Patho Exam 1 (unit 1 and 2)

____: increased amount of normal cells

____: mature cells replaced with squamous cells

____: aka atypical hyperplasia; shape/size/organization change of mature cell into dysfunctional cell

• hyperplasia

• metaplasia

• dysplasia

Atrophy

• atrophy: decreased cell size

• physiologic example?

• pathologic example?

• ovaries atrophy with age (caused by menopause)

• atrophy of adrenal cortex (caused by long term exogenous steroids)

Hypertrophy

• what signal types trigger hypertrophy?

• how does the cell size increase?

• reversible or no?

• physiologic example?

• another physiologic example?

• pathologic example?

• increased functional demand (exercise, increased cardiac workload, cardiac muscle failure)

• growth factors, mechanical stretching

• protein accumulation

• muscle increase from working out; reversible when working out stops

• uterus size increase during pregnancy; reversible after birth

• heart failure; hypertension/stenosis/heart failure/any impairment can cause cardiomegaly to compensate but this negatively effects cardiac function later on

Hyperplasia

• define?

• 2 physiologic examples?

• 2 pathologic examples?

• increase in cell amount

• mammary glands (due to increased estrogen during pregnancy + liver regeneration

• endometrial cells increase + bone spurs (due to long term irritation of one area)

Left ventricular hypertrophy

• cardiac cells cannot divide! = so must undergo hypertrophy

• hypertension > increased vascular resistance > increased cardiac workload > cardiomegaly (to compensate) > abnormal cardiac function > cell death

• On other hand… which cardiac ventricle would have hypertrophy with pulmonary vascular resistance?

right ventricle

Metaplasia

• involves reprogramming of epithelia or connective tissue into what cell type?

• pathologic example?

• what is irreversable metaplasia called?

• squamous noncilliated cells

• bladder (bc kidney stones), bronchi (bc smoking)

• neoplasm (when theres irreversable uncontrolled growth…. ex: cancer)

Dysplasia

• define?

• could become irreversable cancerous (neoplasm)

• pathologic example?

• disorganized cells that are distant from the OG cells in which theyre derived from

• cervical tissue (could turn into cervical cancer)

Common biological derangements of cell injury + death

1. ___ > cell swelling (bc Na stuck inside cell) and metabolic acidosis and hyperkalemia (bc K stuck inside cell) > decreased protein synthesis > decreased membrane transport > lipogenesis

2. ___: destroys cell membrane and structure

3. ____: results in irreversible mitocondria damage + breakdown of cell membrane + DNA damage

4. ____ > released lysosomal enzymes into cytoplasm > cell digests itself

5. ____: results in DNA damage > apoptosis

• decreased ATP

• ROS

• increased Ca in cell

• membrane peremability defect

• protein misfolds

ROS and cell injury

• What causes ROS release?

• 3 Specific pathologies effects of ROS on cells?

• how does TOO much ROS affect cells?

• simple definition of oxidative stress?

• Toxins, reperfusion injury, radiation, stress

• lipid degradation > membrane damage > creates membrane permeability. protein modification > protein dysfunction. DNA damage > mutations > increased cancer risk

• damages cell membrane and structure

• apoptosis > necrosis

• imbalanced antioxidants and ROS

Ischemia

• lack of O2 > failed ATP pump > mitochondrial vacuolization

• lack of O2 > cell undergoes anaerobic respiration (glycolysis) > lactic acid accumulation > metabolic acidosis

• lack of O2 > failed ATP > lipid deposition

Ischemia reperfusion injury (IRI)

• IRI is a complication of ischemia

• increased ATP/O2 usage during ischemia > catabolites develop > increased ROS with reperfusion > bloodflow and O2 restored > xanthine oxidase uses catabolites and O2 to produce ROS > cell membrane damage > Ca influx > mitochondrial dysnfunction > ATP loss > apoptosis > necrosis

• ___ overload in mitochondria (bc membrane got damaged) > drowns organelles and cell swells

• Inflammation (bc cell is damaged so we naturally will inflamm response)

• ___ adhesion to damaged cell = accelerates cell injury! (bc neutrophils increased capillary permeability = more O2 reaches injury site = more ROS)

• Complement system activated: MAC causes cell lysis > more tissue injury

• whats the RX for IRI?

• Ca+

• neutrophil

• antioxidants and anti-inflamm meds

Major burns and cell injury

• what % TBSA concludes as major burn injury?

• increased capillary permeability > edema, hypoalbuminemia, hypovolemia > tissue ischemia (bc edema from 3rd space puts pressure on surrounding tissues) > deceased BP > MODS, decreased cardiac output, hypermetabolic response > resolves in 24 hrs

• traits of hypermetabolic response?

