This C reactive protein binds to the surface of a pathogen and acts as a landing zone for the C1 complement protein. C1 (or an antibody) binds C4 and C2 which is cleaved to C4b and C2a respectively these combine to form C4b2a AKA the the classical C3 convertase. C3 is cleaved to C3a (anaphatoxin) and C3b which combines with the classical convertase forming the Classic C5 Convertase which can actually get us to the MAC

• Alternative Pathway

  • Named because it does not have anything with immune reactions and is activated by bacterial endotoxins, fungi, snake venom etc.

    • Madi’s extra info: Starts with C3 which is activated by water into iC3, which you would think is a problem except water is found in high concentrations at microbe surface. iC3 which binds B, which binds D (a protease) D cleaves B and forms the soluble C3 convertase this chops up a whole bunch of C complement proteins into C3a (anaphylatoxins) and C3b which binds to the pathogen surface. So follow the same steps that we used to form the soluble C3 convertase but this time we’re attached to the microbe forming the alternative C3 convertase. When this binds an extra C3b we form the C-5 convertase which can get us to the MAC

• Lectin Pathway

  • Activated by the binding of plasma mannose-binding lectin to surface carbohydrate on bacteria

    • Madi’s Extra info: The liver produces mannose binding lectin when macrophages release IL-6. This protein binds C4 and cleaves it to C4a (anaphlaxin) and C4b binds the surface. The mannose cleaves C2 to C2a which binds the to C4b forming the classical C3-convertase just like in the classical

Arachidonic acid derivatives

• Derived from phospholipids of cell membranes through the action of phospholipases

• Lipoxygenase pathway

  • leads to the formation of leukotrienes (LTs) these promote chemotaxis and increase vascular permeability, bronchospasm

    • typically seen in anaphylactic shock

  • Lipoxins inhibit chemotaxis and serve as the negative regulators of leukotrienes as well as act in vasodilation, inhibition of neutrophil chemotaxis, monocyte adhesion

• Cyclooxygenase pathway (COX)

  • Prostaglandins (PGs) and thromboxane

    • Prostaglandins cause vasodilation, increase vascular permeability, mediate pain, and fever.

      • Prostacyclin (PGI2) counteracts thromboxane

    • Thromboxane promotes platelet aggregation, thrombrosis, and vasoconstriction

• The Arachidonic acid pathways can be inhibited at many spots

  • Corticosteroids act on phospholipase which is involved in generating the arachidonic acid (knocks out lipoxygenase and cyclogenase)

  • Aspirin knocks out the COX pathways

  • Can be used for treatment of chronic inflammatory disease like RA and asthma

Define how inflammation is classified

Duration

• Acute inflammation is usually sudden onset and last from a few hours to a few days

  • like a cold

• Chronic inflammation last longer usually weeks to months but can even be years

  • Usually related to acute and is a result of the following events

    • Extension of acute inflammation

    • prolonged healing of acute inflammation

    • persistence of causative agents

  • Primary chronic inflammation evolve without a typical acute phase

  • Secondary chronic inflammation is preceded by an acute phase

  • Can also develop as a response to foreign bodies like in chronic lung solicosis

Etiology (AKA what causes it)

• infections

  • you know the vibes (bacteria, fungi, virus, etc)

• chemical causes

  • Organic/inorganic, industrial/medicinal, exogenous/endogenous

• Physical causes

  • trauma, heat, radiation

• foreign bodies

  • like in sutures or thorns

• immune causes

  • typically related to hypersensitivity reactions

Location

• Localized

• widespread

  • Bacteremia in the blood → septic shock (FULL BODY)

Pathological features

• Several forms can be seen with the human eye like changes in skin, eyes, oral mucosa, genitals

  • Or even in surgery

Explain the various pathologic forms of inflammation

• Note: if it ends with -itis its inflammation of whatever the thing is

Serous inflammation

• Characterized by exudate in serum

• Occurs in most early stages of inflammation

• Ex: Skin vesicles in herpes, second degree burn blisters

• The Peritoneum, pleura, and pericardium can also have serous inflammation which are all characterized by accumulation of clear, yellowish fluid in the cavities

• You can get it in the joints like in trauma or RA

Fibrinous Inflammation

• Characterized by an exudate RICH in fibrin (plasma protein)

  • extravasation of fibrin only results through large spaces in the vasculature so the inflammation was BAD

• Ex: strep throat, bacterial pericarditis

  • surface is covered in shaggy, yellow layers of fibrin

• Doesn’t resolve as easily

Purulent inflammation

• Typically caused by pus forming bacteria (strep or staph)

  • Reminder: Pus is full of dead/dying PMNs and necrotic tissue debris

• If there is fibrin in the pus, we can call it fibrinopulent

• Abscess are an example of this where the pus accumulates in the newly formed tissue space

  • Lance and drain that ho

  • If Large abscess rupture it forms a sinus (like popping a pimple and the pus hits the mirror that you just cleaned (open to the world)) or a fistula (a channel forms between 2 pre-existing cavities)

  • Empyema is accumulation of pus in a pre-exsiting cavity

Ulcerative inflammation

• Characterized by formation of an ulcer of the skin/mucosa

  • Reminder: ulcer is an defect involving the epithelium but it may extend into the deep connective tissue

