NUIP 2420: Midterm #1

Stress, Homeostasis, Immunology, Hematology, Pulmonology

homeostasis

• self-regulating process by which living organisms maintain a stable internal environment despite changes in their external surroundings

• “Goldilocks”

physiological stress

as any external or internal condition that challenges the homeostasis of a cell or an organism

includes psychological and physical causes

stimuli

stress serve as ___ in compensatory stress responses

compensatory stress responses

mechanisms the body uses to aid in survival by helping the body to return the body to homeostasis; activated by a stimulus

illness, disability, or potentially death

what happens if the body cannot effectively adapt?

central stress responses

• facilitation of arousal, alertness, vigilance, cognition, attention, and aggression

• inhibition of reproduction and growth

• activation of feedback loops

• involves the brain and cognition

it shuts down more essential systems

what happens in the central stress response if there is longterm stress?

peripheral stress responses

• increased respiration/oxygenation and cardiovascular tone

• nutrition of the brain, heart, and skeletal muscles

• increased metabolism

• increased detoxification of metabolic products and foreign substances

• ex: when you are exercising

stimulus

any physical, chemical, or environmental factors or disturbance that causes deviation of normal body environment

receptor/sensor

• detects changes in the environment and forwards this information to the control center/regulator

• ex: peripheral chemoreceptors detect changes in the pH

control center/regulator

receives and processes the information, compares it to a reference “set point,” then stimulates a response in an effector organ/tissue (if needed)

ex: hypothalamus controls and regulates temperature, BP, circadian rhythms

effectors

• acts to bring about changes in order to restore homeostasis

• ex: renal tubules reabsorb water into the blood stream to change osmolarity

response

the reaction to the stimulus is a corrective measure undertaken to return the body to a normal steady state, and it can oppose or enhance a change or output

negative feedback loop

• reduces or opposes a change happening within the body

• ex: thermoregulation tries to keep the body/achieve normothermia

positive feedback loop

• enhances or amplifies a change/output

• “gas pedal”

• e.g., childbirth: baby’s head presses on the cervix → receptors signal the brain → oxytocin is released → contractions → increased pressure → more contractions

alarm

resist

exhaust

what are the three phases of the stress response?

Amygdala sends a distress signal to the hypothalamus when someone experiences a stressful event

hypothalamus detects a set-point violation and activates

what are the two areas of the brain that become activated by a stressor and what do they do?

• hypothalamus-pituitary-adrenocortical (HPA) axis

• sympatho—adrenomedullary system (SAS)

what are the two mechanisms of stress adaptation?

hypothalamus-pituitary-adrenocortical (HPA) axis

• chronic > acute

• Mediated by the hypothalamus

• production/secretion of glucocorticoids → CORTISOL

• adaptive redirection of energy and behavior

sympatho-adrenomedullary system (SAS)

• acute > chronic

• mediated by the brainstem

• production/secretion of catecholamines → EPI AND NOREPI

• “fight or flight” response

cortisol

• glucocorticoid hormone synthesized in the adrenal cortex

• primary hormone for the stress response

• levels naturally vary throughout the day

increases blood glucose

accelerates K+ excretion

blocks the proliferation of T-cells

stifles inflammatory response via inhibition of histamine

What 4 things does cortisol do when synthesized?

it causes longterm release of cortisol, which blocks the proliferation of t-cells

How does long-term stress cause immunosuppression?

sympatho-adrenal system

• activation is beneficial during times of acute stress/threat

• threat is resolved → stress stimulation stops

• “fight or flight” response

Contractility of cardiac muscle (BP control)

contraction of the iris dilator

piloerection

relaxation of smooth muscles in GI tract, urinary tract, and bronchioles

increase blood glucose levels

What are the functions of catecholamines? (5)

compensatory reserve

• the maximum amount of time or effort possessed by an individual to maintain homeostasis before they can no longer compensate

• varies based on factors like age, health status, and duration/intensity of the stressor

DISABILITY OR DEATH

when compensatory reserve is exhausted, ___ or ___ is imminent

• stop the stimulus

• would close and blood vessel repair

• IV fluids

• supplemental oxygen

• pain management

How can you clinically manage compensatory reserve? (5)

C) adaptation

A patient experiences severe blood loss after a traumatic injury. The body activates mechanisms that increase cardiac output and alter blood vessel constriction in an attempt to maintain adequate tissue perfusion. What concept best describes these responses?

A) Positive feedback

B) setpoint violation

C) adaptation

D) exhaustion

A) Thermoregulation uses negative feedback

B) Blood glucose regulation can involve negative feedback

D) they reduce or oppose a change

Which statements about negative feedback loops are supported by the presentation? Select all that apply.

A) Thermoregulation uses negative feedback

B) Blood glucose regulation can involve negative feedback

C) they amplify the original change until an endpoint is reached

D) they reduce or oppose a change

C) Sympatho-adrenmedullary system

A student is suddenly frightened by a dangerous situation and immediately develops a rapid stress response. Which system is primarily responsible for this acute 'fight-or-flight' response?

