Patho Exam 2

thrombocytopenia, hypercoagulation, white blood cell and lymphoid disorders, brain and motor function, sensory function of eye and ear, stress, fluid/electrolyte balance

What kind of disorders are ITP, TTP, and HIT

Platelet disorders

What is the starting point of all platelet disorders?

low platelet count- all disorders have this same starting point, but have different mechanisms, urgency, and treatment

Mechanism for ITP (immune thrombocytopenia)

Autoantibodies destroy platelets (Type II Mechanism)

Distinguishing feature of ITP

Isolated low platelets; PT/PTT normal

Treatment of ITP

Steriods, IVIG; splenectomy if refractory

Mechanism of TTP (thrombotic thrombocytopenic purpura)

ADAMTS13 deficiency (immune-mediated- adults or genetic- children) cause large vWF complexes remain (unable to be broken down into appropriate sizes) leads to spontaneous platelet clumping as vWF adheres to uninjured vessel walls

vWF

large blood protein that helps blood clot formation id

Distinguishing feature of TTP

symptoms: low platelets, fever, hemolytic anemia (due to RBC’s trying to pass by large endothelial platelet aggregates), neuro changes, renal injury

Treatment of TTP

EMERGENCY: plasma exchange.

platelet transfusion can worsen it; Monoclonal antibodies and corticosteroids can create remission

Mechanism of HIT (Heparin-induced thrombocytopenia

Antibodies target heparin- platelet factor 4 complex

platelet factor 4 complex

body develops this antibody to target heparin

promotes clotting instead of anticoagulation by tricking platelets into thinking there is sever injury that requires clotting

distinguishing feature of HIT

Paradoxical CLOTTING despite low platelets; onset days after heparin starts

HIT treatment

Stop all heparin now; switch to non-heparin anticoagulant

TTP vs. DIC

a common mix-up

both cause organ damage and low platelets, but PT/PTT are usually NORMAL in TTP (clotting factors aren’t consumed)

that is the distinguishing lab picture

PT/PTT blood test

measures how many seconds it takes for your blood to form a clot helping doctors evaluate your body's overall coagulation (clotting) system.

PT

Prothrombin time

Measures clotting time through the extrinsic and common pathways. It is mainly used to check response to blood-thinning medicines like warfarin and to evaluate liver function or vitamin K levels. Normal PT values are usually between 11 and 13.5 seconds, and a normal INR is 0.8 to 1.2.

PTT

Partial thromboplastin time

Measures clotting time through the intrinsic and common pathways. It is frequently used to monitor heparin therapy and check for bleeding disorders like hemophilia A or B. Normal PTT values generally range from 25 to 35 seconds.

INR

International Normalized Ratio

a standardized blood test that measures how long it takes for your blood to clot.

examples of inherited bleeding disorders

Hemophilia A, Hemophilia B. Von Willebrand Disease

Hemophilia A

Deficiency of Factor VIII in coagulation cascade

x-linked recessive inheritance

Hemophilia B

Deficiency of Factor IX in coagulation cascade

x-linked recessive inheritance

Van Willebrand disease

deficiency of Von Willebrand factor (affects platelet adhesion AND factor VIII)

usually autosomal dominant inheritance- the most common inherited bleeding disorder overall

What happens to the intrinsic pathway in Hemophilia A/B

Factor VIII (A) or IX (B) amplify the intrinsic pathway, ultimately disrupting it-

without it, the cascade can’t generate enough thrombin to build a STABLE fibrin mesh

VIII and IX are what conjoin and signal factor X to form stable fibrin clots

Why is bleeding ultimately delayed and not immediate in Hemophila A/B?

The initial platelet plug still forms normally

will have initial halt to bleeding from platelet plug, but after plug degradation, no fibrin clot to stop will cause late bleeding

Classic pattern of bleeding in Hemophilia A/B

normal bleeding right after injury, then re-bleeding hours later as the unstable plug breaks down; deep joint/muscle bleeds are typical

What two jobs does wVF do and why does that cause problems in Van Willebrand disease?

it helps platelets adhere to injured cell walls and it carries/protects factor VIII in circulation

losing the adhesion role produces immediate, platelet-type bleeding (mucosal, easy bruising)

losing the factor VIII protection role cal also produce some factor-deficiency-type bleeding- which is why vWD often looks like a blend of both patterns

What key labs do you assess in patients with bleeding risk?

Platelet count, PT/INR, PTT

helps identify where the problem is occurring

what assessments do you perform on patients with bleeding risk?

Skin (petechiae/ecchymosis), gums, urine/stool for occult blood, neuro checks if head injury risk

precautions taken for patients with bleeding risk

Soft toothbrush, electric razor, avoid IM injections/venipuncture when possible, prolonged pressure after draws

Medication safety for patients with bleeding risk

Caution with NSAIDs/aspirin- they impair platelet function further

no heparin or warfarin

What 3 factors make up Virchow’s Triad?