  • Super common in the stomach or duodenum

Psudeomembranous inflammation

• A special type of ulcerative inflammation that combines with fibrinopulent exudation

• Ex: C-diff secretes exotoxins that kill intestinal cells leading to ulcers and exudations in the form of pseudomembranes

• Ex: Diphtheria

Chronic Inflammation

• We’ve been like this (it last a long time)

• Produces more extensive tissue destruction, heals less readily, and is associated with more serious function loss

• Marked by an exudate full of lymphocytes, macrophages, and plasma cells

• usually accompanied by scarring

  • Chronic pelvic inflammatory disease scars fallopian tubes

• Fibrosis may also occur

Granulomatous Inflammation

• Wouldn’t you know, granulomatous inflammation is characterized by granulomas

  • Granulomas are formed by Ts, macrophages, and multi-nucleated giant cells

• Ex: TB, sarcoidosis

• May be caused by antigens that cause Type IV hypersensitivity reaction

  • Cytokines produced by T cells transform macrophages to epitheliloid cells which combine to form multi-nucleated giant cells

• Often associated with caseous necrosis

Chapter 3: Immunopathology

Describe the types of immune response

• Innate Immunity (primitive and nonspecific)

  • This is what you’re born with

  • Not dependent on exposure

  • Includes Defense Mechanism such as:

    • Mechanical Barriers (skin)

      • Intact skin is probably the best defense

      • 1st line of defense

    • Cellular responses (PMNs, phagocytes, macrophages)

    • Protective proteins (complement, lysosines)

  • Includes the 1st and 2nd lines of defense

    • Second line of defense is the inflammatory response and phagocytosis

• Acquired Immunity (AKA adaptive immunity)

  • based on the ability to determine self vs. nonself

  • Immunocompetence: the whole system is working in unison

    • Opposite of immunodeficient

  • Basically just the B and T cells response

    • ANTIGEN SPECIFIC

  • 3rd line of defense

    • these only engage as a last resort, ie. the other two lines have fallen

Discuss the cells of the immune system and antibodies

• Lymphocytes

  • T Cells

    • CD4 or helper Ts activate macrophages and other cells to do their job better

    • CD8+ or cytotoxic Ts intend to kill any cell infected with microbes or cancer once they are activated

    • T cell receptors (CD8 or CD4) need their antigen presented in MHC (AKA human leukocyte antigen (HLA)).

      • MHC type 1 interact with CD8

      • MHC type 2 interact with CD4

  • B Cells

    • Plasma cells - aka antibody factories

      • 5 classes of immunoglobulins (just bound antibodies)

        • IgM: neutralizes microorganisms, strong complement activator, and usually bind BLOOD GROUP ANTIGENS

        • IgG: acts as an opsonin (seasoning for phagocyte)

        • IgE: mediates hypersensitivity type I reactions or parasite combat (if you see IgE think basophil or mast cells)

        • IgA: protection of mucosal surfaces, this one is found in our secretions

        • IgD: involved in the antigen activation of B cells

          • Basically all immunoglobulin start as IgD and then differentiate

      • Antibodies are all composed of heavy and light chains

        • each chain has a constant region and a variable region

          • Variable region binds antigen

        • Light chains are either Kappa or lambda (not really important)

        • Heavy chains are what make the Ig different

    • Memory B cells - make the response faster next time

    • Natural Killer cells

      • non-specific, we’re here to kill

• Macrophages

  • Phagocytes seen in the acute/immediate reaction

• reminded a lot of these cells are primarily found in lymph tissues which is where the immune response typically begins - stay ready so we don’t have to get ready

Describe the 4 major types of hypersensitivity

Type I Anaphylactic

• The only TRUE allergic reaction mediated by IgE

• After the first exposure, Mast cells get sensitized and cover themselves in IgE, so on the second exposure when IgE grabs the allergen the mast cell degranulates and releases histamine

  • Histamine can go systemic and act on blood vessels resulting in acute edema

  • Where ever the histamine response occurs is where the system is affected

• typically atopic in nature

• immediate response in minutes

• latent response some time after that

• Examples:

  • Hay Fever (allergic rhinitis)

  • Asthma

  • Atopic dermatitis

  • Anaphylactic shock

    • if you wanna be fancy this is a low resistance shock because histamine is a vasodilator

    • Medical Emergency

      • it’s EPI TIME BABY

Type II Cytotoxic Antibody Mediated

• Typically mediated by IgG

• Cells are either killed through lysis via MAC (IgG activates complement) or cytotoxicity (killed by CD8s or NKs)

• Disease Examples:

  • Hemolytic Anemia

    • RBCs get lysed and the bone marrow can’t keep up

    • Lab values are gonna show a high reticulocyte count

    • Symptoms: heart palpitations, palor, SOB, hepatosplenomegaly, fever, abdominal/back pain, bad cases may go into shock

  • Goodpasture’s syndrome

    • Affects the kidneys

    • form of glomerulonephritis

      • rapid progression

    • pretty rare more common in young men

    • IgG is deposited in kidneys or lungs

    • Symptoms: edema, dysuria, HTN,

    • Labs: bolod in urine, RBC cast, protein in urine

    • Treatment: high dose steroids, plasmapheresis, ace inhibitor

  • Grave’s disease

    • Affects the thyroid

    • Over stimulation of the thyroid (antibodies bind TSH receptors)

