Cellular Basis Of Disease Flashcards
Part 1: The Language of Disease
What is Disease or Pathology?
- Pathology =
- Disease =
- Diseases are d_______
How can you tell when someone is in a disease state?
- the physical manifestation of a disease
- defined as both the cause of the initial insult and also the pattern of a response that an organism has to that initial insult
- Dynamic
Often the body’s response to the injury is actually more of a negative manifestation than the initial injury ie. HIV -> AIDS
Concept of “Normal”
- Sources of Variation
- G_______
- A___
- S___
- Sit______
- T_____
- L_______ Conditions
- Variation
- Genetics
- Age
- Sex
- Situational
- Time
- Laboratory Conditions
- For many “normal” physiologic parameters = there is a range (ie BP) based on population sampling*
- Situational ex) someone living at high altitude*
- Time ex) assessing testosterone in men, highest in the morning (assessing hormone levels)*
- Lab ex) diff labs have diff ranges*
The Language of Disease
- Etiology =
- Pathogenesis =
- Clinical Manifestations =
-
“cause”
- Idiopathic: cause of disease unknown
- interaction btwn initial injury and body’s response to it to produce abnormal function - and the ultimate disease that emerges (more so from the body’s response)
-
the observable consequences of a diseae - S/S
- Sign = objective, measurable (fever, rash, abnormal gait)
- Symptom = subjective, felt by patient, must be reported by the patient
Causes of Cell Injury Categories
(3)
Unknown (Idiopathic)
Extrinsic (Physical agent vs. Infectious)
Intrinsic
Intrinsic Causes
- In_____
- Con______
- M_____
- Deg______
- Neo_____
- Imm______
- N_______ Deficiency
- Psy_____
- Inherited
- Congenital
- Metabolic
- Degenerative
- Neoplastic
- Immunologic
- Nutritional Deficiency
- Psychogenic
Caused by the body itself
Extrinsic-Physical Agent Induced Causes
- Animation =
- F_____
- T________
- H_______
- R_______
- El______
- Ch______
- Ia_______
- Inanimate
- Force
- Temperature
- Humidity
- Radiation
- Electricity
- Chemicals
- Iatrogenic - conditions inadvertently caused by medical care (ie. AKI from contrast)
Extrinsic: Infectious Causes
- Animation =
- Pathogenic O_______
- V____/B_____/F_____
- Pro_____
- Pathogenic A_____
- In_____/W______
- Animate
- Organism
- Viruses/Bacteria/Fungi
- Protozoa
- Animals
- Insects/Worms
Unknown Causes of Cell Injury
=
Idiopathic = uknown origin (ie essential HTN)
Factors of Pathogenesis
(4)
- Time = how long exposure was to the injury
- Quantity = how much exposure to injury
- Location = which part of the body (ie DVT vs. PE)
- Morphological Changes = morphological adaptations by cells and tissues in the body
Clinical Manifestations
- Sign =
- Symptoms =
-
Changes with time:
- Latent period =
- Prodromal period =
- Acute Period
- measurable, observable
- subjective, felt/reported by patient
- Changes with time
- period of no S/S, period of quiet
- first appearance of S/S
-
Severity of S/S reach its peak
- after this either recovery or chronic period
- Syndrome: sterotypical combination of signs and symptoms that presents for a disease/is expressed*
- Ex) acute stage viral syndromes such as HIV*
Making a Diagnosis: Methods
- ______ Methods
- S/S
- ______ Methods
- U___alysis (f____ analysis)
- _____ Analysis
- Blood c____, ch_____, c_____, / S____
- T____ Diagnosis
- Electro_______
- Ra_____
This all leads to you making what type of diagnosis?
- Clinical
- Laboratory
- Urinalysis/Fecal
- Blood
- counts, chemistry, culture/ Serology
- Tissue (biopsy)
- Electrocardiogram
- Radiography
Differential Diagnosis
Serology - looks at antibodies (ie. looking at if someone was exposed to Hep B - looking for IgF or IgM)
Part 2 Maintaining Cellular Function
The Cellular Basis of DIsease
- Levels of organization
- specialized ____ -> specialized _____ -> ______ -> organ ______ -> those organ systems help maintain normal _____ of the entire organism
- Cellular Response to Injury
- Interdependence of cells and systems =
- Maintaining Cellular function?
