Cellular Basis Of Disease Flashcards
1
Q
Part 1: The Language of Disease
A
2
Q
What is Disease or Pathology?
- Pathology =
- Disease =
- Diseases are d_______
How can you tell when someone is in a disease state?
A
- 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
3
Q
Concept of “Normal”
- Sources of Variation
- G_______
- A___
- S___
- Sit______
- T_____
- L_______ Conditions
A
- 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*
4
Q
The Language of Disease
- Etiology =
- Pathogenesis =
- Clinical Manifestations =
A
-
“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
5
Q
Causes of Cell Injury Categories
(3)
A
Unknown (Idiopathic)
Extrinsic (Physical agent vs. Infectious)
Intrinsic
6
Q
Intrinsic Causes
- In_____
- Con______
- M_____
- Deg______
- Neo_____
- Imm______
- N_______ Deficiency
- Psy_____
A
- Inherited
- Congenital
- Metabolic
- Degenerative
- Neoplastic
- Immunologic
- Nutritional Deficiency
- Psychogenic
Caused by the body itself
7
Q
Extrinsic-Physical Agent Induced Causes
- Animation =
- F_____
- T________
- H_______
- R_______
- El______
- Ch______
- Ia_______
A
- Inanimate
- Force
- Temperature
- Humidity
- Radiation
- Electricity
- Chemicals
- Iatrogenic - conditions inadvertently caused by medical care (ie. AKI from contrast)
8
Q
Extrinsic: Infectious Causes
- Animation =
- Pathogenic O_______
- V____/B_____/F_____
- Pro_____
- Pathogenic A_____
- In_____/W______
A
- Animate
- Organism
- Viruses/Bacteria/Fungi
- Protozoa
- Animals
- Insects/Worms
9
Q
Unknown Causes of Cell Injury
=
A
Idiopathic = uknown origin (ie essential HTN)
10
Q
Factors of Pathogenesis
(4)
A
- 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
11
Q
Clinical Manifestations
- Sign =
- Symptoms =
-
Changes with time:
- Latent period =
- Prodromal period =
- Acute Period
A
- 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*
12
Q
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?
A
- 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)
13
Q
Part 2 Maintaining Cellular Function
A
14
Q
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 ____
A
- 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
15
Q
The Interior and Exterior Cell Environment
ICF
ECF (2)
A
Intracellular Fluid
Extracellular Fluid
- Interstitial Fluid (btwn cells and blood vessels)
- Intravascular Fluid = plasma within blood vessels
16
Q
Important Factors in Maintaining Cellular Homeostasis
(5)
A
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*
17
Q
Maintaining Cell Volume
- By maintaining _____ and _____ balance
- Water
- _________ system
- Osmolytes (Sodium and Potassium)
- ________ system
- ________ system
- Water
A
- 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)*
18
Q
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 _____
A
- gained
- consumed aka ADH system
- metoblic
- lost
- urine obvs the most significant unless in a diarrheal state etc.