    • Symptoms: Bug eyes, pretibial myxedma,

    • Testing: radioactive iodine

    • Treatment: thyroidectomy or antithyroid meds

  • Myasthenia Gravis

    • Neuromuscular junctions (ACh receptors)

    • typical patient population: Women 20-40

    • symptoms: episodic weakness, easy muscle fragility, ptosis, respiratory compromise

Type III Immune Complex Mediated

• Antibody complexes are put where they aren’t supposed to be, these lead to complement activation and leukocyte response

• Disease Examples:

  • Systemic Lupus Erythematous (SLE)

    • affects multiple systems antibodies against our own nuclei

    • Common in African American women

    • infections, nephritis, and CNS infections occur

    • Labs to run: ANA (antinucleated antibody) or a biopses

    • blood in urine, elevated blood urea nitrogen

  • Posttreptococcal glomerulonephritis

    • Tends to occur in pediatric patients (like 3 yo) post URI

    • group A strep antibodies are deposited in kidney walls

    • URI or strep throat

    • dysuria, HTN

  • Polyarteritis nodosa

    • attacks medium sized muscular arteries

    • may be idiopathic or a type 3

      • typically occurs at age 40-50

    • Affects GI tract, heart, kidney, liver

      • Causes fever, pain, neuropathy, weight loss, asthma

    • typically results in elevated WBC, protein or blood in urine

    • Check biopsy of necroses area or angiogram

    • long term steroid therapy

    • Artus Phenomenon can occur with booster tetanus shots

      • local type III

      • local vasculitis of dermal blood vessels

Type IV Cell Mediated or Delayed Hypersensitivity

• T cell mediated typically occur 24-92 hours post exposure

• Characterized by caseous necrosis (granulomas) surrounded by giant cells, lymphocytes, and epithelioid macrophages

• Disease Examples:

  • Infections with TB, Leprosy, or histoplasma capsulatum (fungi)

  • Reactions to tumors

  • Sarcoidosis

    • characterized by ground glass in X-rays

    • More common in African Americans

    • unknown etiology

    • may have spontaneous resolution or patients may develop chronic granulomas

    • some symptoms: erythema nodosum, may look like a lung infection, weight loss, malaise, fatigue, swollen lymph nodes, dry cough, fever, arthritis, cranial nerve palsy

  • Contact dermatitis

    • Remove stimulus usual resolves

      • me in the cadaver lab

Discuss organ transplantation and blood transfusion

Types of Transplant

• Autograft

  • self to self transplant

  • no chance of rejection (its your own self)

  • Some people will donate their own blood to be used in pregnancy or surgery

• Isograft

  • GENETICALLY identical twins

  • No rejection → complete MHC/HLA match

• Homograft (allograph)

  • Homie to homie transplant

  • Must test for histocompatibility using HLA antigens

    • you want these as close as possible, usually siblings

  • Rejection chance is minimized as much as we can but its still a risk

• Xenograft

  • Species to species transplant

    • like a pig heart valve

  • minimize risk to try to match MHCs

Transplant rejections

• typically allografts

• Providers need to balance immunosuppressants (cyclosporine, prograft) and other meds to avoid illness

• We’ve got all types of transplants: kidney, skin, liver, heart, lung, pancreas, bone marrow

• Hyperacute

  • usually happens during the transplant surgery

  • Due to preformed antibodies

    • Causes a clot (thrombosis) that cuts off blood flow to the organ (hypo-perfusion)

• Acute reaction

  • typically 1-2 weeks after transplant

  • severe inflammation in that region, hypo-perfusion

• Chronic transplant rejection

  • typically months to years after transplant

  • blood vessel damage, hypo-perfusion, die

• Graft Vs. Host reaction

  • mediated by transplanted T lymphocytes (Donor rejects hosts)

  • Most often a complication of bone marrow transplantation → typically attacks multiple organs

    • Skin - exfoliative dermatitis

    • Intestine - malabsorption and diarrhea

    • Liver - jaundice

Blood Transfusion

• The most important thing to match it the ABO type

  • We have natural antibodies against the opposite blood type

    • this prevents transfusion between groups

• The second thing we need to match if the Rh + or -

  • Antibodies form only after sensitization

  • Rh Factor Incompatibility

    • Rh negative mom pregnant Rh positive fetus

      • Usually no antibodies until after the birth because we’re not sensitized

      • On the second pregnancy we see erythroblastosis fetalis which causes hemolysis of the fetal RBCs and kills the fetus

      • Anti Rh immunoglobulin (Rhogam) has be given every pregnancy to prevent sensitization

• Cross matching is important before the transfusion

  • If we don’t cross match and guess wrong, you get intervascular hemolysis

  • If someone is dying and we don’t know the blood type grab O neg (AKA code blood)

• AB is universal recipient, O is universal donor

Describe the major autoimmune diseases

• Abnormal reactions to self antigens

• When diagnosing these look for:

  • autoantibodies in blood

  • direct or indirect evidence that immune mechanism may be the culprit

    • Like if we try a course of steroids and it works really well I have bad news champ

• Genetics play a role

• Familial, linked to HLA haplotypes, sex differences

  • increased incidence in some families

  • HLA 27 is linked to anklysosis spondylysis

  • More common in females

• Can be systemic

  • SLE, Rheumatic fever, RA, systemic scleosis, polyarteritis nodosa

    • SLE where the body makes antibodies (AKA antinuclear antibodies) against ones nuclear components