- Cells don’t have direct ____ to anything
- What cells need to maintain normal function = by body’s system to maintain normalcy of ECF with ______, adequate v_____, p_____
- ICF: we maintain ICF by maintaining the ____
- Levels
- cells -> tissues -> organs -> systems -> function
- Cell response to injury
- = Normal function of a cell allows for normal function of a system and vice versa
- Maintaining cellular function
- access
- Oxygen, Volume, Pressure
- ECF
The Interior and Exterior Cell Environment
ICF
ECF (2)
Intracellular Fluid
Extracellular Fluid
- Interstitial Fluid (btwn cells and blood vessels)
- Intravascular Fluid = plasma within blood vessels
Important Factors in Maintaining Cellular Homeostasis
(5)
Cell Volume (Water and Osmolyte Balance)
Electrolyte Balance
Maintaining pH
Cell Metabolism
Cell Transport
- Cell Volume - too much or too little can cause death*
- Electrolyte - especially Na, K, Ca- effects cell activity*
- pH - V tightly controlled*! (as well as temp) - every enzyme that catalyzes reactions that our body relies - enzymes (proteins will denature if pH is imbalanced)*
- Cell Metabolism - set of chemical reactions that allow cells to generate heat and ATP, conversion of energy (food) into energy in form of heat*
- Cell Transport - normal movement of substances across the membrane*
Maintaining Cell Volume
- By maintaining _____ and _____ balance
- Water
- _________ system
- Osmolytes (Sodium and Potassium)
- ________ system
- ________ system
- Water
- water, osmolyte
- Water
- ADH/Thirst System
- Osmolytes
- Renin-Angiotensin System (systemically)
- Na+/K+ ATPase pumps (intracellulary)
- Water
- Osmolyte balance = osmolarity of ICF = osmolarity of ECF (equal # of osmolytes on both sides)*
- If unbalanced, water follows osmolytes (Na+, K+ are the main ones)*
Systemic Control of Water Balance
- Body water is _____ from two primary sources
- water _____ alone or in food
- water liberated from ______ processes
- Body water is primarily ____ through three routes
- water lost through _____
- water lost through _____
- water lost through _____
- gained
- consumed aka ADH system
- metoblic
- lost
- urine obvs the most significant unless in a diarrheal state etc.
- feces
- sweat
ADH- Thirst System
- Water level drops below normal range
- _____ detects higher concentration of solutes in blood
- _____ creates feelings of ____ and ____ _____ releases more ____
- The person _____ water and ____ stimulates kidneys to reabsorb more water
- Water level rises above normal range
- ______ detects low solute concentration
- ______ releases ___ ADH
- Kidneys reabsorb ____ water
- Water loss
- Hypothalamus
- hypothalamus - thirst and posterior pituitary - more ADH
- dirnks, ADH
- Water gain
- hypothalamus
- Pituitary, less ADH
- less water reabsorbed
Renin-Angiotensin-Aldosterone System (Na+, K+)
-
_____ is an enzyme that converts _____ to ____, ACE turns ___ to ____
- Renin is called the rate _____ enzyme in the production of ang 2 (indirectly)
-
Then ang II does all __ things
- Adrenal cortex is located on top of the kidneys -> _______*** v important part
- RAAS system controls (2) and ___
- There is a normal amount of _____ and _____ in the body, so changes in ___ will cause changes in _____
- Aldosterone stimulates: sodium _____ and potassium ______
-
Renin, antiotensinogen -> ang I, ang 1 t-> ang 2
- limiting
-
5
- aldosterone
- Na+, K+, BP
- Renin, Ang II, BP -> Renin
- retention, excretion
RAAS System Chart
Factors that stimulate Renin secretion (3)
- Decreased BP
- Decreased Sodium
- Increased sympathetic tone
Cellular Control of Osmolyte Balance (Sodium and Potassium)
- Na = high concentration in the ______ fluid
- K = high concentration in the ______ fluid
- The energy to drive the pump is released by ______ of ____
- This sodium potassium pump is so important that 50% of our energy is directed towards them
- Na = extracellular
- K = intracellular
- hydrolysis of ATP
Part 3 Relationship between ECF and ICF
Distribution of Fluids
- Intracellular Fluid (ICF) = ~___% of body weight