A) HPA Axis

B) Renal feedback system

C) Sympatho-adrenmedullary system

D) Parasympathetic nervous system

B) CRH → ACTH → cortisol

Which sequence correctly describes the HPA axis during a stress response?

A) Cortisol → CRH → ACTH

B) CRH → ACTH → cortisol

C) ACTH → CRH → cortisol

D) CRH → cortisol → ACTH

B) relaxation of GI smooth muscle

During an acute stress response, the adrenal medulla releases epinephrine and norepinephrine. Which effect is consistent with the presentation?

A) decreased blood glucose through increased insulin secretion

B) relaxation of GI smooth muscle

C) reduced cardiac contractility

D) increased digestive activity

A) Stifling inflammatory responses

B) Increasing blood glucose through gluconeogenesis

C) inhibiting proliferation of some T-cells

Which functions are associated with cortisol according to the presentation? Select all that apply.

A) Stifling inflammatory responses

B) increasing blood glucose through gluconeogenesis

C) inhibiting proliferation of some T-cells

D) increasing reproductive activity during stress

True!

T/F: The parasympathetic nervous system dominates during a relaxed state and promotes the 'rest and digest' response.

SAS

A person suddenly encounters a dangerous situation and immediately has increased heart rate, dilated pupils, and increased blood glucose. Which stress-response system is primarily responsible?

innate immunity

adaptive immunity

what are the two branches of the immune system?

Bloodborne defenses

physical barrier defenses

what are the two defenses (categories) in innate immunity?

skin

mucous membranes

saliva

flushing action or urine and tears

stomach acid

what are the main 5 physical barriers

they stop the infection before it enters the body

how do physical barriers protect against infection?

complement cascade

phagocytes

What are the two subcategories of bloodborne immunity?

t-cell immunity

b-cell immunity

what are the two categories of immunity in adaptive immunity?

suppressor TC

helper TC

cytotoxic TC

what are the three types of t-cells in adaptive immunity?

t cells

b cells

NK cells

What cells come from the lymphoid progenitor cell line that help with adaptive immunity?

platelets

eosinophils

basophils

erythrocytes

dendritic cells

macrophages

neutrophils

What cells come from the myeloid progenitor cell line that help with innate immunity?

the innate immune system

what are these characteristics of?

• primitive and broad

• immediate reaction

• lower potency

• short response

• no memory

the adaptive immune system

what are these characteristics of?

• highly specific

• takes approx. 3 days

• higher potency and regulation

• long-term

• memory

neutrophils

eosinophils

basophils

what are the three PMN’s to know?

after phagocytosis of a pathogen

presence of certain antibodies

interactions with adaptive immune cells

exposure to certain substances

What are the four stimuli in which granulocytes degranulate?

neutrophils

eosinophils

basophils

mast cells

what are the four main types of granulocytes to know?

tumor necrosis factor alpha

interleukin

lysozymes

interferons alpha, beta, gamma

prostaglandins

What are the 5 main cytokines to know?

mast cells

• less responsive to pathogens

• more responsive to mechanical, chemical, thermal, and immunologic stimuli

• produces HISTAMINE

pattern recognition receptors (PRR)

• expressed on cells near body surfaces (ex: epithelium)

• recognize two patterns

  • infectious agents on surfaces of cells, or floating in the blood

  • damaged cells

• infectious agents on the surfaces of cells or floating in the blood

• damaged cells

what are the two patterns that PRR recognize?

toll-like receptors

• specific class of PRR

• recognize a large variety of infectious agents on cells surfaces or within nucleic acid

• 11 different receptors available

• found on mucosal epithelium, mast cells, neutrophils,macrophages,dendritic cells

cell signaling (chemotaxis of neutrophils to the site)

interferon production (signals to other cells to increase defense)

proinflammatory cytokine release

what activates toll-like receptors? (3)

Chemotaxis

movement of an organism or cell in response to a chemical stimulus

neutrophils

• most abundant and responsive

• phagocyte, granulocyte, PMN

• moves freely in the bloodstream

• rush quickly to the site of an infection or injury when chemical signals tell them there is trouble

macrophage

• phagocyte

• lives in tissue near the interfaces with the outside world

• ingests extracellular pathogens

• has TLRs

• secretes numerous cytokines → increase innate and adaptive immunity

dendritic cells

macrophages

b cells

what are the 3 APC’s?

• APC finds and swallows a foreign invader

• Enzymes break down the pathogen into smaller protein pieces

• The cell attaches these tiny antigens to MHC molecules

• APC travels to a lymph node and presents the complex to a matching naive T cell

What are the steps (starting with engulfing a pathogen) that lead an APC to trigger the adaptive immunity?

Antigen-presenting cells (APCs)

• capture, process, and display foreign pathogen fragments on their surfaces using major histocompatibility complex (MHC) molecules to activate T cells.

• include dendritic cells, macrophages and b cells

MHC I

• present in all cells that have a nucleus + platelets

  • NOT RBCs!!!

• used to identify “self” and signal a healthy cell

• presents antigen when there is an intracellular problem (ex: cancer)

• recruits CD8 T cells

when there is an intracellular problem like cancer

When does MHC 1 trigger cytotoxic T cells?