      • Presents with inflammatory diseases such as flomerulonephritis, dermatitis, arthritis, among others

      • Clinical features of Lupus

        • butterfly rash

        • arthritis

        • kidneys are usually involved

        • anemia

        • enlargement of lymph nodes, spleen

      • Usually treated with NSAIDS but not chronic steroids

• Or Organ specific

  • MS (CNS)

  • Hashimotos, Grave’s (thyroid)

  • Autoimmune hemolytic anemia (blood)

  • Pemphigus vulgaris (skin)

  • Myasthenia Gravis (muscle)

Discuss inherited and acquired immunodeficiency diseases

Primary Immunodeficiency Diseases (Congenital)

• Maybe she’s born with it

• Severe Combined immunodeficiency (Bubble boy with John Travolta)

  • Defect of lymphoid stem cells so no Pre-Bs or Pre-Ts

  • Increase risk of death from opportunistic infections

  • Usually in Pediatric patients

• Isolated deficiency of IgA

  • Most common (1 in 700)

  • patients are often asymptomatic

• DiGeorge Syndrome

  • T-cell deficiency from Thymic dysplasia

    • Caused by a block in the formation of the thymus

  • No Ts so patients get recurrent viral and fungal

  • Usually presents with tetani in the first days of life

  • Treated with thymus or bone marrow transplant

Secondary Immunodeficiency Diseases (Acquired)

• AIDs (acquired immunodeficiency syndrome)

  • Caused by HIV (human immunodeficiency virus) an RNA Virus

    • Reverse transcriptase is the enzyme the virus uses to get all up in the Cell DNA

  • Infects helper Ts cells so you don’t get activation of other immune cells

  • Macrophages and related phagocytic cells can also become infected

  • Treated with AZT for CD4 counts of less than 500

  • Patients typically presents weird infections or really bad cases

    • In the Lungs

      • Pneumocytis carinii, aspergillus fumigatus, candida albicans pneumonia

      • Diffuse interstitial pneumonia

    • In the GI tract

      • Candida albicans, herpes, CMV, stomatitis, esophagitis, MAI, Cyptosporidium enteritis, fungal/bacterial proctitis

    • CNS

      • toxoplasma gondii encephalitis, cyrptococcus neoformans meningititis

Chapter 4: Neoplasms

Define terms used in the field of oncology

• Neoplasia - new growth, uncontrolled abnormal growth

• Tumor - swelling of tissue, not specific to inflammatory event

  • neoplasm is the same thing

• Cancer - (malignant neoplasm) uncontrolled division in a specific area

  • book says its just neoplasm plural

• Oncology

  • Clinical oncology - like in the office with the patient

    • primarily from a diagnostic and therapeutic point of view

  • Experimental oncology - “tip of the spear” experimental sciences

    • in the lab

  • Cancer epidemiology - studying incidence, precedence, survival rates, treatment modalities

    • deal with neoplasia in human population and study the environmental causes tumor

Describe how tumors are classified

• Clinical classification

  • Subjective/objective evaluations done in the clinic with yo eyeballs

• Histologic classification

  • Biopsy with the all pink slides

• Clinicopathologic classification

  • combo of clinical and histologic

Benign Tumors

• The neutral tumors not good or bad

• Growth is slow, expansive

• No Metastases

• Smooth surfaces

• Has a capsule

• No necrosis, no hemorrhage

• Resembles normal tissue

• Cells are typically well differentiated

• Normal nuclei (size and shape; uniform)

• Very few mitoses

• Can still cause pain, but its usually due to pressure

Malignant Tumor

• the bad guys

• Tend to grow fast and be invasive

• WILL metastasize

  • Can occur at any point

  • A primary tumor levels up and forms metastatic clones that are able to degrade lining and are cloaked from immune system

  • Metastatic clone can break off and enter the blood stream or lymph system

    • similar to inflammatory process: margination, diapedesis

  • Can invade other tissue or embolize (form a clot)

  • Early identification and destruction is key

    • Get your paps

• tend to look insane, irregular surface

• No capsule

• You will see necrosis and hemorrhage

  • the cancer needs blood duh, remember all those little extra vessels in Franklin…

  • Tumor-induced angiogenesis: tumor develops its own blood supply

    • feed me more

• Does no resemble the tissue of origin

• Poorly differentiated cells

• Pleomorphic nuclei - all over the place

  • Hypochromic

  • Some big or small

  • you may have a lot of them

• Lots of bad of mitoses

Histologic Classification of Tumors

• Mesenchymal tumor

  • Named formed by the cell or origin + oma (benign) or sarcoma (malignant)

    • fibroma and fibrosarcoma

  • This naming system is used for muscle, bone, and connective tissue

• Epithelial Tumor

  • Named formed by using terms like adenoma/papilloma (benign) and carcinoma (malignant)

    • intestinal adenoma and adenocarcinoma

  • This naming system is used for mucosal tissue and skin

• Tumors of blood cells and lymphocytes → leukemia, lymphoma, multiple myeloma

  • Multiple myeloma is a B cell cancer characterized by bony punchy lesions

    • Bone marrow is basically only plasma cells

    • IgG

Misc.