- Extracellular Fluid
- Interstitial Fluid = ___% of body weight
- Plasma = __% of body weight
- TBW = ____+____
- TBW usually ___% of body weight
- Can vary by (2)
- 40%
- ECF
- 15%
- 5%
- ECF + ICF
- 60%
- body fat %, age
Third space = membrane lined areas, synovial fluid sacs between joints
Composition of Extracellular vs. Intracellular Fluid
- Movement between compartments
- ____ vs ____ & ____ vs. ____ fluid
- ICF vs. ECF, Plasma vs. Interstitial
- Homeostasis*
- -Lots of Na, Cl , Ca outside*
- Lots of K, Mg, proteins, amino acids*
- Intracellular Ca is strongly controlled which is important*
Disrupted Fluid Movement - Intravascular vs. Interstitial - Edema
- Causes of Edema
- Plasma Oncotic Pressure: ______
- Causes =
- Interstitial Oncotic Pressure: ______
- Causes =
- Capillary Blood Pressure: ____
- Causes =
- Plasma Oncotic Pressure: ______
- _______** Obstruction
- Edema = accumulation of fluid in the interstitial space
-
Decreased
- Losses or diminished albumin
- Kidneys usually regulate albumin well -> if AKI/injury -> nephrotic syndrome
- Liver forms albumin (in impaired liver function/starvation -> albumin goes down)
- Losses or diminished albumin
- Increased
- increased capillary permeability (occurs with inflammation/injury) or vascular injury
- Increased
- HTN
- Venous obstruction (blockage or volume overload)
-
Decreased
Capillary Bulk Flow
- Pressures that determine direction of fluid flow:
- Capillary Blood Pressure (“____ pressure”): favors ______
- Capillary Oncotic Pressure (“______ pressure”) favors _______
- Interstitial Hydrostatic Pressure (“_____ pressure”) favors _______
- Interstitial Oncotic Pressure (“_____ pressure”) favors _______
- pushing, ultrafiltration
- pulling, reabsorption
- pushing, reabsorption
- pulling, ultrafiltration
Capillary Bulk Flow Notes
- Microcirculation: made up (3) is the only place that?
- 4 passive forces - if you add up all those forces you get a ___ force
-
2 spaces
-
Vascular Space
- Capillary Blood Pressure =
- Capillary Oncotic Pressure =
-
Interstitial Space
- Interstitial Hydrostatic Pressure =
- Interstitial Oncotic Pressure =
-
Vascular Space
- The only pressure that constantly changes is?
-
Usually theres net _____ bc?
- Bc our immune system lies in the lymphatic system, our ____ is constantly monitored by our immune system
- All that fluid moving through the lymphatic system eventually drains to the?
- capillaries, arterioles, venules - where fluid can cross
- net
-
2 spaces
-
Vascular
- pushes against wall of capillary -> ultrafiltration
- albumin -> reabsorption
-
Interstitial
- reabsorption
-
Is normally 0 bc theres not suppose to be any plasma proteins (albumin) in that space unless - if not 0, it normally pulls fluid out -> edema
- vascular injury and it leaks out
- histamine release enlarges capillaries (intentional escape of albumin
-
Vascular
- Capillary Blood Pressure
-
Ultrafiltration bc our capillaries are always leaking fluid -> so why are we not always edematous? Bc our lymphatic system drains it
- ECF
- Vena cava - heart
Disrupted Fluid Movement - Intravascular vs. Interstitial
Third Space Accumulation
- “Third space” refers to the _______ compartment: body cavities lined with serous ______ ex) (3)
- Third space fluid accumulations (or third spacing) are similar to pitting edema, occurs when there is an imbalance of starling forces (espeically in the case of _____ drainage blockade)
- Examples of third spacing include (2)
- transcellular, membranes (pericardial sac, peritoneal cavity, pleural cavity)
- lymphatic
- ascites, pleural effusions
Third Space Accumulation Notes
-
Ascites happens when albumin gets really ____
- These pts will usually be fluid volume _____ (edema) as well as ___ BP bc fluid is not staying in the vasculature
- ____ produces albumin
- Often seen with ____ failure and ____ bc of drop in albumin -> so you this plasma oncotic pressure that gets very low -> fluid leaks into interstitial space
- Counter pressure from ascites then does what?