Venous Stasis, endothelial injury, and hyper coagulability

Venous statis

blood pooling in veins from immobility, long flights/surgery, heart failure

endothelial injury

damage to the tissue lining from trauma surgery IV catheters, atherosclerosis yperh

hyper coagulability

medical condition where the blood has an increased tendency to form abnormal blood clots

comes from inherited clotting disorders, pregnancy, oral contraceptives, malignancy, dehydration, post-op, cancer

Factor V Lesion (autosomal dominant hypercoagulable condition)

A mutated factor V resists being switched off by Protein C- the clotting cascade’s brake can’t stop it

makes a super clot

clinical clue: the single most common inherited hypercoagulable condition

Prothrombin gene mutation (autosomal dominant hypercoagulable condition)

produces excess prothrombin, raising a baseline thrombin generation

clinical clue: increases venous clot risk, especially combined with other risk factors

Protein C or S deficiency (autosomal dominant hypercoagulable condition)

not enough of the natural anticoagulant that normally inactivates factors Va and VIIIa

clinical clue: recurrent clots, sometimes clots at unusual sites

Antitrombin deficiency (autosomal dominant hypercoagulable condition)

Not enough protein that normally inhibits thrombin directly

clinical clue: often causes resistance to standard heparin dosing

Who would raise suspicion for a genetic hypercoaguablity condition?

an otherwise healthy young patient with an unprovoked DVT/PE or a strong family history of clotting

Deep vein thrombosis (DVT)

usually forms in the deep veins of the leg (or other extremities)

classic signs: unilateral leg swelling, warmth, tenderness, redness

Why does DVT present with swelling and warmth?

no venous return distally to heart leads to pressure in extremity and then swelling and warmth

What increases risk of DVT?

risk rises sharply with immobility (post-op, long travel, hospitalization)

prevention methods for DVT

early ambulation , sequential compression devices, prophylactic anticoagulation

What is prophylactic anticoagulation?

uses medications to prevent harmful blood clots in DVT and PE in high risk patients

Pulmonary Embolism (PE)

A DVT fragment breaks off and travels to the pulmonary vasculature

sudden dyspnea, pleuritic chest pain, tachycardia, hypoxia

a medical emergency- can be rapidly

What treatments are to be avoided in a patient with pulmonary embolism?

Never massage or vigorously manipulate a limb with a suspected DVT- it can dislodge the clot and cause PE

don’t ambulate a patient with PE until anti-coagulated

Explain the steps of (DIC Disseminated Intravascular Coagulation) - Clotting and bleeding at the same time

1. A trigger exposes blood to tissue factor on a massive, systemic scale- not just one injury site

   1. Sepsis, severe trauma/burns, obstetric emergencies, and some cancers each release or expose tissue factor through a different route, but the downstream effect is the same

2. That widespread exposure trigger inappropriate, system-wide activation of the clotting cascade

3. Tiny clots from throughout the microvasculature, consuming massive amounts of platelets and clotting factors

4. Organs suffer ischemic damage from all the micro clots blocking small vessels

5. With clotting factors and platelets now consumed and depleted, the body loses its ability to clot normally

The result: simultaneous, paradoxical clotting AND uncontrolled bleeding in the same patient

What is tissue factor in relation to DIC?

a cell surface protein that acts as the primary starter for blood clot formation when a blood vessel gets damaged. It is also known as coagulation factor III or CD142. [1, 2]

primary trigger that initiates DIC

What is paradoxical clotting in relation to DIC?

The simultaneous and contradictory occurrence of widespread blood clotting (thrombosis) and severe bleeding (hemorrhage)

Key labs in DIC

Falling platelets and fibrinogen, prolonged PT/PTT, rising D-dimer

all trending the wrong way at once

What is a D-dimer?

a small protein fragment that stays in your blood after your body breaks down a blood clot

will be elevated in DIC because of widespread clotting and clot breakdown

Assessment in DIC

Watch for bleeding, (IV sites, gums, GI/GU) AND signs of clotting (limb ischemia, altered mental status)

treatment focus of DIC

Treat the underlying cause (e.g. sepsis)

first, may need blood products (platelets, FFP, cryoprecipitate- able to transfuse only clotting factors) to relate consumed factors

Nursing priority of DIC

This patient can deteriorate quickly- frequent reassessment and early recognition are critical

What is therapeutic range for giving medication?

the blood concentration or dosage of a medication that safely produces the desired healing effect without causing dangerous side effects

Heparin (IV/SubQ) (anticoagulant medication)

monitor PTT (if on continuous IV drip- monitored often)

key nursing point: rapid on/off; reversal agent is protamine sulfate, usually only given in hospital

Warfarin (oral) (anticoagulant medication)