• Tumors of neural cells → ganglionneuroma, neuroblastoma

• Germ Cell tumor → teratoma, embryonal carcinoma, seminoma/dysgerminoma

  • Teratomas are derived from germ cells and contain multiple tissue that are formed from all 3 layers (ectoderm, mesoderm, endoderm) Not metastatic

  • Since teratomas are from germ cells you can get weird stuff like teeth and hair and I love them

• Blastoma: malignant tumors composed of embryonic cells originating from embryonic primordia

  • retinoblastoma - eye

  • neuroblastoma - adrenal medulla or immature neural cells

  • hepatoblastoma - liver

  • nephroblastoma - kidney

  • glioblastomas - brain

• Named after Dude Bros (Eponymic tumors)

  • Hodkin’s - lymph nodes

  • Ewing’s - long bones

  • Kaposi’s - on the skin, usually AIDs patients

Stagin’ and Gradin’

• Staging: based on clinical assessment during gross exam, surgery, x-ray, etc.

  • Uses the TMN system

    • T - size of tumor

      • 1-4 low is good

    • N - lymph node metastases

      • 1-4 low is good

    • M - distant metastases

      • 0-1 low is good

• Grading: based on histologic exams

Discuss the causes of cancer

Exogenous Causes

• Chemical exposure from occupation or environment

• Physical from like the sun, pollution tobacco, alcohol, diet

• biologic from viruses

Endogenous

• Oncogenes - proto-oncogenes are reproduced

  • could be familal

• Tumor Suppressor genes - breakdown in suppression system

Wombo Combo

• 9/10 its usually an interaction between the 2

• When combined there’s exponential increased risk

Describe the clinical manifestation of Neoplasia

• Clinical features depend on type of tumor, location, grade, stage, immune status of host, sensitivity of the tumor cells to therapy

Systemic Symptoms

• Cachexia (generalized weakness)

  • caused by wasting

• Weight loss and loss of appetite (anorexia)

• Neurological symptoms

• Can have obstruction of airways or digestive tube

• Can have have respiratory dyspnea and pneumonia

• Splenomegaly

• Intestinal obstruction

• Abdominal masses

• skin lesions

• Liver enlargement

• ascites (swollen stomach)

• Bleeding in Urinary tract, rectal, vaginal

• thrombosis

• Malaise (general fatigue)

Paraneoplastic Syndrome

• Paraneoplastic syndrome: substances that are secreted by cancer cells that affect other systems

• small cell carcinoma of the lung→ Cushing’s Syndrome

  • May produce ACTH and overstimulate the adrenals

• squamous cell carcinoma of the lung → Hypercalcemia

  • hyper PTH

• renal cell carcinoma → Polycythemia

  • renal cells release hella EPO and we get way more blood

• pancreatic carcinoma → Venous thrombosis

  • Release of thromboplastin

• Thymoma → myasthenia gravis

  • tumor in the thymus blocks ACH receptors as neuromuscular junctions which impairs transmission obviously

Chapter 9: Heme and Lymph Pathology

Describe the Composition of peripheral blood*

• Blood is made up of hematocrit (RBCs), Buffy coat (WBCs, platelets), and Plasma (water, proteins, nutrients, hormones, electrolytes, clotting factors)

• Humans have around 5.5-6L of blood

• Normal blood hematocrit in females is 37-47%, in males its 42-52%

Erythrocytes

• 120 day lifespan

• Made in the bone marrow, recycled in the spleen

• 4 heme group, 4 globins

  • O2 and CO2 bind to the iron in the hemoglobin

  • To make hemoglobin you need: iron, B6, B12, and folic acid

  • Normal hemoglobin levels are 14 in females, 15.5 in males

• A normal reticulocyte (baby RBC) is 1-5% of all RBCs

• MCV (mean cell volume) is how big the cells are

  • low = microcytic

  • high = macrocytic

• MCH (mean corpuscular hemoglobin) is the average hemoglobin on 1 RBC

• MCHC (mean corpuscular hemoglobin) is the average hemoglobin in the total volume

  • Basically MCH/MCV

• A low MCH or MCHC indicates hypochromic

Leukocytes*

• Neutrophils are the most common at 60-70% in blood

  • Defense against bacteria infections

  • survive for like 4 days

  • React to chemotaxis → high motility

  • Phagocytes

• Lymphocytes are found at 25-33%

  • Bs, Ts, NK, and stem cells

  • Last longer than neutrophils

  • Viral infections, mono, whooping cough

• Monocytes are found 3-9%

  • Precursor to macrophages

  • Last longer that neutrophils

  • malaria, TB, fungal infections

• Eosinophils are found at 1-3%

  • Allergic reactions

  • Parasites

  • autoimmune diseases

• Basophils are found at less than 1%

  • allergic reactions

  • Granules contain histamine, heparin, serotonin

  • cancer, chicken pox, hypothyroidism

Thrombocytes (platelets)

• essential clotting factor

• survive like 10 days

Anemia*

• Anemia may result from

  • Decreased creation of RBCs (hematopoesis)

  • Abnormal hematopoesis

    • think genetic

      • Sickle cell (most well known) poorly shaped erythrocytes cannot function properly so patient is always hypoxic

  • Increase loss or destruction of RBCs

    • hemorrhage

    • Over active spleen

    • hemolysis

    • infections (like malaria)