• hypermetabolic response lasts 24 hrs after injury > wound closure/repair

• crazy inflammation and exudation

a. the inflamm resposne triggers diapedesis of neutrophils that increase capillary permeability > increased albumin/fluid enter 3rd space > more edema and hypotension

b. hypotension causes = hypoxia at tissues > failed ATP pump > swell swells and hyperkalemia > metabolic acidosis

c. MODS due to hypoxemia and hypoxia

• loss of plasma fluid causes ____ = contributes to tissue ischemia

• immunosuppression > systemic sepsis

• whats the RX?

• over 20% total body surface area burned

• increased body temp, increased HR, increased blood glucose, deep breathing (hyperpsnea) muscle wasting

• treat within 24 hrs. fluidssss, electrolytes, nutrition, wound management, grafting, infection control meds, regulate their body temp

characteristics of apotosis?

• programmed cell death

• cell shrinks and membrane stays intact

• nucleus fragments

• no inflammatory response it just happens asap

Necrosis and cell death

• necrosis happens after local cell death and auto digestion

• cell swells > organelles are ruptured (bc drowned out by water influx from failed ATP pump) > cell digests itself

• Causes inflammation of neighboring cells

• causes of necrosis?

4 types of necrosis

1. coagulative: caused by? what does cytoplasm look like? examples?

2. liquefactive: caused by? what does cytoplasm look like? examples?

3. caseous (combined liquefactive and coaglative): caused by? what does cytoplasm look life?examples?

4. fat gangrenous: caused by? what does cytoplasm look like? examples?

• prolonged hypoxia, infection, damaged cell membrane

• protein breakdown or hypoxia. denatured cytosplasm. ex: kidneys and heart

• bacterial infxn or hypoxia or strong acids. hydrolyzed cytoplasm. ex: wet gangrene at foot.

• tuberculosis. ex: TB infected lungs. mass apoptosis in cytoplasm. has cheese-appearance

• accidental lipase release. saponified cytoplasm. ex:breasts, abdomen, pancreas

Net filtration

• which vessel end favors filtration?

• which vessel ends favors reabsorption?

• explain how low albumin levels cause edema?

• explain how insufficient heart pumping cause edema?

• explain how increased capillary permeability causes edema?

• arterial

• venous

• hypoalbuminemia causes low oncotic pressure > not enough fluid drawn back into capillaries > fluid remainds in 3rd space

• heart doesnt pump the returning blood back into heart strong enough > high blood volume backflow into capillaries > forces a strong hydrostatic pressure > fluid sucked up into 3rd space

• capillary basically has holes in it > albumin can fit thru and enter 3rd space > albumin attracts fluid thus fluid from blood enters 3rd space (aka tissue oncotic pressure since tissue is pulling in fluid)

Renin angtiotensin aldosterone system

• whats the goal of RAAS?

• list the RAAS system events in order

• what specific mechanisms does RAAS induce to retain Na and water?

• sodium (and water) reabsorption

• angiotensinogen (from liver) > renin (from kidney) > angiotensin 1 > (undergoes ACE enzyme from lungs) > angiotensin 2 (from adrenal glands) > aldosterone (from adrenal gland) = Na and water retention!

• angiotensin 2 causes vasoconstriction = increased BP = increased extracellular fluid/plasma + aldosterone signals kidneys to reabsorb Na

ADH and water balance

• primary organ that controls this?

• what is the goal?

• hypothalamus

• retain water

• increased plasma osmolality (high Na) > brain’s osmoreceptors detect > increase thirst

OR

• increased plasma osmolality (high Na) > brain’s osmoreceptors detect > hypothalamus releases ADH

OR

• increased plasma volume (BP) > heart’s baroreceptors detect > hypothalamus releases ADH

Natriuretic peptides system

• Goal: decrease blood pressure/volume

• This system senses blood volume* changes, not osmolality changes

• Increased total body Na+ (thus fluid) > osmotic shift of water extra cellularly, increased thirst/fluid intake > increased blood volume > atrial stretching detects this > release of ANH (@ atria) and BNP (@ ventricles) > increased GFR, inhibited RAAS system, inhibited Na renal reabsorption > pee > decreased blood pressure/volume

Action potentials

• at resting state, is the membrane negative or positive?

• at resting state, the Na-K pump will maintain a higher concentration of ____ outside cell and higher conentration of _____ inside cell

• what is the ratio of Na and K movement at resting state?

• what happens during depolarization?

• what happens during repolarization?

• negative

• Na

• K

• At rest, its constantly pumping 3 Na out of cell + 2 K into cell

• Na rushes into cell = cell membrane more positive now

• Na exits cell + K enters into cell to restore resting state

Relationship between K and H: pH changes and K balance

• during acidosis, where is H moving and where is K moving?

• during alkalosis, where is H moving and where is K moving?

