Exam 4 Pathophysiology

T3 and T4 production

Hypothalamus

→ thyrotropic RH

Anterior pituitary thyrotropes

→ TSH

Thyroid gland

= T3: active form (7%), inactive form (93%)

T4 is inactive for

3 weeks until it becomes T3 in the thyroid

T3 and T4 is made from

Tyrosine

Negative feedback for T3 and T4 system

• T3 and T4 is - FB for ant. pit. thyrotropes

• Anterior pit, thyrotropes is -FB for hypothalamus

Hypothyroidism

• slows metabolism, feel cold, gain weight, quickly fatigued, high cholesterol

• Myxedema: accumulation of protein complexes in interstitial spaces (causing non-pitted edema)

• Brain starts to compress and swells

Hypothyroidism causes

Hashimoto’s (MC), iatrogenic, drug induced, iodine deficiency, congenital (DiGeorge’s), transient (children or post-partum)

Hyperthyroidism 

• increase metabolism, hot, sweaty, weight loss, increased HR (mimic sympathetic response)

Hyperthyroidism is caused by

1. Grave’s disease: autoimmune aby against TSH receptor (stimulates the receptor)

2. Adenoma

3. Inflammation of thyroid gland

Thyroid storm

extreme example of hyperthyroidism

• release T3 and T4 at toxic levels

• seen in: surgery, sepsis, anesthesia

• mimics sympathetic response, HR gets so high that blood cannot pump

• TX: Lugol’s Iodine (decrease T3 and T4)

Goiter’s Thyroid Gland 

Increase in size→ affects neck; look for areas with the lowest pressure (jugular v. and esophagus)

• Hyperplasia: thyroid gland is enlarged

• Grave’s disease (mimics TSH): causes goiter

• decrease T3 and T4→ increase -FB→ increase TSH

Adrenal cortex 

Distal to kidney

1. Zone glomerulosa: aldosterone (Na+/K+/H+)

2. Zona fasciculata: cortisol

3. Zona reticularis: androgens (affects women libido)

Proximal to kidney

Cortisol (zona fasciculata)

Hyperglycemic state (energy in blood)

1. Glycogen: glycogenolysis (liver)→ glu in blood

2. Mobilize fats: around body and undergo gluconeogenesis

3. Protein degrade: gluconeogenesis (glucose in blood)- amino acids for wound repair

Adrenal cortex pathway

Hypothalamus

→Corticotropic RH

Anterior Pit. Gland Corticotropes

→ ACTH

Adrenal Cortex

= Cortisol

Adrenal cortex -FB mechanisms

• Cortisol is a -FB for ACTH and corticotropic RH

• ACTH is a -FB for corticotropic RH

Corticotropes

pro-opiocortin 

• ACTH

• MSH (pigmentation)

• endogenous opiates (pain)

Adrenal insufficiency (Addison’s)

• decreased cortisol, decrease -FB, increase ACTH

• hyperpigmentation (increase stimulation of MSH), hypo aldosterone

Adrenal hyperplasia (Cushing’s)

Can be congenital, malignancy, or infections

• increase cortisol, hyperglycemic, increase GH

• mobilize fats to trunk= Buffalo hump and Moon face

• protein degradation (muscle atrophy)

• increase androgens (hyperplasia)

  • In women: pseudohermaphrodite

  • In men: precocious puberty (3-5 yo)

Cardiac fibrous tissue (scar tissue)

calcified, rigid bands around the heart 

RA Calcified

SVC backup to the JV

• decreased venous return and back pressure (distention)

• Kussmaul’s sign: exaggerated JVD, constricted pericarditis

Pericarditis

• Friction rub

• Inflamed area= tough, grinding

  • loudest on the left

• Cardiac tamponade: decreased venous return and decreased cardiac output

Pulsus Paradoxus (pericarditis)

a result of pericarditis

• significant decrease in systolic pressure during inspiration due to L sided pressure buildup/compression

Myocarditis (viral)

inflammation of heart muscle without ischemia

• autoimmunity→ viral infection

Endocarditis (bacterial)

between the muscles and the blood

• Damage with clot/thrombus and bacteria that inflames the simple squamous epithelium of the endothelium

Pain in the parietal pericardium

Sympathetic innervation: T5 and T6

• passed to spinal cord to percieve pain

Cardiomyopathies

damage not associated with CHF, can cause CHF

Dilated cardiomyopathy

law of the heart, intrinsic mechanism, in=out

• dilate the myocardium and weaken the heart’s ability to pump blood effectively

Hypertrophic cardiomyopathy

Increase resistance of blood ejecting from the heart

• thick septal wall

• decrease ventricular volume, increase HR

Restrictive cardiomyopathy

Ventricular wall can’t stretch or fill properly

• amyloidosis: aby in tissue

  • antibody fragments= loght chains

Right Congestive Heart Failure (RCHF)

Back pressure towards the IVC, increase BH, filtration, and edema 

• First affected: liver (ascites)

• Second affected: kidney

Left Congestive Heart Failure (LCHF)

back pressure on the pulmonary vein

• lung→ edema

Angina

ischemia (decreased blood flow)