      • in Malaria bacteria invades RBC and causes their lysis

Decreased Production of RBCs (the basics)

• Aplastic Anemia (bone marrow failure)

  • Pancytopenia

  • typically idiopathic

• Myelofibrosis

  • Begins as a myeloproliferative disease and leads to scarring in the bone marrow

• Anemia can be the result of bone marrow being replaced by cancer cells

• Nutrient deficiencies (iron, b12, folate, protein)

  • Iron is the most common nutrient deficient

    • Microcytic hypochromic

    • Can be made worse by intestinal malnutrition syndrome

  • B12 and folate are essential for DNA synthesis and maturation of hemopoietic stem cells - low levels cause megoblastic anemia

  • No protein no cells duh

  • Nutrient deficient anemias are markers for starvation and malnutrition

Anemia Morphology (the basics)

• Normochromic Normocytic

  • RBCs are pretty basic

  • This type of anemia is usually due to hemorrhage or anemia of chronic disease

• Microcytic Hypochromic

  • RBCs are small and pale

  • Iron deficiency

  • Thalassemia

• Macrocytic Normochromic

  • Normal color but BIG cells

  • B12 or folic acid defiency

  • Liver disease

• If the shape of the RBCs is the issue (chronic hypoxia and reduced RBC lifespan)

  • elliptocytosis (oval shaped)

  • Sickle cell

  • spherocytosis (ball shaped)

Let’s talk diseases baby*

• Iron Deficiency Anemia

  • most common form of anemia, typically associated with depletion of ferritin

    • Remember no iron, no Heme

  • Caused by the

    • Increased loss of iron (bleeding)

      • periods, ulcers, polyps, NSAIDS, hookwormds, injury

    • Inadequate intake/absorption (bad diet or GI issues)

      • increase use of antacids

      • intestinal disorders (Crohns, Celiac)

    • Increased iron requirements (preggo)

  • Pathogenesis

    • Iron is absorbed in the intestines and bound to transferritin (the uber for iron) or ferritin (storage form)

      • Ferritin aggregates = hemosiderin

        • test with prussian bliue

    • Iron is lost usually through cell lost

      • recycled in spleen

      • Shed through desquamation

      • menstrual bleeding

  • Pathology

    • Microcytic Hypochromic normal hematopoeisis

  • Clinical Quirks

    • more common in females

      • if you see it in males think occult bleeding

    • Symptoms are palor, weakness, and sometimes in kids you’ll see pica (like they want to ear dirt)

    • Labs: CBC, iron, B12, folate, TIBC, transferritin, ferritin

  • Treatment

    • iron supplements

    • stop the bleeding if necessary

• Megaloblastic Anemia (B12 or folic)

  • Reminder: gastric bypass patients have trouble absorbing B12 and since B12 is only found in animal products vegans must take supplements

  • Most severe form is pernicious anemia which is a lack of intrinsic factor (IF)

    • Pernicious Anemia: atrophic gastritis and lack of intrinsic factor, antibodies may prevent the binding of IF to B12

  • May also be caused by celiac, Crohn’s, parasites, etc.

    • Crohn’s affects the part of the intestine where B12 is absorbed

  • Pathology

    • CBC shows decreased RBCs but they big

    • In pernicious anemia, bone marrow is hypercellular and there’s lots of megaloblast

  • Clinical quirks:

    • Same as all the other anemias

    • Maybe some spinal cord involvement if it gets really bad

      • loss of vibration, proprioception, deep tendon reflexes

      • May persist even after treatments

  • Treatment

    • B12 injections or sublinguals

    • Folate supplements

• Aplastic Anemia (Bone marrow ain’t working)

  • Typically idiopathic in nature or can be due to chemo/radiation/infection

  • Pathology

    • Bone marrow is scarred - consist of fibroblast, fat cells, and scattered lymphocytes

  • Clinical Quirks

    • recurrent infections due to pancytopenia and bleeding

    • Basic anemia symptoms

  • Treatment

    • get a new bone marrow

      • about 60% improve!

Hemolytic Anemias

• RBCs can be destroyed because of structural abnormalities or because of antibodies, infectious agent, mechanical factors

• Common features of hemolytic anemias: reduced RBC life span, increase of erythropoetin (trying to compensate), increased reticulocytes, hyperbilirubinemia (more dead RBCS = more bilirubin = jaundice)

• Sickle Cell

  • A result of a point mutation of the HbA results in the HbS (gotta be homozygous to have the disease)

    • Those with above 80% HbS show all the typical symptoms

    • 40-80% HbS means symptoms are mild to moderate

    • Under 40% your asymptomatic congratulations

  • Most common in African populations (30%)

  • HbS undergoes polymerization (they stick together) at low oxygen tension, so we get “sickling”

    • this can occlude small blood vessel and cause ischemia

    • Gotta avoid high altitudes, strenuous exercise,

  • Sickle cells are destroy in the spleen → increase bilirubin

  • Symptoms start at age 1-2

  • Sickling Crisis are usually induce/aggravated by fever, respiratory diseases, anoxia