• H moves into cells (bc body trying to compensate by moving H from blood into cell storage) + K moves into cell

• H moves out of cells (bc body trying to compensate by moving H from cells into blood) + K moves into cell

HYPERkalemia

• mild hyperkalemia SX: fingers tingliness, restless, cramping, diarrhea, peaked T-wave

• severe hyperkalemia SX: cell unable to repolarize > muscle weakness, lost muscle tone > flaccid paralysis > arrythmia, peaked T-wave, shallow ST segment, wide QRS > cardiac arrest

• Rx?

• correct acid-base balance (bc rmb H affects K), give insulin and* glucose

Hypercalcemia VS Hypocalcemia

Hypercalcemia

• decreased excitability

• SX?

• ex: trosseaus sign (bc the hand is paralyzed in specific position)

• ex: chvoteks sign (bc face muscles twitch easily when touched)

• poor intestinal absorption

• poor perfusion

Hypocalcemia

• increased excitability

• what other vitamin deficiency also causes hypocalcemia?

• bone cancer risk

• SX: muscle cramps, rigid paralysis

• SX: muscle weakness, fatigue, bone fractures, kidney stones

• vitamin D

• cause of resp acidosis?

• cause of resp alkalosis?

• cause of metabolic acidosis?

• cause of metabolic alkalosis?

• resp depression

• alveolar hyperventilation

• body has too little HCO3

• body has too much HCO3

What is normal blood pH?

• what is normal PaCO2 range?

• what is normal HCO3 range?

Whats the normal ratio of HCO3 to PaCO2?

• 7.35-7.45

• 35-45

• 22-28

• 20:1

Local manifestations of inflammation

• edema

• redness

• pain

Systematic manifestations of inflammation

• fever: caused by what?

• leukocytosis: left shift of immature:mature WBCs

• increased plasma protein synthesis (pro-inflamm APCs and anti-inflamm APCs)

• IL1, IL6, alpha factor, exogenous pyrogens

Acute inflammation VS Chronic inflammation

• what immunity cells does acute include? (ex: think of simple cut on finger)

• what immunity cells does chronic include?

• neutrophils, mast cells, platelets

• monocytes, macros, lymphocytes (Tcell, Bcell)

Plasma protein system

1. Complement system

• function of C3a?

• function of C3b?

• function of C5a?

• function of MAC?

2. Coagulation system'

• chronological order of clot formation?

3. Kinin system: goal is to inflame/vasodilate/permeability

• what does bradykinin affect? what can this result in?

• degranulates mast cell to release histamine/prostaglandins + acts as anaphylactic

• opsonization

• chemotactic factor + anaphylactic

• poke holes in pathogen cell membrane > can lead to bronchoconstriction

• X factor > thrombin > fibrinogen > fibrin > clot

• Signals pain to signal inflammation + vasodilation + smooth muscle contraction (

Mast cell degranulation VS Mast cell synthesis

• degranulation is an IMMEDIATE response via: releasing histamine for inflammation + releasing eosinophil chemotactic factor to attract eosinophils to do phagocytosis

• synthesis is a LONG TERM response to: dilate, increase permeability, exudation

• when histamine binds to ___ receptors = pro-inflamm response smooth muscle constriction (ex: bronchoconstriction)

• when histamine binds to___ receptors = anti-inflamm-regulatory response (ex: increased gastric mucosa )

• when histamine binds to lymphoctes, eosinphils, neutrophils, mast cell, what are the effects?

• H1

• H2

• Enhance immune reaction

• stages of wound healing?

• what is regeneration VS resolution in wound healing?

• inflammation, proliferation, remodeling (collagen matrix fills wound > seals > shrinks)

• regeneration is when wound doesnt fully heal + leaves scarring + tissue function is absent or decreased

• resolution is when wound does fully heal + no scarring + tissue function fully restored

• what is clonal diversity + where does it occur?

• what is clonal selection + where does it occur?

• occurs in primary lymphoid organs (Bone marrow and thymus); when naive Tcells and Bcells with a receptor for any antigen are produced

• doccurs in secondary lymphoid organs (spleen, lymph nodes): when differntiated/matured Tcells and Bcells finally have antigen-specific receptors

Antigen processing and presentation

• which 3 cells act as APC?

• who do APC cells activate/show the processed info to?

• Bcells, macrophage, dendritic

• Helper Tcells

Passive vd active vs artifical vs natural immunity GO:

• A natural exposure to antigen (ex: childhood diseases)

• vaccines 

• mother transfer antibodies to fetus 

• antibodies transfer from immune animals → to nonimmune humans 

is active immunity short or long lived?

is passive immunity short or long lived?

• natural active

• artificial active

• natural passive

• natural artificial

• long lived

• short lived

Hypersensitivity type 1

• is an immediate response

• how is it mediated?