- Ppl who have low albumin will have generalized ____ but bc of concentration of _______ in one space such as the belly -> there are concentrated areas
-
LOW
- overloaded, low BP
- Liver
- Liver failure, starvation
- helps the fluid stay in the mesenteric arteries that lines the GI tract = equilibrium
- edema, capillaries
Part 4 ECF Electrolyte Balance
Alterations in the Movement of fluids between ICF and ECF
Altered _____, _____, and _____ Balance
Types of Alterations (3)
Sodium, Chloride, Water
Isotonic, Hypertonic, Hypotonic
- Sodum and Potassium imbalances most effect - “excitable tissues” aka nervous system and muscular system*
- Hencesodium alterations effect things like LOC*
- Potassium alterations effect cardiac function*
Isotonic Alterations
- Change in ___ accompanied by _____ changes in ____ and ____
- Isotonic volume depletion (2)
- Isotonic volume excesses (2)
- TBW, proportional, electrolyte and water
- Hemorrhage, Severe wound drainage
- Excess IV fluids, Hypersection
Volume change, no change in osmolarity
Hypertonic Alterations
- Osmolarity of ECF is _____
- Hypernatremia: ______ water intake, inappropriate administration of ______ saline, etc
- Water deficit: ______ water intake, impaired _____ conservation of water
- Hyperchloremia: accompanies any excess of _____ or deficit of _____, excess ammonium chloride _____, etc
- elevated
- inadequate, hypertonic
- inadequate, renal
- sodium, bicarbonate, diuretic
Common causes of hypertonicity -> hyperglycemia, hyerchloresterolemia
Hypotonic Alterations
- Osmolarity of ECF is ____ than normal
- Hyponatremia: D_____, V_____, D_____, B____, Di_____, etc
- Water excess: ______ urine formation, S _ _ _ _, etc
- Hypochloremia: accompanies any deficit of ____ or excess of _____, v____ ( loss of HCL), etc
- less
- Diuretics, Vomiting, Diarrhea, Burns, Dilutional, etc
- Decreased, SIADH
- deficit sodium, excess bicarb, vomiting
Diuretics block retention of sodium -> hyponatremia
Potassium Balance
- Maintained Systemically via =
- Maintained Within the cell via =
- Several other factors influence serum potassium levels by causing ICF/ECF shifts such as (3)
- Aldoserone mediated renal regulation
- NA/K ATPase pumps
- ECF/ICF pH
- Insulin
- Catecolamines
Potassium Balance
ECF/ICF pH
- Acidosis = K+ moves ___ the cell
- Alkalosis = K+ moves ___ the cell
- out
- in
- Acidosis = H+ ions into cell pushes K out -> hyperkalemia* (bc H+ is positively charged, it has to kick K+ out to balance net charge)
- Acidotic states, potassium shifts out of the cell -> hyperkalemia*
- Alkalotic = H+ ions pushed out of cell -> K+ moves in -> hypokalemia*
- If you correct the acidosis or alkalosis you correct the hyper/hypokalemia*
- All exhcnage between cell and blood stream happens at capillaries that allow free movement by diffiusion*
Potassium Balance
Insulin
- Increased insulin = K+ moves _____ cell
- into
- Potassium is required for glycogen synthesis,when insulin brings glucose into cell*
- So when insulin binds to its receptor, it will cause the uptake of both potassium and glucose to facilitate glycogen syntehsis*
- Mild hyperkalemia tx = kaexylate*
- Severe hyperkalemia tx = insulin + glucose if person has normal sugar*
Potassium Balance
Catecolamines
- B2 adrenergics = K+ moves ____ the cell
- a2 adrenergics = K+ moves ____ the cell
- into
- out
Catecolamines (epi, norepi) - they can bind to adrenergic receptors -> can cause potassium movement -> but isn’t strong enough to create serum level changes
Factors controlling K metabolism
- Factors that shift K+ into cells (4)
- Factors that shift K+ out of cells (5)
Part 5 ECF pH Balance and Cellular Metabolism
Acid Base Balance
- The pH of body fluids greatly affect the structure and function of _____, including ______ systems (pH of arterial blood is about ____-____)
- The _____ and ______ are the primary regulators of acid-base balance
- The pH of fluids are maintained through the use of _____ systems. Buffers are ____ acids and bases that can _____ excess ___ or ___ thereby preventing fluctuations in pH
- proteins, enzyme, (7.38-7.42)
- lungs, kidneys
- Buffer, weak, absorb, H+ or OH-
- pH of fluids and body temp change proteins in the body -> start to denature, enzymatic function is disrupted*
- Buffers can absorb or donate H+ to balance pH of a solutiion - each buffer system has a different range of pH that they work best in - so they work together to handle a wider range of pH changes*