• Thalassemia

  • Caused by a genetic defect in synthesis of HbA so less globin is made

    • T-beta: less beta chain is made

      • worse and more common

    • T-alpha: less alpha chain is made

    • T _____ minor: one of four chains effected, heterzygotes

    • T _____ major: severe usually lethal

      • Children usually die due to lack of hemoglobin unless transfused

  • Usually of mediterranean descent

  • Clinical quirks

    • Microcytic Hypochromic

    • T-major results in hepatosplenomegaly, iron overload

    • Slow growth

  • There’s no cure

• Hereditary Spherocytosis

  • Genetic defect of structural proteins of RBCs (looks like a ball)

  • Destabilization of membrane and thus lysis in spleen

  • Autosomal dominant 1 in 5000 white people

  • The balls can not adapt to microcirculation, if there’s a vasoconstriction the ball cannot go through

  • Clinical Quirks

    • typical anemia

    • splenomegaly and jaundice

  • Treatment

    • Get rid of the spleen (does NOT help the RBCs in microcirculation)

• Immune Hemolytic Anemia

  • IgG binds to a RBC autoantigen, activating complement which lyses RBCs (hypersensivity type II)

  • idiopathic or due to drugs/environment

Polycythemia

• Typically due to clonal proliferation of hematopoietic stem cells, myleoproliferative disorders, NEOPLASTIC.

• In secondary polycythemia you see increase erythropoietin

• Basic clinical features: easy clotting, HTN, appeared flushed, neuro symptoms, erythroid hyperplasia in the bone marrow, Vera (bone marrow cells look off)

• Typically treated by

  • Phlebotomy, blood letting

  • In the case of Vera, use chemo drugs

Leukopenia

• Most important are neutropenia (agranulocytosis) and lymphopenia

  • Neutropenia = low neutrophils

  • Lymphopenia = low lymphocytes

    • Selective lymphopenia is like a specific type (AIDS, CD4s)

• Maybe caused by chemo, environmental and industrial chemicals, radiation and some chronic diseases damage the bone marrow

• can be a part of aplastic anemia\

• Clinical Quirks

  • Neutropenia: recurrent bacterial infections

  • Lymphopenia: frequent bacterial, viral, fungal, and or parasitic infections

  • long term leukopenia and aplastic anemia are often fatal

• Treatment

  • stop exposure

  • give poietins

Leukocytosis (white count)

Etiology and pathogenesis

• Small increase due to fighting infections so usually benign

  • Neutrophils are high: bacterial infection

  • Eosinophils are high: parasite

  • Lymphocytosis: usually viral, chronic infections (TB), autoimmune

• Sometimes its just inflammation

• Swollen lymph nodes in URI, EBV, and early AIDS

  • If the lymphadenopathy is persistent get a biopsy

WBC and Plasma Malignancies*

Etiology and pathogenesis

• idiopathic or can be caused by a virus/activation of an oncogene

  • EBV - flu like symptoms, mono or burkitt’s lymphoma (children/sub-saharan Africans)

  • Human T Cell leukemia/lymphoma virus (HTLV-1)

    • Can be injected and causes lymphoma so its oncogenic

  • T-lymphotropic virus - same fam as HIV

  • Burkitt’s lymphoma can also be caused by translocation of chromosomal fragments 8 and 14

  • Philly Chromosome (short 22) can cause chronic myelogenous leukemias

• Clinical Quirks

  • Bone marrow infiltration

  • increased number of immature blood cells

  • neoplastic stem cells show genetic changes

  • Anemia

  • recurrent infections

    • usually cause of death

  • uncontrolled bleeding

  • Note: children leukemias are often acute, adults are chronic

Acute Lymphocytic Leukemia

• Myeloproliferative disease that peaks in patients at the age of 5

  • incidence however rises in old people

• Most common form of leukemia in kids

• Rapid progression

• 66% cure rate

  • without treatment though its lethal in 3-6 months

  • Chemo

• Clinical Quirks

  • bone pain

  • recurrent infections

  • weakness

  • bleeding into the skin/major organs

  • lymphadenopathy

  • splenomegaly

Acute Myeloid Leukemia

• Most common leukemia in adults (40% of all leukemias though)

  • mostly elderly patients

• at least 20% malignant myeloblast in bone marrow

• Lethal in 6 months without treatments

  • with treatment (chemo) 5 year survival is 15-30%

• Characterized by AUER RODS on smear

Chronic Myelongenous Leukemia (CML)

• 15% of all leukemias

• rare before adolescence and incidence increases with age

• disease of pluripotent stem cells

• Most patients die in 3 years

• Better Prognosis if the patient has philly chromosomes

• Treatment: chemo, radiation, bone marrow transplant (lead to a 70% chance of 3 year survival)

  • Gleevec is promising and causes remission in 90%

• Clinical Quirks

  • Slow onset

  • mild anemia

  • hypermetabolism

  • fatigue

  • recurrent infections

  • splenomegaly and clotting are common

• Phase of CML

  • Chronic 2-3 years

    • marked leukocytosis of eosinophils and basophils

    • <10 blast in bone marrow on biopsy

    • increase platelet and megakaryocytes (platelet precursors)

  • Accelerated (50% of patients)

    • >10% blast in bone marrow

      • typically ends in blast crisis

    • >20% basophils in blood

    • unresponsive to treatment

  • Sudden onset (other half)

    • cannot be treated

Chronic Lymphocyte Leukemia

• 25% of all leukemias found in old people

• Slow progression (7-9 years)