Monitor PT/INR (frequent until medication discontinued)

Key nursing point: slow onset (days); reversal is vitamin K; many food/drug interactions (vitamin K-rich foods) causing dietary alterations- eat the same amount of vitamin K foods daily

Direct acting oral coagulants (DAOCs) (e.g. apixaban, rivaroxaban)

(anticoagulant medication)

routine monitoring generally not required- no need to draw labs

Key Nursing Point: fewer interactions than warfarin, but reversal options are more limited depending on the agent

Low molecular weight heparin (e.g., enoxaparin/ Lovenox)

(anticoagulant medication)

routine monitoring generally not required- be aware of change in renal labs

given in hospital usually,

monitor renal function because it is dosed through kidney

Key nursing point: fixed subcutaneous does; longer, more predictable onset than IV heparin; reversible with protamine sulfate is only partial; renal dosing adjustment required, can be used inpatient and outpatient

do not have the potential for HIT to happen

Neutropenia

lack of white blood cells

neutrophils are the primary phagocyte in acute inflammation- too few and infection risk rises sharply

neutropenia and chemotherapy

the most common cause you’ll see clinically.

Most agents can’t tell a cancer cell from a normal dividing cell; they target rapidly dividing cell and bone marrow progenitors divide constantly- making them predictable collateral damage

What bone marrow problems can cause neutropenia?

Bone marrow disease or infiltration

leukemia crowding out normal precursors and limits proper function of WBC

other causes of neutropenia

certain medications, severe infections, autoimmune destruction of neutrophils

Neutropenic precaution

• Strict hand hygiene for everyone entering the room

• avoid fresh flowers/plants, raw fruits/vegetables per facility policy, live vaccines (don’t have the ability to have immune response)

• fever in a neutropenic patient is a medical emergency (“neutropenic fever”)- classic inflammatory signs may be blunted or absent

• private room may be indicated depending on severity

What common mechanism do all leukemia types share?

uncontrolled proliferation of abnormal white cells crowds out normal bone marrow function- producing the same triad seen in any marrow failure: anemia, infection risk, and bleeding risk together

Speed classifications of Leukemia

Acute (rapid onset, immature cells)

Chronic (slower onset, more mature cells)

Cell line classifications of leukemia

Myeloid line: RBC, WBC, platelets

Lymphoid line: B-cells, T-cells, natural killer cells

AML

acute myeloid leukemia

CML

Chronic myeloid leukemia

ALL

acute lymphoblastic leukemia (most common childhood leukemia)

CLL

chronic lymphocytic leukemia (most common adult leukemia)

What actually turns a marrow cell leukemic?

THINK: like a filing mistake inside a chromosome that jams the cell’s “stop dividing” switch

1. A filing mistake happens

   1. a piece of one chromosome breaks off and swaps places with a piece of a different chromosome (translocation) like tearing a page out one book and gluing it into another

2. Two genes get welded together

   1. if the break lands in the middle of two gens, their pieces fuse into one brand new gene that never existed before- a “fusion” gene

CML example of a marrow cell turning leukemic

BCR-ABL

• a piece of chromosome 9 swaps with chromosome 22. The ABL gene and BCR gene fuse together creating the Philadelphia chromosome’s BCR-ABL gene

The “stop” switch jams ON

• BCR-ABL makes a protein that tells the cell to keep dividing- permanently stuck in the ON position. The cell never gets the signal to stop or mature normally. Causes over production of WBCs crowding out all other cells in bone marrow.

What does the oncogene “look like” when a marrow cell turns leukemic?

a gene permanently switched on driving nonstop division with no off switch

What raises the odds of marrow cells turning leukemic?

• ionizing radiation exposure

• benzene and certain industrial chemical exposures

• prior chemotherapy (specifically alkylating agents) used to treat another cancer

• Down syndrome- trisomy 21 carries a markedly increased risk of ALL

• most cases still occur with no identifiable single cause- an accumulation of acquired mutations over time

lymphoma

cancer of the lymphoid tissue

• unlike leukemia lymphoma typically presents as a solid mass in lymphoid tissue rather than circulating abnormal cells

Hodgkin Lymphoma

Defining Feature: presence of Reed-Stenburg cells on microscopic exam

• Spreads in a predictable, orderly pattern from one lymph node group to adjacent ones

• generally has a more favorable prognosis than non-Hodgkin lymphoma

main symptom seen in Hodgkin lymphoma and why it happens

Painless, enlarged lymph node (often cervical or supraclavicular)

• malignant lymphocytes multiply and enlarge the node itself- there’s no infection or inflammation stretching the capsule quickly, which is why to doesn’t hurt the way an infected node would