MHC II

• present ONLY on APCs

• used to display antigen after phagocytosis as a means to stimulate an adaptive immune system response

• presents antigen when there is an extracellular problem

• recruits CD4 t-cells

when there is an extracellular problem

When does MHC 1 trigger CD4 T cells?

dendritic cells

• can be derived from lymphoid and (primarily) myeloid

• professional phagocytes

• reside in tissues with macrophages that interface with the outside world

• migrate to lymph nodes where they interact with T cells and B-cells to initiate/mediate the adaptive immune system

cytokine stimulation

activates T-cells

What happens when dendritic cells travel to the lymph nodes and interact with T-cells and B-cells?

• allergies

• some autoimmune diseases such as Lupus and IBS

What alterations in dendritic cell function are associated with?

complement cascade

set of serum proteins that can be activated early in pathogen invasion by bacterial products or by the adaptive immune system via antigen-antibody complexes

• recruitment of inflammatory cells

• opsonization

• killing of pahtogens

what are the three primary effects once complement has been activated?

PMN’s

monocytes

What cells does the complement cascade recruit for an inflammatory cell?

opsonization

• triggered by complement activation

• pathogen is coated in opsonins (complement proteins or antibodies) to facilitate ingestion by phagocytes

the Membrane Attack complex (MAC) pokes holes in the membrane of pathogen leading ot cell lysis and death

How does complement activation killing pathogens?

coagulation (clotting) cascade

• activated by complement and inflammatory cytokines

• increases thromboxane, platelet-activating factor, fibrinogen

• platelets = inflammatory mediators

kinins

• activated by the coagulation/clotting cascade

• stimulate vasodilation, increases capillary permeability, and pain

increases blood flow to the area, which increases nutrients and immune cells going to the area

why do blood vessels dilate with inflammation?

allow immune cells and proteins to reach injured or infected tissues

why does capillary permeability increase with inflammation (“capillary leak”)?

NK cells

• tumor rejection

• destruction of infected cells

• release of perforin and granzymes → apoptosis

• main targets: tumor cells and viruses

inflammation

protective response to injury that includes vascular, cellular, and chemical components which facilitate the delivery of blood plasma and cells to the site of the injury

• dilute toxins and prevent further injury via edema

• remove pathogens and cell debris via phagocytosis

• initiate healing and repair

• wall off infection

What are the 4 functions of inflammation?

1. brief vasoconstriction

2. vasodilation that brings increased blood flow to the area

3. endothelial cells retract, opening the spaces between cells and allowing fluids to move out of the vessel

What are the steps of the vascular response of inflammation?

brings cells, fluids, and proteins to the area of injury, and causes the skin near the injury to become red and warm

what happens when blood vessels dilate in inflammation?

fluid exudation

• leakage of fluid, cells, and proteins from blood vessels into nearby tissues due to inflammation or injury

• can be serous, cloudy, or purulent

1. macrophages and mast cells in the tissue recruit PMN’s

2. Neutrophils adhere to contracted endothelial cells and move through the spaces

3. neutrophils phagocytize pathogens/debris and release hydrolytic enzymes

4. opsonization

What are the steps in the cellular response of inflammation?

margination

• apart of cellular response to inflammation

• the physiological process where white blood cells (leukocytes) move away from the center of blood flow and drift toward the inner walls (endothelium) of blood vessels

Diapedesis

• apart of the cellular response to inflammation

• Process by which white blood cells squeeze through the walls of blood vessels to enter surrounding tissues.

vasodilation

Increased vascular permeability

chemotaxis of inflammatory and adaptive immune cells

What are the localized effects of cytokines?

stimulate increased production of leukocytes, glucocorticoids, and acute phase proteins

What are the systemic effects of cytokines?

acute phase proteins (APP’s)

• proteins that change their serum concentration by >25% in response to inflammatory cytokines

  • primarily IL-1B, IL-6, and TNF-α

• primarily produced/regulated by the liver → also by epithelial and endothelial cells

fever

leukocytosis

increased cortisol

decreased thyroxine and serum iron

What systemic effects do APP’s play a role in for the inflammatory response?

positive acute phase proteins

what are these examples of?

• C-reactive protein

• serum amyloid A

• haptoglobin

• complement

• fibrinogen

negative acute phase proteins

what are these examples of?

• albumin

• transferrin

• transthyretin

there will be decrease levels of albumin

What happens to albumin when there is a lot of inflammation?

macrophages promote inflammation during the acute phase reaction and then promote healing of damaged tissue/remodeling

what happens when there is a chemical response in inflammation?

• pain/tenderness

• warmth

• erythema

• edema

what are localized clinical manifestations of inflammation?

• fever

• diaphoresis

• anorexia

• weight loss/wasting

• somnolence

what are systemic clinical manifestations of inflammation?

acute phase proteins/reactants

CBC with differential

What are blood tests that can show inflammation?

• C-reactive protein

• erythrocyte sedimentation rates

• fibrinogen, complement, albumin

What are the three specific acute phase protein tests that can show inflammation?

it shows all immunes cells and specific amounts of them

why do you need a CBC with differential to test for inflammation?