Major Buffer Systems
(4)
- **Bicarbonate (HCO3-/H2CO3)
- Hemoglobin (Hb-/HHb)
- Proteins (Pr/Hpr) (both intracelular and extracellular)
- Phosphate (HPO4-/H2PO4-)
- Most important buffer system is Bicarbonate (HCO3- weak base, H2CO3 weak acid), bicarbonate is derived from CO2 - our body takes CO2 (a waste product of metaboiism and puts it to work, which is why we hold onto quite a bit)*
- Hemoglobin can bind to an extra hydrogen ion*
- Proteins can be a negatively charged protein or neutral protein that is bound to a hydrogen ion*
- Phosphate has ability to move back and forth into weak acid and base*
Bicarbonate Buffer System
Regulated by ____ Regulated by _______
___ + ____ <—> ______ <—> _____ + _____
- Respiratory ____ and _____ effects PCO2 and therefore CO2 available for _____ ____ production
- _____ effect (___ to ____)
- The kidneys regulate _____ levels of ___ and ___ by controlling HCO3- conservation (______) and H+ secretion (______)
- _____ effect (___ to ___)
Lungs Kidneys
CO2 + H2O <–Ca–> H2CO3 <—> HCO3- + H+
- rate, depth, carbonic acid
- Rapid (min - hours)
- plasma, HCO3- and H+, HCO3- reabsorption, H+ excretion
- Slow (hours-days)
- Again bicarbonate is the most important buffer system - and is the only one we activvely manipulate - respiratory and renal system*
- How does CO2 become a weak acid and base?*
- In presence of water and enzyme carbonic anhydrase produces carbonic acid (H2CO3)*
- Carbonic acid then can go back and forth between carbonic acid and bicarbonate and free H+ ion*
- So if you have alkalosis, the respiratory rate can raise CO2 levels by hypoventilation -> therefore making more H+ ions at the end of that formula*
Respiratory vs. Metabolic Acidosis/Alkalosis
-
Causes of Metabolic Acidosis:
- ______ Noncarbonic Acids (3) etc
- Bicarbonate ____ (3) etc
-
Causes of Metabolic Alkalosis
- Excess ____ of Noncarbonic acids (4) etc
- _____ Bicarbonate intake
-
Metabolic Acidosis
- Increased: Ketoacidosis, Uremia (buildup of uric acid), Ingestion
- Loss: Diarrhea, Renal Failure, Proximal tubule acidosis
-
Metabolic Alkalosis
- Loss: prolonged vomiting, GI suctioning, hyperaldosteronism, diuretic therapy
- Excess bicarb intake
Respiratory acidosis (hypoventilation), alkalosis (hyperventilation) -> any other cause is a metabolic cause
Resp and Metabolic systems compensate for each other when the other is causing acidosis/alkalosis
Acid Base Balance Chart
Cell Metabolism
-
Cell Metabolism =
- Mono/Polysacharides = short/long chains of ______
-
3 steps of Metabolism
- ______ = process by which ____ ( polysaccharides, fructose, lactose) that’s consumed and put through ______ to form ______then
- ______
- ______ -> oxidative phosphorlyation
- Each of these steps in metabolism yields ____
-
process by which the cells in the body take in energy substrates (food-protein, carb, polysaccharides and fat) we metabolize these foods in order to synthesize ATP (how our body stores energy for future use)
- sugars
-
3 steps
- Glycolysis = glucose -> glycolysis -> intermediates
- Krebs cycle
- Electron transport
- ATP
Cell Metabolism
- By far the biggest yield of ATP is in the ____ step = which is the only use your body has for ____ and really only in this last step of metabolism that oxygen is used -> but enough energy to maintain systems to stay ____
-
About 75% of energy of that is yielded gets released in the form of ___
- How our body maintains a _____ body temp (98.6), no matter the outside condition
- And only 25% is actually harnessed to form ____
- S the greatest product of metabolism is not ATP, its actually _____.
- last, oxygen, alive
- heat, stable body temp
- ATP
- heat
Controll of Cell Transport
- Passive Transport (needs no energy) **
- (3)
-
Active Transport
- (2)
- Passive
- Simple Diffusion
- Osmosis
- Facilitated Diffusion
- Active
- Secondary Active Transport (uses movement of ions)
- Primary Active Transport (used ATP)
- Another important part of cell function is cell transport - controlling movement of substrates across plasma membrane*
- Baseline permeability of plasma membraneis the most basic form of control*
- Bc the primary structural component of the membrane is lipi -> anything lipid soluble is going to easily cross the membrane (anything lipid does not have a charge)*
- On the other hand, anything that DOES have a charge/polarity cannot freely cross the membrane, needs assistance from a poor or more active mechanism*