- feces
- sweat
19
Q
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
A
- Water loss
- Hypothalamus
- hypothalamus - thirst and posterior pituitary - more ADH
- dirnks, ADH
- Water gain
- hypothalamus
- Pituitary, less ADH
- less water reabsorbed
20
Q
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 ______
A
-
Renin, antiotensinogen -> ang I, ang 1 t-> ang 2
- limiting
-
5
- aldosterone
- Na+, K+, BP
- Renin, Ang II, BP -> Renin
- retention, excretion
21
Q
RAAS System Chart
Factors that stimulate Renin secretion (3)
A
- Decreased BP
- Decreased Sodium
- Increased sympathetic tone
22
Q
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
A
- Na = extracellular
- K = intracellular
- hydrolysis of ATP
23
Q
Part 3 Relationship between ECF and ICF
A
24
Q
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)
A
- 40%
- ECF
- 15%
- 5%
- ECF + ICF
- 60%
- body fat %, age
Third space = membrane lined areas, synovial fluid sacs between joints
25
Composition of Extracellular vs. Intracellular Fluid
## Footnote
* 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*
26
Disrupted Fluid Movement - Intravascular vs. Interstitial - Edema
## Footnote
* Causes of Edema
* Plasma Oncotic Pressure: \_\_\_\_\_\_
* Causes =
* Interstitial Oncotic Pressure: \_\_\_\_\_\_
* Causes =
* Capillary Blood Pressure: \_\_\_\_
* Causes =
* \_\_\_\_\_\_\_\*\* 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)*
* Increased
* increased capillary permeability (*occurs with inflammation/injury)* or vascular injury
* Increased
* HTN
* Venous obstruction (blockage or volume overload)
27
Capillary Bulk Flow
## Footnote
* Pressures that determine direction of fluid flow:
1. **Capillary Blood Pressure** ("\_\_\_\_ pressure"): favors \_\_\_\_\_\_
2. **Capillary Oncotic Pressure** ("\_\_\_\_\_\_ pressure") favors \_\_\_\_\_\_\_
3. **Interstitial Hydrostatic Pressure** ("\_\_\_\_\_ pressure") favors \_\_\_\_\_\_\_
4. **Interstitial Oncotic Pressure** ("\_\_\_\_\_ pressure") favors \_\_\_\_\_\_\_
1. pushing, ultrafiltration
2. pulling, reabsorption
3. pushing, reabsorption
4. pulling, ultrafiltration
28
Capillary Bulk Flow Notes
## Footnote
* *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*
1. *Vascular Space*
1. *Capillary Blood Pressure =*
2. *Capillary Oncotic Pressure =*
2. *Interstitial Space*
1. *Interstitial Hydrostatic Pressure =*
2. *Interstitial Oncotic Pressure =*
* *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 *
1. *Vascular*
1. *pushes against wall of capillary -\> ultrafiltration*
2. *albumin -\> reabsorption*
2. *Interstitial*
1. *reabsorption*
2. *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*
1. *vascular injury and it leaks out*
2. *histamine release enlarges capillaries (intentional escape of albumin*
* *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*
29
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
30
Third Space Accumulation Notes
## Footnote
* *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*
31
Part 4 ECF Electrolyte Balance
32
Alterations in the Movement of fluids between ICF and ECF
## Footnote
**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*
33
Isotonic Alterations
## Footnote
* 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
## Footnote
*Volume change, no change in osmolarity*
34
Hypertonic Alterations
## Footnote
* 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*
35
Hypotonic Alterations
## Footnote
* 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*
36
Potassium Balance
## Footnote
* 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**
37
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*
38
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*
39
Potassium Balance
Catecolamines
* B2 adrenergics = K+ moves ____ the cell
* a2 adrenergics = K+ moves ____ the cell
* into
* out
## Footnote
*Catecolamines (epi, norepi) - they can bind to adrenergic receptors -\> can cause potassium movement -\> but isn't strong enough to create serum level changes*
40
Factors controlling K metabolism
## Footnote
* Factors that shift K+ into cells (4)
* Factors that shift K+ out of cells (5)
41
Part 5 ECF pH Balance and Cellular Metabolism
42
Acid Base Balance
## Footnote
* 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*
43
Major Buffer Systems
## Footnote
(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*
44
Bicarbonate Buffer System
## Footnote
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*
45
Respiratory vs. Metabolic Acidosis/Alkalosis
## Footnote
* **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
46
Acid Base Balance Chart
47
Cell Metabolism
## Footnote
* *Cell Metabolism =*
* *Mono/Polysacharides = short/long chains of \_\_\_\_\_\_*
* *3 steps of Metabolism *
1. *\_\_\_\_\_\_ = process by which ____ ( polysaccharides, fructose, lactose) that's consumed and put through ______ to form \_\_\_\_\_\_then*
2. *\_\_\_\_\_\_*
3. *\_\_\_\_\_\_ -\> 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*
1. *Glycolysis = glucose -\> glycolysis -\> intermediates*
2. *Krebs cycle*
3. *Electron transport*
* *ATP*
48
Cell Metabolism
## Footnote
* *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
49
Controll of Cell Transport
## Footnote
1. **Passive Transport** *(needs no energy)* ****
* (3)
2. **Active Transport**
* ****(2)
1. Passive
* Simple Diffusion
* Osmosis
* Facilitated Diffusion
2. 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*