• Can transform which lessens our prognosis

• Clinical Quirks

  • SMUDGE CELLS in smear

  • indistinguishable from normal lymphs

  • reduced infection resistance

• Treatment

  • unresponsive to chemo

Lymphomas *

• 3% of all malignant diseases

  • no such thing as a benign lymphoma

• *Most lymphomas have a B cell Phenotype*

• More common in adults but happen at all ages

• Malignant cells often infiltrate primary lymphoid tissue

• Diagnose with lymph node biopsy, immunohistology, Flow cytometry, genetic analysis

• Non-Hodgkins Lymphomas (NHLs)

  • Most often involve lymph nodes, bone marrow, spleen, thymus but can also be extranodal

  • Spill into blood → lymphoblastic/lymphocytic leukemia

  • Clinical quirks

    • Lymph node enlargement (lone wolf or pack life)

    • Fatigue, malaise, weight loss, hypermetabolism, anemia, leukopenia, recurrent infections, autoimmune phenomenon

    • Extranodal tumor spread → brain with multiple neuro symptoms

  • Follicular

    • Most common in US in elderly

    • slow growing

    • usually mild symptoms

    • chemo is not effective

    • at terminal stage body is overwhelmed by tumor burden

  • Diffuse large B cells (DLBL)

    • Most aggressive NHL with several forms

    • tumor cells spread

    • complete remission in 75% with chemo

  • Burkitt’s

    • Highly malignant

    • cells prone to apoptosis

    • chemo works good and can almost completely cure

    • Common in sub-Saharan Africa due to EBV

      • Tumor of mandible/face

    • Outside endemic

      • rare but affects kids and young adults

      • abdominal mass

• Hodkin’s Lymphoma (HL)*

  • Rare monoclonal lymphoid neoplasm with 4 feature

    • presents in young adults

      • Peaks at 25-55

    • cervical lymph nodes

    • involves scattered large mononuclear Hodkin and multinucleated Reed-Sternberg Cells* on a background of non-neoplastic inflammatory cells

    • Characteristic neoplastic cells are often surrounded by T cells

    • 5 types

      • Nodular Sclerosis

      • Mixed cellularity

      • lymphocyte predominance

      • lymphocyte depletion

      • lymphocyte rich

    • Prognosis depends on spread, staging is important

      • Stage 1: 1 region

      • Stage 2: 2 or more lymph node regions same side of diaphragm

      • Stage 3: involvement on both sides of diaphragm

      • Stage 4: extranodal tissue involvement

Multiple Myeloma*

• Malignant disease of PLASMA cells

  • a single cell undergoes a malignant conversion

  • clonal expansion, so its monoclonal

• Disease of old age (>45)

• Normochromic anemia

• Mild leukopenia

• Thrombocytopenia

• Bone fractures common

• Quirks:

  • Bence jones protein in urine

  • *Punched out bony lesions in calvaria, vertebrae, long bones on xray*

  • Hypercalcemia

    • calcium is released from bones and deposited in kidneys

  • Renal failure → typically what kills the patient

• Diagnosis

  • based on xrays, serum electrophoresis, bone marrow biopsy

• Prognosis

  • grim, chemo is ineffective

Vascular Disorders

• Mechanical trauma causing small bruises, wounds, hematomas

• Vessel wall weakness

  • depends on tissue strength

  • as we age it gets worse (Senile purpura)

  • Scurvy marked by multiple hemorrhages (remember the PINK song from Spongebob)

    • intracellular matrix of vessels require vitamin C

• Immune mechanism can damage vessels

Platelet Disorders*

• Quantitative: decrease number

• Qualitative: abnormal structure or function

• Congenital or acquired

• Aspirin prevents platelet aggregation and factor 3 release

• Thrombocytopenia is < 100,000 platelets

• Prolonged post-op bleeding or spontaneous bleeding

• Decreased production from

  • aplastic anemia

  • leukemia

  • drugs that damage megakaryocytes

  • infection (rubella)

• Treatment

  • transfusion of blood or platelets

  • but you have to fix the problem

• Increased Destruction

  • Note: A transfusion reaction can cause hemolytic anemia

  • autoimmune, drug induced, ITP, maternal paternal platelet antigen mismatch

• Idiopathic thrombocytopenia purpura: idiopathic, maybe autoimmune

DIC (disseminated intravascular coagulation)

• Consumptive coagulopathy

• We clot a lot and use up all of our clotting factors so if a bleed occurs theres’s none left

• The clots can often cause ischemia or shock

• Labs:

  • low platelets

  • Elevated D dimer

  • Decreased fibrinogen

  • prolongation of PT/PTT

Hemophilia

• Congenital is common but can also be aquired

• Hemophilia A = no Factor VIII

  • mild, moderate, severe

• Hemophilia B = no factor IX

• X linked disease so women can be carriers but men only need one copy to be affected

• New mutations are 20% of cases

• prolonged aPTT

• there’s specific test to distinguish A or B

Clotting Factor Deficiencies

• chronic liver disease affects most clotting factors (they’re made in the liver)

• Vitamin K is needed for Factors II, VII, IX, X

  • Vitamin K is produced by gut bacteria and transported to blood stream with fat cells

  • Deficiencies can be caused by antibiotics, the inability to absorb, pancreatic disorders, warfarin