Stable (classical) angina

Felt on exertion

• atherosclerotic plaques from coronary arteries that increases resistance and limits blood flow

• Receptors C3→T4 

Variant Prinzmetal Angina

Vasospasm= vasoconstriction of coronary arteries

• Hyperactive sympathetic response

• defective handling of Ca++→ Ca influx

• decreased prostaglandin (PGI)

Unstable/Pre-Infarction Angina

increased frequency of stable angina, increase severity (thrombosis risk)

Aortic regurg

increase vent volume, increase workload, RVH

• water hammer pulse (sys-up, dia-down)

Pulm pressure of ____, is edema

30-50

ECG

• P-wave: atrial depol

• QRS complex: vent depol

• T-wave: vent repol

Sinus bradycardia 

<60 bpm

• due to increased vagal stimulation (parasympathetic rest and relax)

Sinus tachycardia

>100 bpm

• increased sympathetic innervation (C3→ T4)

• decreased parasympathetic/vagal innervation

Sinus dysrhythmia

irregular increase or decrease of patter; cyclic with respiration (regularly irregular)

Sinus arrest

SA node failure, escape pacemaker (typically in AV node)

Premature atrial contraction

ectopic pacemaker, ectopic focus, retrograde

• ectopic focus conducting to AV node

Atrial flutter (coordinated)

160-350 bpm, 2-4 p-waves for every Q-wave

Atrial fibrillation (uncoordinated)

more than 350 bpm, thrombus, not moving blood

1st degree AV block

taking too long to send signals, delayed

2nd degree AV Block Mobitz 1

PR interval gets longer and longer until a QRS is dropped

2nd degree AV Block Mobitz 2

sudden drop of a QRS 

3rd degree AV Block

complete block, no communication between atria and ventricles 

Ventricular Dysrhythmias

• Bundle block: alternate route

• PVC: ectopic focus, retrograde transmission (ectopic is pacemaker)

• Ventricular Bigemini (2 faced): normal and premature QRS

• Vent Tachy (160-250 bpm): decrease diastolic filling

• Vent Fib: (thrombus): uncoordinated cardiac muscle contractions (no pulse)

Aneurysm

1. Berry: circle of willis

2. Fusiform

3. Sacular

4. Dissecting (lethal, tear bifurcates)

Hypertension

tone, increase BH pushing forward/outward

• tunica media had to push harder (thick)

• smooth muscle undergoes hyperplasia and decreased the diameter of the blood vessel

• increase resistance, slow blood flow

• increase workload of the heart 

Vasoconstrictor HTN (sympathetic)

• Alpha 1 adrenergic receptor: vasoconstriction, lo affinity for epi and NE

• Beta 2 adrenergic receptor: smooth muscle dilation, hi affinity for epi and NE 

Hemodynamic HTN

1. Increased renin

• Angiotensinogen→ Angiotensin 1 and 2 (hi)

  • increase aldosterone, increase Na+ absorption, increase B.V., increase blood pressure

2. Decreased renin

• Inapropriate high aldosterone

• Normal aldosterone (essential/idiopathic)

• low aldosterone (hi Na+ intake)

Atherosclerotic plaques

1. atherosclerosis monocyte

2. macrophages (orchestrate healing)

• Pick up LDL and tranform into foam cells

  • diabetic mutated B100 cells 

3. Foam cells (LDL-oxidize)

4. Proinflammatory cytokines

Fat, LDL, cholesterol foam cells= fat streak

Red streak: rip endothelium and form clot, thromboembolis (extrinsic clotting cascade)

Deep Vein Thrombosis (DVT)

Virchow’s Triad

1. Venous stasis: pooled blood (low flow)

2. Hypercoagulability: increased TH→ filtered out edema and concentrate plasma proteins

3. Venous wall injury: inflammation 

Disseminated Intravascular Coagulation (DIC)

Activate clotting cascade

1. Excessive activation of thrombin= excess clotting

2. Excess conversion to plasmin= excess bleeding 

Shock (decreased BP)

1. Hypovolemia

• hemorrhage, plasma loss (diarrhea, vomiting), decrease BP no perfusion

2. Cardiogenic

• damage to the heart, restricted filling of the heart

3. Distributive

• inflammation, causes extensive distributive vasodilation (systemically)

  • Clin med: sepsis 

Islets of Langerhan (endocrine pancreas)

• Alpha cell: glucagon (fasting hormone)

• Beta cell: insulin (storage hormone)

Type 1 Diabetes mellitus

juvenille onset, insulin-dependent

• destroy B-cells (insulin)

• cause acromegaly

• autoimmunity can lead to type 1 DM

Type 2 Diabetes Mellitus

adult onset, insulin and independent (can become independent)

• insulin receptor is insensitive (not responding)

• large adipose (obese): dilate receptors, not as effective

Gestational diabetes

In pregnancy, can develop to Type 2

• Hx, obese, 5+ children

• placental hormone 

  • somatomammotropin: insulin insensitive (more nutrients in the blood for the baby)

  • glucagon dominant, fasting state