“B” symptoms of Hodgkin lymphoma and why it happens

fever, night sweats, weight loss

• the tumor cells release cytokines that trigger a systemic inflammatory-type response, the same chemical signals infection would produce- driving fever, disrupted temperature regulation overnight, and a hypermetabolic, weight losing state

• along with node makes for poorer prognosis

Non-Hodgkin Lymphoma

• a large, diverse group of lymphoid cancers (no Reed-Stenburg cells)

• spread is far less predictable- can appear in multiple, non adjacent sites at once

• more common overall than Hodgkin lymphoma

main Non Hodgkin lymphoma symptom and why they happen

Swelling in multiple, scattered lymph node groups

• because spread doesn’t follow an orderly node-to-node path, malignant cells can pop in unconnected locations at the same time, instead of moving predictably outward from one site

Non Hodgkin lymphoma “B” symptoms and why they happen

fever, night sweats , weight loss

• driven by the same tumor-released cytokines as in Hodgkin lymphoma; in both types, their presence is an important prognostic finding

what actually triggers lymphoma

a malignant lymphocyte usually starts from a normal immune cell exposed to a specific, identifiable trigger

viral drivers of lymphocyte formation

EBV is strongly associated with Hodgkin lymphoma- Reed-Stenburg cells are frequently EBV positive, meaning the virus can push an infected B cell toward malignant transmmubiformation

immunosuppression related to lymphocyte formation

transplant rejection on immunosuppressants and patients with HIV/AIDS have sharply higher non-Hodgkin lymphoma risk- normal immune surveillance would otherwise catch these abnormal cells

chronic antigenic stimulation in relation to lymphocyte formation

long standing H. pylori infection can drive gastric Mucosa associated lymphoid tissue (MALT) lymphoma- years of chronic immune activation in one location raises the odds of a transformation event there

Multiple Myeloma

cancer of the antibody-making cells

plasma cells are mature B cells that secrete antibodies. Here, one clone multiples out of control

what is actually happening in multiple myeloma

• a single clone of plasma cells proliferates uncontrollably in the bone marrow

• that clone overproduces one abnormal antibody type, called an M-protein, while crowding out normal marrow function. The M-protein and the bone-damaging signal on the right are two separate products of the same malignant cell- one doesn’t cause the other

etiology of multiple myeloma

most cases arise from MGUS (monoclonal gammopathy of undetermined significance), a common usually silent precursor state that occasionally progresses to full myeloma over years. Age is the single biggest risk factor

(change in protein structure)

why bone pain and fractures happen in multiple myeloma

myeloma cells release cytokines (such as IL-6) that tell nearby bone marrow cells to ramp up RANKL (a signaling molecule). RANKL then activates osteoclasts (cells that eat bone) to resorb bone faster that it can rebuild, producing pathologic fractures and the classic “punched-out” lesions in imaging

why does kidney injury happen in multiple myeloma?

here the M-protein’s light chain fragments ate the direct cause - they are filtered by the kidneys and damage the renal tubules

why does hypercalcemia happen in multiple myeloma?

follows directly from the RANKL-driven bone breakdown above as bone resorbs faster than normal, calcium is released into the blood

nursing priority of multiple myeloma

fall/fracture precautions, monitoring renal function and calcium levels, and pain management

neural organization

the chain of command from brain to muscle- the foundation for everything else otm

motor disorders

what happens when a specific link in the chain from brain to muscle breaks

brain function disorders

what happens when the brain itself is injured, compressed, or short-circuits

the chain of command: upper motor neuron to lower neuron muscle

1. upper motor neuron

   1. cell body in the brain (motor cortex) the signal originates here and travels down the spinal cord

2. lower motor neuron

   1. cell body in the spinal cord; the signal exits here and travels through a peripheral nerve

3. neuromuscular junction

   1. where the nerve signal is chemically passed via (acetylcholine) to the muscle

4. muscle contraction

   1. the end result- voluntary movement actually happens

A lesion anywhere along this chain produces a different predicable clinical procedure

Why are deep tendon reflexes used as an assessment tool?

A reflex bypasses the brain entirely, which is exactly why it's such a useful, fast way to check the health of a specific nerve pathway.

the reflex arc

1. a stimulus (e.g. a reflex hammer tap on a tendon) activates a sensory receptor

2. the sensory neuron carries that signal directly into the spinal cord

3. inside the spinal cord, the signal synapses directly onto a motor neuron- no brain involvement needed

4. the motor neuron carries the signal back out to the muscle, producing the reflex (e.g. the knee jerk)

5. because this circuit is so direct, an abnormal reflex (absent diminished, or exaggerated) points to a problem at a specific, localizable level of the nervous system

Upper Motor Neuron (UMN) lesion

• stiffening of muscle tone

• hyperrelexsive (exaggerated) reflexes

• Positive Babinski sign (abnormal)

• little to no atrophy in muscle bulk early on

EXAMPLE: Stroke affecting the motor cortex