• what triggers this hypersensitivity? examples?

• SX?

• RX?

• igE mediated from mast cells

• environmental allergens (ex: food allergy, hay fever, bee sting)

• itching, hives, watery eyes, watery nose, cramps, swelling, bronchospasm

• antihistamines for local rxn; epinephrine for systematic rxn (anaphylaxis)

Hypersensitivity type 2

• how is it mediated?

• what triggers this hypersensitivity? examples?

• SX?

• igM or igG; is tissue-specific

• igG or igM binds to specific tissue antigen > activates complement cascade > damaged cell membrane/lysis/phagocytosis

• autoimmune hemolytic anemia, ABO-mismatched bloodtype, graves disease

Hypersensitivity type 3

• how is it mediated?

• what triggers this hypersensitivity? examples?

• SX?

• RX?

• immune complex mediated; not tissue/cell specific

• antibody (igG or igM)and antigen fuse into 1 molecule > circulates in blood > deposits in tissues/joints > complement activation > damage to tissue

• lupus, glomerulonephritis, arthritis, raynaud syndrome (where fingertips lose circulation and turn purple)

Hypersensitivity type 4

• is a slow, delayed response

• how is it mediated?

• what triggers this hypersensitivity? examples?

• SX?

• RX?

• Tcell mediated

• over-reactive Cytotoxic Tcells cause direct cell damage + Helper Tcells produce too much ROS into tissue = cell lysis

• graft rejection, TB skin test, type 1 diabetes

HIV/AIDS

• person is asymptomatic until CD4 count reaches below what value?

• Early SX?

• Late SX (when HIV progressed into AIDS)?

• below 200

• fatigue, sore throat, fever

• weight loss, anorexia, cacexia, person is super susceptible to infections/cancer

Infections

• stages of infxn in order?

• are exotoxins from gram (+) or gram (-)?

• examples of exotoxins?

• note abt exotoxins: theyre immunogenic (meaning the un-activated version of the bacteria can be turned into vaccine)

• are endotoxins from gram (+) or gram (-)?

• examples of endotoxins?

• ^^ their SX/effects?

• transmission > colonization > invasion (when it penetrates cells) > dispersal > tissue damage

• gram positive

• diptheria, tetanus

• gram negative

• LPS (within cell walls)

• fever, swelling/vasodilation, coagulation (← can cause septic shock from ischemic induced hypoxia)

____: bacteria in blood; doesnt rlly cause any immune rxn

____: bacteria in specific tissue circulates into blood > actively multiplies in blood > causes IMMEDIATE life threatening immune response

____: more life threatening; characterized by prolonged hypotension and hypoxia

• bacteremia

• sepsis/septicemia

• septic shock

when do antibodies attack replicating virions?

after virions replicate intracellularly, they’re about to leave the cell and re-wear their protective coats. right before virions can put on coats, thats when antibodies either neutralize (antibody binds to virus so it cant bind to another healthy cell) or opsonizes (flags!) the virion

General adaption syndrome

1. Alarm stage

• what happens here?

2. Resistance and adaption stage

• what happens here?

3. Allostatic overload

• what happens here?

What is allostasis

What is allostatic load

What is allostatic overload

• sympathetic nervous system triggered > releases epinephrine + hypothalamus triggered > releases cortisol (cortisol raises blood glucose too)

• body continues producing epinephrine and cortisol

• body is exhausted from prolonged stress > adaption unsuccessful > progressive breakdown of immune system/compensation mechanisms > death

• body’s adaptive response to stress

• wear and tear = leads to disease

• exaggerated body’s response to stress (ex: chronic inflammation, chronically high cortisol, etc….)

Cytokines

• ___: induces inflamm, apoptosis, phagocytosis, chemotaxis, Tcell/Bcell proliferation

Interleukins

• ___: induces fever

• ____: induces wound healing

Inferferons

• ____: warns neighboring cells to protect themselves against virus

• ____: increases mucosal secretion

• alpha factor

• IL 1 and IL6

• IL2

• IF1

• IF 3

REVIEW ALL TYPES OF SHOCK

OKAY i will

describe the formation of chromosomes

DNA double helix wraps around histones to form nucleosomes > nucleosomes coil into chromatin > chromatin condense into chromosomes

Cell injury mechanisms: hypoxia

• Increased altitude > hypoxia > decreased ATP synthesis > anaerobic metabolism > increased lactic acid > metabolic acidosis > increased circulating K in blood (hyperkalemia)

• Na-K pump failure > increased Na and Ca accumulation inside cell + increased accumulation of K outside cell > cell swells > hyperkalemia

• alveolar-capillary damage > increased capillary permeability > interstitial fluid > pulmonary edema > hypoxemia > hypoxia > dysthymia, cardiac arrest